Can CBD oil help with cancer, and if so, how? 

  • The results of a 2014 study revealed that a Cannabis sativa extract with a high content of cannabidiol weakened colon cancer formation and inhibited cancer cell proliferation via the activation of cannabinoid receptors(1).
  • A 2016 study published in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry found that cannabinoids could impede the growth of tumor cells(2)
  • A study published in the journal Oncotarget in 2019 demonstrated that CBD could initiate cell death and make glioblastoma cancer cells more sensitive to radiation, without affecting healthy cells(3).
  • CBD might also enhance the uptake or increase the potency of certain drugs used for cancer treatment, as a 2020 review published by the National Cancer Institute suggests(4).

Best CBD Oil for Cancer

Editor's Pick

Spruce 750mg Lab Grade CBD Oil

Specifically formulated to be more palatable to CBD users
Spruce 750mg Lab Grade CBD Oil Bottle
  • Overall Clinical Score
    99%
    Editor's Pick
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...New CBD users
  • Summary

    Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.

    Pro's
    Cons's
     Mid-strength  No other flavors
     Natural peppermint flavor
     Made from 100% organic and natural ingredients
  • Features
    Discount pricing available?20% Off Coupon Code: CBDCLINICALS
    Source
    Source of Hemp
    Kentucky, USA & North Carolina, USA
    FormOil Tincture
    IngredientsOrganic Hemp Seed Oil, Full Spectrum CBD Oil
    Type
    Type of CBD
    Full Spectrum
    Extraction
    Extraction Method
    Moonshine extraction method
    How to take itUnder tongue
    Potency
    Potency - CBD Per Bottle
    750 mg per bottle
    Carrier OilOrganic Hemp Seed Oil
    Concentration
    CBD Concentration Per Serving
    25mg of CBD per dropper full (1ml)
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
    FlavoursPeppermint
    Price Range$89 ($75.65 for subscriptions, 15% discount from regular price)
    $/mg CBD
    Price ($/mg)
    $0.12/mg ($0.10/mg with subscription)
    Shipping
    Shipping/Time to delivery
    2-4 business days (first class USPS)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    ContaminantsOrganic, Non-GMO, no pesticides, no herbicides, no solvents or chemical fertilizers, No preservatives or sweeteners
    AllergensVegan, Gluten free
    Refund policyWithin 30 days
    Recommended forNew CBD users
    Countries servedUSA only (all 50 states)
Check Latest Prices
Best Organic

Nuleaf Naturals 725mg Full Spectrum CBD Oil

Perfect for anyone who are looking for CBD products that promote a healthy body and mind.
Nuleaf Naturals 725mg Full Spectrum CBD Oil
  • Overall Clinical Score
    99%
    Best Organic
  • Clinical Scores
    Value
    Quality
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    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Health conscious
  • Summary

    Natural remedy for various illnesses. There are approximately 300 drops in this 0.5 FL OZ bottle, where 1 drop = 2.4 mg of CBD.

    Pro's
    Cons's
     Pure CBD hemp  No other flavors
     All natural
     Approximately 300 drops total
  • Features
    Discount pricing available?20% Off Coupon Code: CBDCLINICALS20
    Source
    Source of Hemp
    Colorado, USA
    FormOil Tincture
    IngredientsUSDA Certified Organic Hemp Oil, Full Spectrum Hemp Extract
    Type
    Type of CBD
    Full Spectrum CBD
    Extraction
    Extraction Method
    CO2 Method
    How to take itUnder the tongue for approximately 30 seconds before swallowing
    Potency
    Potency - CBD Per Bottle
    725mg of CBD per 0.5 FL OZ (15ml)
    Carrier OilOrganic Hemp Oil
    Concentration
    CBD Concentration Per Serving
    48.33mg to a max of 51.82mg per 1ml
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
    FlavoursNatural
    Price Range$99.00 - 1-pack, $434.00 - 6-pack
    $/mg CBD
    Price ($/mg)
    1-pack - $0.13, 6-pack - $0.59
    Shipping
    Shipping/Time to delivery
    2-3 Days via USPS
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    ContaminantsNo additives or preservatives, Non-GMO, NO herbicides, pesticides, or chemical fertilizers
    AllergensNot specified
    Refund policyWithin 30 days
    Recommended forHealth conscious
    Countries servedUSA (all 50 states) and over 40 countries including Australia, Azerbaijan, Beliza, Bosnia & Herzegovina, Brazil, Chile, China, Croatia, Czech Republic, Estonia, France, Hong Kong, Hungary, Ireland, Israel, Japan, Latvia, Lebanon, Lithuania, Macao, Malaysia, Malta, Netherlands, New Zealand, Oman, Parguay, Poland, Portugal, Saudi Arabia, Serbia, Singapore, South Korea, Sweden, Switzerland, United Arab Emirates, United Kingdom, Uruguay, and many more.
Check Latest Prices
Best Customer Service

Sabaidee Super Good Vibes CBD Oil

4x the strength of a regular cbd oil
Sabaidee Super Good Vibes CBD Oil
  • Overall Clinical Score
    99%
    Best Customer Service
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Patients who are looking for serious CBD oil support
  • Summary

    Super Good Vibes CBD Oil provides the purest and highest quality Cannabidiol (CBD) on the market as well as other high quality phytocannabinoids, terpenes, vitamins, omega fatty acids, trace minerals, and other beneficial for your health elements, which all work together to provide benefits.

    Pro's
    Cons's
     Extra strong  No other flavors
     Significant benefits with just a few drops
     100% Natural ingredients
  • Features
    Discount pricing available?15% Off Coupon Code: CBDCLINICALS15
    Source
    Source of Hemp
    Colorado, USA
    FormOil Tincture
    IngredientsCannabidiol (CBD), Coconut Medium-chain triglycerides (MCT) Oil, Peppermint oil
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2-extraction
    How to take itUsing 1-3 servings per day as needed is a good start to determine how much you need
    Potency
    Potency - CBD Per Bottle
    1000 mg per bottle
    Carrier OilCoconut MCT Oil
    Concentration
    CBD Concentration Per Serving
    33.5 mg per dropper (1ml)
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
    FlavoursPeppermint
    Price RangeSingle Bottle - $119.95, 2-Pack - $109.97 each, 3-Pack - $98.31 each, 6-Pack - $79.99 each
    $/mg CBD
    Price ($/mg)
    Single bottle - $0.010, 2-Pack - $0.011, 3-Pack - $0.009, 6-Pack - $0.007
    Shipping
    Shipping/Time to delivery
    3-5 Business days
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    ContaminantsContaminant-free
    AllergensVegan and Gluten-free
    Refund policyWithin 30 days
    Recommended forPatients who are looking for serious CBD oil support
    Countries servedUSA only (all 50 states)
Check Latest Prices
Natural Alternative

cbdMD CBD Oil Tinctures

Uses USA hemp that is grown on non-GMO farms, and is both vegan and gluten-free
cbdMD CBD Oil Tinctures Products
  • Overall Clinical Score
    99%
    Natural Alternative
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...CBD users with different needs
  • Summary

    cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.

    Pro's
    Cons's
     Plenty of concentrations to choose from for all people with various kinds of needs  cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options
     Has vegan, organic, and gluten-free ingredients
     Affordable pricing
     Affordable pricing
  • Features
    Discount pricing available?15% Off Coupon Code: cbdMD15
    Source
    Source of Hemp
    Kentucky, USA
    FormOil Tincture
    IngredientsCannabidiol (CBD), MCT Oil, and Flavoring
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2 extraction method
    How to take itUnder tongue
    Potency
    Potency - CBD Per Bottle
    300 mg - 7500 mg / 30 ml bottle, 1000 mg - 1500 mg / 60 ml bottle
    Carrier OilOrganic Coconut MCT Oil
    Concentration
    CBD Concentration Per Serving
    30 ml: 300 mg - 10 mg per dropper (1ml), 750 mg - 25 mg per dropper (1ml), 1500 mg - 50 mg per dropper (1ml), 3000 mg - 100 mg per dropper (1ml), 5000 mg - 166.6 mg per dropper (1ml), 7500 mg - 250 mg per dropper (1ml), 60 ml: 1000 mg - 16.6 mg per dropper (1ml), 1500 mg - 25 mg per dropper (1ml)
    Drug TestContaining less than 0.3% THC, there are still trace amounts
    FlavoursNatural, Berry, Orange and Mint
    Price Range30 ml Bottles: $29.99 for 300 mg, $69.99 for 750 mg, $99.99 for 1500 mg, $149.99 for 3000 mg, $239.99 for 5000 mg, $339.99 for 7500 mg 60 ml Bottles: $74.99 for 1000 mg, $99.99 for 1500 mg
    $/mg CBD
    Price ($/mg)
    30 ml - $0.05 - $0.10, 60 ml - $0.06 - $0.07
    Shipping
    Shipping/Time to delivery
    2-5 Business days (via Fedex)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants100% organic, non-GMO, and vegan-certified
    AllergensVegan, Gluten free
    Refund policyWithin 30 days
    Recommended forCBD users with different needs
    Countries servedUSA only (all 50 states)
Check Latest Prices

Why People Are Turning to CBD for Cancer

Whether one is struggling with this disease or knows someone who has received a cancer diagnosis, the question of whether CBD may help has probably crossed someone’s mind. 

A 2016 study published in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry examined the use of cannabinoids as anticancer agents(5). 

According to the study, which was conducted on animal models of cancer, there was evidence supporting the idea that cannabinoids could impede the growth of tumor cells.

CBD might also enhance the uptake or increase the potency of certain drugs used for cancer treatment, as another review published by the National Cancer Institute (NCI) suggested(6). 

There are several promising studies about CBD’s use in cancer treatment:

  • A study published in the journal Oncotarget in 2019 demonstrated that CBD could initiate cell death and make glioblastoma cells more sensitive to radiation, without affecting healthy cells(7).

Glioblastoma is cancer that can occur in the brain or spinal cord.

  • A review of several studies showed cannabinoids as promising compounds in the treatment of gliomas(8). Results were published in the Journal of Neuro-Oncology in 2014. 

Glioma is a tumor type that starts in the glial cells that surround nerve cells and help them function.

  • Results of a 2012 study published in the Indian Journal of Urology suggested that cannabinoids should be considered as agents for the management of prostate cancer(9).
  • Another research in the journal Breast Cancer Research and Treatment showed the efficacy of CBD in pre-clinical representations of metastatic breast cancer(10). 

The researchers found that CBD significantly reduced breast cancer cell invasion and proliferation.

  • The results of a 2014 study revealed that a standardized Cannabis sativa extract with a high content of cannabidiol weakened colon cancer formation. 

The same high-CBD extract inhibited colorectal cancer cell proliferation via the activation of CB1 and CB2 receptors(11). 

The results, which were published in Phytomedicine, might have some clinical relevance for the use of cannabis-based medicines in cancer patients

  • On the other hand, a recent review in the Journal of Pancreatic Cancer focused on the potential use of cannabinoids for the treatment of pancreatic cancer(12). 

Data showed that cannabinoids might help slow down the growth and invasion of tumors. 

The authors concluded that cannabinoids, such as CBD and THC, might be useful adjuncts for the treatment of pancreatic cancer.

  • Data presented in a 2019 review indicated that CBD might have had a role in the striking response in one lung cancer patient as a result of the self-administration of CBD oil(13). 

The patient took CBD oil for a month, without making any other distinct lifestyle, drug, or dietary changes.

  • In another study, the authors found a promising relationship between cannabis and bladder cancer(14).

After adjusting for age, race or ethnicity, and body mass index, researchers found that using tobacco only was linked to an increased risk of bladder cancer.

Cannabis use only was connected to a 45% reduction in bladder cancer incidence.

While research has demonstrated that cannabis smoke still generates carcinogens, the correlation between inhaled marijuana and cancer remains inconclusive.

Still, further work is necessary to better assess the impact of CBD on malignant cells and its potential application in the treatment of cancer.

How CBD Oil Works to Help With Cancer

There are many types of cancer treatment, such as surgery, radiation therapy, chemotherapy, immunotherapy, targeted therapy, hormone therapy, stem cell transplant, and precision medicine(15). 

The types of treatment that individuals with cancer receive depend on the type of cancer they have and how advanced it is.

Some people with cancer have only one treatment. However, most people have a combination of treatments(16). 

The aim of most cancer treatment is to achieve remission, which means all signs and symptoms of cancer have disappeared. 

When remission is unlikely, treatment can help relieve symptoms to help individuals with cancer feel as comfortable as possible and may allow them to live longer. This is called palliative treatment(17).

CBD for Nausea and Vomiting

Doctors use chemotherapy to cure cancer, reduce the prospect of its return, or slow or stop its growth. Chemotherapy can also be used to shrink tumors.

While this treatment is valuable, it also brings about side effects that patients may feel the need to delay or quit the treatment altogether. 

According to the National Cancer Institute, typical side effects of chemotherapy include fatigue, nausea, diarrhea, mouth sores, hair loss, and anemia(18).

Fortunately, most side effects are short-term and can be managed. They tend to gradually improve once treatment stops, and the normal, healthy cells recover(19). 

Studies have demonstrated that CBD might help with some of these cancer symptoms. 

A 2014 review from the European Journal of Pharmacology established the potential of cannabis to limit or prevent nausea and vomiting from a wide range of causes(20).

A 2011 study published in the British Journal of Pharmacology showed that, as an antiemetic (preventing nausea), CBD might help reduce nausea and vomiting induced by chemotherapy(21).

CBD for Pain and Inflammation

Pain is the most common symptom in cancer patients, while inflammation is implicated in cancer development and progression.

During cancer treatment, about six out of ten people say they experience pain. People with advanced cancer are slightly more likely to experience pain(22).

CBD may be useful in treating different types of chronic pain(23).

A study published in the Journal of Pain and Symptom Management showed that THC:CBD extract was efficacious for pain relief in patients with advanced cancer pain not fully relieved by potent opioids(24). 

CBD may also help with inflammation. A 2016 animal study from the European Journal of Pain showed that CBD applied on the skin might help reduce pain and inflammation due to arthritis(25). 

CBD’s potent anti-inflammatory properties were also demonstrated in a 2018 study published in the Journal of Pharmacology and Experimental Therapeutics(26). 

Inflammation may also be the cause of certain diseases and disorders, such as central nervous system (CNS) vasculitis (the inflammation of blood vessel walls in the spine or brain), inflammatory bowel disease (IBS), rheumatoid arthritis, and high blood pressure, and cardiovascular diseases(27).

CBD for Improved Appetite

People who go through cancer treatment may experience loss of appetite, which can make it challenging to maintain a healthy weight.

Appetite stimulation by cannabinoids has been studied for several decades, particularly in relation to weight loss and malnutrition associated with cancer, acquired immunodeficiency syndrome (AIDS), or anorexia nervosa.

A study on the relationship between cannabinoids and food intake suggested that endocannabinoids could impact energy balance and food intake within the brain(28).

A 2018 study conducted on 2,409 CBD users found that 6.35% experienced increased hunger as a side effect(29).

Meanwhile, in a study done on children with epilepsy, results varied. Some children experienced increases in appetite, while others experienced decreases(30). 

More longitudinal research is necessary to understand the full effects of CBD on appetite, as it seems to vary. 

Many factors may influence hunger when taking CBD, including genetics and the type of product used.

CBD for Anxiety, Stress, and Sleep Problems

Individuals diagnosed with cancer may experience emotions that induce anxiety, sadness, fear, sleep problems, and confusion.

A 2017 study published in Current Psychiatry Reports suggested that medium or high-dose CBD is associated with an increase in the percentage of total sleep(31).

Research published in the journal Therapeutic Advances in Medical Oncology in 2019 indicated that taking CBD oil might help address anxiety and sleep disorders(32). 

Results showed that CBD might help patients fall asleep and reduce the frequency of waking up at night.

The data also supported the use of cannabis to address the debilitating symptoms of cancer and its treatments, including chemotherapy-induced nausea and vomiting, loss of appetite, and pain.

The authors of a 2019 study published in the Brazilian Journal of Psychiatry looked at CBD’s effects on anxiety and stress(33). 

In the study, the group that took 300 mg of CBD experienced the most noticeable reduced stress response. 

Results demonstrated that CBD could help reduce the response to stressful environmental factors when given in the optimal dosage.

In a 2019 study published in The Permanente Journal, sleep and anxiety scores were measured in human subjects, and the findings showed that CBD could hold benefits for anxiety-related disorders(34).

CBD for Tumor Growth

Several studies in the journal Molecular Cancer Therapeutics showed CBD-induced cell death of breast cancer cells, suggesting that the use of CBD oil might also suppress tumor growth(35).

In a 2017 study published in the International Journal of Oncology, the results showed that the use of CBD in conjunction with anti-leukemia drugs made the drugs more effective(36).

Researchers found that when certain cannabinoids are paired together, the resulting product could be combined with conventional anti-leukemia drugs, allowing the dose of the toxic agents to be substantially reduced yet remain effective.

Research in the journal Future Medicinal Chemistry demonstrated that cannabinoids might also prove beneficial in certain types of cancers activated by chronic inflammation(37)

In such instances, cannabinoids, as anti-inflammatory agents, could either directly prevent tumor growth or suppress inflammation.

The Endocannabinoid System Explained: How CBD Oil Helps in Apoptosis and Immunity

The endocannabinoid system (ECS) is primarily responsible for the regulation of different body functions, including mood, behavior, appetite, pain, sleep, and energy. 

The ECS also impacts cell growth and apoptosis. Apoptosis is a natural body process where the cells are destroyed as part of a particular organism’s growth. 

Cancer is caused by the abnormal proliferation and mutation of cells. Cancer cells develop because they no longer recognize the body’s signals that encourage or destroy cell growth.

A review published in the journal Toxicologic Pathology was conducted to examine apoptosis, the process of programmed cell death(38).

The results of the study indicated that apoptosis should be carefully regulated because too few or too many cell deaths lead to diseases, including developmental abnormalities, autoimmune diseases, neurodegeneration, or cancer.

Apoptosis, also referred to as cellular suicide, is a normal process of cellular self-destruction that serves a healthy and defensive role in the body.

Cancer cells no longer acknowledge the body’s signals that encourage or destroy cell growth. Thus, as these cells grow and divide, they proliferate uncontrollably.

The endocannabinoid system is essential in the body because it also helps in regulating cell growth and death.

As cancer cells reproduce more rapidly than the endocannabinoid system can manage, metastasis occurs. 

Metastasis is the process where cancer cells invade through the healthy tissues from the place where they first formed and spread to another part of the body.

The endocannabinoid system has two primary receptors: CB1 receptors are mostly found in the brain, while CB2 receptors are situated in the immune system.

THC is the cannabinoid that latches onto the CB1 receptors and is responsible for mood, behavior, and other brain functions.

On the other hand, CBD binds to CB2 receptors, signaling for ‘invaders’ that are damaging to the body.

Apoptosis helps support the immune system through the critical role it plays during viral infections, killing off invaded cells before they spill over with virus particles. 

For example, when a harmful invader, such a cold or flu virus, or the coronavirus that causes COVID-19, gets into the body, the immune system mounts an attack,  

This attack, known as an immune response, involves various cells and unfolds over time. This act of self-sacrifice hampers the spread of viruses and can save the whole organism(39).

The receptor activation helps the endocannabinoid system signal a warning to counteract the formation of tumors, impeding cancer development through inhibiting reproduction, metastasis, and tumor development.

Mixed Results

The studies on cannabinoids, including CBD and THC, and their impact on cancer and its symptoms did not always yield positive results. 

The National Cancer Institute (NCI) reviewed numerous studies on the correlation between marijuana use and cancer and found that the research results varied(40).

Studies published in the journal Cancer Medicine in 2018 looked into the current state and future perspectives of cannabinoids in cancer biology(41).

While cannabinoids showed antitumor activity in animal models of cancer, further longitudinal studies are still needed to verify their efficacy and safety on humans.

In a 2019 study in the Bosnian Journal of Basic Medical Sciences, researchers recognized the antitumor effects of cannabinoids in various cancer types(42).

However, these antitumor effects of cannabinoids have to prevail over their known immunosuppressive effects, which can potentially promote the production or formation of tumors.

In a study published in 2010 in the European Journal of Immunology, researchers using a mouse model found that cannabinoids can initiate the suppression of the immune system(43).

Although this particular research involved cannabis containing tetrahydrocannabinol (THC), the results indicate that cannabinoids could make users more susceptible to some types of cancer.

CBD research is still limited when it comes to cancer prevention. Scientists would have to conduct longitudinal studies of humans with CBD alone, controlling for frequency of use and dosing.

The Pros and Cons of CBD Oil for Cancer 

The Pros

  • Studies have shown that CBD may help with cancer symptoms, such as nausea, vomiting, inflammation, sleep problems, anxiety, stress, depression, cancer pain, and loss of appetite.
  • Studies have also shown that CBD may help suppress tumor growth and strengthen immunity.
  • CBD has been well-received by several health agencies, like the World Health Organization (WHO), which states that CBD “is generally well-tolerated with a good safety profile”(44). CBD oil may be safer than most over-the-counter and prescription drugs that may have many side effects.
  • CBD is non-addictive, says Nora Volkow, director of the National Institute on Drug Abuse (NIDA) in a 2015 article. This characteristic makes CBD safe for daily intake(45). 
  • CBD oil may be purchased without a prescription in locations where they are legally available.

The Cons

  • Studies are too limited to determine whether or not CBD is an effective treatment for conditions other than the ones approved by the U.S. Food and Drug Administration (FDA).
  • As with the use of any natural chemical compound, there are risks involved in using CBD. According to the Mayo Clinic, possible side effects of CBD include drowsiness, dry mouth, diarrhea, fatigue, and reduced appetite(46). 
  • CBD has been shown to interact with other drugs and alter how the body metabolizes certain medications, as a 2017 research revealed(47). Consult with a health professional experienced in cannabis use before starting a CBD regimen or combining it with current prescription medications.
  • The lack of regulation on CBD products makes it difficult to determine whether the CBD gummies, tinctures, patches, balms, and gelcaps contain what the product label claims.

A 2107 review published in the Journal of the American Medical Association revealed labeling inaccuracies among CBD products. Some products had less CBD than stated, while others had more(48). 

How CBD Oil Compares to Alternative Treatments for Cancer

Alternative cancer treatments may not directly cure cancer. However, these treatments may help individuals with cancer cope with symptoms caused by cancer and cancer treatments

Common symptoms, such as anxiety, fatigue, nausea and vomiting, pain, difficulty sleeping, and stress, may be lessened by alternative treatments (49).

Mayo Clinic’s recommendations can be summarized as follows:

When experiencing:Consider trying these alternative treatments:
AnxietyHypnosis, massage, meditation, relaxation techniques
FatigueExercise, massage, relaxation techniques, yoga
Nausea and vomitingAcupuncture, aromatherapy, hypnosis, music therapy
PainAcupuncture, aromatherapy, hypnosis, massage, music therapy
Sleep problemsExercise, relaxation techniques, yoga
StressAromatherapy, exercise, hypnosis, massage, meditation, tai chi, yoga

Aromatherapy and essential oils may be used safely by cancer patients for short-term benefits. 

These benefits include reducing anxiety and depression symptoms and improving sleep, according to a 2012 study(50).

Meanwhile, studies have found that massage can help relieve pain in people with cancer. It may also help relieve anxiety, fatigue, and stress(51).

CBD is also used in aromatherapy and massage, taking advantage of the cannabis plant’s terpenes that are used to create an essential oil. 

Terpenes are responsible for the flavors and aroma of cannabis and influence its effects by interacting with cannabinoids.

When combined with other essential oils, CBD stimulates one’s sense of smell and heightens the soothing benefits of a massage. 

When applied topically, CBD oil gets absorbed into the skin and targets cannabinoid receptors found in the skin’s mast cells and nerve fibers. 

The reaction gives a calming, anti-inflammatory effect with localized benefits all over the skin and muscles. 

Massages are used as a wellness and healing practice, and with an infusion of pure CBD hemp extract, the therapeutic benefits increase.

How to Choose the Right CBD for Cancer 

As shown in clinical trials and studies on cannabis and cannabinoids, CBD is not the only cannabinoid found in cannabis that can help treat cancer symptoms

Hence, when choosing a CBD product, opt for one that contains the full spectrum of phytonutrients from hemp, including trace amounts of THC, terpenes, fatty acids, flavonoids, and essential oils.

Those with allergies to THC may use a broad-spectrum CBD oil, which is like full-spectrum CBD but without the THC that makes the user high.

However, regardless of the form of CBD product of choice, careful consideration must still be employed in selecting the best CBD oil to help suppress tumor growth and proliferation and relieve cancer symptoms.

The following factors are essential to ensure the safety and reliability of the CBD products purchased:

  1. Research on the exact legal stipulations applicable to CBD in the area where it would be bought and used.
  2. Purchase only high-quality, non-GMO CBD products from legitimate and reliable brands. The majority of companies that manufacture the best CBD oil products grow their hemp from their own farm, or they purchase from licensed hemp producers.
  3. Research product reviews before buying from an online store. When purchasing from a physical store or dispensary, check whether the store is authorized by the government to sell CBD.
  4. Knowing the extraction methods used in making the CBD oil is also essential. Researchers of a study indicate that the Supercritical-CO2 process is recognized as safe by the United States Food and Drug Administration (FDA) in pharmaceutical manufacturing(52). 
  5. One important thing to look for in CBD products is certification codes. Several certification authorities approve certain products only after some thorough screening tests. 
  6. Compare company claims about their products’ potency with that of the third-party lab results. Look for a certificate of analysis for every product purchased.

Best CBD Oil for Cancer

Editor's Pick

Spruce 750mg Lab Grade CBD Oil

Specifically formulated to be more palatable to CBD users
Spruce 750mg Lab Grade CBD Oil Bottle
  • Overall Clinical Score
    99%
    Editor's Pick
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...New CBD users
  • Summary

    Each bottle of the 750mg CBD oil tincture contains 25mg of CBD per dropper full. The oil is peppermint flavor to mask any unpleasant tastes related to CBD.

    Pro's
    Cons's
     Mid-strength  No other flavors
     Natural peppermint flavor
     Made from 100% organic and natural ingredients
  • Features
    Discount pricing available?20% Off Coupon Code: CBDCLINICALS
    Source
    Source of Hemp
    Kentucky, USA & North Carolina, USA
    FormOil Tincture
    IngredientsOrganic Hemp Seed Oil, Full Spectrum CBD Oil
    Type
    Type of CBD
    Full Spectrum
    Extraction
    Extraction Method
    Moonshine extraction method
    How to take itUnder tongue
    Potency
    Potency - CBD Per Bottle
    750 mg per bottle
    Carrier OilOrganic Hemp Seed Oil
    Concentration
    CBD Concentration Per Serving
    25mg of CBD per dropper full (1ml)
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
    FlavoursPeppermint
    Price Range$89 ($75.65 for subscriptions, 15% discount from regular price)
    $/mg CBD
    Price ($/mg)
    $0.12/mg ($0.10/mg with subscription)
    Shipping
    Shipping/Time to delivery
    2-4 business days (first class USPS)
    Lab Tests
    Lab Testing Transparency
    Third Party Lab Tested post formulation for safety and potency, available on website
    ContaminantsOrganic, Non-GMO, no pesticides, no herbicides, no solvents or chemical fertilizers, No preservatives or sweeteners
    AllergensVegan, Gluten free
    Refund policyWithin 30 days
    Recommended forNew CBD users
    Countries servedUSA only (all 50 states)
Check Latest Prices
Best Organic

Nuleaf Naturals 725mg Full Spectrum CBD Oil

Perfect for anyone who are looking for CBD products that promote a healthy body and mind.
Nuleaf Naturals 725mg Full Spectrum CBD Oil
  • Overall Clinical Score
    99%
    Best Organic
  • Clinical Scores
    Value
    Quality
    Strength
    Customer Service
    Lab Testing Transparency
    Effectiveness
    Perfect for...Health conscious
  • Summary

    Natural remedy for various illnesses. There are approximately 300 drops in this 0.5 FL OZ bottle, where 1 drop = 2.4 mg of CBD.

    Pro's
    Cons's
     Pure CBD hemp  No other flavors
     All natural
     Approximately 300 drops total
  • Features
    Discount pricing available?20% Off Coupon Code: CBDCLINICALS20
    Source
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    FormOil Tincture
    IngredientsUSDA Certified Organic Hemp Oil, Full Spectrum Hemp Extract
    Type
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    Full Spectrum CBD
    Extraction
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    CO2 Method
    How to take itUnder the tongue for approximately 30 seconds before swallowing
    Potency
    Potency - CBD Per Bottle
    725mg of CBD per 0.5 FL OZ (15ml)
    Carrier OilOrganic Hemp Oil
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    48.33mg to a max of 51.82mg per 1ml
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
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    Recommended forHealth conscious
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Sabaidee Super Good Vibes CBD Oil

4x the strength of a regular cbd oil
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    Super Good Vibes CBD Oil provides the purest and highest quality Cannabidiol (CBD) on the market as well as other high quality phytocannabinoids, terpenes, vitamins, omega fatty acids, trace minerals, and other beneficial for your health elements, which all work together to provide benefits.

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     Extra strong  No other flavors
     Significant benefits with just a few drops
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    Discount pricing available?15% Off Coupon Code: CBDCLINICALS15
    Source
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    Colorado, USA
    FormOil Tincture
    IngredientsCannabidiol (CBD), Coconut Medium-chain triglycerides (MCT) Oil, Peppermint oil
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2-extraction
    How to take itUsing 1-3 servings per day as needed is a good start to determine how much you need
    Potency
    Potency - CBD Per Bottle
    1000 mg per bottle
    Carrier OilCoconut MCT Oil
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    33.5 mg per dropper (1ml)
    Drug TestContains 0.3% THC but there is a chance you may test positive for marijuana
    FlavoursPeppermint
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    Single bottle - $0.010, 2-Pack - $0.011, 3-Pack - $0.009, 6-Pack - $0.007
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    Countries servedUSA only (all 50 states)
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Natural Alternative

cbdMD CBD Oil Tinctures

Uses USA hemp that is grown on non-GMO farms, and is both vegan and gluten-free
cbdMD CBD Oil Tinctures Products
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    cbdMD’s CBD oil tinctures are made using only CBD sourced from medical hemp and MCT oil as a carrier oil. Tinctures are offered in orange, mint, natural, and berry flavors. Safe for daily use, the oil tinctures are packaged with a built-in rubber dropper to adjust CBD dosage easily. The packaging is made to be easy to transport and discreet to use.

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     Plenty of concentrations to choose from for all people with various kinds of needs  cbdMD uses MCT as its carrier oil so individuals who are allergic with coconuts should consider other brand options
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    Discount pricing available?15% Off Coupon Code: cbdMD15
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    FormOil Tincture
    IngredientsCannabidiol (CBD), MCT Oil, and Flavoring
    Type
    Type of CBD
    Broad Spectrum
    Extraction
    Extraction Method
    CO2 extraction method
    How to take itUnder tongue
    Potency
    Potency - CBD Per Bottle
    300 mg - 7500 mg / 30 ml bottle, 1000 mg - 1500 mg / 60 ml bottle
    Carrier OilOrganic Coconut MCT Oil
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    CBD Concentration Per Serving
    30 ml: 300 mg - 10 mg per dropper (1ml), 750 mg - 25 mg per dropper (1ml), 1500 mg - 50 mg per dropper (1ml), 3000 mg - 100 mg per dropper (1ml), 5000 mg - 166.6 mg per dropper (1ml), 7500 mg - 250 mg per dropper (1ml), 60 ml: 1000 mg - 16.6 mg per dropper (1ml), 1500 mg - 25 mg per dropper (1ml)
    Drug TestContaining less than 0.3% THC, there are still trace amounts
    FlavoursNatural, Berry, Orange and Mint
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    30 ml - $0.05 - $0.10, 60 ml - $0.06 - $0.07
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    Shipping/Time to delivery
    2-5 Business days (via Fedex)
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    Third Party Lab Tested post formulation for safety and potency, available on website
    Contaminants100% organic, non-GMO, and vegan-certified
    AllergensVegan, Gluten free
    Refund policyWithin 30 days
    Recommended forCBD users with different needs
    Countries servedUSA only (all 50 states)
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CBD Dosage for Cancer 

The most effective therapeutic dose of CBD for any particular medical condition is still unknown, Peter Grinspoon, M.D., said in an article posted in Harvard Health(53).

CBD is mostly marketed as a supplement, not a medication. Currently, the U.S. Food and Drug Administration (FDA) does not regulate the safety and purity of dietary supplements. 

Thus, CBD consumers cannot know for sure that the product they buy has active ingredients at the dose listed on the label. The CBD product may also contain other unknown elements. 

The American Cancer Society supports the need for more longitudinal and extensive research on cannabinoids for cancer patients

The Society recognizes the need for more effective therapies that can overcome the often debilitating side effects of cancer and its treatment(54).

Clinical trials testing CBD as a single drug or in combination therapies in treating cancer are both warranted and urgently needed.

How to Take CBD Oil for Cancer 

Currently, there is no clinical evidence that using CBD oil can treat or prevent cancer, says Pharmacist Jason Hou. 

Hou is an integrative medicine specialist who manages Memorial Sloan Kettering’s About Herbs database.

Still, some people use CBD to alleviate cancer symptoms. 

When CBD oil is ingested, some amount gets absorbed and becomes available in the bloodstream. 

Then, when CBD binds to the cannabinoid receptors throughout the body, they trigger biological effects. 

Other CBD edible products, such as CBD tincture, CBD gummies, and CBD gelcaps are likely absorbed and metabolized (broken down) in a similar manner as CBD oil

CBD oil tincture may also be taken sublingually, with drops placed under the tongue. 

According to studies, CBD oil has a sublingual bioavailability of 13% to 19%, with some studies putting it as high as 35%(55).

Bioavailability is the extent and rate to which a compound or an active drug ingredient is absorbed and becomes readily available for the body to use(56).

CBD may also be used in massage therapies or applied as a lotion, cream, balm, or salve. There is, however, limited absorption through the skin with topical CBD oil.

For topical products, look for keywords on the product labels that indicate that the product uses nanotechnology, encapsulation, or micellization of CBD. 

These words indicate that their solution can carry CBD through the dermal layers, rather than just staying on the skin.

CBD oil vapes are one of the quickest ways to get CBD into the body since it enters the bloodstream through the lungs, without going through the digestive system. 

However, the American Cancer Society Cancer Action Network (ACS CAN), the Society’s advocacy affiliate, opposes the smoking or vaping of medical marijuana and other cannabinoids in public places. 

Carcinogens in marijuana smoke pose numerous health hazards to the patient and others in the patient’s presence(57).

Comparing CBD and THC

CBD comes from cannabis and is naturally found in hemp plants. CBD is one of more than 100 cannabinoids that occur naturally within the plant. This compound is also commonly used to produce CBD hemp oil supplements. 

Cannabis oil is a term used to refer to any extract of the cannabis plant, including marijuana plant and hemp plant, that removes the plant’s naturally thick, viscous oil from dried or fresh cannabis.

Medical marijuana, also called medical cannabis, is made of dried parts of the Cannabis sativa plant.

Hemp seed oil is produced by extracting the oil from the seeds of the hemp plant itself. This oil is abundant in nutrients, such as omega-3 and omega-6 fatty acids, making it ideal for digestion. 

Although some people refer to “hemp extract” as hemp oil, the term “hemp oil” is synonymous with the term “hemp seed oil.”

Chemical compounds in cannabis, called cannabinoids, have shown various potential benefits by activating the body’s endocannabinoid system (ECS)

The ECS is involved in regulating a variety of body processes and functions, including sleep, appetite, pain, and immune system response(58).

The body produces endocannabinoids, which are neurotransmitters that bind to cannabinoid receptors in the nervous system.

The medicinal efficacy of cannabis can be optimized by incorporating the various cannabinoids, flavonoids, and terpenes that are intrinsic components of cannabis plants.

CBD is non-psychoactive, contrasting with THC (delta-9-tetrahydrocannabinol), another primary cannabinoid

THC is the most significant factor contributing to the high associated with using cannabis. 

Consuming CBD without any THC does not produce those effects, which means that nearly everyone should be able to function as they usually do when taking CBD. 

The lack of high lets one continue with work, school, and other commitments without a decrease in performance. 

The absence of psychoactive effects also makes CBD oil safe to take, even for those who must pass regular or random drug tests.

CBD oil must not contain any THC for CBD not to induce psychoactive effects. 

Products containing CBD isolates do not have THC, while full-spectrum CBD oil products do. 

The full spectrum of cannabinoids, terpenes, fatty acids, and essential oils extracted from the plant all work together in synergy. 

This synergy magnifies the therapeutic benefits of individual cannabinoids and produces a phenomenon known as the “entourage effect.”

Any product that one buys should also state the percentage of THC, information which one can also get from its certificate of analysis.

CBD and Synthetic Cannabinoids in FDA-Approved Drugs

CBD is used in the treatment of some types of epilepsy, such as Dravet’s Syndrome, a complex disorder in children that is associated with a high rate of mortality and drug-resistant seizures.

Epidiolex (cannabidiol) oral solution is the first drug approved by the FDA for the treatment of seizures in individuals two years of age and older(59). 

The scientific study of cannabinoids has led to two FDA-approved drugs, dronabinol, and nabilone. These medications contain THC in pill form(60).  

Some of the medical benefits of THC include:

  • increased appetite
  • reduced nausea
  • pain relief
  • decreased inflammation (swelling and redness)
  • better muscle control

THC was also shown to help stop the growth of cancer cells

In a 2014 study with rodents published in Molecular Cancer Therapeutics, results suggested that purified extracts from whole-plant marijuana can delay the progression of cancer cells from one of the most severe types of brain tumors(61).  

Dronabinol and nabilone are both synthetic forms of THC and are used to treat nausea caused by chemotherapy. 

These drugs also increase appetite in patients with extreme weight loss caused by acquired immunodeficiency syndrome (AIDS).

The United Kingdom, several European countries, and Canada have approved nabiximols (Sativex), a CBD and THC-infused mouth spray. 

Sativex is used for muscle control problems due to multiple sclerosis (MS), although it is not FDA-approved.

Sativex mouth spray has demonstrated its efficacy not only for helping with pain management in patients with chronic neuropathic pain, pain due to nerve damage, peripheral neuropathic pain, advanced cancer pain, and rheumatoid arthritis but also for spasticity due to multiple sclerosis (MS)(62). 

Conclusion

The mechanism by which CBD works is still not fully understood. However, experts recognize its ability to work through a variety of pathways in the body and induce different therapeutic effects. More scientific research is still needed.

It is essential to understand both the possible benefits and cancer risks of CBD in medical use, either as adjunct cancer therapy or for improving health conditions

Consult with a doctor experienced in cannabis use before using CBD or cannabis products to alleviate cancer symptoms or treat diseases.

For more information on cancer and the different types of cancer, cancer.gov may be an excellent resource. 

Cancer.gov is the website for the National Cancer Institute (NCI), the U.S. government’s principal agency for cancer research. 

NCI links users of cancer.gov website directly to the National Library of Medicine (NLM)’s PubMed database for journal citations.


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  2. Velasco G, Hernández-Tiedra S, Dávila D, Lorente M. The use of cannabinoids as anticancer agents. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:259–266. DOI:10.1016/j.pnpbp.2015.05.010.
  3. Ivanov VN, Wu J, Wang TJC, Hei TK. Correction: Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells. Oncotarget. 2019;10(65):7012–7013. Published 2019 Dec 10. DOI:10.18632/oncotarget.27352.
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  12. Sharafi G, He H, Nikfarjam M. Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer. J Pancreat Cancer. 2019;5(1):1–7. Published 2019 Jan 25. DOI:10.1089/pancan.2018.0019.
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  25. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016;20(6):936–948. DOI:10.1002/ejp.818.
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  31. Babson KA, Sottile J, Morabito D. Cannabis, Cannabinoids, and Sleep: a Review of the Literature. Curr Psychiatry Rep. 2017;19(4):23. DOI:10.1007/s11920-017-0775-9.
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  36. Scott KA, Dalgleish AG, Liu WM. Anticancer effects of phytocannabinoids used with chemotherapy in leukaemia cells can be improved by altering the sequence of their administration. Int J Oncol. 2017;51(1):369–377. DOI:10.3892/ijo.2017.4022.
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  61. Scott KA, Dalgleish AG, Liu WM. The combination of cannabidiol and Δ9-tetrahydrocannabinol enhances the anticancer effects of radiation in an orthotopic murine glioma model. Mol Cancer Ther. 2014;13(12):2955-2967. DOI:10.1158/1535-7163.MCT-14-0402.
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What is Cancer?

Cancer is a non-contagious disease caused by the abnormal, uncontrolled growth of cells. Our bodies are constantly making new cells and normally cells grow and multiply in a systematic way. However, in someone with cancer, they behave abnormally and may grow into a tumour. These tumours can be benign (not cancerous) or malignant (cancerous). Cancer cells also have the ability to spread throughout the body – this is known as metastases.

Cause of Cancer in Children

For the majority of children with cancer, it is not possible to identify an exact cause or explanation for developing cancer. Fewer than 5% of childhood cancers are due to genetic conditions.

It is important to remember that nothing you or your child did caused the cancer to happen. Nothing you could have done, would have prevented the cancer occurring.

Common Childhood Cancers

Acute leukaemia (including lymphoblastic and myeloid types) are the most common, representing 35% of all childhood cancers

Other common cancers include:

Central nervous system tumours – 17%
Lymphomas or tumours of lymphatic tissue – 11%
Neuroblastoma and Neural Crest Tumours – 8%
Wilms’ Tumour – 7%
Rhabdomyosarcoma and Soft Tissue Sarcomas – 5%

Late Effects
At the Kids Cancer Centre (KCC), the motto is ‘Cure is not enough.’ The aim of the Oncology team is to have survivors who are free of handicaps caused by their disease or its treatment, who are able to keep up and compete with their peers, who are employable, insurable and able to take their rightful place in society.

Since the 1960s, the proportion of children surviving five years or more after being diagnosed with cancer has risen from less than 25 per cent to about 80 per cent. In Australia and other western countries, it is estimated one in every 640 young adults (aged 16 to 45) will be a survivor of childhood cancer. This translates into about 21,000 survivors in Australia.

Care and follow-up of this expanding long-term survivor group has become a vital part of paediatric oncology.

During the first five years after diagnosis, the main focus of the medical team is on detecting early complications of therapy and checking for any signs the disease is coming back. This changes when a child passes the five-year mark from diagnosis, at which point the main focus shifts to identifying signs of any late effects of therapy.

Hugo’s Story
At only 36 hours old, little Hugo was admitted to Sydney Children’s Hospital, Randwick (SCH), where he was diagnosed with Hirschsprung’s Disease, a medical condition that affects the bowels causing chronic constipation

Alyssa’s Story
When ten-month-old Alyssa developed rashes around her ankles, her mum Amanda rushed her to Sydney Children’s Hospital, Randwick, fearing she had meningitis. While this was ruled out, doctors told her devastated parents little Alyssa had infantile ALL – Acute Lymphoblastic Leukaemia. Alyssa

Jayden’s Story
Jayden has a rare and incurable blood clotting disorder, Severe Haemophilia A. It means he is missing a clotting factor (Factor VIII) in his blood and for the rest of his life is prone to spontaneous bleeding, especially internally.

Ashleigh’s Story
I first experienced pain when exercising in the summer of 2010. I initially visited a podiatrist and physiotherapist which seemed to provide short term relief. My pain escalated rapidly in April 2012, so I decided to make an appointment with a new GP who organized a bone scan that showed a large

Ashleigh’s Story
I first experienced pain when exercising in the summer of 2010. I initially visited a podiatrist and physiotherapist which seemed to provide short term relief. My pain escalated rapidly in April 2012, so I decided to make an appointment with a new GP who organized a bone scan that showed a large pelvic mass and following this, a number of investigations in the hospital.

I was told by doctors that I had Ewing’s Sarcoma of my pelvis. This is a cancer that occurs in the bone. The cancer started in my pelvis but had spread through to my spine and brain. I was in an adult hospital and the initial consultant had heard about the Youth Cancer Service with medical expertise of looking after young adults with cancer.

The team had a clinical trial open and although I was older than most patients, my consultant had organized for me to have my treatment here so I had an opportunity of the best chance of survival.

Dr Antoinette Anazodo explained everything to me carefully and clearly so I would understand the course of treatment and knew in detail the steps I would need to take to treat the cancer. The treatment would involve 12 months of chemotherapy as well as surgery radiotherapy and then a transplant. If I went through this, the chance of me surviving was still only 25%.

In May of 2012, I started chemotherapy treatment and received this in Sydney Children’s Hospital under the care of the Sydney Youth Cancer Team.

After three months of intense chemotherapy I was told that the tumour had responded really well to treatment and no active cells could be seen on the PET scan. It was then time to have the operation to remove the tumor. I had the tumour resected and also needed a hip replacement. After the operation I was told that some areas of my pelvic mass had active cells in so I needed to have further radiotherapy to the pelvis. This made me feel very anxious about my future fertility and I was seen by the adolescent gynecology team to discuss options for fertility preservation again.

Chemotherapy was hard but I was lucky to have lots of support around me. My family came to every appointment; they allowed me to make decisions and supported me when making decisions was very difficult. The Sydney Youth Cancer Team gave me appropriate information and support so I could understand my treatment and the effects on my body. I felt supported and trusted the decisions I made.

This has been the longest year of my life. It also happened to be my HSC year. My illness and treatment made me completely unable to study or attend school and having the education counselor available to help me understand my options was invaluable. I celebrated my 18th birthday in an isolation room having my transplant but I have been able to get through the year thanks to the medical and psychosocial support I received by the Sydney Youth Cancer Team. I am a much stronger person and have lots of hopes and dreams which are still positive. I am having some time to recover from treatment but next year I will start training to be a nurse. I would like to help others in the way I have been helped.

Alyssa’s Story
When ten-month-old Alyssa developed rashes around her ankles, her mum Amanda rushed her to Sydney Children’s Hospital, Randwick, fearing she had meningitis. While this was ruled out, doctors told her devastated parents little Alyssa had infantile ALL – Acute Lymphoblastic Leukaemia.

Alyssa went through months of intensive chemotherapy treatment and spent more than 18 months in the Hospital. Her mum Amanda said Alyssa reached a lot of milestones in the Hospital, including her first steps. “She had just undergone chemo and she got down and just started walking up and down the corridor, I was in floods of tears and so were the nursing staff,” she said.

After going through months of intensive chemotherapy and dealing with the many side-effects including nausea, Alyssa underwent a cord transplant eight months after being diagnosed. She spent about four months in isolation in the Hospital, to ensure she didn’t contract any infections after the transplant and then her parents were allowed to take her home. They kept her basically in isolation at home for another few months away from anywhere they thought she may get sick.

Since then, Alyssa has finished treatment and is now in remission, much to the delight of her parents and older sister. She’s at pre-school, enjoying swimming lessons and now only comes into the Hospital once every eight weeks. She recently celebrated her third birthday at home with her family.

“Alyssa wouldn’t be here without the dedication of the Hospital staff,” Amanda said. “We were made to feel by the staff that Alyssa was only child being treated, which of course is not true, such was the dedication of the doctors and nurses.”

“We never felt alone during our time at the Hospital, there was always someone going in to bat for Alyssa’s life.”

“We will be forever grateful to the Hospital, the staff and anyone who has ever donated.”

 

Jatropha curcas L.

1. NAME
1.1 Scientific name
1.2 Family
1.3 Common name(s)
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First-aid measures and management principles
2.5 Poisonous parts
2.6 Main toxins
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features
3.1.2 Habitat
3.1.3 Distribution
3.2 Poisonous parts of the plant
3.3 The toxin(s)
3.3.1 Name(s)
3.3.2 Description, chemical structure, stability
3.3.3 Other physico-chemical characteristics
3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
4.2 High risk circumstances
4.3 High risk geographical areas
5. ROUTES OF ENTRY
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Others
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination by route of exposure
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemcial analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
8.5 Overall Interpretation of all toxicological analyses and
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 CNS
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Others
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ears, nose, throat: local effects
9.4.10 Hematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Others
10. MANAGEMENT
10.1 General principles
10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological/toxinological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic treatment
10.4 Decontamination
10.5 Elimination
10.6 Antidote/antitoxin treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
11.2 Internally extracted data on cases
11.3 Internal cases
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
13.1 Clinical and toxicological
13.2 Botanical
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

POISONOUS PLANTS
1. NAME
1.1 Scientific name
Jatropha curcas
1.2 Family
Euphorbiaceae
1.3 Common name(s)
Barbados nut
Black vomit nut
Curcas bean
Kukui haole
Physic nut
Purge nut
Purgeerboontjie
Purging nut tree
2. SUMMARY
2.1 Main risks and target organs
Dehydration and cardiovascular collapse as a result of
haemorrhagic gastro-enteritis. Central nervous system
depression.
2.2 Summary of clinical effects
Symptoms are largely those associated with gastro-intestinal
irritation. There is acute abdominal pain and a burning
sensation in the throat about half an hour after ingestion of
the seeds, followed by nausea, vomiting and diarrhoea. The
vomitus and faeces may contain blood. In severe
intoxications dehydration and haemorrhagic gastroenteritis can
occur. There may be CNS and cardiovascular depression and
collapse; children are more susceptible.
2.3 Diagnosis
Diagnosis by case history and presenting symptoms. A definite
diagnosis can only be made if there is a history of
ingestion and the ingested plant material has been positively
identified as Jatropha.
2.4 First-aid measures and management principles
INGESTION: Unless the patient is unconscious, convulsing, or
unable to swallow give fluids (milk or water) to dilute. Seek
medical assistance. In hospital or a health care facility
induce vomiting unless the patient has already vomited, or
perform gastric lavage. Administer activated charcoal and a
cathartic to hasten elimination, although in the presence of
diarrhoea this is unecessary.
SKIN: Wash the affected area well with plenty of water and
use a mild soap.
EYE: Flush the eye with copious amounts of water for at least
15 minutes. If irritation persists seek medical assistance.

2.5 Poisonous parts
All parts are considered toxic but in particular the seeds.
2.6 Main toxins
Contains a purgative oil and a phytotoxin or toxalbumin
(curcin) similar to ricin in Ricinis.
3. CHARACTERISTICS
3.1 Description of the plant
3.1.1 Special identification features

Jatropha curcas is a large coarse annual shrub or
small short lived tree which can grow 3.5 to 4.5
metres (8-15 feet) tall. It has thin, often
greenish bark which exudes copious amounts of watery
sap when cut.
Leaves: dark green; alternate, simple,ovate to
slightly lobed with 3-5 indentations. Up to 15 cm
wide. Petioles 10cm (4 inches) long. Flowers:
yellow to green in colour, borne in axils of the
leaves and being small are mostly hidden by foliage.
Fruit: small capsule-like, round fruit; about 2.5 –
4 cm (1-1.5 inches) in diameter. These are green and
fleshy when immature, becoming dark brown when ripe
and splitting to release 2 or 3 black seeds each
about 2 cm (3/4 inch) long. The meat of the seeds is
white and oily in texture and are reported to have an
agreeable taste. (Micromedex, 1974-1994)

3.1.2 Habitat
Widely cultivated as an ornamental. Prefers arid
environments.
3.1.3 Distribution
Native to tropical America, but is now cultivated
widely in tropical countries throughout the world.
It is grown occasionally in warmer parts of
Australia and is naturalised in a few places in
Queensland and the Northern Territory. In Florida it
is found chiefly south of Orlando. It is also a
common plant in the Hawaiian Islands. Introduced to
southern Africa, the plant has spread from
Mozambique through Zambia to the Transvaal and Natal.
This species is also found throughout the warmer
parts of Asia.
3.2 Poisonous parts of the plant
3.3 The toxin(s)
3.3.1 Name(s)
MAIN TOXINS:

Curcin – a phytotoxin (toxalbumin), found mainly in
the seeds and also in the fruit and sap.

Purgative oil – the seed yields 40% oil, known as
hell oil, pinheon oil, oleum infernale or oleum
ricini majoris, which contains small amounts of an
irritant curcanoleic acid, which is related to
ricinoleic acid and crotonoleic acid, the principle
active ingredients of castor oil and croton oil
respectively (Joubert et al., 1984).

OTHER TOXINS:

This genera also may contain hydrocyanic acid (CRC
Critical Reviews in Toxicology 1977).
There may be a dermatitis producing resin (Lampe &
Fagerstrom, 1968).
There may be an alkaloid, and a glycoside which

produce cardiovascular and respiratory depression.
Tetramethylpyrazine (TMPZ), an amide alkaloid has
been obtained from the stem of J. podagrica (Ojewole
& Odebiyi, 1981).
Atropine-like effects have also been reported
following ingestion of Jatropha multifida (Aplin
1976).

3.3.2 Description, chemical structure, stability
Curcin:
Phytotoxins or toxalbumins are large, complex protein
molecules of high toxicity. They resemble bacterial
toxins in structure and physiological effects.
Phytotoxins are heat labile, and can be positively
identified by precipitin reactions with sera
containing known antibodies (Kingsbury 1964). Curcin
is said to be highly irritant and remains in the
seed after the oil has been expressed.

Tetramethylpyrazine (TMPZ):
CAS: 1124-11-4
MW: 136.22
Molecular formula: C8-H12-N2

3.3.3 Other physico-chemical characteristics
Curcin is unable to penetrate cell walls, this has
been indicated by the fact that these proteins do not
affect protein synthesis by Ehrlich ascites cells.
This is thought to be because they lack a carrier
moiety or at least the galactose-binding groups by
which ricin binds to cell membranes. This was
discovered when it was found that the activity of
curcin in cell-free systems is not increased by
treatment with 2-mercaptoethanol, which greatly
enhances the inhibitory effect of ricin and abrin by
splitting their molecules into an effector and a
carrier moiety (Stirpe et al.,1976).
3.4 Other chemical contents of the plant
No further information was available at the time of
preparation of the monograph.
4. USES/CIRCUMSTANCES OF POISONING
4.1 Uses
Jatropha is an ornamental plant naturalised in many tropical
areas. The roots, stems, leaves seeds and fruits of the
plant have been widely used in traditional folk medicine in
many parts of West Africa. The seeds of J. curcas have been
used as a purgative, antihelminthic and abortifacient as well
as for treating ascites, gout, paralysis and skin diseases.
The seed oil of the plant has been used as an ingredient in
the treatment of rheumatic conditions, itch and parasitic
skin diseases, and in the treatment of fever, jaundice and
gonorrhoea, as a diuretic agent, and a mouth-wash. The leaf
has been used as a haemostatic agent and the bark as a fish
poison. In certain African countries people are accustomed
to chewing these seeds when in need of a laxative.
J. curcas seeds have been found to be highly effective against

Strongyloides papillosus infection in goats (Adam & Magzoub,
in press). It has also been suggested that J. curcas seeds
could be a useful chemotherapeutic agent provided that it is
active at a non-lethal dose (Adam, 1974). This may be
because of it’s reported antihelminthic activity.

4.2 High risk circumstances
As these plants are grown as an ornamental they will often be
found in gardens and public areas and therefore will be
easily accessible. As Jatropha are fruit bearing and the
seeds have a pleasant taste, the plants are particularly
attractive to children.
This species of plant is not usually eaten by animals but
drought leading to an acute shortage of grass creates a
situation in which animals are forced to consume the plants
and their constituents in varying amounts.

4.3 High risk geographical areas
Found in tropical countries throughout the world; including
tropical America, warmer parts of Australia (Queensland and
the Northern Territory), Florida (chiefly south of Orlando),
Hawaiian Islands and Africa (Mozambique, Zambia, Transvaal,
Natal), Asia.
5. ROUTES OF ENTRY
5.1 Oral
All cases of systemic poisoning have resulted from ingestion
of plant material (in most cases the seeds).
5.2 Inhalation
No relevant information at the time of preparation of the
monograph.
5.3 Dermal
No relevant information at the time of preparation of the
monograph.
5.4 Eye
No relevant information at the time of preparation of the
monograph.
5.5 Parenteral
No relevant information at the time of preparation of the
monograph.
5.6 Others
No relevant information at the time of preparation of the
monograph.
6. KINETICS
6.1 Absorption by route of exposure
INGESTION: Phytotoxins are well absorbed from the
gastrointestinal tract. The onset of symptoms may be developed
one or more hours.
6.2 Distribution by route of exposure
No relevant information at the time of preparation of the
monograph.
6.3 Biological half-life by route of exposure
No relevant information at the time of preparation of the
monograph.
6.4 Metabolism
Curcin – phytotoxins are partly metabolised in the digestive
tract.

6.5 Elimination by route of exposure
No relevant information at the time of preparation of the
monograph.
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
7.1 Mode of action
Phytotoxins (toxalbumins): It has been suggested that in vivo
phytotoxins act as proteolytic enzymes, owing their toxicity
to the breakdown of critical proteins and the accumulation of
ammonia (Kingsbury, 1964).

Tetramethylpyrazine (TMPZ): Has been found to possess a non-
specific spasmolytic and vasodilator activity (Ojewole &
Odebiyi, 1981). These actions may account, at least in
part, for the reported hypotensive (depressor) effects of
the amide alkaloid in experimental animals. TMPZ has also
been found to possess neuromuscular-blocking effects similar
to d-tubocurarine (Ojewole & Odebiyi, 1980).

7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
In some instances as few as three seeds have
produced toxic symptoms. In others,
consumption of as many as 50 seeds has
resulted in relatively mild symptoms. There
is one report where the ingestion of only
one seed in an adult has produced toxic
symptoms. It has been suggested that there
may be two strains one with toxic seeds and
one without (Kingsbury, 1964). Curcin, the
phytotoxin or toxalbumin found in Jatropha
curcas is similar to ricin the phytotoxin
found in the castor bean (Ricinis). The
minimum lethal dose of ricin, when
administered by injection, may be as small
as 0.00000001% of body weight, although
oral toxicity is probably several hundred
times less (Kingsbury, 1964).
7.2.1.2 Children
Toxicity is thought to be the same as for
adults, thus, as few as 1-3 seeds may
produce toxic symptoms.
7.2.2 Animal data
Poisoning from ingestion of the seeds of the Jatropha
plant is well known in veterinary practice and
autopsy findings include, severe gastro-enteritis,
nephritis, myocardial degeneration,
haemagglutination, and subepicardial and
subendocardial haemorrhages as well as renal
subcortical and subpleural bleeding.

One study found a high mortality rate in mice fed 50%
and 40% J. curcas. The important symptoms of
poisoning included diarrhoea, inability to keep
normal posture, depression and lateral recumbency.
The degree of the pathological changes observed in

the small intestines, liver, heart, kidneys, and
lungs was related to the level of Jatropha in the
diet. The most marked pathological changes were
catarrhal enteritis, erosions of the intestinal
mucosa, congestion and haemorrhages in small
intestines, heart and lungs and fatty changes in the
liver and kidneys (Adam, 1974).

Another oral dosing study undertaken using mice found
that curcin, as compared with crotin found in the
seeds of croton tiglium, had a slightly more rapid
action with symptoms beginning at 12 hours and most
deaths occurring within 48 hours of poisoning. An
acute LD50 of 9.11mg/mouse was calculated at 48 hours
and a delayed LD50 of 5.83mg/mouse was calculated at
7 days. The behaviour of the animals was similar to
that of mice treated with crotins, except for some
neurological symptoms (waddling, fine tremors,
rocking, occasionally convulsions), which were
present especially among animals poisoned with the
highest doses of curcin. Post-mortem examinations
showed lesions in the liver, pancreas and spleen,
hyperaemia of the intestine, sometimes ascites; the
whole picture resembled that of rats poisoned with
ricin. (Stirpe et al.,1976)

In young ruminants oral doses of 0.5 to 10g/kg/day
caused death after dosing for periods ranging from 1
day to 2 weeks. The clinical, haematological, and
pathological changes indicated that J. aceroides
reduced the ability of the liver to synthesize
protein, although there was no evidence of
interference with the excretion of bilirubin. Kidney
dysfunction and haemoconcentration also occurred.
Postmortem and histological findings were similar to
those found above in studies with mice. (Barri et
al., 1983)

A study assessing the acute oral toxicity of J.
curcas showed that different ruminants had different
susceptibilities to the effect of J. curcas. Calves
which received 0.25 or 1g/kg died within 19 hours of
administration, whilst goats given similar daily
doses were either killed or died within 7 to 21
days. It was not established whether this species
difference lies in direct cytotoxic action or in the
capacity with which the active substances contained
in J. curcas seed are converted in vivo to
metabolites more or less toxic than the parent
compounds. (Ahmed & Adam, 1979)

Feeding chicks seeds produced growth depression,
hepatonephropathies, and haemorrhages. (Micromedex
1974-1994)

7.2.3 Relevant in vitro data

In vitro phytotoxins cause agglutination of
erythrocytes (Joubert et al., 1984). It has been
observed that the seeds of J. curcas contain
proteins that are toxic to animals and inhibit
protein synthesis in a cell-free system (lysate of
rabbit reticulocytes), but not in whole cells
(Stirpe et al., 1976).
7.3 Carcinogenicity
The seed oil of J. curcas was found to contain skin tumour
promoters in a two-stage mouse carcinogenesis experiment. The
“irritant fraction” contained in the methanol extract of the
seed oil when partially purified induced ornithine
decarboxylase in mouse skin and inhibited the specific
binding of 3H-12-O-tetradecanoylphorbol-13-acetate to a
particulate fraction of mouse skin. After initiation with 7,
12-dimethylbenz[a]anthracene (DMBA), this “irritant fraction”
induced tumours in the skin of 36% of the mice tested in 30
weeks (Horiuchi et al., 1987).
7.4 Teratogenicity
No relevant information at the time of preparation of the
monograph.
7.5 Mutagenicity
No relevant information at the time of preparation of the
monograph.
7.6 Interactions
No relevant information at the time of preparation of the
monograph.
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
No relevant information at the time of
preparation of the monograph.
8.1.1.2 Biomedical analyses
No relevant information at the time of
preparation of the monograph.
8.1.1.3 Arterial blood gas analysis
No relevant information at the time of
preparation of the monograph.
8.1.1.4 Haematological analyses
No relevant information at the time of
preparation of the monograph.
8.1.1.5 Other (unspecified) analyses
No relevant information at the time of
preparation of the monograph.
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
No relevant information at the time of
preparation of the monograph.
8.1.2.2 Biomedical analyses
No relevant information at the time of
preparation of the monograph.
8.1.2.3 Arterial blood gas analysis
No relevant information at the time of
preparation of the monograph.
8.1.2.4 Haematological analyses

No relevant information at the time of
preparation of the monograph.
8.1.2.5 Other (unspecified) analyses
No relevant information at the time of
preparation of the monograph.
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
No relevant information at the time of
preparation of the monograph.
8.1.3.2 Biomedical analyses
No relevant information at the time of
preparation of the monograph.
8.1.3.3 Arterial blood gas analysis
No relevant information at the time of
preparation of the monograph.
8.1.3.4 Haematological analyses
No relevant information at the time of
preparation of the monograph.
8.1.3.5 Other (unspecified) analyses
No relevant information at the time of
preparation of the monograph.
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
No relevant information at the time of
preparation of the monograph.

8.2.1.2 Advanced Qualitative Confirmation Test(s)
Extraction of J. curcas seeds for the
preparation of crude curcin has used 8 x
250ml of ethyl ether. The ether has been
removed by filtering. The resulting powder
is then dried and then extrated with 1L of
cold 0.005M-sodium phosphate buffer, pH
7.2, containing 0.2M-NaCl/100g of seeds.
The mixture is stirred and left overnight.
After centrifugation the supernatant is
brought to 100% saturation with solid
(NH4)2SO4. The protein precipitate is then
collected by centrifugation and dissolved
in a minimum amount of phosphate/NaCl buffer
and then dialysed for 24-48 hour against a
continuous flow of the same buffer. At the
end of dialysis a brown precipitate remains
and is removed by centrifugation. (Stirpe et
al., 1976)

Analysis of this crude preparation using a
column of Sephadex G-100 has eluted three
peaks referred to as curcin I, II and III.
These proteins were found to have different
properties, curcin I is more toxic and
brings about different symptoms and lesions
in vivo, whereas curcin II was much more
active on protein synthesis (Stirpe et al.,
1976).

8.2.1.3 Simple Quantitative Method(s)
No relevant information at the time of
preparation of the monograph.
8.2.1.4 Advanced Quantitative Method(s)
No relevant information at the time of
preparation of the monograph.
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
No relevant information at the time of
preparation of the monograph.
8.2.2.2 Advanced Qualitative Confirmation Test(s)
No relevant information at the time of
preparation of the monograph.
8.2.2.3 Simple Quantitative Method(s)
No relevant information at the time of
preparation of the monograph.
8.2.2.4 Advanced Quantitative Method(s)
No relevant information at the time of
preparation of the monograph.
8.2.2.5 Other Dedicated Method(s)
No relevant information at the time of
preparation of the monograph.
8.2.3 Interpretation of toxicological analyses
No relevant information at the time of preparation of
the monograph.
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemcial analysis
8.3.1.1 Blood, plasma or serum
No relevant information at the time of
preparation of the monograph.
8.3.1.2 Urine
No relevant information at the time of
preparation of the monograph.
8.3.1.3 Other fluids
No relevant information at the time of
preparation of the monograph.
8.3.2 Arterial blood gas analyses
No relevant information at the time of preparation of
the monograph.
8.3.3 Haematological analyses
No relevant information at the time of preparation of
the monograph.
8.3.4 Interpretation of biomedical investigations
No relevant information at the time of preparation of
the monograph.
8.4 Other biomedical (diagnostic) investigations and their
interpretation
No relevant information at the time of preparation of the
monograph.
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
No relevant information at the time of preparation of the
monograph.
8.6 References
No relevant information at the time of preparation of the
monograph.

9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
Symptoms of poisoning are likely to be similar for
species of Jatropha. There is usually a delay of an
hour or more between consumption of the plant and
the occurrence of symptoms. Symptoms are largely
those associated with gastro-intestinal irritation.
There is acute abdominal pain and a burning sensation
in the throat about half an hour after ingestion of
the seeds followed by nausea, vomiting and profuse
watery diarrhoea. In severe poisoning, these
symptoms progress to haemorrhagic gastroenteritis and
dehydration. Polydipsia can be extreme. Salivation
and sweating may occur. There may be skeletal
muscle spasm. Intense hyperpnoea or a quick panting
respiration is seen together with hypotension and
electrocardiographic abnormalities. There may be
CNS and cardiovascular depression, children are more
susceptible; this may be either a direct effect of
toxins or secondary to dehydration.

In one report, as well as gastrointestinal symptoms,
atropine-like effects developed eight hours after
ingestion of Jatropha multifida (Aplin, 1976).
Symptoms included sweating, dry skin and mouth,
slight mydriasis, mild tachycardia and flushing of
facial skin and persisted for four hours.

9.1.2 Inhalation
No relevant information at the time of preparation of
the monograph.

9.1.3 Skin exposure
Primary chemical irritation from mechanical and/or
chemical injury (Lampe & Fagerstrom, 1968).

9.1.4 Eye contact
Primary chemical irritation from mechanical and/or
chemical injury.
9.1.5 Parenteral exposure
No relevant information at the time of preparation of
the monograph.
9.1.6 Other
No relevant information at the time of preparation of
the monograph.
9.2 Chronic poisoning
9.2.1 Ingestion
No relevant information at the time of preparation of
the monograph.
9.2.2 Inhalation
No relevant information at the time of preparation of
the monograph.
9.2.3 Skin exposure
No relevant information at the time of preparation of
the monograph.

9.2.4 Eye contact
No relevant information at the time of preparation of
the monograph.
9.2.5 Parenteral exposure
No relevant information at the time of preparation of
the monograph.
9.2.6 Other
No relevant information at the time of preparation of
the monograph.
9.3 Course, prognosis, cause of death
In non-fatal cases the course of intoxication is short; the
patient may become asymptomatic within 24 hours. Recovery
seems to be the rule.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Hypotension with a fast weak pulse. Shock due to
fluid and electrolyte loss may occur.
Electrocardiographic abnormalities.
9.4.2 Respiratory
Hyperpnoea.
9.4.3 Neurological
9.4.3.1 CNS
There may be CNS depression either as a
direct result of toxins or secondary to
hypotension. Seizures have been mentioned in
association with toxalbumin poisoning, but
generally in animal cases or in symptom
summaries rather than actual case reports
(Micromedex, 1974-1994).
9.4.3.2 Peripheral nervous system No relevant information at the time of
preparation of the monograph.

9.4.3.3 Autonomic nervous system
There have been reports of salivation,
sweating and abdominal cramping occurring
in human intoxications of Jatropha
macrorhiza root (Consroe and Glow, 1975).
This suggests some cholinergic activity.

Contrary to this, atropine-like effects have
been reported (Aplin, 1976); thus diminished
cholinergic stimulation may be evident.
Mydriasis, dry mouth, flushed hot dry skin,
tachycardia, etc..

9.4.3.4 Skeletal and smooth muscle The muscles and extremities may be
contracted by spasms. Intestinal spasm can
be severe.
9.4.4 Gastrointestinal
Acute abdominal pain and a burning sensation in the
throat about half an hour after ingestion of the
seeds. This is followed by nausea, vomiting and
profuse watery diarrhoea. The vomitus and faeces
may contain blood. Lesions are those of
haemorrhagic gastro-intestinal inflammation.

9.4.5 Hepatic
Liver damage may occur in serious cases of toxalbumin
poisoning. There may be increases ALT, total
bilirubin, and AST. (Micromedex, 1974-1994)
9.4.6 Urinary
9.4.6.1 Renal
Oliguria, probably secondary to hypotension
rather than direct renal toxicity.
Urinalysis may reveal haemoglobinuria and
albuminuria.
9.4.6.2 Others
No relevant information at the time of
preparation of the monograph.
9.4.7 Endocrine and reproductive systems
No relevant information at the time of preparation of
the monograph.
9.4.8 Dermatological
Dermatitis as a result of primary chemical irritation
possibly in conjunction with mechanical injury can
occur in most, if not all, individuals. Reactions
occur soon after exposure. The severity of the
reaction is dependent on the extent and duration of
contact. Hypersensitisation may also develop.
9.4.9 Eye, ears, nose, throat: local effects
Retinal haemorrhages, optic nerve injury have been
reported in toxalbumin poisoning (Micromedex, 1974-
1994).
9.4.10 Hematological
Haemoconcentration secondary to fluid loss.
Toxalbumins are haemagluttinating. Effects in
poisoning are minimal even though the effect is
prominent in vitro. (Micromedex, 1974-1994)
9.4.11 Immunological
No relevant information at the time of preparation of
the monograph.
9.4.12 Metabolic
9.4.12.1 Acid base disturbances
Acid base disturbances are not typical in
toxalbumin poisoning (Micromedex, 1974-1994)
9.4.12.2 Fluid and electrolyte disturbances
Dehydration which is often severe. Electrolyte
disturbances.
9.4.12.3 Others
No relevant in formation at the time of
prparation of the monograph.
9.4.13 Allergic reactions
Stated as being a primary chemical irritant (Lampe &
Fagerstrom, 1968), but hypersensitivity reactions may
occur in susceptible individuals. The inflammation
resulting from primary chemical irritant effects of
Jatropha is a predisposing factor to the development
of contact allergy.
9.4.14 Other clinical effects
Toxoalbumin poisoning may produce fever (Micromedex,
1974-1994).
9.4.15 Special risks

No relevant information at the time of preparation of
the monograph.
9.5 Others
Oedematous swelling of several organs.
10. MANAGEMENT
10.1 General principles
The management of Jatropha poisoning is similar to that for
the castor bean (Ricinis). Decontamination is indicated for
all known or suspected poisonings. There is no antidote.
Rehydration, either voluntary water ingestion or i.v. fluid
administration, to counteract fluid lost due to vomiting and
diarrhoea is critical. Treatment is essentially symptomatic
and supportive. The more critical analyses and investigations
are fluid and electrolytes, acid-base status, full blood
count, and renal and hepatic function. Monitor level of
consciousness. Specific therapy may be indicated for
haemorrhagic gastrointestinal damage, skeletal muscle and
gastrointesinal spasm, excessive salivary secretions and
haemoglobinuria. After substantial exposures to toxalbumin
containing plants, an observation period of up to 8 hours is
advised.

10.2 Relevant laboratory analyses and other investigations
10.2.1 Sample collection
Blood and urine sample collection.
10.2.2 Biomedical analysis
Complete blood count, electrolytes, blood urea
nitrogen, creatinine, acid-base status, glucose,
prothrombin time, liver enzymes, amylase, and
urinalysis.
10.2.3 Toxicological/toxinological analysis
No relevant information at the time of preparation of
the monograph.
10.2.4 Other investigations
Monitor hepatic, renal, pancreatic, and red blood
cell function.
10.3 Life supportive procedures and symptomatic treatment
Fluid and electrolyte status may deteriorate suddenly and
severely. Give IV fluids and electrolyte as necessary to
restore and maintain fluid and electrolyte balance. Monitor
renal function and alkalinize urine to minimize effects of
haemoglobinuria. Treat haemorrhagic gastro-intestinal damage
as for peptic ulceration. Observe for signs of CNS depression
and initiate assisted ventilation if necessary.

10.4 Decontamination
In all cases of ingestion or suspected ingestion, if the
patient is seen sufficiently soon (within 1-2 hours of
ingestion), induce emesis with Ipecac Syrup or perform gastric
lavage unless vomiting has been extensive.
10.5 Elimination
Administer activated charcoal and a cathartic to enhance and
hasten elimination, although severe diarrhoea may make this
unnecessary. Cathartic administration must be cautious due to
the risk of exacerbating purgation and fluid loss.

Phytotoxins are non dialysable. However, methods for
eliminating the toxins from the blood (haemodialysis,
peritoneal dialysis, charcoal haemoperfusion etc.) have been
suggested as useful, whether this removes plant toxins other
than phytotoxins from the blood and therefore improves the
prognosis and hastens the recovery, is yet to be
demonstrated. A possible indication for this would be life-
threatening CNS or respiratory depression (not secondary to
hypovolaemia) which is unresponsive to other supportive
measures.

10.6 Antidote/antitoxin treatment
10.6.1 Adults
No antidote. Many antidotes have been investigated
for toxalbumin poisoning, but no specific treatments
are available. (Micromedex, 1974-1994)
10.6.2 Children
No antidote. Many antidotes have been investigated
for toxalbumin poisoning, but no specific treatments
are available. (Micromedex, 1974-1994)
10.7 Management discussion
In cases of poisoning where dehydration has been severe close
follow up of renal function is imperative.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Case History: A 3-year-old Hawaiian-Caucasian boy was
admitted to Kauikeoani Children’s Hospital on September 20,
1958, because of persistent vomiting and diarrhoea. The
episodes were of sudden onset following the ingestion of
several large black seeds gathered from an over-hanging branch
of a neighbour’s tree (later identified as Jatropha curcas).
He was unable to retain any ingested food or water. Each
intake was vomited almost immediately after ingestion. The
vomitus was said to contain the white granulated material and
the particles of the black shells. After several bouts of
vomiting, the child started to have watery bowel movements.
The stools contained seed particles also. Three and a half
hours following the ingestion of the seeds, the child
appeared lethargic. His skin felt cold and clammy. The
child was admitted to the hospital in severe dehydration. The
family and past history were non-contributory.
Blood pressure was 100/70; pulse 130; respiration 40;
temperature 99.8°F (rectal). The patient appeared lethargic,
cyanotic, and acutely ill. The peripheral vessels were
constricted. Severe dehydration was indicated by the poor
skin turgor, sunken eyeballs, and deepening periorbital
shadows. The bowel sounds were hyperactive. The remainder
of the physical examination was within normal limits. The
haemoglobin was 14.2gm/100mL, the red blood cell count , 5.4
million, and the platelets were normal. The white blood cell
count was 27,000 per cu mm, and the differential was normal.
The urine showed a trace of albumin, and elements consisting
of 2-4 white blood cells per high power field and many
granular and some hyaline casts. The carbon oxide level was
17mEq/L; chlorides, 101mEq/L; and potassium, 4.4mEq/L. The
stool cultures were negative for pathogens.

The child was given 1000mL of isotonic electrolyte solution.
Blood was drawn for type and cross matching. The patient was
oliguric for the first 24 hours. He responded to treatment,
and twenty hours after admission he was able to tolerate oral
feedings without any vomiting or diarrhoea, and was voiding
well. He was discharged from the hospital after 3 days
without complication. (Ho 1960).

Case History: Two sisters aged 5 and 3 years respectively
were rushed to Ahmadu Bello University Teaching Hospital,
Zaria, Nigeria, with a history of vomiting and drowsiness
about 5 hours after ingesting unspecified quantities of ripe
seeds of J. curcas. They had each vomited between 6 and 10
times within the hour preceding their arrival. There had
been no diarrhoea and the vomitus consisted of a whitish
material mixed with the food they had taken 2 hour
previously. On examination they were well-fed children,
afebrile, not pale, jaundiced or cyanosed but moderately
dehydrated. There was neither abdominal tenderness nor any
abnormal finding on rectal examination. They were both
restless, drowsy but rousable and their pupils were normal
and reactive. Laboratory investigations revealed normal
haemoglobin, normal liver-function tests and mild alkalosis.
Treatment consisted of rehydration with intravenous fluids
and sedation with small doses of promethazine hydrochloride.
They recovered rapidly and were both discharged some 48 hours
after admission. (Abdu-Aguye et al.,1986).

Case History: An 18 year old, well developed Caucasian male
was admitted to hospital at 11:45 p.m. because of persistent
vomiting, diarrhoea and drowsiness. The patient had ingested
3 pieces (about 2 inches in diameter) of a plant root
(identified as Jatropha macrorhiza) about 4 hours earlier;
symptoms emerged about 1 hour after ingestion. Except for
drowsiness and tenderness of all quadrants of the abdomen,
physical examination and haematologic and urinary laboratory
values of the patient showed no striking abnormalities. Bed
rest was prescribed and tap water was given ad libitum to
quench the paitients extreme polydipsia. After an uneventful
nights sleep, the patient was discharged at 10:30 the next
morning without complications. (Consroe and Glow, 1975).

Case History: A 48 year old, well developed Caucasian male
was admitted to hospital at 3 p.m. because of persistent
diarrhoea after ingesting an unknown quantity of a sweet
tasting potato-like plant root (identified as Jatropha
macrorhiza) at 8 a.m. Bouts of severe vomiting and diarrhoea
about every 3 minutes appeared 45 to 60 minutes after
ingestion and persisted throughout most of the afternoon.
The patient also complained of drowsiness, perspiration,
salivation, polydipsia, cramps in the legs and abdomen and of
feeling cold and clammy. Physical examination revealed a poor
skin turgor, sunken eyeballs excessive salivary secretions
and no lesions of mouth or throat. there was tenderness in
all quadrants of the abdomen and deep tendon reflexes were

hyperactive and intermittent muscle spasms in toes and calfs
were apparent. Vital signs and urinary and haematological
values were normal except for elevations in haematocrit (60%)
and haemoglobin (20.2gm/100ml). Initially, 1 litre of 5%
dextrose in water, atropine (0.5mg im.) and diazepam (5mg,
im.) every 6-8 hours as needed were prescribed. After a
restful night, the patient was discharged at 9 a.m., the
following morning without complications. (Consroe and Glow,
1975).

11.2 Internally extracted data on cases
No relevant information at the time of preparation of the
monograph.
11.3 Internal cases
No relevant information at the time of preparation of the
monograph.
12. ADDITIONAL INFORMATION
12.1 Availability of antidotes/antitoxins
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
13.1 Clinical and toxicological
Abdu-Aguye I, A Sannusi, R A Alafiya-Tayo, S R Bhusnurmath.
(Jul 1986) Acute Toxcity Studies with Jatropha curcas L.
Human Toxicology, 5(4):269-274.

Adam S E I. (Mar 1974) Toxic effects of Jatropha Curcas in
mice. Toxicology, 2(1):67-76.

Adam S E I, M Magzoub. Preliminary observations on the
anthelmintic activity of Jatropha curcas against
strongyloides and Haemonchus infections in goats and sheep.
Topical Animal Health Production 25: (in press). Cited in
Ahmed & Adam, 1979.

Ahmed O M M, S E I Adam. (Jul 1979) Effects of Jatropha
curcas on Calves. Veterinary Pathology 16(4):476-482.

Aplin T E H. (May 1976) Poisonous Garden Plants and Other
Plants Harmful to Man in Australia. Western Australia
Department of Agriculture, Bulletin 3964.

Barri M E S, T O Onsa, A A Elawad, N Y Elsayed, I A Wasfi, E M
Abdul Bari, S E I Adam. (1983) Toxicity of Five Sudanese
Plants to Young Ruminants. Journal of Comparative Pathology,
93:559-575.

Consroe P F, Glow D E. (1975). Clinical Toxicology of the
Desert Potato : Two Case Reports of Acute Jatropha Macrorhiza
Root Ingestion. Arizona Medicine, 23(6):475-477.

CRC Critical Review in Toxicology. (Nov 1977). Higher Plant
Genera and their toxins, pp 213-237

Ho Richard K B. (March-April 1960). Acute Poisoning From the
Ingestion of Seeds of Jatropha Curcas. Medical Journal of

Hawaii, 19(4):421-423.

Horiuchi T, H Fujiki, M Hirota, M Suttajit, M Suganuma, A
Yoshioka, V Wongchai, E Hecker, T Sugimura. (Mar 1987)
Presence of tumor promoters in the seed oil of Jatropha
curcas L. from Thailand. Japanese Journal of Cancer
Research, 78(3):223-236.

Joubert P H, J M M Brown, I T Hay, P D B Sebata. (May 1984).
Acute poisoning with Jatropha curcas (purging nut tree) in
children. South African Medical Journal, 65:729-730.

Kingsbury J M. Poisonous Plants of the United States and
Canada, 1964.

Lampe and Fagerstrom. (1968). Plant Toxicity and Dermatitis
– A Manual for Physicians. The Williams and Wilkins Company,
Baltimore.

Ojewole J A O, O O Odebiyi. (1980) Neuromuscular and
Cardiovascular Actions of Tetramethylpyrazine from the Stem of
Jatroha Podagrica. Planta Medica, 38:332-338.

Ojewole J A O, O O Odebiyi. (1981) Mechanism of the
Hypotensive Effect of Tetramethylpyrazine, an Amide Alkaloid
from the Stem of Jatropha podagrica.

Stirpe F, A Pession-Brizzi, E Lorenzoni, P Strocchi, L
Montanaro, S Sperti. (Apr 1976) Studies on the Proteins from
the Seeds of Croton tiglium and of Jatropha curcas. Toxic
properties and inhibition of protein synthesis in vitro.
Biochemistry Journal, 156(1):1-6.

13.2 Botanical
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)

June 1994
Juliette Begg and Tania Gaskin
National Toxicology Group
P.O. Box 913
Dunedin
NEW ZEALAND

See Also:
Jatropha gossypiifolia (PIM 643)
Jatropha hastafa (PIM 644)
Jatropha macrorhiza (PIM 645)
Jatropha multifida (PIM 646)
Jatropha podagrica (PIM 647)

Methandriol
1. NAME
1.1 Substance
1.2 Group
1.3 Synonyms
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
3.2 Chemical structure
3.3 Physical properties
3.3.1 Colour
3.3.2 State/form
3.3.3 Description
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Storage conditions
4. USES
4.1 Indications
4.1.1 Indications
4.1.2 Description
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF EXPOSURE
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Other
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their interpretation
8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 Central nervous system
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ear, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Other
9.6 Summary
10. MANAGEMENT
10.1 General principles
10.2 Life supportive procedures and symptomatic/specific treatment
10.3 Decontamination
10.4 Enhanced elimination
10.5 Antidote treatment
10.5.1 Adults
10.5.2 Children
10.6 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
12. Additional information
12.1 Specific preventive measures
12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

Methandriol

International Programme on Chemical Safety
Poisons Information Monograph 906
Pharmaceutical

This monograph does not contain all of the sections completed. This
mongraph is harmonised with the Group monograph on Anabolic Steroids
(PIM G007).

1. NAME

1.1 Substance

Methandriol

1.2 Group

ATC Classification:
A14 (Anabolic Agents for Systemic Use)
A14A (Anabolic steroids)

1.3 Synonyms

Méthandriol; MAD; Mestenediol; Methylandrostenediol;
Methandriolum

1.4 Identification numbers

1.4.1 CAS number

521-10-8

1.4.2 Other numbers

1.5 Main brand names, main trade names

Methandrol(R) (Becker, Austria); Methostan(R)
(Schering Corp./ Essex);
Metildiolo(R) (Orma, Italy); Metocryst(R) (Leo, Denmark);
Troformone(R) (Biomedica, Italy)

1.6 Main manufacturers, main importers

2. SUMMARY

2.1 Main risks and target organs

There is no serious risk from acute poisoning, but
chronic use can cause harm. The main risks are those of
excessive androgens: menstrual irregularities and
virilization in women and impotence, premature cardiovascular
disease and prostatic hypertrophy in men. Both men and women

can suffer liver damage with oral anabolic steroids
containing a substituted 17-alpha-carbon. Psychiatric changes
can occur during use or after cessation of these
agents.

2.2 Summary of clinical effects

Acute overdosage can produce nausea and gastrointestinal
upset. Chronic usage is thought to cause an increase in
muscle bulk, and can cause an exageration of male
characteristics and effects related to male hormones.
Anabolic steroids can influence sexual function. They can
also cause cardiovascular and hepatic damage. Acne and male-
pattern baldness occur in both sexes; irregular menses,
atrophy of the breasts, and clitoromegaly in women; and
testicular atrophy and prostatic hypertrophy in men.

2.3 Diagnosis

The diagnosis depends on a history of use of oral or
injected anabolic steroids, together with signs of increased
muscle bulk, commonly seen in “body-builders”. Biochemical
tests of liver function are often abnormal in patients who
take excessive doses of oral anabolic steroids.

Laboratory analyses of urinary anabolic steroids and their
metabolites can be helpful in detecting covert use of these
drugs.

2.4 First aid measures and management principles

Supportive care is the only treatment necessary or
appropriate for acute intoxication. Chronic (ab)users can be
very reluctant to cease abuse, and may require professional
help as with other drug misuse.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Naturally-occuring anabolic steroids are synthesised in
the testis, ovary and adrenal gland from cholesterol via
pregnenolone. Synthetic anabolic steroids are based on the
principal male hormone testosterone, modified in one of three
ways:

alkylation of the 17-carbon
esterification of the 17-OH group
modification of the steroid nucleus

(Murad & Haynes, 1985).

3.2 Chemical structure

Chemical name:
Androst-5-ene-3,17-diol, 17-methyl-, (3beta,17beta)-

Molecular formula
C20H32O2

3.3 Physical properties

3.3.1 Colour

3.3.2 State/form

3.3.3 Description

3.4 Other characteristics

3.4.1 Shelf-life of the substance

3.4.2 Storage conditions

Protect from light.

Vials for parenteral administration should be stored
at room temperature (15 to 30°C). Visual inspection
for particulate and/or discoloration is
advisable.

4. USES

4.1 Indications

4.1.1 Indications

Anabolic agent; systemic
Anabolic steroid
Androstan derivative; anabolic steroid
Estren derivative; anabolic steroid
Other anabolic agent
Anabolic agent for systemic use; veterinary
Anabolic steroid; veterinary
Estren derivative; veterinary

4.1.2 Description

The only legitimate therapeutic indications for
anabolic steroids are:

(a) replacement of male sex steroids in men who have
androgen deficiency, for example as a result of loss
of both testes

(b) the treatment of certain rare forms of aplastic
anaemia which are or may be responsive to anabolic
androgens.

(ABPI Data Sheet Compendium, 1993)

(c) the drugs have been used in certain countries to
counteract catabolic states, for example after major
trauma.

4.2 Therapeutic dosage

4.2.1 Adults

4.2.2 Children

Not applicable

4.3 Contraindications

Known or suspected cancer of the prostate or (in men)
breast.
Pregnancy or breast-feeding.
Known cardiovascular disease is a relative contraindication.

5. ROUTES OF EXPOSURE

5.1 Oral

Anabolic steroids can be absorbed from the
gastrointestinal tract, but many compounds undergo such
extensive first-pass metabolism in the liver that they are
inactive. Those compounds in which substitution of the 17-
carbon protects the compound from the rapid hepatic
metabolism are active orally (Murad and Haynes, 1985).
There are preparations of testosterone that can be taken
sublingually.

5.2 Inhalation

Not relevant

5.3 Dermal

No data available

5.4 Eye

Not relevant

5.5 Parenteral

Intramuscular or deep subcutaneous injection is the
principal route of administration of all the anabolic
steroids except the 17-alpha-substituted steroids which are
active orally.

5.6 Other

Not relevant

6. KINETICS

6.1 Absorption by route of exposure

The absorption after oral dosing is rapid for
testosterone and probably for other anabolic steroids, but
there is extensive first-pass hepatic metabolism for all
anabolic steroids except those that are substituted at the
17-alpha position.

The rate of absorption from subcutaneous or intramuscular
depots depends on the product and its formulation. Absorption
is slow for the lipid-soluble esters such as the cypionate or
enanthate, and for oily suspensions.

6.2 Distribution by route of exposure

The anabolic steroids are highly protein bound, and is
carried in plasma by a specific protein called sex-hormone
binding globulin.

6.3 Biological half-life by route of exposure

The metabolism of absorbed drug is rapid, and the
elimination half-life from plasma is very short. The duration
of the biological effects is therefore determined almost
entirely by the rate of absorption from subcutaneous or
intramuscular depots, and on the de-esterification which
precedes it (Wilson, 1992).

6.4 Metabolism

Free (de-esterified) anabolic androgens are metabolized
by hepatic mixed function oxidases (Wilson, 1992).

6.5 Elimination by route of exposure

After administration of radiolabelled testosterone,
about 90% of the radioactivity appears in the urine, and 6%
in the faeces; there is some enterohepatic recirculation
(Wilson, 1992).

7. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

The toxic effects are an exaggeration of the
normal pharmacological effects.

7.1.2 Pharmacodynamics

Anabolic steroids bind to specific receptors
present especially in reproductive tissue, muscle and
fat (Mooradian & Morley, 1987). The anabolic steroids
reduce nitrogen excretion from tissue breakdown in
androgen deficient men. They are also responsible for
normal male sexual differentiation. The ratio of
anabolic (“body-building”) effects to androgenic
(virilizing) effects may differ among the members of
the class, but in practice all agents possess both
properties to some degree. There is no clear evidence
that anabolic steroids enhance overall athletic
performance (Elashoff et al, 1991).

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

No data available.

7.2.1.2 Children

No data available.

7.2.2 Relevant animal data

No data available.

7.2.3 Relevant in vitro data

No data

7.3 Carcinogenicity

Anabolic steroids may be carcinogenic. They can
stimulate growth of sex-hormone dependent tissue, primarily
the prostate gland in men. Precocious prostatic cancer has
been described after long-term anabolic steroid abuse
(Roberts & Essenhigh, 1986). Cases where hepatic cancers have
been associated with anabolic steroid abuse have been
reported (Overly et al, 1984).

7.4 Teratogenicity

Androgen ingestion by a pregnant mother can cause
virilization of a female fetus (Dewhurst & Gordon,
1984).

7.5 Mutagenicity

No data available.

7.6 Interactions

No data available.

7.7 Main adverse effects

The adverse effects of anabolic steroids include weight
gain, fluid retention, and abnormal liver function as
measured by biochemical tests. Administration to children can
cause premature closure of the epiphyses. Men can develop
impotence and azoospermia. Women are at risk of
virilization.

8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)

8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their
interpretation

8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations

Biomedical analysis
The following tests can be relevant in the investigation of
chronic anabolic steroid abuse:
a) full blood count
b) electrolytes and renal function tests
c) hepatic function tests
d) testosterone
e) Lutenizing hormone
f) prostatic acid phosphatase or prostate related antigen
g) blood glucose concentration
h) cholesterol concentration

Toxicological analysis
-urinary analysis for anabolic steroids and their
metabolites

Other investigations
-electrocardiogram

8.6 References

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Nausea and vomiting can occur.

9.1.2 Inhalation

Not relevant

9.1.3 Skin exposure

Not relevant

9.1.4 Eye contact

Not relevant

9.1.5 Parenteral exposure

Patients are expected to recover rapidly after
acute overdosage, but there are few data. “Body-
builders” use doses many times the standard
therapeutic doses for these compounds but do not
suffer acute toxic effects.

9.1.6 Other

Not relevant

9.2 Chronic poisoning

9.2.1 Ingestion

Hepatic damage, manifest as derangement of
biochemical tests of liver function and sometimes
severe enough to cause jaundice; virilization in
women; prostatic hypertrophy, impotence and
azoospermia in men; acne, abnormal lipids, premature
cardiovascular disease (including stroke and
myocardial infarction), abnormal glucose tolerance,
and muscular hypertrophy in both sexes; psychiatric
disturbances can occur during or after prolonged
treatment (Ferner & Rawlins, 1988; Kennedy, 1992; Ross
& Deutch, 1990; Ryan, 1981; Wagner, 1989).

9.2.2 Inhalation

Not relevant

9.2.3 Skin exposure

Not relevant

9.2.4 Eye contact

Not relevant

9.2.5 Parenteral exposure

Virilization in women; prostatic hypertrophy,
impotence and azoospermia in men; acne, abnormal
lipids, premature cardiovascular disease (including
stroke and myocardial infarction), abnormal glucose
tolerance, and muscular hypertrophy in both sexes.
Psychiatric disturbances can occur during or after
prolonged treatment. Hepatic damage is not expected
from parenteral preparations.

9.2.6 Other

Not relevant

9.3 Course, prognosis, cause of death

Patients with symptoms of acute poisoning are expected
to recover rapidly. Patients who persistently abuse high
doses of anabolic steroids are at risk of death from
premature heart disease or cancer, especially prostatic
cancer. Non-fatal but long-lasting effects include voice
changes in women and fusion of the epiphyses in children.
Other effects are reversible over weeks or months.

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

Chronic ingestion of high doses of anabolic
steroids can cause elevations in blood pressure, left
ventricular hypertrophy and premature coronary artery
disease (McKillop et al., 1986; Bowman, 1990; McNutt
et al., 1988).

9.4.2 Respiratory

Not reported

9.4.3 Neurological

9.4.3.1 Central nervous system

Stroke has been described in a young
anabolic steroid abuser (Frankle et al.,
1988).

Pope & Katz (1988) described mania and
psychotic symptoms of hallucination and
delusion in anabolic steroid abusers. They
also described depression after withdrawal
from anabolic steroids. There is also
considerable debate about the effects of
anabolic steroids on aggressive behaviour

(Schulte et al., 1993) and on criminal
behaviour (Dalby, 1992). Mood swings were
significantly more common in normal
volunteers during the active phase of a trial
comparing methyltestosterone with placebo (Su
et al., 1993).

9.4.3.2 Peripheral nervous system

No data available

9.4.3.3 Autonomic nervous system

No data available

9.4.3.4 Skeletal and smooth muscle

No data available

9.4.4 Gastrointestinal

Acute ingestion of large doses can cause nausea
and gastrointestinal upset.

9.4.5 Hepatic

Orally active (17-alpha substituted) anabolic
steroids can cause abnormalities of hepatic function,
manifest as abnormally elevated hepatic enzyme
activity in biochemical tests of liver function,and
sometimes as overt jaundice.

The histological abnormality of peliosis hepatis has
been associated with anabolic steroid use (Soe et al.,
1992).

Angiosarcoma (Falk et al, 1979) and a case of
hepatocellular carcinoma in an anabolic steroid user
has been reported (Overly et al., 1984).

9.4.6 Urinary

9.4.6.1 Renal

Not reported

9.4.6.2 Other

Men who take large doses of anabolic
steroids can develop prostatic hypertrophy.
Prostatic carcinoma has been described in
young men who have abused anabolic steroids
(Roberts & Essenhigh, 1986).

9.4.7 Endocrine and reproductive systems

Small doses of anabolic steroids are said to
increase libido, but larger doses lead to azoospermia
and impotence. Testicular atrophy is a common clinical
feature of long-term abuse of anabolic steroids, and
gynaecomastia can occur (Martikainen et al., 1986;
Schurmeyer et al., 1984; Spano & Ryan, 1984).

Women develop signs of virilism, with increased facial
hair, male pattern baldness, acne, deepening of the
voice, irregular menses and clitoral enlargement
(Malarkey et al., 1991; Strauss et al., 1984).

9.4.8 Dermatological

Acne occurs in both male and female anabolic
steroids abusers. Women can develop signs of
virilism, with increased facial hair and male pattern
baldness.

9.4.9 Eye, ear, nose, throat: local effects

Changes in the larynx in women caused by
anabolic steroids can result in a hoarse, deep voice.
The changes are irreversible.

9.4.10 Haematological

Anabolic androgens stimulate erythropoesis.

9.4.11 Immunological

No data available

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

No data available.

9.4.12.2 Fluid and electrolyte disturbances

Sodium and water retention can
occur, and result in oedema; hypercalcaemia
is also reported (Reynolds, 1992).

9.4.12.3 Others

Insulin resistance with a fall in
glucose tolerance (Cohen & Hickman, 1987),
and hypercholesterolaemia with a fall in high

density lipoprotein cholesterol, have been
reported (Cohen et al., 1988; Glazer, 1991;
Webb et al., 1984).

9.4.13 Allergic reactions

No data available

9.4.14 Other clinical effects

No data available

9.4.15 Special risks

Risk of abuse

9.5 Other

No data available

9.6 Summary

10. MANAGEMENT

10.1 General principles

The management of acute overdosage consists of
supportive treatment, with fluid replacement if vomiting is
severe. Chronic abuse should be discouraged, and
psychological support may be needed as in the treatment of
other drug abuse. The possibility of clinically important
depression after cessation of usage should be borne in
mind.

10.2 Life supportive procedures and symptomatic/specific treatment

Not relevant

10.3 Decontamination

Not usually required.

10.4 Enhanced elimination

Not indicated

10.5 Antidote treatment

10.5.1 Adults

None available

10.5.2 Children

None available

10.6 Management discussion

Not relevant

11. ILLUSTRATIVE CASES

11.1 Case reports from literature

A 38-year old man presented with acute urinary
retention, and was found to have carcinoma of the prostate.
He had taken anabolic steroids for many years, and worked as
a “strong-man” (Roberts and Essenhigh, 1986).

A 22-year old male world-class weight lifter developed severe
chest pain awaking him from sleep, and was shown to have
myocardial infarction. For six weeks before, he had been
taking high doses of oral and injected anabolic steroids.
Total serum cholesterol was 596 mg/dL (HDL 14 mg/dL, LDL 513
mg/dL) (McNutt et al., 1988). Values of total cholesterol
concentration above 200 mg/dL are considered undesirable.

A 22-year old body builder took two eight-week courses of
anabolic steroids. He became severely depressed after the
second course, and when the depression gradually receded, he
had prominent paranoid and religious delusions (Pope and
Katz, 1987).

A 19-year old American college footballer took intramuscular
testosterone and oral methandrostenolone over 4 months. He
became increasingly aggressive with his wife and child. After
he severely injured the child, he ceased using anabolic
steroids, and his violence and aggression resolved within 2
months (Schulte et al, 1993).

12. Additional information

12.1 Specific preventive measures

Anabolic steroid abuse amongst athletes, weight
lifters, body builders and others is now apparently common at
all levels of these sports. Not all abusers are competitive
sportsmen.
There is therefore scope for a public health campaign, for
example, based on gymnasia, to emphasize the dangers of
anabolic steroid abuse and to support those who wish to stop
using the drugs.

12.2 Other

No data available.

13. REFERENCES

ABPI Data Sheet Compendium (1993) Datapharm Publications,
London.

Bowman S. (1990) Anabolic steroids and infarction. Br Med J;
300:

Cohen JC & Hickman R. (1987) Insulin Resistance and diminished
glucose tolerance in powerlifters ingesting anabolic steroids. J
Clin Endocrinol Metab 64: 960.

Cohen JC, Noakes TD, & Spinnler Benade AJ. (1988)
Hypercholesterolemia in male power lifters using Anabolic
Androgenic Steroids. The Physician and Sports medicine 16:
49-56.

Dalby JT. (1992) Brief anabolic steroid use and sustained
behavioral reaction. Am J Psychiatry 149: 271-272.

Dewhurst J. & Gordon RR (1984). Fertility following change of
sex: a follow-up. Lancet: ii: 1461-2.

Elashoff JD, Jacknow AD, Shain SG, & Braunstein GD. (1991) Effects
of anabolic-androgenic steroids on muscular strength. Annals Inter
Med 115: 387-393.

Falk H, Thomas LB, Popper H, Ishak KG. (1979). Hepatic
angiosacroma associated with androgenic-anabolic steroids. Lancet
2; 1120-1123.

Ferner RE & Rawlins MD (1988) Anabolic steroids: the power and the
glory? Br Med J 1988; 297: 877-878.

Frankle MA, Eichberg R, & Zacharian SB. (1988) Anabolic Androgenic
steroids and stroke in an athlete: case report. Arch Phys Med
Rehabil 1988; 69: 632-633.

Glazer G. (1991) Atherogenic effects of anabolic steroids on serum
lipid levels. Arch Intern Med 151: 1925-1933.

Kennedy MC. (1992). Anabolic steroid abuse and toxicology. Aust NZ
J Med 22: 374-381.

Malarkey WB, Strauss RH, Leizman DJ, Liggett M, & Demers LM.
(1991). Endocrine effects in femal weight lifters who self-
administer testosterone and anabolic steroids. Am J Obstet
Gynecol 165: 1385-1390.

Martikainen H, Alen M, Rahkila P, & Vihko R. (1986) Testicular
responsiveness to human chorionic gonadotrophin during transient
hypogonadotrophic hypogondasim induced by androgenic/anabolic
steroids in power athletes. Biochem 25: 109-112.

McKillop G, Todd IC, Ballantyne D. (1986) Increased left
ventricular mass in a body builder using anabolic steroids. Brit J
Sports Med 20: 151-152.

McNutt RA, Ferenchick GS, Kirlin PC, & Hamlin NJ. (1988) Acute
myocardial infarction in a 22 year old world class weight lifter
using anabolic steroids. Am J Cardiol 62: 164.

Mooradian JE, Morley JE, Korenman SG. (1987) Biological actions
of androgens. Endocrine Reviews 8:1-27.

Murad F, & Haynes RC. (1985). Androgens. in. Ed: Goodman Gilman
A, Goodman L S, Roll T W, Murad F. The Pharmacological Basis of
Therapeutics, 7th edition, Macmillan, New York: 1440-1458

Overly WL et al. (1984). Androgens and hepatocellular carcinoma in
an athlete. Ann Int Med 100: 158-159.

Pope GR, & Katz DL. (1988). Affective and psychotic symptoms
associated with anabolic steroid use. Am J Psychiatry 145:
487-490.

Reynolds Ed. (1992) Martindale-The Extra Pharmacopeia. The
Pharmaceutical Press. London.

Roberts JT, & Essenhigh DM. (1986) Adenocarcinoma of prostate in
40-year old body builder. Lancet 2: 742.

Ross RB, & Deutsch S I.(1990) Hooked on hormones. JAMA 263:
2048-2049.

Ryan A J. (1981) Anabolic steroids are fool’s gold. Fed Proc 40:
2682-2688.

Schurmeyer T, Belkien L, Knuth UA, & Nieschlag E. (1984)
Reversible azoospermia induced by the anabolic steroid
19-nortestosterone. Lancet i: 417-420.

Soe KL. Soe M. & Gluud C. (1992). Liver pathology associated with
the use of anabolic-androgenic steroids. Liver 12: 73-9.

Schulte HM, Hall MJ, & Boyer M. (1993). Domestic violence
associated with anabolic steroid abuse. Am J Psychiatr 150:
348.

Spano F, & Ryan W G. (1989) Tamoxifen for gynecomastia induced by
anabolic steroids? New Engl J Med 311: 861-862.

Strauss RH, Liggett MT, & Lanese RR. (1984) Anabolic steroid use
and perceived effects in 10 weight-trained women athletes JAMA
253: 2871-2873.

Su T-P, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, & Rubinow
DR. (1993) Neuropsychiatric effects of anabolic steroids in male
normal volunteers. JAMA 269: 2760-2764.

Wagner JC (1989). Abuse of drugs used to enhance athletic
performance. Am J Hosp Pharm 46: 2059-2067

Webb O L, Laskarzewski P M, & Glueck, CJ. (1984) Severe depression
of high-density lipo protein cholesterol levels in weight lifters
and body builders by self-administered exogenous testerone and
anabolic-andorgenic steroids. Metabolism 33: 971-975.

Wilson J D. (1992). Androgens. In: Goodman Gilman A., Rall T W,
Nies A S, & Taylor P. Goodman and Gilman’s Pharmacological Basis
of Therapeutics. McGraw-Hill, Toronto. Pages 1413-1430.

14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)

Author: Dr R. E. Ferner,
West Midlands Centre for Adverse Drug Reaction
Reporting,
City Hospital Dudley Road,
Birmingham B18 7QH
England.
Tel: +44-121-5074587
Fax: +44-121-5236125
Email: [email protected]

Date: 1994

Peer review: INTOX Meeting, Sao Paulo, Brazil, September 1994
(Drs P.Kulling, R.McKuowen, A.Borges, R.Higa,
R.Garnier, Hartigan-Go, E.Wickstrom)

Editor: Dr M.Ruse, March 1998

TAMOXIFEN
(Group 1)
For definition of Groups, see Preamble Evaluation.

VOL.: 66 (1996) (p. 253)

CAS No.: 10540-29-1
Chem. Abstr. Name: (Z)-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine

CAS No.: 54965-24-1
Chem. Abstr. Name: (Z)-2-[4-(1,2-Diphenyl-1-butenyl)phenoxy]-N,N-dimethylethanamine,
2-hydroxy-1,2,3-propanetricarboxylate (1:1)

5. Summary of Data Reported and Evaluation
5.1 Exposure data
Tamoxifen has been available since the early 1970s for the first-line treatment of metastatic breast cancer in postmenopausal women. Since the 1980s, it has become the therapy of choice for this condition. Tamoxifen has also become the adjuvant therapy of choice for treatment of postmenopausal, node-positive women with positive oestrogen-receptor or progesterone-receptor levels and, since the early 1990s, for the treatment of postmenopausal, node-negative women with positive oestrogen-receptor or progesterone-receptor levels. It is also widely used in treating postmenopausal receptor-negative women and premenopausal women with node-negative, receptor-positive disease. When used as adjuvant therapy, tamoxifen reduces the annual rates of both death from and recurrence of breast cancer by about 25%. Tamoxifen is commonly given at doses of 20 mg daily for periods of two to five years in the adjuvant setting, although doses of up to 40 mg daily have been used in the past. Several clinical trials are in progress to study the efficacy of tamoxifen in preventing breast cancer in healthy women believed to be at high risk of developing the disease.

Tamoxifen has been widely adopted as the first-line therapy of choice for hormone-responsive male breast cancer and is frequently used as adjuvant therapy for oestrogen receptor- or progesterone receptor-positive male breast cancer.

Tamoxifen is registered for use in nearly 100 countries and cumulative use since 1973 is estimated at 7 million patient-years.

5.2 Human carcinogenicity data

The potential effect of tamoxifen in increasing the risk of endometrial cancer has been reported in one adequate cohort study, four adequate case-control studies and 14 randomized controlled trials.

In the cohort study, based on follow-up of registered cases of breast cancer in the population-based Surveillance, Epidemiology and End Results (SEER) database in the United States, the only available data on therapy were those reported at the time of initial registration. Both groups of women with reported tamoxifen use and those with no such reported use had elevated rates of endometrial cancer compared with the rates expected from the SEER database as a whole. The risk was significantly greater for women with reported tamoxifen use. The similar stage distribution in the two groups suggests a lack of serious detection bias in this study. The absence of hysterectomies could not be confirmed in this study.

The case-control studies were based on the identification of a series of women with breast cancer who had subsequently been diagnosed with endometrial cancer, with tamoxifen exposure assessed in comparison with breast cancer patients who had not developed endometrial cancer. In two of these, case and control selection was based on the records of population-based cancer registries, and two used the same source as well as hospital-based cancer registries. For the Swedish study, although an increased risk of endometrial cancer for tamoxifen use was found, the only information on treatment was that recorded in the cancer registry. Further, the absence of hysterectomy in the control series could not be confirmed. For the remaining three case-control studies, more detailed data on treatment and on hysterectomies were obtained from medical records. In the studies in France and the Netherlands, a nonsignificant elevation of risk for endometrial cancer with use of tamoxifen was found, with a significant increase in risk with increasing duration of therapy in one. In the United States study, which reported on shorter duration of use, the point estimate of risk was less than unity.

Although several potential confounders were not systematically addressed in most studies, the Working Group considered that these were unlikely to have had a major effect on the reported relative risks.

In most of the randomized trials, small numbers of endometrial cancers were reported, and for many the data were not reported in a way that corrected for the greater survival time in most trials of the tamoxifen-treated patients compared to the control series. In two of the largest trials, however, there was a strong and statistically significant association between risk for endometrial cancer and use of tamoxifen. Although there may have been a tendency for publication bias and there is some possibility of a detection bias as a result of investigations in women with side-effects from tamoxifen, the magnitude of the risk found in the two large trials is unlikely to be explained by such biases. Further, for the trials that reported deaths in women with endometrial cancer, to date there have been eight deaths in women allocated to tamoxifen treatment groups and one in those not allocated to tamoxifen.

One case series reported significantly more high-grade endometrial tumours in tamoxifen-treated cancer patients than in patients without prior tamoxifen use. However, in at least six other studies, this difference was not found.

The SEER-based cohort study found a significantly reduced risk for contralateral breast cancers in the tamoxifen-treated women, compared with women with no reported tamoxifen use. The case-control study from the United States also reported a significant reduction of risk for contralateral cancers of the breast following tamoxifen use.

Although for some small trials there seemed to be little difference in the numbers of contralateral breast cancers in tamoxifen-treated women compared with controls, for the large trials, there was a substantially and significantly reduced risk for contralateral breast cancer in tamoxifen-treated women compared with controls. Further, in an overview analysis of nearly all trials published in 1992 with data available to 1990, there was a significant reduction of 39% in contralateral breast cancers in the tamoxifen-treated groups.

For all other cancer sites, no significant excess of any cancer has been found in either the cohort study or the trials. Although an excess of gastrointestinal cancer was reported following a combined analysis of three Scandinavian trials, this has not yet been confirmed by other studies.

5.3 Animal carcinogenicity data

Tamoxifen was tested for carcinogenicity by oral administration in one study in mice and in eight studies in rats, only one of which was a formal two-year study. In mice, the incidences of benign ovarian and testicular tumours were increased. In rats, tamoxifen induced preneoplastic liver lesions and benign or malignant liver tumours. In one study, the incidence of some tumours in hormone-dependent tissues was decreased, including in the mammary gland, although reduced weight gain may have been a contributing factor. In two studies in which tamoxifen was tested by subcutaneous implantation in intact or ovariectomized female mice, it inhibited mammary tumour development in both.

In mice, tamoxifen was reported to inhibit 3-methylcholanthrene-induced cervical cancer and virus-induced leukaemia. In several studies in both male and female rats, tamoxifen enhanced the hepatocarcinogenicity of previously administered N-nitrosodiethylamine. In one study in rats, tamoxifen enhanced the development of N-nitrosodiethylamine-induced kidney tumours. In a number of studies in rats, tamoxifen inhibited 7,12-dimethylbenz[a]anthracene-induced mammary tumour development. In two studies in hamsters, tamoxifen inhibited hormonal carcinogenesis induced by 17b-oestradiol in the kidney and zeranol in the liver.

5.4 Other relevant data

Orally administered tamoxifen is well absorbed and maximum plasma levels are reached in about 5 h. Steady-state concentrations of tamoxifen in humans are reached in 3-4 weeks and those of the primary metabolite, N-desmethyltamoxifen, in about eight weeks. Tissue concentrations tend to be higher than plasma concentrations. Metabolism involves phenyl hydroxylation, alkyl hydroxylation, demethylation and N-oxide formation. Metabolism results in more products in man and rats than in mice. Much higher oral doses of tamoxifen are required for rats or mice to achieve plasma concentrations similar to human levels.

Tamoxifen is an antioestrogen with complex pharmacology encompassing variable species-, tissue-, cell-, gene-, age- and duration of administration-specific effects from oestrogen-like agonist actions to complete blockade of oestrogen action. This complexity is consistent with the various, and sometimes paradoxical, effects that have been associated with tamoxifen administration in animals and humans.

The most frequent side-effects of tamoxifen administration are hot flushes and vaginal discharge. Tamoxifen has effects on the human uterus, inducing atrophy, hyperplasia and, less frequently, polyps. Randomized placebo-controlled trials revealed a slight increase of thromboembolic events, but also a protective effect regarding myocardial diseases, according to hospital admission rates and deaths. Tamoxifen administration has been shown to decrease blood total cholesterol and low-density lipoprotein-cholesterol concentrations in a number of studies. Several preliminary trials have suggested mildly positive effects of tamoxifen in preserving bone mineral density in postmenopausal women, but much longer follow-up is required to confirm t his potentially beneficial effect.

The acute toxicity of tamoxifen in experimental animals is low. In repeated-dose studies in rats, tamoxifen induced hypertrophy, but not cell proliferation, in the endometrial epithelium; endometrial hyperplasia was, however, reported in mice. Furthermore squamous metaplasia and atrophy of the uterine epithelium was observed in chronic studies in rats. Induction of cytochromes P450 and preneoplastic lesions have been detected in the livers of rats.

Ocular toxicity, including lipidosis of the retina and cornea and increased incidence of cataract, was reported in studies in rats of chronic exposure to tamoxifen.

In the presence of human, mouse, rat and hamster microsomes, tamoxifen binds covalently to protein. Tamoxifen has oestrogenic effects on human fetal genital tracts grown in athymic mice. In rats, doses above 2 mg/kg body weight produce irregular ossification of ribs in the fetus, which is thought to be secondary to reduction of the size of the uterus of the dam. No effects on the fetus have been reported in rabbits, marmosets or cynomolgus monkeys.

There is no direct evidence that tamoxifen is active in tests for gene mutation. Evidence for the genotoxic potential of tamoxifen is supported by data obtained on DNA adduct formation in rodent liver cells in vitro and in vivo, and in rodent and human liver microsomal systems; on unscheduled DNA synthesis in rat hepatocytes in vitro; and on the induction of clastogenic events both in vitro, in genetically-engineered human cells, and in vivo in rat liver.

There is evidence from 32P-postlabelling studies that three metabolites, (a-hydroxytamoxifen, 4-hydroxytamoxifen and (Z)-1,2-diphenyl-1-(4-hydroxyphenyl)but-1-ene (metabolite E) can be further metabolized to products that react with DNA. The major DNA adduct formed in rodent liver cells has been identified as (E)-(a-(N2-deoxyguanosinyl) tamoxifen. Human hepatocytes do not form detectable DNA adducts when treated in vitro with tamoxifen; they form 300-fold lower levels of adducts than rat and mouse hepatocytes when treated with a-hydroxytamoxifen.

Preliminary studies indicate that tamoxifen does not give rise to detectable levels of DNA adducts in human liver in vivo or in human endometrium in vitro and in vivo.

Mechanistic considerations

Tamoxifen increases liver tumour incidence in rats, which may involve both DNA damage leading to increased numbers of initiated cells and oestrogen receptor-mediated clonal expansion of those initiated cells.

The available evidence suggests that tamoxifen is carcinogenic in rat liver by a genotoxic mechanism. Preliminary information from studies of human tissues suggests that humans are less susceptible to the genotoxicity of tamoxifen. Tamoxifen also possesses tumour-promoting activity in the rat liver.

Several studies have shown that the liver contains significant quantities of oestrogen receptor in hepatocytes, Kupffer cells and endothelial cells.

Tamoxifen acts as an oestrogen agonist and/or antagonist by binding directly to the oestrogen receptor. In some tissues, such as breast, tamoxifen exhibits antioestrogenic properties by binding to the oestrogen receptor with high affinity. The tamoxifen-oestrogen receptor complex is incapable of binding to DNA-responsive elements. Thus, oestrogen receptor binding does not result in normal transcriptional activity. In other tissues, such as bone and liver, tamoxifen acts as a partial agonist, possibly because cells from those tissues contain a different array of DNA binding sites, thereby leading to typical oestrogen-mediated changes in gene expression and subsequent biological effects on growth and differentiation. Therefore, tissue-specific effects of tamoxifen-oestrogen receptor on gene expression may be involved in the ability of tamoxifen to increase or decrease tumour risk.

5.5 Evaluation

There is sufficient evidence in humans for the carcinogenicity of tamoxifen in increasing the risk for endometrial cancer and there is conclusive evidence that tamoxifen reduces the risk for contralateral breast cancer in women with a previous diagnosis of breast cancer.

There is inadequate evidence in humans for the carcinogenicity of tamoxifen in other organs.

There is sufficient evidence in experimental animals for the carcinogenicity of tamoxifen.

Overall evaluation

Tamoxifen is carcinogenic to humans (Group 1) and there is conclusive evidence that tamoxifen reduces the risk of contralateral breast cancer.

(Dr Cuzick dissociated himself from the evaluation process because he considered that the range of evaluation statements available within the framework of the Monographs was not suitable for this agent.)

For definition of the italicized terms, see Preamble Evaluation

Synonyms for Tamoxifen
1-para-b-Dimethylaminoethoxyphenyl-trans-1,2-diphenylbut-1-ene
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]ethyldimethylamine

Synonyms for Tamoxifen citrate
Apo-Tamox
Citofen
Dignotamoxi
Duratamoxifen 5
Emblon
ICI-46474
Jenoxifen
Kessar
Ledertam
Noltam
Nolvadex
Nourytam
Novofen
Oestrifen
Oncotam
Retaxim
Tafoxen
Tam
Tamaxin
Tamifen
Tamofen
Tamone
Tamoplex
Tamoxasta
Tamox-Gry
Z-Tamoxifen citrate
Tamoxigenat
Tamox-Puren
Taxfeno
Terimon
Valodex
Zemide
Zitazonium
Last updated 05/22/97

See Also:
TAMOXIFEN CITRATE (PIM 517)

Tamoxifen citrate
1. NAME
1.1 Substance
1.2 Group
1.3 Synonyms
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Brand names, Trade names
1.6 Manufacturers, Importers
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
3.2 Chemical structure
3.3 Physical properties
3.3.1 Properties of the substance
3.3.2 Properties of the locally available formulation
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Shelf-life of the locally available formulation
3.4.3 Storage conditions
3.4.4 Bioavailability
3.4.5 Specific properties and composition
4. USES
4.1 Indications
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF ENTRY
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Other
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their interpretation
8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 CNS
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ear, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Other
9.6 Summary
10. MANAGEMENT
10.1 General principles
10.2 Relevant laboratory analyses
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific treatment
10.4 Decontamination
10.5 Elimination
10.6 Antidote treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
11.2 Internally extracted data on cases
11.3 Internal cases
12. Additional information
12.1 Availability of antidotes
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

PHARMACEUTICALS
1. NAME
1.1 Substance
Tamoxifen
1.2 Group
Anti-oestrogen, non-steroidal derivative of triphenyl ethylene
ATC: L02B A01
1.3 Synonyms
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]-N,N-dimethylethylamine citrate
ICI 46 474
[trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene]
1.4 Identification numbers
1.4.1 CAS number
10540
1.4.2 Other numbers
Tamoxifen citrate: 54965-24-1
1.5 Brand names, Trade names
Emblon (Berk)
Noltam (Lederle)
Nolvadex (ICI)
Nolvadex-D (ICI)
Nolvadex forte(ICI)
Tamofen (Tillotts)
1.6 Manufacturers, Importers
Berk Pharmaceuticals Ltd., ICI Pharmaceuticals (UK).,
Lederle Laboratories., Tillotts Laboratories.
2. SUMMARY
2.1 Main risks and target organs
There is no record of serious effects from tamoxifen after
acute overdosage.

Adverse effects in therapeutic use are usually mild. They
include effects caused by antagonism of endogenous oestrogens:
hot flushes, non-specific gastrointestinal effects (nausea and
vomiting), central nervous system effects, and rare ocular
effects. Adverse haematological effects have been reported,
also isolated cases of death from peliosis hepatis and from
hyperlipidaemia.

In the treatment of breast cancer, hypercalcaemia and tumour
flare can occur.
2.2 Summary of clinical effects
Anti-oestrogenic effects in women treated with tamoxifen
include vasomotor symptoms (hot flushes), vaginal bleeding and
(in premenopausal women) irregular menses, and pruritus
vulvae. Nausea and vomiting can occur.

Dizziness, lethargy, depression, irritability and cerebellar
dysfunction have been described.

Reversible retinopathy with macular oedema has been reported
after high cumulative doses (>7g), and corneal changes can
occur.

Thrombocytopenia or leukopenia have been associated with
tamoxifen treatment. Thromboembolism, which may be due to the
disease rather than the treatment, has been recorded in women
given tamoxifen for breast cancer.
2.3 Diagnosis
Based on history of exposure and occurrence of adverse effects
such as hot flushes, nausea, vomiting, ocular disorders,
tumour flare, hypercalcemia, vaginal bleeding and CNS signs
and symptoms.
2.4 First aid measures and management principles
General measures such as inducing emesis or gastric lavage may
be indicated in massive overdosage.

Treatment is symptomatic.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Synthetic.
3.2 Chemical structure
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]-N,N-
dimethylethylamine citrate

C26H29NO, C6H8O7

[trans-1-(4-beta-dimethylaminoethoxyphenyl)-1, 2-diphenylbut-1-ene]

Molecular weight = 563.6

pKa = 8.85
3.3 Physical properties
3.3.1 Properties of the substance
Solubility in water at 37 °C = 0.05 g/100 ml.
3.3.2 Properties of the locally available formulation
No data available.
3.4 Other characteristics
3.4.1 Shelf-life of the substance
Assumed to be at least 5 years.
3.4.2 Shelf-life of the locally available formulation
Assumed to be at least 5 years.
3.4.3 Storage conditions
Store between 15 and 30 °C
Protect from light
3.4.4 Bioavailability
(to be added)
3.4.5 Specific properties and composition
(to be added by centre).
4. USES
4.1 Indications
Treatment of advanced breast cancer and adjuvant
treatment of early breast cancer.
Treatment of anovulatory infertility.
4.2 Therapeutic dosage
4.2.1 Adults
Breast cancer: initial dose 10 mg twice daily;
if no response after 1 month, 20 mg twice daily.

Infertility: regular menstruation, 10 mg twice daily on
days 2,3,4 and 5 of cycle, increasing to 20 mg twice
daily and 40 mg twice daily in successive cycles if
ovulation does not occur.

Amenorrhoea: 10 mg twice daily on 4 successive days,
increasing to 20 mg twice daily and 40 mg twice daily
after intervals of 45 and 90 days if ovulation does not
occur.
4.2.2 Children
No data available.
4.3 Contraindications
Pregnancy is an absolute contraindication because of the anti-
oestrogenic effects.
5. ROUTES OF ENTRY
5.1 Oral
Usual route of entry
5.2 Inhalation
Not relevant.
5.3 Dermal
Not relevant.
5.4 Eye
Not relevant.
5.5 Parenteral
Not relevant.
5.6 Other
Not relevant.
6. KINETICS
6.1 Absorption by route of exposure
Peak concentrations occur 4-7 h after oral dosing. Peak
concentrations after single oral doses of 20 mg are about 40
µ/l. There is no information on absolute bioavailability.
(Martindale, 1989; Buckley & Goa, 1989; Lien et al., 1989)
6.2 Distribution by route of exposure
Tamoxifen is more than 99% protein-bound in serum,
predominantly to albumin. In patients with breast cancer,
concentrations of tamoxifen and its metabolites in pleural,
pericardial and peritoneal effusion fluid are between 20 and
100% of those in serum, but only trace amounts enter the
cerebrospinal fluid. Concentrations in breast cancer tissue
exceed those in serum.

The volume of distribution is 50-60 l/kg (Martindale, 1989;
Buckley & Goa, 1989; Lien et al., 1989)
6.3 Biological half-life by route of exposure
The elimination is biphasic, with an initial half-life of
around 7 h and a terminal half-life of 7-11 days. (Martindale,
1989; Buckley & Goa, 1989; Lien et al., 1989)
6.4 Metabolism
Tamoxifen citrate undergoes extensive hepatic metabolism to:

1-(4-ethanolyloxyphenyl)-1,2-diphenylbut-1-ene (the primary
alcohol)
N-desmethyl tamoxifen
4-hydroxy tamoxifen
4-hydroxy-N-desmethyl tamoxifen

N-desdimethyl tamoxifen

(Martindale, 1989; Buckley & Goa, 1989; Lien et al., 1989)
6.5 Elimination by route of exposure
The major excretory route is via the bile as metabolites and
enterohepatic recirculation occurs. Less than 1% is excreted
in the urine. (Martindale, 1989; Buckley & Goa, 1989; Lien et
al., 1989).
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
The adverse effects observed are due mainly to its anti-
oestrogen effect, as Tamoxifen and certain of its
metabolites antagonise the effects of oestrogens in
oestrogen-sensitive tissues.
7.1.2 Pharmacodynamics
Tamoxifen and several of its metabolites (particularly 4-
hydroxytamoxifen) bind to nuclear oestrogen receptors in
oestrogen-sensitive tissues, and also to a microsomal
protein termed the ‘anti-oestrogen binding site’.
Tamoxifen interferes with the physiological sequence by
which oestrogen binds to its receptor, is translocated
in the nucleus and then activates messenger RNA
synthesis. Although the tamoxifen-receptor complex is
transported in the nucleus in the same way as oestrogen-
receptor complex, it fails to activate synthesis of
mRNA. (Buckley & Goa, 1990)

A meta-analysis of published trials in breast cancer
(Early Breast Cancer Trialists, 1988) demonstrates a
reduction in odds of death of about 20% over the first 5
years from diagnosis in women aged over 50 years.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
There is no information on the acute toxicity of
tamoxifen in overdosage.

The lowest cumulative dose of tamoxifen known to
have induced retinopathy, an adverse effect
which is recognised to be dose-dependent, is 7.7
g (Griffiths, 1987)
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
In some animal species, oestrogenic agonist effects
become manifest at dosages equivalent to 10-100 times
the human therapeutic dose (ABPI, 1989).
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
A case-control study (Hardell, 1988) showed a significantly
increased relative risk of carcinoma of the uterus in women
previously treated with tamoxifen AND who had previously had
radiotherapy involving the uterus. The study showed an
increase in relative risk with tamoxifen treatment alone which

was NOT statistically significant (see also Section 7.4).
7.4 Teratogenicity
Studies in neonatal male (Taguchi, 1987) and female (Taguchi &
Nishizuka, 1985) mice at relative doses 10 times higher than
those used in humans have shown genital tract abnormalities
similar to those caused by diethylstilboestrol, a known
transplacental carcinogen (diethylstilboestrol causes vaginal
adenosis, which predisposes to clear cell carcinoma).
7.5 Mutagenicity
Tamoxifen is believed not to be mutagenic (Martindale, 1989).
7.6 Interactions
Tamoxifen POTENTIATES the anticoagulant effect of warfarin,
and this interaction can be life-threatening (Tenni et al,
1989; Ritchie & Grant, 1989).
7.7 Main adverse effects
Adverse effects are usually mild. Thrombocytopenia,
leukopenia, thromboembolism, peliosis hepatis and
hyperlipidaemia have been mentioned in case reports.

Severe hypercalcaemia can occur rarely when treatment is
started in patients with metastases to bone.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis

8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
No data available.
9.1.2 Inhalation
No data available.
9.1.3 Skin exposure
No data available.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
Retinal damage and keratitis have been reported in
patients after large cumulative doses of tamoxifen,
generally over 180 mg per day for more than 1 year
(Buckley & Goa, 1989), though sometimes with smaller
doses (Griffiths, 1987). There seems to be correlation
between long-term tamoxifen administration and
endometrical proliferation (Uziely et al, 1993).
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
No data available.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
No data available.
9.4.3 Neurological
9.4.3.1 CNS
A case of depression, syncope, and
incoordination has been described during therapy
with 10 mg twice daily (Pluss et al., 1984). The

symptoms resolved when tamoxifen was
discontinued and reappeared when treatment was
restarted.
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Nausea and vomiting occur with therapeutic doses in some
patients, and are anticipated in overdosage (ABPI, 1989)
9.4.5 Hepatic
A fatal case of peliosis hepatis has been reported in a
woman treated with tamoxifen for 2 years after
mastectomy for carcinoma (Loomus et al., 1983).
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
A case of persistent nocturnal priapism has been
reported (Fernando & Tobias, 1989).
9.4.7 Endocrine and reproductive systems
The anti-oestrogenic effects of tamoxifen in
premenopausal women receiving therapeutic doses can
cause irregular menses.

Anti-oestrogenic adverse effects in women treated with
tamoxifen include vasomotor symptoms (hot flushes),
vaginal bleeding and pruritus vulvae (Buckley & Goa,
1989).
9.4.8 Dermatological
No data available.
9.4.9 Eye, ear, nose, throat: local effects
Treatment has been associated with retinal and corneal
changes: see para 9.2.
9.4.10 Haematological
Thromboembolism may be more common in patients treated
with tamoxifen, though this is not certain, as patients
with cancer are at increased risk anyway.
A small reduction in antithrombin III concentration was
noted in a study of 11 postmenopausal women treated
with tamoxifen, but it was clinically insignificant,
and no significant reduction was seen in a group of
premenopausal women (Jordan et al., 1987).

Thrombocytopenia and leukopenia can occur during
therapy, but are not usually severe (ABPI, 1989). One
case of severe myelosuppression has been reported
(International Adjuvant Therapy Organisation, 1985).
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances

Severe hypercalcaemia, associated with
increased bone resorption, has been noted when
patients with bony metastases commenced
therapy (Martindale, 1989).
9.4.12.3 Others
Severe hyperlipidaemia is occasionally seen,
and has been ascribed to an oestrogenic effect
(Noguchi et al., 1987)
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Pregnancy, breast feeding, enzyme deficiencies: no data
available (see sections 7.3 and 7.4)
9.5 Other
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
It is unlikely that serious acute toxicity would occur, and
management is supportive. The stomach should be emptied
after massive overdosage.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
No data available.
10.2.2 Biomedical analysis
Urea, creatinine and electrolytes may be helpful in
the assessment of patients who are vomiting.
10.2.3 Toxicological analysis
Not relevant.
10.2.4 Other investigations
Not relevant.
10.3 Life supportive procedures and symptomatic/specific
treatment
Nausea and vomiting may make intravenous fluid replacement
necessary.
10.4 Decontamination
Gastric lavage may be of value in massive overdosage, but
there are no data on this subject.
10.5 Elimination
Therapy to enhance elimination is not likely to be effective,
given the large volume of distribution.
10.6 Antidote treatment
10.6.1 Adults
Not relevant.
10.6.2 Children
Not relevant.
10.7 Management discussion
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No data available.
11.2 Internally extracted data on cases
One manufacturer (ICI) is aware of the case of a woman aged
51 years who claimed to have swallowed 100 x 10 mg tablets

of tamoxifen, and who suffered no ill effects (JI Landles,
personal communication).
11.3 Internal cases
No data available.
12. Additional information
12.1 Availability of antidotes
Not relevant.
12.2 Specific preventive measures
No data available.
12.3 Other
No data available.
13. REFERENCES
ABPI (Association of the British Pharmaceutical Industry) (1989)
Data Sheet Compendium. London.

Buckley M M-T, Goa KL (1989). Tamoxifen: a reappraisal of its
pharmacodynamic and pharmacokinetic properties and therapeutic
use. Drugs, 37: 451-490.

Early Breast Cancer Trialists Collaborative Group (1988).
Effects of adjuvant tamoxifen and of cytotoxic therapy on
mortality in early breast cancer. New Eng. J. Med., 319: 1681-
1692.

Fernando IN, Tobias JS (1989). Priapism in patient on tamoxifen.
Lancet; i:436

Griffiths MFP (1987). Tamoxifen retinopathy at low dosage. Am.
J. Ophthalmol., 104: 185-6.

Hardell L (1988). Pelvic irradiation and tamoxifen as risk
factors for carcinoma of cervix uteri. Lancet, ii: 1432.

International Adjuvant Therapy Group (1985). Myelosuppression
occurring after receiving tamoxifen for breast cancer. Br, J.
Radiol., 58: 1220.

Jordan VC, Fritz NF, Tormey DC (9187). Long-term adjuvant
therapy with tamoxifen: effect on sex hormone binding globulin
and antithrombin III. Cancer Res., 47: 4517-4519.

Lien EA, Solheim E, Lea OA et al (1989). Distribution of 4-
hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in
human biological fluids during tamoxifen treatment. Cancer Res.,
49: 2175-2183.

Lipton A, Harvey HA, Hamilton RW (1984). Venous thrombosis as a
side effect of tamoxifen treatment. Cancer Treatment Reports, 68:
887-889.

Loomus GN, Aneja P, Bota RA (1983). A case of peliosis hepatis
in association with tamoxifen therapy. Am. J. Clin. Path., 80:
881-882.

Reynolds EF, Ed (1989). Martindale, The Extra Pharmacopoeia. 29th
edition. Pharmaceutical Press, London.

Merck Index (1983). 10th edition. Merck & Co., Inc., Rahaway,
NJ.

Noguchi M, Taniya T, Tajiri K et al (1987). Fatal
hyperlipidaemia in a case of metastatic breast cancer treated by
tamoxifen. Br. J. Surg., 74: 586-487.

Pluss JL, Dibella NJ (1984). Reversible central nervous system
dysfunction due to tamoxifen in a patient with breast cancer.
Ann. Int. Med., 101: 652.

Ritchie LD, Grant SMT (1989). Tamoxifen-warfarin interaction:
the Aberdeen Hospitals file. Br. Med. J., 298: 1253.

Taguchi O (1987). Reproductive tract lesions in male mice
treated neonatally with tamoxifen. Biol. Reproduc., 37: 113-116.

Taguchi O, Noguchi M (1985). Reproductive tract abnormalities in
female mice treated neonatally with tamoxifen. Am. J. Obs.
Gynecol., 151: 675-678.

Tenni P, Lalich DL, Byrne MJ (1989). Life threatening
interaction between tamoxifen and warfarin. Br. Med. J. 298: 93.

Uziely B, Lewin A, Brufman G, Dorembus D, Mor-Josef S- (1993).
The effect of tamoxifen on the endometrium. Breast Cancer Res.
Treat. 26(1): 101-5.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Dr R.E. Ferner
Northern Drug and Therapeutics Centre
The Wolfson Unit
Royal Victoria Infirmary
Newcastle-upon-Tyne NE1 4LP
United Kingdom

Tel: 44-91-2328511
Fax: 44-91-2323613

Date: 15 April 1990

Peer Review: Strasbourg, France, April 1990

Review: IPCS, May 1994

See Also:
Tamoxifen (IARC Summary & Evaluation, Volume 66, 1996)

Nandrolone phenylpropionate
1. NAME
1.1 Substance
1.2 Group
1.3 Synonyms
1.4 Identification numbers
1.4.1 CAS number
1.4.2 Other numbers
1.5 Main brand names, main trade names
1.6 Main manufacturers, main importers
2. SUMMARY
2.1 Main risks and target organs
2.2 Summary of clinical effects
2.3 Diagnosis
2.4 First aid measures and management principles
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
3.2 Chemical structure
3.3 Physical properties
3.3.1 Colour
3.3.2 State/form
3.3.3 Description
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Storage conditions
4. USES
4.1 Indications
4.1.1 Indications
4.1.2 Description
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF EXPOSURE
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Other
6. KINETICS
6.1 Absorption by route of exposure
6.2 Distribution by route of exposure
6.3 Biological half-life by route of exposure
6.4 Metabolism
6.5 Elimination by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
7.2.1.2 Children
7.2.2 Relevant animal data
7.2.3 Relevant in vitro data
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their interpretation
8.5 Overall Interpretation of all toxicological analyses and toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
9.1.2 Inhalation
9.1.3 Skin exposure
9.1.4 Eye contact
9.1.5 Parenteral exposure
9.1.6 Other
9.2 Chronic poisoning
9.2.1 Ingestion
9.2.2 Inhalation
9.2.3 Skin exposure
9.2.4 Eye contact
9.2.5 Parenteral exposure
9.2.6 Other
9.3 Course, prognosis, cause of death
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
9.4.2 Respiratory
9.4.3 Neurological
9.4.3.1 Central nervous system
9.4.3.2 Peripheral nervous system
9.4.3.3 Autonomic nervous system
9.4.3.4 Skeletal and smooth muscle
9.4.4 Gastrointestinal
9.4.5 Hepatic
9.4.6 Urinary
9.4.6.1 Renal
9.4.6.2 Other
9.4.7 Endocrine and reproductive systems
9.4.8 Dermatological
9.4.9 Eye, ear, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
9.4.12.2 Fluid and electrolyte disturbances
9.4.12.3 Others
9.4.13 Allergic reactions
9.4.14 Other clinical effects
9.4.15 Special risks
9.5 Other
9.6 Summary
10. MANAGEMENT
10.1 General principles
10.2 Life supportive procedures and symptomatic/specific treatment
10.3 Decontamination
10.4 Enhanced elimination
10.5 Antidote treatment
10.5.1 Adults
10.5.2 Children
10.6 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
12. Additional information
12.1 Specific preventive measures
12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)

Nandrolone phenylpropionate

International Programme on Chemical Safety
Poisons Information Monograph 909
Pharmaceutical

This monograph does not contain all of the sections completed. This
mongraph is harmonised with the Group monograph on Anabolic Steroids
(PIM G007).

1. NAME

1.1 Substance

Nandrolone phenylpropionate

1.2 Group

ATC Classification:
A14 (Anabolic Agents for Systemic Use)
A14A (Anabolic steroids)

1.3 Synonyms

Nandrolone Hydrocinnamate; Nandrolone Phenpropionate;
19-Norandrostenolone Phenylpropionate;
Nortestosterone Phenylpropionate; NSC-23162

1.4 Identification numbers

1.4.1 CAS number

62-90-8

1.4.2 Other numbers

1.5 Main brand names, main trade names

Activin; Durabolin; Durabolin; Hybolin; Nandrolone
Phenpropionate Injection; 23, Nandrolone Phenylpropionate
Injection; Stenabolin; Docabolin (multi-ingredient
preparation); Docabolina (multi-ingredient preparation)

1.6 Main manufacturers, main importers

2. SUMMARY

2.1 Main risks and target organs

There is no serious risk from acute poisoning, but
chronic use can cause harm. The main risks are those of
excessive androgens: menstrual irregularities and
virilization in women and impotence, premature cardiovascular

disease and prostatic hypertrophy in men. Both men and women
can suffer liver damage with oral anabolic steroids
containing a substituted 17-alpha-carbon. Psychiatric changes
can occur during use or after cessation of these
agents.

2.2 Summary of clinical effects

Acute overdosage can produce nausea and gastrointestinal
upset. Chronic usage is thought to cause an increase in
muscle bulk, and can cause an exageration of male
characteristics and effects related to male hormones.
Anabolic steroids can influence sexual function. They can
also cause cardiovascular and hepatic damage. Acne and male-
pattern baldness occur in both sexes; irregular menses,
atrophy of the breasts, and clitoromegaly in women; and
testicular atrophy and prostatic hypertrophy in men.

2.3 Diagnosis

The diagnosis depends on a history of use of oral or
injected anabolic steroids, together with signs of increased
muscle bulk, commonly seen in “body-builders”. Biochemical
tests of liver function are often abnormal in patients who
take excessive doses of oral anabolic steroids.

Laboratory analyses of urinary anabolic steroids and their
metabolites can be helpful in detecting covert use of these
drugs.

2.4 First aid measures and management principles

Supportive care is the only treatment necessary or
appropriate for acute intoxication. Chronic (ab)users can be
very reluctant to cease abuse, and may require professional
help as with other drug misuse.

3. PHYSICO-CHEMICAL PROPERTIES

3.1 Origin of the substance

Naturally-occuring anabolic steroids are synthesised in
the testis, ovary and adrenal gland from cholesterol via
pregnenolone. Synthetic anabolic steroids are based on the
principal male hormone testosterone, modified in one of three
ways:

alkylation of the 17-carbon
esterification of the 17-OH group
modification of the steroid nucleus

(Murad & Haynes, 1985).

3.2 Chemical structure

Chemical Name: 3-Oxoestr-4-en-17beta-yl 3-phenylpropionate;

Alternative: 17beta-Hydroxyestr-4-en-3-one 3-
phenylpropionate.

Molecular Formula: C27H34O3

Molecular Weight: 406.6

3.3 Physical properties

3.3.1 Colour

White to creamy-white

3.3.2 State/form

Solid-crystals

3.3.3 Description

Crystalline powder with a slight characteristic
odour. Practically insoluble in water; soluble in
alcohol.

3.4 Other characteristics

3.4.1 Shelf-life of the substance

3.4.2 Storage conditions

Store in airtight containers. Protect from
light.

Vials for parenteral administration should be stored
at room temperature (15 to 30°C). Visual inspection
for particulate and/or discoloration is
advisable.

4. USES

4.1 Indications

4.1.1 Indications

Anabolic agent; systemic
Anabolic steroid
Androstan derivative; anabolic steroid
Estren derivative; anabolic steroid
Other anabolic agent

Anabolic agent for systemic use; veterinary
Anabolic steroid; veterinary
Estren derivative; veterinary

4.1.2 Description

The only legitimate therapeutic indications for
anabolic steroids are:

(a) replacement of male sex steroids in men who have
androgen deficiency, for example as a result of loss
of both testes

(b) the treatment of certain rare forms of aplastic
anaemia which are or may be responsive to anabolic
androgens.

(ABPI Data Sheet Compendium, 1993)

(c) the drugs have been used in certain countries to
counteract catabolic states, for example after major
trauma.

4.2 Therapeutic dosage

4.2.1 Adults

4.2.2 Children

Not applicable

4.3 Contraindications

Known or suspected cancer of the prostate or (in men)
breast.
Pregnancy or breast-feeding.
Known cardiovascular disease is a relative contraindication.

5. ROUTES OF EXPOSURE

5.1 Oral

Anabolic steroids can be absorbed from the
gastrointestinal tract, but many compounds undergo such
extensive first-pass metabolism in the liver that they are
inactive. Those compounds in which substitution of the 17-
carbon protects the compound from the rapid hepatic
metabolism are active orally (Murad and Haynes, 1985).
There are preparations of testosterone that can be taken
sublingually.

5.2 Inhalation

Not relevant

5.3 Dermal

No data available

5.4 Eye

Not relevant

5.5 Parenteral

Intramuscular or deep subcutaneous injection is the
principal route of administration of all the anabolic
steroids except the 17-alpha-substituted steroids which are
active orally.

5.6 Other

Not relevant

6. KINETICS

6.1 Absorption by route of exposure

The absorption after oral dosing is rapid for
testosterone and probably for other anabolic steroids, but
there is extensive first-pass hepatic metabolism for all
anabolic steroids except those that are substituted at the
17-alpha position.

The rate of absorption from subcutaneous or intramuscular
depots depends on the product and its formulation. Absorption
is slow for the lipid-soluble esters such as the cypionate or
enanthate, and for oily suspensions.

6.2 Distribution by route of exposure

The anabolic steroids are highly protein bound, and is
carried in plasma by a specific protein called sex-hormone
binding globulin.

6.3 Biological half-life by route of exposure

The metabolism of absorbed drug is rapid, and the
elimination half-life from plasma is very short. The duration
of the biological effects is therefore determined almost
entirely by the rate of absorption from subcutaneous or
intramuscular depots, and on the de-esterification which
precedes it (Wilson, 1992).

6.4 Metabolism

Free (de-esterified) anabolic androgens are metabolized
by hepatic mixed function oxidases (Wilson, 1992).

6.5 Elimination by route of exposure

After administration of radiolabelled testosterone,
about 90% of the radioactivity appears in the urine, and 6%
in the faeces; there is some enterohepatic recirculation
(Wilson, 1992).

7. PHARMACOLOGY AND TOXICOLOGY

7.1 Mode of action

7.1.1 Toxicodynamics

The toxic effects are an exaggeration of the
normal pharmacological effects.

7.1.2 Pharmacodynamics

Anabolic steroids bind to specific receptors
present especially in reproductive tissue, muscle and
fat (Mooradian & Morley, 1987). The anabolic steroids
reduce nitrogen excretion from tissue breakdown in
androgen deficient men. They are also responsible for
normal male sexual differentiation. The ratio of
anabolic (“body-building”) effects to androgenic
(virilizing) effects may differ among the members of
the class, but in practice all agents possess both
properties to some degree. There is no clear evidence
that anabolic steroids enhance overall athletic
performance (Elashoff et al, 1991).

7.2 Toxicity

7.2.1 Human data

7.2.1.1 Adults

No data available.

7.2.1.2 Children

No data available.

7.2.2 Relevant animal data

No data available.

7.2.3 Relevant in vitro data

No data

7.3 Carcinogenicity

Anabolic steroids may be carcinogenic. They can
stimulate growth of sex-hormone dependent tissue, primarily
the prostate gland in men. Precocious prostatic cancer has
been described after long-term anabolic steroid abuse
(Roberts & Essenhigh, 1986). Cases where hepatic cancers have
been associated with anabolic steroid abuse have been
reported (Overly et al, 1984).

7.4 Teratogenicity

Androgen ingestion by a pregnant mother can cause
virilization of a female fetus (Dewhurst & Gordon,
1984).

7.5 Mutagenicity

No data available.

7.6 Interactions

No data available.

7.7 Main adverse effects

The adverse effects of anabolic steroids include weight
gain, fluid retention, and abnormal liver function as
measured by biochemical tests. Administration to children can
cause premature closure of the epiphyses. Men can develop
impotence and azoospermia. Women are at risk of
virilization.

8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis

8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations

8.4 Other biomedical (diagnostic) investigations and their
interpretation

8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations

Biomedical analysis
The following tests can be relevant in the investigation of
chronic anabolic steroid abuse:
a) full blood count
b) electrolytes and renal function tests
c) hepatic function tests
d) testosterone
e) Lutenizing hormone
f) prostatic acid phosphatase or prostate related antigen
g) blood glucose concentration
h) cholesterol concentration

Toxicological analysis
-urinary analysis for anabolic steroids and their
metabolites

Other investigations
-electrocardiogram

8.6 References

9. CLINICAL EFFECTS

9.1 Acute poisoning

9.1.1 Ingestion

Nausea and vomiting can occur.

9.1.2 Inhalation

Not relevant

9.1.3 Skin exposure

Not relevant

9.1.4 Eye contact

Not relevant

9.1.5 Parenteral exposure

Patients are expected to recover rapidly after
acute overdosage, but there are few data. “Body-
builders” use doses many times the standard
therapeutic doses for these compounds but do not
suffer acute toxic effects.

9.1.6 Other

Not relevant

9.2 Chronic poisoning

9.2.1 Ingestion

Hepatic damage, manifest as derangement of
biochemical tests of liver function and sometimes
severe enough to cause jaundice; virilization in
women; prostatic hypertrophy, impotence and
azoospermia in men; acne, abnormal lipids, premature
cardiovascular disease (including stroke and
myocardial infarction), abnormal glucose tolerance,
and muscular hypertrophy in both sexes; psychiatric
disturbances can occur during or after prolonged
treatment (Ferner & Rawlins, 1988; Kennedy, 1992; Ross
& Deutch, 1990; Ryan, 1981; Wagner, 1989).

9.2.2 Inhalation

Not relevant

9.2.3 Skin exposure

Not relevant

9.2.4 Eye contact

Not relevant

9.2.5 Parenteral exposure

Virilization in women; prostatic hypertrophy,
impotence and azoospermia in men; acne, abnormal
lipids, premature cardiovascular disease (including
stroke and myocardial infarction), abnormal glucose
tolerance, and muscular hypertrophy in both sexes.
Psychiatric disturbances can occur during or after
prolonged treatment. Hepatic damage is not expected
from parenteral preparations.

9.2.6 Other

Not relevant

9.3 Course, prognosis, cause of death

Patients with symptoms of acute poisoning are expected
to recover rapidly. Patients who persistently abuse high
doses of anabolic steroids are at risk of death from
premature heart disease or cancer, especially prostatic
cancer. Non-fatal but long-lasting effects include voice
changes in women and fusion of the epiphyses in children.
Other effects are reversible over weeks or months.

9.4 Systematic description of clinical effects

9.4.1 Cardiovascular

Chronic ingestion of high doses of anabolic
steroids can cause elevations in blood pressure, left
ventricular hypertrophy and premature coronary artery
disease (McKillop et al., 1986; Bowman, 1990; McNutt
et al., 1988).

9.4.2 Respiratory

Not reported

9.4.3 Neurological

9.4.3.1 Central nervous system

Stroke has been described in a young
anabolic steroid abuser (Frankle et al.,
1988).

Pope & Katz (1988) described mania and
psychotic symptoms of hallucination and
delusion in anabolic steroid abusers. They
also described depression after withdrawal
from anabolic steroids. There is also
considerable debate about the effects of
anabolic steroids on aggressive behaviour
(Schulte et al., 1993) and on criminal
behaviour (Dalby, 1992). Mood swings were
significantly more common in normal
volunteers during the active phase of a trial
comparing methyltestosterone with placebo (Su
et al., 1993).

9.4.3.2 Peripheral nervous system

No data available

9.4.3.3 Autonomic nervous system

No data available

9.4.3.4 Skeletal and smooth muscle

No data available

9.4.4 Gastrointestinal

Acute ingestion of large doses can cause nausea
and gastrointestinal upset.

9.4.5 Hepatic

Orally active (17-alpha substituted) anabolic
steroids can cause abnormalities of hepatic function,
manifest as abnormally elevated hepatic enzyme
activity in biochemical tests of liver function, and
sometimes as overt jaundice.

The histological abnormality of peliosis hepatis has
been associated with anabolic steroid use (Soe et al.,
1992).

Angiosarcoma (Falk et al, 1979) and a case of
hepatocellular carcinoma in an anabolic steroid user
has been reported (Overly et al., 1984).

9.4.6 Urinary

9.4.6.1 Renal

Not reported

9.4.6.2 Other

Men who take large doses of anabolic
steroids can develop prostatic hypertrophy.
Prostatic carcinoma has been described in
young men who have abused anabolic steroids
(Roberts & Essenhigh, 1986).

9.4.7 Endocrine and reproductive systems

Small doses of anabolic steroids are said to
increase libido, but larger doses lead to azoospermia
and impotence. Testicular atrophy is a common clinical
feature of long-term abuse of anabolic steroids, and
gynaecomastia can occur (Martikainen et al., 1986;
Schurmeyer et al., 1984; Spano & Ryan, 1984).

Women develop signs of virilism, with increased facial
hair, male pattern baldness, acne, deepening of the
voice, irregular menses and clitoral enlargement
(Malarkey et al., 1991; Strauss et al., 1984).

9.4.8 Dermatological

Acne occurs in both male and female anabolic
steroids abusers. Women can develop signs of
virilism, with increased facial hair and male pattern
baldness.

9.4.9 Eye, ear, nose, throat: local effects

Changes in the larynx in women caused by
anabolic steroids can result in a hoarse, deep voice.
The changes are irreversible.

9.4.10 Haematological

Anabolic androgens stimulate erythropoesis.

9.4.11 Immunological

No data available

9.4.12 Metabolic

9.4.12.1 Acid-base disturbances

No data available.

9.4.12.2 Fluid and electrolyte disturbances

Sodium and water retention can
occur, and result in oedema; hypercalcaemia
is also reported (Reynolds, 1992).

9.4.12.3 Others

Insulin resistance with a fall in
glucose tolerance (Cohen & Hickman, 1987),
and hypercholesterolaemia with a fall in high
density lipoprotein cholesterol, have been
reported (Cohen et al., 1988; Glazer, 1991;
Webb et al., 1984).

9.4.13 Allergic reactions

No data available

9.4.14 Other clinical effects

No data available

9.4.15 Special risks

Risk of abuse

9.5 Other

No data available

9.6 Summary

10. MANAGEMENT

10.1 General principles

The management of acute overdosage consists of
supportive treatment, with fluid replacement if vomiting is
severe. Chronic abuse should be discouraged, and
psychological support may be needed as in the treatment of
other drug abuse. The possibility of clinically important
depression after cessation of usage should be borne in
mind.

10.2 Life supportive procedures and symptomatic/specific treatment

Not relevant

10.3 Decontamination

Not usually required.

10.4 Enhanced elimination

Not indicated

10.5 Antidote treatment

10.5.1 Adults

None available

10.5.2 Children

None available

10.6 Management discussion

Not relevant

11. ILLUSTRATIVE CASES

11.1 Case reports from literature

A 38-year old man presented with acute urinary
retention, and was found to have carcinoma of the prostate.
He had taken anabolic steroids for many years, and worked as
a “strong-man” (Roberts and Essenhigh, 1986).

A 22-year old male world-class weight lifter developed severe
chest pain awaking him from sleep, and was shown to have
myocardial infarction. For six weeks before, he had been
taking high doses of oral and injected anabolic steroids.
Total serum cholesterol was 596 mg/dL (HDL 14 mg/dL, LDL 513
mg/dL) (McNutt et al., 1988). Values of total cholesterol
concentration above 200 mg/dL are considered undesirable.

A 22-year old body builder took two eight-week courses of
anabolic steroids. He became severely depressed after the
second course, and when the depression gradually receded, he
had prominent paranoid and religious delusions (Pope and
Katz, 1987).

A 19-year old American college footballer took intramuscular
testosterone and oral methandrostenolone over 4 months. He
became increasingly aggressive with his wife and child. After
he severely injured the child, he ceased using anabolic
steroids, and his violence and aggression resolved within 2
months (Schulte et al, 1993).

12. Additional information

12.1 Specific preventive measures

Anabolic steroid abuse amongst athletes, weight
lifters, body builders and others is now apparently common at
all levels of these sports. Not all abusers are competitive
sportsmen.
There is therefore scope for a public health campaign, for
example, based on gymnasia, to emphasize the dangers of
anabolic steroid abuse and to support those who wish to stop
using the drugs.

12.2 Other

No data available.

13. REFERENCES

ABPI Data Sheet Compendium (1993) Datapharm Publications,
London.

Bowman S. (1990) Anabolic steroids and infarction. Br Med J;
300:

Cohen JC & Hickman R. (1987) Insulin Resistance and diminished
glucose tolerance in powerlifters ingesting anabolic steroids. J
Clin Endocrinol Metab 64: 960.

Cohen JC, Noakes TD, & Spinnler Benade AJ. (1988)
Hypercholesterolemia in male power lifters using Anabolic
Androgenic Steroids. The Physician and Sports medicine 16:
49-56.

Dalby JT. (1992) Brief anabolic steroid use and sustained
behavioral reaction. Am J Psychiatry 149: 271-272.

Dewhurst J. & Gordon RR (1984). Fertility following change of
sex: a follow-up. Lancet: ii: 1461-2.

Elashoff JD, Jacknow AD, Shain SG, & Braunstein GD. (1991) Effects
of anabolic-androgenic steroids on muscular strength. Annals Inter
Med 115: 387-393.

Falk H, Thomas LB, Popper H, Ishak KG. (1979). Hepatic
angiosacroma associated with androgenic-anabolic steroids. Lancet
2; 1120-1123.

Ferner RE & Rawlins MD (1988) Anabolic steroids: the power and the
glory? Br Med J 1988; 297: 877-878.

Frankle MA, Eichberg R, & Zacharian SB. (1988) Anabolic Androgenic
steroids and stroke in an athlete: case report. Arch Phys Med
Rehabil 1988; 69: 632-633.

Glazer G. (1991) Atherogenic effects of anabolic steroids on serum
lipid levels. Arch Intern Med 151: 1925-1933.

Kennedy MC. (1992). Anabolic steroid abuse and toxicology. Aust NZ
J Med 22: 374-381.

Malarkey WB, Strauss RH, Leizman DJ, Liggett M, & Demers LM.
(1991). Endocrine effects in femal weight lifters who self-
administer testosterone and anabolic steroids. Am J Obstet
Gynecol 165: 1385-1390.

Martikainen H, Alen M, Rahkila P, & Vihko R. (1986) Testicular
responsiveness to human chorionic gonadotrophin during transient
hypogonadotrophic hypogondasim induced by androgenic/anabolic
steroids in power athletes. Biochem 25: 109-112.

McKillop G, Todd IC, Ballantyne D. (1986) Increased left
ventricular mass in a body builder using anabolic steroids. Brit J
Sports Med 20: 151-152.

McNutt RA, Ferenchick GS, Kirlin PC, & Hamlin NJ. (1988) Acute
myocardial infarction in a 22 year old world class weight lifter
using anabolic steroids. Am J Cardiol 62: 164.

Mooradian JE, Morley JE, Korenman SG. (1987) Biological actions
of androgens. Endocrine Reviews 8:1-27.

Murad F, & Haynes RC. (1985). Androgens. in. Ed: Goodman Gilman
A, Goodman L S, Roll T W, Murad F. The Pharmacological Basis of
Therapeutics, 7th edition, Macmillan, New York: 1440-1458

Overly WL et al. (1984). Androgens and hepatocellular carcinoma in
an athlete. Ann Int Med 100: 158-159.

Pope GR,, & Katz DL. (1988). Affective and psychotic symptoms
associated with anabolic steroid use. Am J Psychiatry 145:
487-490.

Reynolds Ed. (1992) Martindale-The Extra Pharmacopeia. The
Pharmaceutical Press. London.

Roberts JT, & Essenhigh DM. (1986) Adenocarcinoma of prostate in
40-year old body builder. Lancet 2: 742.

Ross RB, & Deutsch S I.(1990) Hooked on hormones. JAMA 263:
2048-2049.

Ryan A J. (1981) Anabolic steroids are fool’s gold. Fed Proc 40:
2682-2688.

Schurmeyer T, Belkien L, Knuth UA, & Nieschlag E. (1984)
Reversible azoospermia induced by the anabolic steroid
19-nortestosterone. Lancet i: 417-420.

Soe KL. Soe M. & Gluud C. (1992). Liver pathology associated
with the use of anabolic-androgenic steroids. Liver 12:
73-9.

Schulte HM, Hall MJ, & Boyer M. (1993). Domestic violence
associated with anabolic steroid abuse. Am J Psychiatr 150:
348.

Spano F, & Ryan W G. (1989) Tamoxifen for gynecomastia induced by
anabolic steroids? New Engl J Med 311: 861-862.

Strauss RH, Liggett MT, & Lanese RR. (1984) Anabolic steroid use
and perceived effects in 10 weight-trained women athletes JAMA
253: 2871-2873.

Su T-P, Pagliaro M, Schmidt PJ, Pickar D, Wolkowitz O, & Rubinow
DR. (1993) Neuropsychiatric effects of anabolic steroids in male
normal volunteers. JAMA 269: 2760-2764.

Wagner JC (1989). Abuse of drugs used to enhance athletic
performance. Am J Hosp Pharm 46: 2059-2067

Webb O L, Laskarzewski P M, & Glueck, CJ. (1984) Severe depression
of high-density lipo protein cholesterol levels in weight lifters
and body builders by self-administered exogenous testerone and
anabolic-andorgenic steroids. Metabolism 33: 971-975.

Wilson J D. (1992). Androgens. In: Goodman Gilman A., Rall T W,
Nies A S, & Taylor P. Goodman and Gilman’s Pharmacological Basis
of Therapeutics. McGraw-Hill, Toronto. Pages 1413-1430.

14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)

Author: Dr R. E. Ferner,
West Midlands Centre for Adverse Drug Reaction
Reporting,
City Hospital Dudley Road,
Birmingham B18 7QH
England.
Tel: +44-121-5074587
Fax: +44-121-5236125
Email: [email protected]

Date: 1994

Peer review: INTOX Meeting, Sao Paulo, Brazil, September 1994
(Drs P.Kulling, R.McKuowen, A.Borges, R.Higa,
R.Garnier, Hartigan-Go, E.Wickstrom)

Editor: Dr M.Ruse, March 1998

See Also:
Nandrolone (PIM 910)

Cancer is the unrestrained proliferation of abnormal cells in the body. Typical side effects of cancer treatments, such as nausea, vomiting, pain, sleep problems, and loss of appetite, can be debilitating.

There are promising studies about CBD’s use in cancer treatment, although, to date, there have been no CBD-oil derived products approved by the U.S. Food and Drug Administration (FDA) to treat cancer, its symptoms, or side effects caused by its treatment.

The National Cancer Institute (NCI) examined several studies regarding the correlation between cannabis and cancer, and the research showed mixed results.

Cannabinoids and cannabis itself may be used either as a health care tool or as a complementary treatment for people who may need help managing the symptoms of cancer and the side effects of cancer therapy.

However, if one is planning on adding it to his or her existing treatment plan, it is highly recommended to consult a health professional first.

For people looking to include CBD in their cancer treatment, several product recommendations would also be listed in this article.

Best CBD Products for Cancer

As more and more people turn towards safe and alternative therapies, the interest in plant-derived medicines grows exponentially. This trend is excellent news for everyone, but particularly for people who live with cancer.

In 2018, cancer was responsible for nearly 10 million deaths around the world. This number is appalling considering the technological advances in modern medicine in the past years.

While the survival rates after a cancer diagnosis are on the upsurge, this figure still emphasizes the necessity for more research and treatment options.

This article includes a consolidation of the best CBD oils for cancer. The brands included are recommended for their high quality, based on potency, extraction methods, and the soil in which the hemp has been cultivated. 

What is Cannabidiol (CBD)?

Marijuana and hemp are varieties of the Cannabis sativa plant, and both plants contain varying quantities of cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), their active ingredients.

Both THC and CBD are extracted from hemp and marijuana using similar processes. However, hemp contains less THC than a typical marijuana plant.  

Marijuana plants typically contain 5-10% THC, although certain strains may contain more. Also, trace amounts of THC may still be found in CBD oil.

CBD is not psychoactive, meaning there is less possibility that CBD could cause drowsiness, mental confusion, or hallucinations that are often associated with THC.

The 2018 Farm Bill stipulates that, legally, hemp oil cannot contain more than 0.3 percent THC.

Hemp oil or marijuana oil?

Marijuana oil is a liquid created by extracting THC and CBD from marijuana buds using a solvent.

This type of cannabis oil usually contains high amounts of THC, low quantities of CBD, and other beneficial cannabinoids found in marijuana.

Meanwhile, hemp oil is cannabis oil extracted from hemp strains that are rich in CBD with only trace amounts of THC.

Aside from being rich in CBD, hemp oil also contains essential fats that our bodies need to function correctly, such as omega 6 and omega 3 fatty acids and linoleic acid. 

What makes high-quality cannabis oil?

Several factors are essential when extracting cannabis oil.

  • Quality of the starting material

The quality of strain genetics, the freshness of the starting material, and the part of the plant extracted are all critical considerations.

  • Effective extraction method

An excellent extraction method prevents product defects, such as lackluster flavor or contamination.

  • Proper post-processing.

Refinement processes involve drying and storing practices, purging excess solvents, and isolating specific cannabinoids.

Benefits of CBD Oil

There have been reports that certain cannabinoids like THC and CBD may be beneficial for specific ailments and disorders.

Researchers conducted a systematic review to carefully examine the effectiveness of medical cannabis for psychiatric, movement, and neurodegenerative disorders

Results of the trials suggest potential benefits of cannabinoids for anxiety, anorexia nervosa, dementia, PTSD, Alzheimer’s disease, Huntington’s disease, Tourette syndrome, and Parkinson’s disease. 

However, insufficient and low-quality evidence make the results inconclusive. Improved knowledge of the precise action of cannabinoids at the cellular level could facilitate the development of cannabinoid formulations, as well as conduct further clinical trials on the symptoms of the disease.

Meanwhile, data from studies show that a single dose of CBD reduces resting blood pressure and blood pressure response to stress, indicating that CBD may be beneficial in the treatment of cardiovascular disorders, such as hypertension.

Side Effects of CBD Oil

CBD is considered safe. However, some people, particularly those who are taking other prescription medications, could still experience side effects from using CBD oil. It can interact with other pharmaceuticals like blood thinners.

CBD can cause side effects, such as dry mouth, diarrhea, fatigue, drowsiness, and changes in appetite, although they are often well-tolerated. 

The unreliability of the dosage and purity of CBD in products may also be an issue. 

A Penn Medicine study of 84 CBD products purchased online shows that almost 70 percent of them are either over or under labeled, causing potential serious harm to its consumers.

Thus, experts encourage people to talk to their doctor first before adding CBD oil to their existing treatment plan. A discussion on how one should take the oil and what concentration is best for an individual would benefit the patient’s health condition.

CBD for Symptoms of Cancer

According to the Centers for Disease Control and Prevention (CDC), “In 2016, 1,658,716 new cases of cancer were reported, and 598,031 people died of cancer in the United States. For every 100,000 people, 436 new cancer cases were reported, and 156 died of cancer. One of every four deaths in the United States is due to cancer.”

To date, Epidiolex is the only CBD product that has received FDA approval, and it is only used in the treatment of seizures associated with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) in patients 2 years of age and older.

No CBD products have been FDA-approved to cure cancer or its symptoms or to alleviate the side effects of cancer treatment.

However, two marijuana-based drugs, dronabinol and nabilone, have been approved to help with nausea and vomiting caused by chemotherapy.

Dronabinol (Marinol) is available in capsule form and contains THC.

Nabilone (Cesamet) is a synthetic cannabinoid that acts similarly to THC.

If one is considering using medical marijuana or medical cannabis as a supplement to his or her cancer therapy, a consultation with a doctor about how best to administer it is the best course of action.

Cancer in Pregnancy

Cancer during pregnancy is not a typical occurrence. Pregnancy-associated cancer constitutes a clinical situation that is difficult to manage.

According to statistics, 1 in every 1000 pregnant women is diagnosed with cancer. Studies indicate that breast cancer, melanoma, cervical cancer, lymphoma, and acute leukemia are commonly diagnosed malignancies during pregnancy.

Among these types of malignancies, breast cancer is the most common. A review revealed that breast cancer affects approximately 1 in 3000 pregnant women.

Experts at the Canadian Cancer Society expect that the number of pregnant women with cancer could increase as more women are waiting until they are older to have children. The risk of developing most cancers increases as women age.

Cancer Treatment while Pregnant

Years ago, many doctors recommended terminating the fetus when treating cancer during pregnancy.  Today, however, more women are choosing to treat their disease while they are pregnant.

Every situation is different. Although treatment choices for pregnant women with cancer are the same as those for non-pregnant women with cancer, when and how treatments are given might be different for pregnant women.

Thus, a discussion with a health professional of all the advantages and disadvantages of receiving cancer treatment during pregnancy is an excellent course of action.

A pregnant woman’s treatment options would depend on many factors, including the type of cancer she has, where her cancer is located, her cancer stage, how far along she is in her pregnancy, and her personal choices.

Say No to CBD When Pregnant

The U.S. Food and Drug Administration (FDA) has informed the public of the severe risks related to the use of cannabis products, including those containing CBD, for women who are pregnant or breastfeeding.

There are numerous potential adverse health effects from using marijuana and other products containing THC during pregnancy and while breastfeeding.

The U.S. Surgeon General advised consumers against marijuana use during pregnancy, as it may affect fetal brain development. THC could enter the fetal brain from the mother’s bloodstream.

The Surgeon General VADM Jerome said, “I am emphasizing the importance of protecting our nation from the health risks of marijuana use in adolescence and during pregnancy. Recent increases in access to marijuana and its potency, along with misperceptions of the safety of marijuana, endanger our most precious resource, our nation’s youth.”

The Surgeon General also advised that marijuana may intensify the risk of a newborn with lower than average birth weight. Research also suggests an increased risk of preterm birth and stillbirth.

There is still a lot to know about the mechanisms of CBD and its impact on the body of a cancer patient to make sure that it does not interact adversely with existing cancer treatments or other medications.

CBD oil may complement other treatments for cancer. However, if one is planning on adding it to his or her existing treatment plan, it is an excellent idea to discuss it with a doctor first.

Cancer is the second leading cause of death in women during the reproductive years.

The Consortium of Cancer in Pregnancy Evidence (CCoPE) was established to develop up-to-date, evidence-based information on the diagnosis, management, prognosis and fetal outcome of cancer in pregnancy.

Much of the data produced by the Consortium of Cancer in Pregnancy Evidence (CCoPE) have been published in peer reviewed journals in North America and Europe over the last five years. 

Cancer in Pregnancy

The occurrence of cancer during pregnancy is a rare and challenging event. But as more and more women delay child-bearing until later in life, the rate of cancer in pregnancy is expected to rise. New clinical practice guidelines have been prepared by the Chemotherapy During Pregnancy Working Group and approved by the Executive and Council of the Society of Obstetricians and Gynecologists of Canada.

Cancer in Pregnancy: Management of complications associated with cancer or antineoplastic treatment during pregnancy

Professional Summary

The treatment of choice for a large spectrum of hypercoagulable states during pregnancy is heparin. As an alternative, and probably a therapy that will become the future’s 1st line choice are the low molecular weight heparins.

Coumarin is not an option during pregnancy for the majority of the cases.

Erythropoietin does not cross the placenta and is associated with minimal side effects to the mother that are generally well tolerated. No fetal complications were reported.

The data regarding the safety of bisphosphonates and hematopoietic growth factors during pregnancy is scarce, and no firm recommendation can be made at this time.

Most antibiotics are not contraindicated during pregnancy, with the exception of the use of tetracycline during the 2nd and 3rd trimester.

Most of the analgesics are quite safe during pregnancy, as no malformations were noticed with first trimester use of most of them. Their main effect of narcotics analgesics is on fetal respiratory system, and these newborns should be watched carefully during delivery for signs of withdrawal or respiratory depression.

Cancer is the second leading cause of death in women during the reproductive years. Its incidence is between 0.07% to 0.1% of pregnancies. The diagnosis of cancer during pregnancy imposes major therapeutic decisions — optimal maternal treatment must be balanced against the risks to the fetus. The malignant disease and its treatment have specific complications that may have special importance during pregnancy. These include, among others, bone marrow depression with neutropenia and infections, anemia and thrombocytopenic bleeding. Both pregnancy and cancer are associated with hypercoagulability and thromboembolism. Also, skeletal manifestations of cancer like osteoporosis, bone pain, pathological fractures and hypercalcemia may require specific treatment during pregnancy. Thus, these complications of cancer or its treatment may expose the pregnant woman to additional medications including anticoagulants, antibiotics, analgesics and new treatment modalities such as hematopoietic growth factors and bisphosphonates. This is a general overview of the use of these therapeutic measures during pregnancy.

Anticoagulants Heparin

Heparin is a natural, water soluble, mucopolysaccharide which is being used for almost 80 years. Heparin exerts most of its anticoagulant activity by binding to antithrombin III, a naturally occurring anticoagulant. This complex inhibits a number of coagulation factors, mainly IIa and Xa. Other coagulation factors – IX, XI, XII are also inhibited. Heparin does not cross the placenta in appreciable amounts. No reports linking the use of heparin during gestation with congenital defects have been located.

Oral anticoagulants — Coumarin

Oral anticoagulants cross the placenta and can enter the fetal circulation. Since 1966 when the first case of “coumarin embryopathy” was described, the literature regarding the adverse outcome of the fetus following maternal exposure to coumarin has expanded. Most of the reports addressed the following problems associated with the use of coumarin during pregnancy: embryopathy, central nervous system defects, stillbirth, spontaneous abortions, prematurity and hemorrhage.

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