- Cannabidiol (CBD), a non-psychoactive and non-intoxicating compound in hemp plants, may have therapeutic benefits, such as alleviating symptoms of anxiety disorders(1).
- Animal studies also suggested CBD’s anti-inflammatory and pain-relieving properties. However, further CBD studies on humans are needed to validate this(2).
- Epidiolex is the only FDA approved CBD-based pharmaceutical drug at this time(3). It is formulated to help manage the symptoms of childhood epilepsy.
- Although CBD oil supplements generally promote wellness and are mostly available over the counter, they still pose some risks and side effects. CBD is not recommended for pregnant, breastfeeding, and those taking other medications.
The Cannabis sativa plant has two significant compounds, tetrahydrocannabinol (THC) and cannabidiol (CBD)(4).
These prevalent active cannabinoids interact in the human body’s endocannabinoid system (ECS) and may have notable health beneficial effects(5). However, they have different characteristics.
CBD is a non-psychoactive and non-intoxicating component ordinarily present in the industrial hemp plant(6). CBD does not induce psychosis or the feeling of being “high” like THC, the predominantly present cannabinoid in medical marijuana that induces psychoactive effects.
However, THC and CBD tend to have an inverse relationship with each other(7). A pharmacological study on rodents hypothesized that CBD blocked some effects of THC on mice(8).
CBD products have three classifications: CBD with less than 0.3% THC, CBD with more than 0.3% THC, and pharmaceutical CBD. A CBD product with more than 0.3% THC is considered illegal on the federal level(9).
Some of the possible therapeutic effects of CBD oil include pain relief(10). A study on CBD oil’s effectiveness on pediatric anxiety and insomnia caused by post-traumatic stress disorder (PTSD) suggested the possible effectiveness of CBD oil in reducing anxiety and insomnia secondary to PTSD(11).
Hemp vs. Marijuana
Marijuana and hemp plants come from the same species of plant, called cannabis. Both plants have naturally occurring phytocannabinoids, like CBD and THC.
Medicinal marijuana is commonly derived from the leaves and flowers of the cannabis plant. It is one of the most widely used psychotropic drugs in the United States(12). It gives a mind-altering effect due to the high THC content.
Tetrahydrocannabinol or THC has the same chemical structure as an endogenous cannabinoid in the brain, called anandamide. Anandamide functions as a neurotransmitter, influencing pleasure, memory, thinking, concentration, coordination, and sensory concentration.
THC attaches itself to cannabinoid receptors, which results in the disruption of various mental and physical functions(13).
The effects of THC may potentially result in dependence or addiction. This tendency ensues when the person’s brain adapts to the massive doses of marijuana, resulting in reduced production and sensitivity to endocannabinoid neurotransmitters(14).
Meanwhile, the industrial hemp plant is mainly cultivated for its high fiber content and is now recognized as a source of cannabidiol. Hemp’s low THC content, when combined with other chemical compounds, like terpenes and other cannabinoids, work together to optimize wellness.
CBD products from hemp extract do not have the same psychoactive effect on the human body’s nervous system as the other cannabis plant, marijuana. CBD weakly binds with brain cannabinoid receptors and does not give a euphoric effect(15).
The US Farm Bill 2018 legalized industrial hemp production and its extracts with no more than 0.3% THC(16). It allows the cultivation of hemp and the transfer of hemp-derived products across the states.
Before the 2018 Farm Bill, the 2014 Farm Bill allowed programs for studying market interest in products that use hemp(17).
Note that hemp is a term used to classify cannabis varieties with less than 0.3% THC content in dry weight(18). The variant of cannabis with 4% to 15% THC is considered marijuana(19).
CBD oil products derived from this particular strain of cannabis plants are legal under the US Food and Drug Administration (FDA). However, the use of CBD oil products is still under strict regulations, and the law may differ from state to state.
The only FDA-approved CBD for medical use is an anti-seizure drug called Epidiolex(20). It is the first purified pharmaceutical-grade CBD medication used to treat Dravet syndrome and Lennox-Gastaut syndrome.
Epidiolex is dispensed only in specialty pharmacies.
Safeness of CBD
The FDA stated that the benefits of Epidiolex, a CBD oil-based drug for epilepsy, supersede its risks(21). Not all acclaimed medical benefits of CBD are backed by scientific studies.
Additionally, CBD has some proven side effects, including drowsiness, dry mouth, reduced appetite, and fatigue(22).
The FDA spearheads regulation of CBD oil products in the US. Hemp-derived CBD is principally used as an ingredient in food or beverages, dietary supplements, cosmetic, and personal care products rather than used for medical purposes(23).
CBD’s Possible Benefits and Uses
Most CBD products highlight CBD’s potential benefits in anxiety and pain management(24).
Research on the comparison of the efficacy of CBD: THC ratio and THC extract alone was conducted on 177 patients with continuous cancer pain despite chronic opioid dosing(25).
The tests were done during a two-week, randomized, multi-center, placebo-controlled, double-blind, parallel-group trial.
The study suggested that the THC: CBD extract showed significant effects on cancer-related pain relief. The group that took THC: CBD exhibited mild to medium adverse effects(26).
A study done by the National Institutes of Health (NIH) stated that CBD may help mitigate chronic pain and inflammation by interacting with the brain’s neurotransmitters(27).
The National Institutes of Health (NIH) is a medical research agency under the United States Department of Health and Human Services (USDHHS).
Researchers in a cross-sectional study of cannabidiol users noted that the top three medical conditions targeted by CBD users are pain, anxiety, and depression(28).
A study on CBD’s effect on high blood pressure hypothesized that a single CBD dose may decrease the resting blood pressure and the blood pressure response to stress(29).
Furthermore, CBD may also be useful in suppressing the main causal factors of Alzheimer’s disease(30).
There is only one pharmaceutical-grade federally approved CBD product in the United States, Epidiolex.
Epidiolex is a CBD-only drug used to treat childhood epilepsy, like Dravet and Lennox-Gastaut syndromes. It is taken orally and dosed depending on body weight. The starting dose of Epidiolex is 10mg/kg daily up to 20mg/kg daily(31).
Recent clinical trials reported CBD’s benefits in reducing seizure frequency among children and young adults(32).
Sativex is GW Pharmaceuticals’ THC and CBD product approved in the United Kingdom, Europe, and Canada(33). It is formulated to help with spasticity and neuropathic pain in multiple sclerosis and adjunctive analgesia for moderate to severe cancer pain.
Unlike Epidiolex, Sativex is not advised to be used by children and adolescents and is mainly for elderly patients’ consumption(34). It comes in a spray, and it is for buccal use only.
Interactions Between CBD and Other Drugs
Although CBD-infused products have beneficial effects, it can also inhibit the human cytochrome P-450 system (CYP450) from metabolizing certain drugs, leading to an increase in other drug’s processing time(35).
The cytochrome P-450 is an enzyme system found in the liver responsible for the absorption and breaking down of toxic compounds in the drugs a person consumes(36).
CBD’s ability to alter the CYP450 system and induce higher levels of certain drugs may lead to adverse side effects or an overdose(37).
Some of the drugs known to impact the activity of CYP450 enzymes are steroids, antihistamines, HIV antivirals, immune modulators, antibiotics, anesthetics, antipsychotics, antidepressants, anti-epileptics, and beta-blockers(38).
CBD may also exhibit pharmacodynamic interactions with other drugs(39). Pharmacodynamic interaction occurs when drugs directly influence each other’s effects(40).
For example, cannabinoids, such as CBD and THC, and opioids may block the release of pain-generating neurotransmitters in the brain and spinal cord through a G protein-coupled mechanism(41).
Cannabinoids’ synergistic effects with opioids were reported in a study conducted to gauge the impact of cannabinoid-opioid interaction in chronic pain(42).
The study discussed that the synergy of cannabinoids and opioids may increase the analgesic effects of opioids and may help in administering low doses of opioids and lessen its side effects(43).
A study on the analgesic and anti-inflammatory effects of formulated full-spectrum cannabis extract stated that the presence of these phytocannabinoids has a potential role in neuropathic pain treatment(44)
CBD Types and Potencies
Three known types of cannabidiol may be used in CBD-derived products. These CBD types are full-spectrum CBD, broad-spectrum CBD, and CBD isolates, with each type offering potential benefits.
The presence or absence of terpenes and other cannabinoids in each CBD type may affect how a specific CBD type works.
A study explored the entourage effect in managing the symptoms of mood disorders and anxiety disorders. Results showed that the entourage effect or the synergy between the cannabinoids and terpenes may contribute to CBD’s positive effects in treating some psychiatric symptoms(45).
Each CBD type may exhibit different levels of bioavailability. Transdermal application, the administration of topical CBD products directly to the skin, may help alleviate chronic pain(46).
The CBD potency or CBD amount per serving of each CBD type depends on the hemp strain, hemp cultivation process, and the extraction method.
Full-spectrum CBD is a whole plant-derived CBD with THC, terpenes, and other cannabinoids present in its formulation.
The combination of phytocannabinoids creates an entourage effect, where the active ingredients interact synergistically, maximizing the benefits of the hemp extract(47).
Broad-spectrum CBD contains all the cannabinoids present in the hemp plant, excluding THC. The most potent THC-free products are usually broad-spectrum CBD products(48).
Broad-spectrum CBD products are considered the middle ground between full-spectrum CBD and CBD isolates(49).
CBD isolate is a crystalline substance of 99% pure cannabidiol. It does not have any THC, other cannabinoids, or terpenoids.
CBD isolate is the purest form of CBD and may be used as an ingredient in food or skincare products(50). Isolates are often flavorless and odorless.
Due to the absence of other active cannabinoids, CBD isolates do not result in an entourage effect. They seem to have a narrower therapeutic window yielding potential benefits than full-spectrum CBD and broad-spectrum CBD(51).
People who want more potent doses of CBD may prefer CBD isolates.
Risks and Side Effects
CBD products are often promoted as over-the-counter food supplements(52). However, they may pose risks and side effects among users.
The Food Standard Agency (FSA) does not recommend dosing CBD products to pregnant, breastfeeding, or people who are taking other medications(53).
Some of CBD’s probable adverse effects are somnolence (drowsiness), diarrhea, dry mouth, reduced appetite, and fatigue(54).
According to a study, some CBD products may have brief periods of intoxication due to THC contamination(55). These risks may be attributed to some product labels not giving accurate information on dosage and purity.
Ongoing Research on CBD
The increasing interest in CBD and its possible medicinal benefits promotes more research regarding its implication to certain conditions and its possible adverse effects.
The Food and Drug Administration (FDA) advocates scientific research regarding cannabis and its constituents.
According to the clinical studies and case reports from the International Association for Cannabis Medicines, predominant research on CBD is on its effects on pain, anxiety, and cancer(56).
Another field that researchers explore is the potential benefits of full-spectrum CBD products to drug dependency and withdrawal.
These studies may lead to new and approved pharmaceutical-grade CBD-based drugs. However, further research is needed to understand CBD’s potential use as a medication and supplement.
Methods of Consumption and Dosage
CBD may be in the form of oil and tinctures, edibles, vapes, and topicals. Some of the most common ways to use CBD are ingesting it orally, sublingually, or under the tongue, through vaping, mixing with food or drinks, or physical application.
Tinctures are often ingested sublingually. It is often infused with carrier oils, such as coconut oil or hempseed oil. The standard starting dose for tinctures is 2.5mg to 5mg of CBD(57). It is directly absorbed into the blood vessels and is effective after 15 to 30 mins of serving(58).
Orally-taken CBD includes edibles, like gummies and dietary supplements. It is one of the most prominent forms of CBD for first-time users(59). These edibles are quickly taken on the go. However, the bioavailability of these orally ingested CBD may be lower than other forms.
It takes longer for the body to absorb and for the effects to take place. It usually takes 30 minutes after ingestion.
Inhalation by Vaporization
A faster way to absorb CBD in the body is through inhalation or vaping. It is one of the most common ways to consume CBD. Its instant effects may be felt within seconds or minutes of inhaling vaporized CBD(60).
CBD comes in the form of vape juice that is poured into a device called a vape pen.
CBD topicals are common for joint pain and muscle pain relief. It may be a balm, salve, cream, or lotion. These products are absorbed through the skin. Topicals may have quicker relieving effects compared to the ingestible CBD products(61).
Storage is vital in preserving the potency of the CBD product(62). Proper storage prevents the degradation of substances in the products.
CBD products must be stored in a cool, dry place. Putting them in a warm place may promote the growth of molds and bacteria, while freezing temperatures may change its consistency(63).
In storing CBD oil products, it is best to avoid storing them in places with direct light. The lids should also be shut tight to ensure the CBD product’s high quality and effectiveness(64).
Any changes in the CBD oil’s color may be a sign of expiration. Most brands indicate that CBD products may last up to one to two years only.
CBD is not a cure-all medication for various diseases. Although it has shown potential health benefits and advantages on well-being, there is not enough scientific evidence to conclude this.
There are also risks and side effects to consider.
CBD does not show on drug tests. However, drug tests may detect THC in full-spectrum CBD oil, primarily when used in high doses for an extended period.
According to a paper published in the Journal of Analytical Toxicology, vaped cannabis with 0.39% THC may test positive urine tests(65).
CBD products that are not third party-verified may cause a false positive on a urine drug test. It is recommended to use products made with CBD isolates that often have high doses of CBD and zero THC to avoid false positives.
Other natural alternatives for hemp-derived CBD is the magnolia extract, believed to have active cannabinoids together with its main compounds, magnolol and honokiol(66).
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