CBD Clinicals is reader-supported. When you buy through links on our site, we may earn an affiliate commission. Learn more

Does CBD interact with Xanax and other benzodiazepines (tranquilizers and sedatives)?

  • Alprazolam (Xanax) is mainly metabolised by CYP3A4 (a type of enzyme that belongs to the CYP450 family), as confirmed by a Japanese study in the Yamagata University School of Medicine(1). Found mostly in the liver and small intestine, the CYP3A4 enzyme is responsible for breaking down many of the medicines that enter the body.
  • In a Japanese study published in Life Sciences, it was indicated that CBD (cannabidiol) most potently inhibited the catalytic activity of the human CYP3A system of enzymes(2).
  • When the CYP450 family of enzymes is influenced in this way, it leads to higher levels of certain drugs in the system at one time, which can cause unwanted side effects, and sometimes, an overdose(3).
  • Authors of a study published in Cannabis and Cannabinoid Research do not recommend that cannabis can or should be used as an alternative or supplement to medically indicated and prescribed benzodiazepines(4).
  • Given that the benzodiazepines are metabolized by the same enzymes that CBD inhibits, taking CBD with Xanax or any other benzodiazepine is not recommended.  It is crucial to consult with a doctor experienced in cannabis use before including CBD in a regimen.

Can CBD be taken with Xanax?

Alprazolam (Xanax) is a benzodiazepine. Benzodiazepines are categorized under a group of medicines called central nervous system (CNS) depressants, which are medicines that calm down the nervous system by acting on the GABA receptors(5).

Enzymes are proteins made from amino acids, and they help speed up chemical reactions in the body.

A family of enzymes, called Cytochrome P450, are essential for the metabolism of many medicines and compounds within the human body.

CYP3A4, which belongs to the CYP450 family, contributes to the detoxification of the bile acid, the termination of steroid hormones activity, and elimination of chemicals in food and medicines.

Alprazolam (Xanax) is mainly metabolised by the CYP3A4 system of enzymes, as confirmed by a Japanese study in the Yamagata University School of Medicine(6)

Mainly found in the liver and the intestine, CYP3A4 is an enzyme involved in the metabolism of almost half the drugs in use today(7).

The drugs affecting CYP3A4 activity inhibit or induce the metabolism of the benzodiazepines metabolized by this enzyme. The enzymes cause side effects or reduce the therapeutic effects of these drugs(8).

There have been no clinical trials or case studies documenting a Xanax and CBD interaction. 

However, CBD has been shown to inhibit the cytochrome P450’s ability to metabolize certain drugs, leading to an overall increase in processing times(9).

In a Japanese study published in Life Sciences, it was indicated that CBD most potently inhibited the catalytic activity of human CYP3A enzymes, especially CYP3A4 and CYP3A5(10).

When the CYP450 system is influenced in this way, it leads to higher levels of certain drugs in the system at one time, which can cause unwanted side effects, and sometimes, an overdose(11).

This interaction is due to how CBD interacts with the endocannabinoid system, a complex cell-signaling system in the body. If the side effects are not correctly understood, the risks could be dangerous.

When more of the medication enters the bloodstream than average, it could increase the side effects of Xanax. 

Common side effects of Xanax include fatigue, changes in patterns and rhythms of speech, memory problems, poor coordination, lack of appetite, irritability or trouble sleeping.

Less common side effects of Xanax include ear congestion, vomiting of blood, hyperventilation, irregular heartbeats, seizures, and uncontrolled twisting movements of the legs, neck, trunk, or arms(12).

Thus, consult with a doctor experienced in cannabis use before including CBD in a regimen that includes Xanax. 

Also, using Xanax with other medications like itraconazole (Sporanox) or ketoconazole (Nizoral) is not recommended, as using any of them together may increase the chance of serious side effects. 

However, there may be cases when the combination of Xanax with other medications, such as the ones mentioned above, is unavoidable. In situations like this, the doctor may change the dose or how often Xanax is used, or give special instructions about the use of food, alcohol, or tobacco(13).

Can another benzodiazepine be a substitute for Xanax so CBD oil can be taken?

Cytochrome P450(CYP)3A4 is one of the CYP enzymes catalyzing oxidative metabolism, and is involved in the metabolism of many drugs. 

Among benzodiazepines, alprazolam, triazolam, brotizolam and midazolam are mainly metabolized by CYP3A4. Meanwhile, quazepam, diazepam (Valium) and flunitrazepam are partly metabolised by this enzyme(14).

Thus, taking CBD oil with any other benzodiazepine may lead to the same interactions, given that the benzodiazepines mentioned above are metabolized by the same enzymes that CBD inhibits.

Can CBD replace Xanax?

There is no specific study that shows CBD as a safe replacement for Xanax or any benzodiazepine medication.

The only study that came close to examining the possible impact of THC (tetrahydrocannabinol) and CBD among subjects who used benzodiazepine is that of a 2019 study published in the journal Cannabis and Cannabinoid Research(15)

Researchers of the said study found that approximately 45 percent of the subjects had stopped taking benzodiazepine within about six months of beginning medical cannabis. Many of them also reported decreased daily distress due to medical conditions after being prescribed cannabis.

However, medical cannabis given to the subjects contained varying levels of THC and CBD(16)

Thus, it cannot be concluded that it was CBD alone that brought about the improved condition among the subjects who discontinued their use of benzodiazepines. 

Also, the distribution of cannabinoid (CBD and THC) proportions was not significantly different among patients who continued and those who discontinued benzodiazepines.

The researchers were not able to gain access to information on cannabis strains, growth and producers. Nor were they able to generalize the results to products that were available in Canada.

Still, study author Chad Purcell and his team from Dalhousie University do not recommend that cannabis can or should be used as an alternative or supplement to medically indicated and prescribed benzodiazepines (17). 

Also, one essential reminder is not to stop taking Xanax without checking first with a doctor. 

The doctor will want the Xanax dose gradually reduced before completely stopping it, which may prevent a worsening of the medical condition and reduce any possibility of withdrawal symptoms, like convulsions (seizures), stomach or muscle cramps, sweating, tremors, vomiting, or unusual behavior.

Note that Xanax may be habit-forming. Thus, if the medicine is not working as well, do not use more than the prescribed dose, and call a doctor for instructions.

Also, do not take other medications, including prescription or nonprescription over-the-counter medicines or supplements, unless they have been discussed with a doctor(18).

What to Know Before Using Alprazolam

When using medication, the risks must be weighed against its benefits. For taking alprazolam, the following points should be considered:

Allergies

Tell the doctor of any unusual or allergic reaction to this medicine or any other medicines. Also, tell a healthcare professional of any other forms of allergies, such as allergies to foods, preservatives, dyes, or animals. For non-prescription products, carefully read the ingredients on the package label.

Pediatric

Appropriate studies have not been done on the relationship of age to the effects of alprazolam in children. Safety and efficacy have not been known.

Geriatric

Studies conducted to date have not demonstrated geriatric-specific problems that would limit the usefulness of alprazolam in the elderly. 

However, older adults are likely to have unwanted effects (e.g., severe drowsiness, dizziness, confusion, clumsiness, or unsteadiness) and kidney, liver, or lung problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Pregnancy

Studies in pregnant women have shown a risk to the fetus, according to Mayo Clinic. However, the benefits of therapy in a life-threatening situation or a severe disease may outweigh the potential risk.

Breastfeeding

Studies of alprazolam use in breastfeeding women have demonstrated harmful infant effects, according to Mayo Clinic. An alternative to this medicine should be prescribed, or breastfeeding should be stopped while using this medicine.

Alprazolam and Other Drug Interactions 

Specific medicines should not be used together at all. However, in some cases, two different medicines may be used together even if an interaction might occur. 

In these cases, a doctor may want to change the dose, or other precautions may be necessary. 

When one is taking this medicine, a healthcare professional must know of any of the medicines listed below. Taking this medicine with any of the following medicines is discouraged. 

A doctor may decide not to treat individuals with this medication or change some of the other medicines they take.

  • Delavirdine
  • Flumazenil
  • Itraconazole
  • Ketoconazole

Taking this medicine with any of the following medications is usually not recommended, but may be required in some cases. If both medicines are prescribed together, a doctor may change the dose, and how often the medicines are used.

  • Alfentanil
  • Amobarbital
  • Benzhydrocodone
  • Boceprevir
  • Bromazepam
  • Bromopride
  • Buprenorphine
  • Butabarbital
  • Butalbital
  • Butorphanol
  • Cannabidiol
  • Carbamazepine
  • Carbinoxamine
  • Carisoprodol

For a complete list, click here(19).   

A Close Look at Benzodiazepines

An article on Harvard Health says that for many years, benzodiazepines continued to be the most popular prescription tranquilizers and sedatives(20).

Benzodiazepines, sometimes called benzos, have a standard basic chemical structure, and they increase the activity of the receptors for the neurotransmitter gamma-aminobutyric acid (GABA). 

GABA inhibits the activity of neurons, slowing down the brain and nervous system, so benzos are calming and promote sleep. 

Benzodiazepines differ primarily in how quickly they are absorbed, how long their effects last, and how long they take to leave the system.

Benzodiazepines are also prescribed for acute seizures, severe muscle spasms, tremors, and alcohol and drug withdrawal symptoms. However, their main uses are still in the treatment of insomnia and anxiety(21).

Meanwhile, according to an article posted by the Anxiety and Depression Association of America, benzodiazepines, such as alprazolam, clonazepam, diazepam, and lorazepam, promote relaxation and reduce muscular tension, including other physical symptoms of anxiety. 

Benzodiazepines are also frequently used for short-term management of anxiety, such as for minor medical procedures(22).

Long-term Use of Benzodiazepines

In a 2015 study published by Australian Prescriber, the authors said that there are well-recognised harms from long-term use of benzodiazepines. These include dependency, cognitive decline and falls(23).

Over the last two decades, the quantity of benzodiazepines on every prescription has increased, and alprazolam became the second most popular drug(24)

Of specific concern are those who have been taking benzodiazepines for over six months. There are a few indications for long-term therapy, and they are controversial(25).

Benzo-related problems include misuse, dependency, driving impairment, and morbidity and mortality related to overdose and withdrawal(26)

In the elderly, benzos have been linked to cognitive decline, dementia and falls(27). Also, there is evidence of increased mortality with long-term use(28).

In February 2014, in response to a surge in illicit use, alprazolam was rescheduled to Schedule 8. Alprazolam has more significant toxicity in overdose and associated mortality compared with other benzodiazepines(29)

The effect of this rescheduling is yet to be determined, as this barrier to prescribing has placed a new focus on benzo dependence. 

However, there is a lack of research on the optimal management of benzo dependence, according to the authors of the review published by Australian Prescriber(30).

Benzodiazepine Substitution

Some benzodiazepines, like alprazolam, appear to have a higher propensity for misuse and are more dangerous in overdose. 

The reasons for this propensity include perception of intoxication, potency relative to the formulation (e.g. a single 2 mg alprazolam tablet is equivalent to four 5 mg diazepam tablets), shorter half-life and risk of withdrawal phenomena(31)

A common approach is substituting these shorter half-life drugs, such as alprazolam, with more extended half-life drugs, such as diazepam(32). 

When tapering benzodiazepines, fewer patients taking more extended half-life drugs drop out. 

However, there is a lack of robust evidence supporting substitution. Studies in older patients have found gradual withdrawal without substitution can be successful(33). 

Abrupt cessation of benzodiazepines after a period of 1–6 months of use can cause life-threatening seizures so the dose should be gradually reduced(34).

Benzodiazepines and Post-Traumatic Stress Disorder (PTSD)

Benzodiazepines were once the primary agents in PTSD treatment(35).

Individuals with post-traumatic stress disorder (PTSD) show a higher rate of panic disorder than other people. People with panic disorder regularly suffer intense episodes of anxiety, known as panic attacks(36).

 Alprazolam and clonazepam have been used extensively, but the efficacy of benzodiazepines against the significant PTSD symptoms has not been proven in controlled studies(37).

These agents are effective against anxiety, insomnia and irritability, but they should be used with great caution because of the high frequency of comorbid substance dependence in patients with PTSD. Patients should be fully informed of the risks and benefits of these medications, including the risks of dependency and withdrawal after abrupt discontinuation.

Although benzodiazepine drugs are widely used in patients with post-traumatic stress disorder (PTSD), available evidence suggests that they are not sufficient and may even be harmful, concluded a 2015 systematic review and meta-analysis in the July Journal of Psychiatric Practice(38).

“Benzodiazepines are ineffective for PTSD treatment and prevention, and risks associated with their use tend to outweigh potential short-term benefits,” wrote Dr Jeffrey Guina and colleagues from Wright State University, Dayton, Ohio. 

They also found evidence to suggest that using benzodiazepines in patients with recent trauma can even increase the risk of developing PTSD.

Potential Ways CBD Helps with Depression and Anxiety

CBD has been shown to possess potential medical benefits, from nausea to blood pressure to inflammation(39).

CBD oil, which is derived from the cannabis plant, is available in tincture or vape liquid, or CBD-infused foods and beverages.

CBD oil has also shown promise as possible depression and anxiety medications, which could be why those who live with these disorders are interested in this natural approach.

In one 2019 Brazilian study, subjects received either oral CBD or a placebo 90 minutes before they underwent a simulated public speaking test(40)

The researchers indicated that a 300-mg dose of CBD was the most helpful at significantly reducing anxiety during the test.

In the study, no significant differences in anxiety levels were observed on the subjects given the placebo, a 150-mg dose of CBD, and a 600-mg dose of CBD.

In another study, CBD oil has even been used to safely alleviate insomnia and anxiety in children with PTSD(41).

CBD has also exhibited antidepressant-like effects in some animal studies(42).

These characteristics are associated with CBD’s potential ability to trigger the brain’s receptors for serotonin, a neurotransmitter that regulates mood and social behavior.

For example, other studies have demonstrated that treatment with CBD improved complex, sleep‐related behaviors for people with Parkinson’s disease(43).

Also, animal and test-tube studies have shown that CBD may decrease inflammation and help prevent the neurodegeneration associated with Alzheimer’s disease(44).

In one study, researchers gave CBD to mice genetically predisposed to Alzheimer’s disease, finding that it helped prevent cognitive decline(45).

Though CBD is generally well-tolerated and considered safe, it may cause adverse reactions in some people.

Side effects noted in studies include(46):

  • Diarrhea
  • Fatigue
  • Changes in appetite and weight

CBD also interacts with several medications. Thus, before starting to use CBD oil, discuss it with a doctor to avoid potentially harmful interactions(47).

This reminder is essential when taking supplements or medications that come with a grapefruit warning. 

Both CBD and grapefruit interfere with cytochromes P450 (CYPs), the enzymes that are essential to drug metabolism.

One study showed that CBD-rich cannabis extracts have the potential to cause liver toxicity(48).

Although the study above was done on mouse models, there have also been a handful of human studies related to chronic pain, anxiety, and stress. 

A 2010 study published in the Journal of Psychopharmacology indicated that CBD oil was associated with a decreased level of subjective anxiety, suggesting that CBD can reduce anxiety in patients experiencing social anxiety disorders(49).

Clinical trials have shown promising results for treating anxiety symptoms with CBD. A 2011 study found that CBD helped lessen anxiety in subjects that were put through a stressful public speaking simulation(50). 

A 2015 study published in Neuropathics found parallel evidence supporting CBD’s anxiolytic properties. 

The authors stated, “Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with the need for further study”(51).

The National Institute on Drug Abuse (NIDA) recently concluded one of the most comprehensive CBD studies involving human subjects(52).  

NIDA uses multiple sources to monitor the prevalence and trends regarding drug use in the United States(53). 

Researchers of the said NIDA study evaluated CBD in comparison with THC, Alprazolam, and placebo in healthy recreational drug users to determine whether or not CBD should still be a Schedule I drug or be recommended for deregulation.

Subjects received different doses of the alprazolam capsule for 18 days. Then, a series of assessment questions were given, and vital signs and ECG readings were evaluated. Researchers completed the study in May 2018. However, results for publication are still pending.

Conclusion

The high rate of dependency and misuse among Xanax users may be the reason why there is an interest in alternative, Xanax-free treatments, including CBD oil. 

CBD’s antidepressant-like and anxiolytic-like effects have been shown in several studies, such as the 2014 study that was published in the CNS and Neurological Disorders – Drug Targets(54). 

However, CBD is also known to interact with several medications. Thus, before using CBD oil, discuss it with a doctor and ask for medical advice to avoid potentially harmful interactions.

To date, the U. S. Food and Drug Administration (FDA) has not approved an application for cannabis for the treatment of any disorder or medical condition except for one cannabis-derived drug, Epidiolex, and three cannabis-related drug products(55)

Epidiolex contains a purified form of the drug substance CBD for the treatment of seizures associated with Lennox-Gastaut syndrome or Dravet syndrome in patients two years of age and older.

There have been no clinical trials or case studies, specifically documenting a Xanax and CBD interaction. However, taking CBD oil or CBD products with Xanax or any other benzodiazepine may lead to adverse interactions such as elevated levels due to reduced clearance from the body, given that benzodiazepines are metabolized by the same enzymes that CBD inhibits.


  1. Otani, K. Cytochrome P450 3A4 and Benzodiazepines. Seishin Shinkeigaku Zasshi. 2003;105(5):631-42. Retrieved from  https://www.ncbi.nlm.nih.gov/pubmed/12875231.
  2. Yamaori S, Ebisawa J, Okushima Y, Yamamoto I, Watanabe K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011 Apr 11;88(15-16):730-6. doi: 10.1016/j.lfs.2011.02.017. Epub 2011 Feb 26.DOI: 10.1016/j.lfs.2011.02.017.
  3. CBDOilReview.org.Retrieved from https://cbdoilreview.org/cbd-cannabidiol/cbd-p-450-enzyme.
  4. Dolan, Eric. (2019, May 8). A significant number of cannabis patients discontinue use of benzodiazepines. Retrieved from https://www.psypost.org/2019/05/a-significant-number-of-cannabis-patients-discontinue-use-of-benzodiazepines-53636.
  5. Ibid.
  6. Otani, K. Cytochrome P450 3A4 and Benzodiazepines. Seishin Shinkeigaku Zasshi. 2003;105(5):631-42. Retrieved from  https://www.ncbi.nlm.nih.gov/pubmed/12875231.
  7. CYP3A4 cytochrome P450 family 3 subfamily A member 4 [ Homo sapiens (human) ]. Retrieved from https://www.ncbi.nlm.nih.gov/gene/1576.
  8. Otani, K. op. cit.
  9. CBDOilReview.org. op. cit.
  10. Yamaori S. op. cit.
  11. CBDOilReview.org. op. cit.
  12. Mayo Clinic. (2020, Feb 1). Alprazolam (Oral Route). Retrieved from : https://www.mayoclinic.org/drugs-supplements/alprazolam-oral-route/side-effects/drg-20061040?p=1.
  13. Ibid.
  14. Otani, K. op. cit.
  15. Chad Purcell, Andrew Davis, Nico Moolman, and S. Mark Taylor.Cannabis and Cannabinoid Research.Sep 2019.214-218.http://doi.org/10.1089/can.2018.0020.
  16. Ibid.
  17. Dolan, Eric. op. cit..
  18. Mayo Clinic. op. cit.
  19. Ibid.
  20. Harvard Health Publishing. (2019. March 15). Retrieved from https://www.health.harvard.edu/mind-and-mood/benzodiazepines_and_the_alternatives.
  21. ibid.
  22. Roy-Byrne, P. What Medications Are Used to Treat Anxiety Disorders? Retrieved from https://adaa.org/learn-from-us/from-the-experts/blog-posts/what-medications-are-used-treat-anxiety-disorders.
  23. Brett J, Murnion B. Management of benzodiazepine misuse and dependence. Aust Prescr. 2015;38(5):152–155. doi:10.18773/austprescr.2015.055.
  24. Islam MM, Conigrave KM, Day CA, Nguyen Y, Haber PS. Twenty-year trends in benzodiazepine dispensing in the Australian population. Intern Med J 2014;44:57-64.
  25. Lader M. Benzodiazepines revisited–will we ever learn? Addiction 2011;106:2086-109.
  26. Brett J. op. cit.
  27. Billioti de Gage S, Bégaud B, Bazin F, Verdoux H, Dartigues JF, Pérès K, et al. Benzodiazepine use and risk of dementia: prospective population based study. BMJ 2012;345:e6231; Pariente A, Dartigues JF, Benichou J, Letenneur L, Moore N, Fourrier-Réglat A. Benzodiazepines and injurious falls in community dwelling elders. Drugs Aging 2008;25:61-70; Ballokova A, Peel NM, Fialova D, Scott IA, Gray LC, Hubbard RE. Use of benzodiazepines and association with falls in older people admitted to hospital: a prospective cohort study. Drugs Aging 2014;31:299-310.
  28. Charlson F, Degenhardt L, McLaren J, Hall W, Lynskey M. A systematic review of research examining benzodiazepine-related mortality. Pharmacoepidemiol Drug Saf 2009;18:93-103.
  29. Isbister GK, O’Regan L, Sibbritt D, Whyte IM. Alprazolam is relatively more toxic than other benzodiazepines in overdose. Br J Clin Pharmacol 2004;58:88-95; Rintoul AC, Dobbin MD, Nielsen S, Degenhardt L, Drummer OH. Recent increase in detection of alprazolam in Victorian heroin-related deaths. Med J Aust 2013;198:206-9.
  30. Brett J. op. cit.
  31. Ibid.
  32. Liebrenz M, Boesch L, Stohler R, Caflisch C. Agonist substitution–a treatment alternative for high-dose benzodiazepine-dependent patients? Addiction 2010;105:1870-4.
  33. Denis C, Fatséas M, Lavie E, Auriacombe M. Pharmacological interventions for benzodiazepine mono-dependence management in outpatient settings. Cochrane Database Syst Rev 2006;3:CD005194; Campbell AJ, Robertson MC, Gardner MM, Norton RN, Buchner DM. Psychotropic medication withdrawal and a home-based exercise program to prevent falls: a randomized, controlled trial. J Am Geriatr Soc 1999;47:850-3.
  34. Brett J. op. cit.
  35. Lange JT, Lange CL, Cabaltica RB. Primary care treatment of post-traumatic stress disorder. Am Fam Physician. 2000 Sep 1;62(5):1035-40, 1046.
  36. Perelman School of Medicine. Panic Disorder. Retrieved from https://www.med.upenn.edu/ctsa/panic_symptoms.html. 
  37. Friedman MJ. Current and future drug treatment for posttraumatic stress disorder patients. Psychiatr Ann. 1998;28:461–8.
  38. Guina J, Rossetter SR, DeRHODES BJ, Nahhas RW, Welton RS. Benzodiazepines for PTSD: A Systematic Review and Meta-Analysis. J Psychiatr Pract. 2015 Jul;21(4):281-303. doi: 10.1097/PRA.0000000000000091.
  39. Parker LA, Rock EM, Limebeer CL. Regulation of nausea and vomiting by cannabinoids. Br J Pharmacol. 2011;163(7):1411–1422. doi:10.1111/j.1476-5381.2010.01176.x; Jadoon KA, Tan GD, O’Sullivan SE. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. JCI Insight. 2017;2(12):e93760. Published 2017 Jun 15. doi:10.1172/jci.insight.93760; Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. doi:10.4155/fmc.09.93.
  40. Linares IM, Zuardi AW, Pereira LC, et al. Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test. Braz J Psychiatry. 2019;41(1):9–14. doi:10.1590/1516-4446-2017-0015.
  41. Shannon S, Opila-Lehman J. Effectiveness of Cannabidiol Oil for Pediatric Anxiety and Insomnia as Part of Posttraumatic Stress Disorder: A Case Report. Perm J. 2016;20(4):16-005. doi:10.7812/TPP/16-005.
  42. Zanelati TV, Biojone C, Moreira FA, Guimarães FS, Joca SR. Antidepressant-like effects of cannabidiol in mice: possible involvement of 5-HT1A receptors. Br J Pharmacol. 2010;159(1):122–128. doi:10.1111/j.1476-5381.2009.00521.x; Long LE, Chesworth R, Huang XF, et al. Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice. PLoS One. 2012;7(4):e34129. doi:10.1371/journal.pone.0034129.
  43. Chagas MH et al. Cannabidiol can improve complex sleep-related behaviours associated with rapid eye movement sleep behaviour disorder in Parkinson’s disease patients: a case series. J Clin Pharm Ther. 2014 Oct;39(5):564-6. doi: 10.1111/jcpt.12179. Epub 2014 May 21. DOI: 10.1111/jcpt.12179.
  44. Watt G, Karl T. In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease. Front Pharmacol. 2017;8:20. Published 2017 Feb 3. doi:10.3389/fphar.2017.00020.
  45. Cheng D1, Spiro AS2, Jenner AM2, Garner B2, Karl T3.Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J Alzheimers Dis. 2014;42(4):1383-96. doi: 10.3233/JAD-140921.DOI: 10.3233/JAD-140921.
  46. Iffland K, Grotenhermen F. An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies. Cannabis Cannabinoid Res. 2017;2(1):139–154. Published 2017 Jun 1. doi:10.1089/can.2016.0034.
  47. Welty TE, Luebke A, Gidal BE. Cannabidiol: promise and pitfalls. Epilepsy Curr. 2014;14(5):250–252. doi:10.5698/1535-7597-14.5.250.
  48. Ewing LE, Skinner CM, Quick CM, et al. Hepatotoxicity of a Cannabidiol-Rich Cannabis Extract in the Mouse Model. Molecules. 2019;24(9):1694. Published 2019 Apr 30. doi:10.3390/molecules24091694.
  49. Crippa JA et al. Neural basis of anxiolytic effects of cannabidiol (CBD) in generalized social anxiety disorder: a preliminary report. J Psychopharmacol. 2011 Jan;25(1):121-30. doi: 10.1177/0269881110379283. Epub 2010 Sep 9. DOI: 10.1177/0269881110379283.
  50. Bergamaschi MM, Queiroz RH, Chagas MH, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011;36(6):1219–1226. doi:10.1038/npp.2011.6.
  51. Blessing, E.M., Steenkamp, M.M., Manzanares, J. et al. Cannabidiol as a Potential Treatment for Anxiety Disorders. Neurotherapeutics 12, 825–836 (2015). https://doi.org/10.1007/s13311-015-0387-1.
  52. NIDA. Retrieved from https://clinicaltrials.gov/ct2/show/NCT03398083.
  53. NIDA. Trends & Statistics. Retrieved from https://www.drugabuse.gov/related-topics/trends-statistics.
  54. Welty TE. op. cit.
  55. FDA. (2020, Jan 15). FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD). Retrieved from https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd.

More Info

Less Info

One of the more common benzodiazepine prescriptions for those who struggle with conditions like panic disorder or anxiety is called Xanax, also known as Alprazolam (with a chemical name of 8-Chloro-1-methyl-6-phenyl-4H-1,2,4- -triazolo(4,3-a) 1,4) benzodiazepine, molecular formula of C17H13ClN4, and molecular weight of 308.8). This medication is quite potent and has many drug interactions, making it one of the more worrisome anxiety medications on the market. As an alternative to benzos like this, many people have considered trying CBD or cannabidiol. The effects of this natural substance are similar in potency, but there are fewer worries about how it could harm someone or interact with other medications. It gives people who are allergic to these types of medications an alternative that can provide relief as well. It could be the best possible option for those who struggle with anxiety, whether they have ever been medicated or not. 

Understanding Xanax

Xanax is a type of medication called a benzodiazepine that comes in a white to off-white color. It is a solid crystal described as Virtually insoluble in water; soluble in alcohol; sparingly soluble in acetone; freely soluble in chloroform; slightly soluble in ethyl acetate. It alters the chemicals within the brain by forcing it to try and rebalance itself. 

Some people can tolerate this substance, but many also struggle with the effects that can be incredibly strong. There are also many people who cannot take this medication for one reason or another.

These people include: 

  • Anyone with narrow-angle glaucoma
  • Anyone taking itraconazole 
  • Anyone taking ketoconazole 
  • Anyone allergic to the following medications: Librium, Serax, Klonopin, Ativan, Tranxene, or Valium 
  • Anyone under 18 years of age 

Some people must find out first from their doctors if this medication is safe for them to take, and these people include: 

  • Anyone who has seizures or has been diagnosed with epilepsy 
  • Anyone taking narcotic pain medications 
  • Anyone with liver or kidney disease, especially if the disease was caused by alcohol or drugs
  • Anyone who struggles with depression
  • Anyone that is currently showing suicidal ideations or behaviors 
  • Anyone with any type of breathing disorder, such as asthma 

There are also several side effects that come along with using Xanax. These include: 

  • An overwhelming feeling of exhaustion or falling asleep 
  • Less balance than is normal as falls are more common with people on this medication 
  • Feeling anxious when first waking up in the morning, but this subsides as the day goes on
  • Trouble remembering things or staying focused on a task at hand 
  • Thoughts that race and are hard to stay focused on 
  • An increase in energy 
  • Behavior that changes to include risks that someone would not normally take 
  • Feeling agitated or becoming hostile 

Rarer side effects can happen, and if they are noticed, a doctor should be notified immediately. These include the following: 

  • Hallucinations
  • Increased heart rate
  • Fluttering of the heart
  • Depressed mood
  • Thinking about suicide
  • Tremors
  • Uncontrolled movement or twitches in the muscles
  • Seizures
  • Eye problems
  • Reproductive issues
  • The inability to remain awake
  • Trouble breathing
  • Hives
  • Renal trouble
  • Swelling of the head in any form (lips, throat, face, tongue, etc.)

Other effects that are possible with Xanax include: 

  • Hypothermia
  • Allergic reactions
  • Poisoning

Dangers of Xanax

One of the most important dangers that come along with taking this medication is the fact that it can lead to addiction. The body becomes reliant on it to relax or sleep, making the body act in such a way that it makes the user seek more. Abuse has been known to happen, so these prescriptions need to be doled out only to those who truly need the medication and monitored very closely. Anyone who develops withdrawal symptoms before the next dose needs to speak to his or her doctor right away. This is what happens when the body becomes dependent on the medication. In this case, another medication or type of relief needs to be sought out.

Safer Alternatives to Anxiety Medications

Many options can be used instead of medications when someone struggles with conditions like panic or anxiety disorder or social anxiety. Some people need to change how they do things, while others need an actual substance to help them with the overwhelming feelings that arise. For those that can change habits and feel better, some options include: 

  • Regularly exercising can help ease anxiety by allowing the body to move around actively. Plus, exercise releases endorphins, which are mood enhancers in their own right. Exercise has the benefit of also helping with self-esteem and self-confidence, plus it allows people to gain bonds with others who partake in similar activities in a safe manner. 
  • Eating healthy foods that vary can also help when anxiety is a common issue. The more nutrient-dense a diet is, the more the body can naturally pull items out of the foods that it needs. This type of diet also helps get plenty of fiber into the body, which helps scrape out any toxins left that may lead to physical or mental struggles. 
  • Spending time with positive people can help keep the negativity away, which can reduce the anxiety that someone feels. Ideally, these people should be close friends or family members who can make the anxious person feel happy, silly, or calm. If these are not an option, then seeking out time with a pet could also provide social relief. 
  • Avoiding sugar and caffeine can help when someone is struggling with anxiety as there is no up and then down in a person’s focus or mood. When people regularly consume sugar or caffeine, the mood and focus lift because of the stimulant. Then when it wears off, the effect brings the mood and ability to focus back down, often below where it started. 
  • Volunteering is a great way to reduce anxiety. Being able to help someone else can be very uplifting, plus it can also help people feel less isolated, which can exacerbate anxiety. It can also help to see that there are other people out there who struggle in their own ways, allowing the person with anxiety to feel more accepted. 
  • Ensuring that people get plenty of sleep can help them alleviate a lot of anxiety. It is very important to allow the body to heal during sleep, which does not happen if sleep is interrupted or is not enough. Plus, sleep deprivation also leads to more anxiety instead of helping it get better. A solid eight hours can help with the symptoms of anxiety, along with any health-related issues that came from a lack of sleep.
  • Getting outside now and again can help with anxiety. The natural benefits from sunlight (vitamin D) and fresh air can improve someone’s mood and make them naturally more relaxed. Plus, it can allow someone who may feel isolated by his or her anxiety to feel a bit more open about what he or she is feeling. 
  • Meditation is a great way to avoid anxiety. It should be full of positive imagery so that the person meditating can foresee positive things happening in his or her life. This can be done one longer time each day, or even in small, three-minute increments, whatever allows the person to get the most benefit out of the time spent. 
  • Alcohol brings moods down, no matter how good or bad a mood one has to begin with. If alcohol is consumed regularly, it can add to feelings of depression or anxiety. Cutting this out of the diet can help improve the health of the person and his or her mood. Plus, then there is no worry about developing issues related to the consumption of alcohol. 
  • Focusing on the positive helps people notice good things around them instead of feeling like something is always going to go wrong. Anxiety often starts from a negative emotion or thought and grows from there. By focusing on positive thinking, feeling grateful, or looking back at a happier memory, it can improve someone’s resiliency and allow that person to feel calm instead of anxious. 
  • Being forgiving can go a long way towards decreasing anxiety. Holding on to something negative can bring one’s mood down or make someone feel anxious about a situation that is days, weeks, months, or even years old. By forgiving, it allows the person to move on without the weight of that event. Even if the person does not share that he or she forgave those who wronged them, the effect can help the anxious party. 
  • Stress almost always leads to increased anxiety. The stress may have nothing to do with the anxiety, but usually, the two are related. The best way to remove the anxiety that comes from stress is to reduce or remove the stress itself. Start by identifying the stressors and then come up with solutions. The more proactive someone is, the more he or she typically benefits from the practice.
  • Looking for a reason to feel good is sometimes enough. When people feel as though they do not fit in, it can increase anxiety exponentially. By finding a reason to get up, get out, or to go somewhere that he or she fits in, it can bring down how much anxiety he or she feels and can also give that person the strength to fight back against whatever is causing the anxiety. 

For those who need some type of substance to help them feel better, one of the best options available is CBD oil. It brings about a sense of peace and calm without the side effects of medications. Plus, CBD helps almost immediately. Other medications can also work. However, they each carry their own risks and chances of interaction with other medications that someone may be taking or bringing out a negative emotion as an effect. 

How Does CBD Help with Anxiety? 

In order to understand how CBD has the potential to help with anxiety, it is best to understand first where it comes from. There are two species of a cannabis plant, the one that gets people high, and one that does not. The species of cannabis that gets people high is marijuana, and it gets people high because it contains THC. The species of cannabis that does not get people high is hemp, and it contains CBD. THC gets people high because it has a psychoactive compound that reacts with the brain. CBD is a similar compound, called cannabinoid, but it has no psychoactive component in it. It simply relaxes the body and helps improve the overall function of the body. 

One of the most common side effects of using CBD products of any sort is the ability to relax the central nervous system. This does not depress the system. Instead, it allows it to slow down and function properly. Many people with anxiety have so much going on; every part of their body is trying to move at super high speeds. The ability to slow down allows the body and brain to catch up and then sync back up. This means every part of the body works more efficiently, and people feel as though they are more in control. That simple change can be the start of someone being less overwhelmed by his or her anxiety.

Whenever a product containing CBD is consumed, the product works its way through the endocannabinoid system. This is the pathway of the brain that reads signals being sent from the various parts of the body. There are CB receptors all over the body, but there are many of them along this system. These receptors are supposed to open up when a message is sent, accept the message, read what is going on, and respond accordingly. In some instances, these receptors do not open. By adding CBD, these receptors recognize that they should be opening, and they start to receive messages again, all through natural means. It allows the body to begin regulating itself the way it was meant to, and it allows people with anxiety to feel like they are back in control, at least to some degree. 

The FDA had already recognized that CBD could help with some medical ailments when in 2018, it approved a CBD-based medicine to help with seizure disorders. Studies are already underway that are showing how CBD can help with other issues, like: 

  • Anxiety, depression, and PTSD 
  • Parkinson’s patients 
  • MS patients who have chronic pain 
  • Glaucoma patients who struggle with inner-ocular pressure 
  • Cardiac patients 
  • Numerous types of cancer 
  • Alcohol and drug withdrawals
  • Schizophrenic patients 
  • Patients with high blood pressure 

How Does Someone Get CBD? 

There are many places people can buy CBD products since they are legal. Online buying is one of the easiest because it is easy to research the quality before purchasing anything from a vendor. However, it does mean that some research should still be done prior to buying about what method of ingestion the anxious party is going to want to use. There are quite a few methods to choose from. They include: 

  • Drops: Oil drops are called a tincture. These drops are put under the tongue and allowed to sit for about 30 seconds before the person swallows. These drops are able to enter the bloodstream quickly and start becoming effective in minutes. 
  • Vape: Vaping or smoking CBD oil allows the person to inhale the effects, getting the CBD into the system in seconds. However, these tend to wear off more quickly than drops, and the person vaping or smoking needs to buy the device to smoke the oil with. 
  • Edibles: There are several edibles available with CBD in them, including food additives, gummies, and even lollipops. These take a few minutes to get into the system in some instances, or they may take a little longer if mixed with a meal. 
  • Skin: Many different CBD options are out there if someone wants to absorb CBD through the skin. There are lotions, balms, sprays, and ointments that can be rubbed over larger areas of the body. Plus, there are also dabbers if just one small area hurts as the oil can be dabbed directly on the sore part of the body. 

Does CBD Come with Any Risks? 

There are a few side effects that could come with taking CBD. However, nearly all of them are short-term problems that stop once the body adjusts to the new substance, or the right dosage is found. These issues include minor problems like: 

  • Occasionally feeling a bit more tired. This is usually a very limited problem that stops within a short time of starting a CBD regimen. 
  • Having a dry mouth is common for those taking CBD. It is usually easy to overcome with an increase in how much water someone drinks each day. 
  • Some people feel dizzy after taking CBD, but that is typically only because of how it can reduce blood pressure. Once the body gets used to the new substance, this goes away. 
  • Occasionally, people notice some diarrhea when they first start with CBD, but once the correct dose for a person’s size is found, this also disappears. 

The best way to avoid any of these effects is to start by taking small doses or using it sparingly, then increasing in small increments. Then, if any of these effects start to happen, the dose can slowly be lowered again until the right amount is found. Starting with a higher dose is likely going to cause stomach upset or diarrhea, but once the dose is brought back down, nearly all of these effects permanently stop. 

When it comes to getting the best quality CBD, that takes a little bit of research. It should only be purchased from a vendor that can show results on the product itself. Tests should be run to show the CBD came from hemp that does not contain problematic levels of the psychoactive chemical in the plant. That way, the buyer can ensure the highest quantity of CBD as possible. It is important to research the finest CBD around before buying because that allows the buyer to have the best chances of getting the relief he or she was looking for in the first place. 

More Information on Xanax

Xanax belongs to the group ATC classification index, Psycholeptics (N05)/  Anxiolytics (N05B)/Benzodiazepine derivatives (N05BA). Target organ is the central nervous system, causing depression of respiration and consciousness.

Summary of Clinical Effects

Central nervous system (CNS) depression and coma, or paradoxical excitation, but deaths are rare when  benzodiazepines are taken alone. Deep coma and other manifestations of severe CNS depression are rare. Sedation, somnolence, diplopia, dysarthria, ataxia and intellectual impairment are the most common adverse effects of benzodiazepines. Overdose in adults frequently involves co-ingestion of other CNS depressants, which act synergistically to increase toxicity. Elderly and very young children are more susceptible to the CNS depressant action. Intravenous administration of even therapeutic doses of benzodiazepines may produce apnoea and hypotension.

Dependence may develop with regular use of benzodiazepines, even in therapeutic doses for short periods. If benzodiazepines are discontinued abruptly after regular use, withdrawal symptoms may develop.  The amnesia produced by benzodiazepines can have medico-legal consequences.

Diagnosis

The clinical diagnosis is based upon the history of benzodiazepine overdose and the presence of the clinical signs of benzodiazepine intoxication. Benzodiazepines can be detected or measured in blood and urine using standard analytical methods. This information may confirm the diagnosis but is not useful in the clinical management of the patient.

A clinical response to flumazenil, a specific benzodiazepine antagonist, also confirms the diagnosis of benzodiazepine overdose, but the administration of this drug is rarely  justified.

First Aid Measures and Management Principles

Most benzodiazepine poisonings require only clinical observation and supportive care. It should be remembered that benzodiazepine ingestions by adults commonly involve co-ingestion of other CNS depressants and other drugs. Activated charcoal normally provides adequate gastrointestinal decontamination. Gastric lavage is not routinely indicated.

Emesis is contraindicated. The use of flumazenil is reserved for cases with severe respiratory or cardiovascular complications and should not replace the basic management of the airway and respiration. The routine use of flumazenil is contraindicated because of potential complications, including seizures.  Renal and extracorporeal methods of enhanced elimination are not effective.

Overall Interpretation of All Toxicological Analyses and Toxicological Investigations

For toxicological analyses: whole blood 10 mL; urine 25 mL and gastric contents 25 mL.

Biomedical analysis: Blood gases, serum electrolytes, blood glucose and hepatic enzymes when necessary in severe cases.

Toxicological analysis: Qualitative testing for benzodiazepines is helpful to confirm their presence, but quantitative levels are not clinically useful. More advanced analyses are not necessary for the treatment of the poisoned patient due to the lack of correlation between blood concentrations and clinical severity (Jatlow et al., 1979; MacCormick et al., 1985; Minder, 1989). 

TLC and EMIT: These provide data on the presence of benzodiazepines, their metabolites and possible associations with other drugs.

GC or HPLC: These permit identification and quantification of the benzodiazepine which caused the poisoning and its metabolites in blood and urine.

Acute Poisoning Through Ingestion

The onset of impairment of consciousness is relatively rapid in benzodiazepine poisoning.  Onset is more rapid following larger doses and with agents of shorter duration of action. The most common and initial symptom is somnolence.  This may progress to coma Grade I or Grade II (see below) following very large ingestions. Reed Classification of Coma (Reed et al., 1952)

Coma Grade I:   Depressed level of consciousness, response to painful stimuli. Deep tendon reflexes and vital signs intact.

Coma Grade II:  Depressed level of consciousness, no response to painful stimuli. Deep tendon reflexes and vital signs intact.

Coma Grade III: Depressed level of consciousness, no response to painful stimuli. Deep tendon reflexes absent. Vital signs intact.

Coma Grade IV:  Coma grade III plus respiratory and circulatory collapse.

 

Acute Poisoning Through Parenteral Exposure

Overdose by the intravenous route results in symptoms similar to those associated with ingestion, but they appear immediately after the infusion, and the progression of central nervous system (CNS) depression is more rapid. Acute intentional poisoning by this route is uncommon and most cases are iatrogenic. Rapid intravenous infusion may cause hypotension, respiratory depression and apnoea.

Chronic Poisoning Through Ingestion

Toxic effects associated with chronic exposure are secondary to the presence of the drug and metabolites and include depressed mental status, ataxia, vertigo, dizziness, fatigue, impaired motor coordination, confusion, disorientation and anterograde amnesia. Paradoxical effects of psychomotor excitation, delirium and aggressiveness also occur. These chronic effects are more common in the elderly, children and patients with renal or  hepatic disease.

Administration of therapeutic doses of benzodiazepines for 6 weeks or longer can result in physical dependence, characterized by a withdrawal syndrome when the drug is discontinued. With larger doses, the physical dependence develops more rapidly.

Chronic Poisoning Through Parenteral Exposure

The chronic parenteral administration of benzodiazepines may produce thrombophlebitis and tissue.

Course, Prognosis, and Cause of Death 

Benzodiazepines are relatively safe drugs even in overdose. The clinical course is determined by the progression of the neurological symptoms. 

Deep coma or other manifestations of severe central nervous system (CNS) depression are rare with benzodiazepines alone.  Concomitant ingestion of other CNS depressants may result in a more severe CNS depression of longer duration.

The therapeutic index of the benzodiazepines is high and the mortality rate associated with poisoning due to benzodiazepines alone is very low. Complications in severe poisoning include respiratory depression and aspiration pneumonia. Death is due to respiratory arrest.

Systematic Description of Clinical Effects

Cardiovascular: Hypotension, bradycardia and tachycardia have been reported with overdose (Greenblatt et al., 1977; Meredith & Vale 1985). Hypotension is more frequent when benzodiazepines are ingested in association with  other drugs (Hojer et al., 1989). Rapid intravenous injection is also associated with hypotension.

Respiratory: Respiratory depression may occur in benzodiazepine overdose and the severity depends on dose ingested, amount absorbed, type of benzodiazepine and co-ingestants. Respiratory depression requiring ventilatory support has occurred in benzodiazepine overdoses (Sullivan, 1989; Hojer et al.,1989). 

The dose-response for respiratory depression varies between individuals.  Respiratory depression or respiratory arrest may rarely occur with therapeutic doses. 

Benzodiazepines may affect the control of ventilation during sleep and may worsen sleep apnoea or other sleep-related breathing disorders, especially in patients with chronic obstructive pulmonary disease or cardiac failure (Guilleminault, 1990).

Neurological: Central nervous system (CNS) depression is less marked than that produced by other CNS depressant agents (Meredith & Vale, 1985). Even in large overdoses, benzodiazepines usually produce only mild symptoms and this distinguishes them from other sedative-hypnotic agents. 

Sedation, somnolence, weakness, diplopia, dysarthria, ataxia and intellectual impairment are the most common neurological effects. The clinical effects of severe poisoning are sleepiness, ataxia and coma Grade I to Grade II (Reed). 

The presence of more severe coma suggests the possibility of co-ingested drugs. Certain of the newer short-acting benzodiazepines (temazepam, alprazolam and triazolam) have been associated with several fatalities and it is  possible that they may have greater acute toxicity (Forrest et al., 1986). 

The elderly and very young children are more susceptible to the CNS depressant action of benzodiazepines.

The benzodiazepines may cause paradoxical CNS effects, including excitement, delirium and hallucinations. Triazolam has been reported to produce delirium, toxic psychosis, memory impairment and transient global amnesia (Shader & Dimascio, 1970; Bixler et al, 1991). Flurazepam has been associated with nightmares and hallucinations.

There are a few reports of extrapyramidal symptoms and dyskinesias in patients taking benzodiazepines (Kaplan & Murkafsky, 1978; Sandyk, 1986).

The muscle relaxation caused by benzodiazepines is of CNS origin and manifests as dysarthria, incoordination and difficulty standing and walking. 

Oral benzodiazepine poisoning will produce minimal effects on the gastrointestinal tract (GI) tract but can occasionally cause nausea or vomiting (Shader & Dimascio, 1970).

A case of cholestatic jaundice due focal hepatic necrosis was associated with the administration of diazepam (Tedesco & Mills, 1982).

  Vesical hypotonia and urinary retention has been reported in association with diazepam poisoning (Chadduck et al.,1973). 

As for the endocrine and reproductive systems, galactorrhoea with normal serum prolactin concentrations has been noted in 4 women taking benzodiazepines (Kleinberg et al., 1977). 

Gynaecomastia has been reported in men taking high  doses of diazepam (Moerck & Majelung, 1979). Raised serum concentrations of oestrodiol were observed in men taking diazepam 10 to 20 mg da 9.4.8 Dermatological

Bullae have been reported following overdose with nitrazepam and oxazepam (Ridley, 1971; Moshkowitz et al., 1990). Allergic skin reactions were attributed to diazepam at a rate of 0.4 per 1000 patients (Brigby, 1986).  

For eye, ear, nose, throat, local effects include brown opacification of the lens that occurred in 2 patients who used diazepam for several years (Pau Braune, 1985).

Allergic Reactions

Hypersensitivity reactions including anaphylaxis are very rare (Brigby, 1986). Reactions have been attributed to the vehicle used for some parenteral diazepam formulations (Huttel et al., 1980). 

There is also a report of a type I hypersensitivity reaction to a lipid emulsion of diazepam (Deardon, 1987). Hypothermia was reported in 15% of cases in one series. (Martin, 1985; Hojer et al., 1989). 

Special Risks on Pregnancy

Passage of benzodiazepines across the placenta depends on the degree of protein binding in mother and fetus, which is influenced by factors such as stage of pregnancy and plasma concentrations of free fatty acids in mother and fetus (Lee et al., 1982). 

Adverse effects may persist in the neonate for several days after birth because of immature drug metabolising  enzymes. Competition between diazepam and bilirubin for protein binding sites could result in hyperbilirubinemia in the neonate (Notarianni, 1990).

 The abuse of benzodiazepines by pregnant women can cause withdrawal syndrome in the neonate. The administration of benzodiazepines during childbirth can produce hypotonia, hyporeflexia, hypothermia and respiratory depression in the newborn. 

Benzodiazepines have been used in pregnant patients and early reports associated diazepam and chlordiazepoxide with some fetal malformations, but these were not supported by later studies (Laegreid et al., 1987; McElhatton, 1994).

Special Risks on Breastfeeding

Benzodiazepines are excreted in breast milk in significant amounts and may result in lethargy and poor feeding in neonates.  Benzodiazepines should be avoided in nursing mothers (Brodie, 1981; Reynolds, 1996).

Dependence and Withdrawal

Benzodiazepines have a significant potential for abuse and can cause physical and psychological dependence. Abrupt cessation after prolonged use causes a withdrawal syndrome (Ashton, 1989). 

The mechanism of dependence is probably related to functional deficiency of GABA activity. 

Withdrawal symptoms include anxiety, insomnia, headache, dizziness, tinnitus, anorexia, vomiting, nausea, tremor, weakness, perspiration, irritability, hypersensitivity to visual and auditory stimuli, palpitations, tachycardia and postural hypotension. 

In severe and rare cases of withdrawal from high doses, patients may develop affective disorders or motor dysfunction: seizures, psychosis, agitation, confusion, and hallucinations (Einarson, 1981; Hindmarch et al, 1990; Reynolds, 1996).

The time of onset of the withdrawal syndrome depends on the half-life of the drug and its active metabolites; the symptoms occur earlier and may be more severe with short-acting benzodiazepines. Others risk factors for withdrawal syndrome include prolonged use of the drug, higher dosage and abrupt cessation of the drug.

Abuse

Benzodiazepines, particularly temazepam, have been abused both orally and intravenously (Stark et al., 1987; Funderburk et al, 1988).

Criminal Uses

The amnesic effects of benzodiazepines have been used for criminal purposes with medicolegal consequences (Ferner, 1996).

Management

Most benzodiazepine poisonings require only clinical observation and supportive care. It should be remembered that benzodiazepine ingestions by adults commonly include other drugs and other CNS depressants. 

Activated charcoal normally provides adequate gastrointestinal decontamination. Gastric lavage is not routinely indicated. Emesis is contraindicated. 

The use of flumazenil is reserved for cases with severe respiratory or cardiovascular complications and should not replace the basic management of the airway and respiration. Renal and extracorporeal elimination methods are not effective.

Life Supportive Procedures and Symptomatic/Specific Treatment

The patient should be evaluated to determine adequacy of airway, breathing and circulation. Continue clinical observation until evidence of toxicity has resolved. Intravenous access should be available for administration of fluid. 

Endotracheal intubation, assisted ventilation and supplemental oxygen may be required on rare occasions, more commonly when benzodiazepines are ingested in large amounts or with other CNS depressants.

Decontamination

Gastric lavage is not routinely indicated following benzodiazepine overdose. Emesis is contraindicated because of the potential for CNS depression. Activated charcoal can be given orally.

Antidote Treatment for Adults

Flumazenil, a specific benzodiazepine antagonist at central GABA-ergic receptors is available. Although it effectively reverses the CNS effects of benzodiazepine overdose, its use in clinical practice is rarely indicated. Use of 

Flumazenil is specifically contraindicated when there is history of co-ingestion of tricyclic antidepressants or other drugs capable of producing seizures (including aminophylline and cocaine), benzodiazepine dependence, or in patients taking benzodiazepines as an anticonvulsant agent. 

In such situations, administration of Flumazenil may precipitate seizures (Lopez, 1990; Mordel et al., 1992).

Adverse effects associated with Flumazenil include hypertension, tachycardia, anxiety, nausea, vomiting and benzodiazepine withdrawal syndrome. The initial intravenous dose of 0.3 to 1.0 mg may be followed by further doses if necessary. 

The absence of clinical response to 2 mg of flumazenil within 5 to 10 minutes indicates that  benzodiazepine poisoning is not the major cause of CNS depression or coma. 

The patient regains consciousness within 15 to 30 seconds after injection of flumazenil, but since it is metabolised more rapidly than the benzodiazepines, recurrence of toxicity and CNS depression can occur and the patient should be carefully monitored after  initial response to flumazenil therapy. 

If toxicity recurs, further bolus doses may be administered or an infusion commenced at a dose of 0.3 to 1.0 mg/hour (Meredith et al., 1993).

Antidote Treatment for Children

The initial intravenous dose of 0.1 mg should be repeated each minute until the child is awake. Continuous intravenous infusion should be administered at a rate of 0.1 to 0.2 mg/hour (Meredith et al., 1993).

Most benzodiazepine poisonings require only clinical observation and supportive care. Flumazenil is the specific antagonist of the effects of benzodiazepines, but the routine use for the treatment of benzodiazepine overdosage is not recommended. 

The use of Flumazenil should only be considered where severe CNS depression is observed. This situation rarely occurs, except in cases of mixed ingestion.

 The administration of flumazenil may improve respiratory and cardiovascular function enough to decrease the need for intubation and mechanical ventilation, but should never replace basic management principles.

Flumazenil is an imidazobenzodiazepine and has been shown to reverse the sedative, anti-convulsant and muscle-relaxant effects of benzodiazepines. In controlled clinical trials, flumazenil significantly antagonizes benzodiazepine-induced coma arising from anaesthesia or acute overdose. 

However, the use of flumazenil has not been shown to reduce mortality or sequelae in such cases. The administration of flumazenil is more effective in reversing the effects of benzodiazepines when they are the only drugs producing CNS toxicity. 

Flumazenil does not reverse the CNS depressant effects of non-benzodiazepine drugs, including alcohol. 

The diagnostic use of flumazenil in patients presenting with coma of unknown origin can be justified by its high therapeutic index and the fact that this may limit the use of other diagnostic procedures (CT scan, lumbar puncture, etc). 

Flumazenil is a relatively expensive drug and this may also influence its use, especially in areas with limited resources.

Featured Posts


Best CBD Oil for High Blood Pressure (Hypertension)

16,114 views

Why People Are Taking CBD for High Blood Pressure? According to the Centers for Disease Control and Prevention (CDC), high blood pressure can harden the arteries, which decreases the flow of blood and oxygen to the heart, leading to heart disease(5). In a 2015 study conducted by researchers from the...

Read more

CBD Oil for Kids with Anxiety

3,565 views

Why People are Turning to CBD for Children with Anxiety? CBD has become a popular OTC treatment that parents give their children, says Doris Trauner, M.D., professor of neurosciences and pediatrics at the University of California San Diego School of Medicine and a physician at San Diego’s Rady Children’s Hospital....

Read more

CBD for Thyroid

1,921 views

Best CBD Products for Thyroid Issues. Finding high-quality CBD products that are potent and safe is essential. Thus, to help patients decide on which CBD product is best for them, a list is given below of the top recommended products that work best to ease inflammation.

Read more

Can CBD Treat Vertigo?

4,602 views

Why People Are Turning To CBD For Vertigo? Treatment for vertigo symptoms depends on what is causing it. For those who want to go natural, CBD is an excellent option, given its many potential benefits. In a study that utilized data from the National Ambulatory Medical Care Surveys to study...

Read more