Benzodiazepines
{Benzos, Blues, BZDs, Tranks, Z-Bars, Downers}
Risks
Depression
Benzos are primarily used for anxiety, which usually co-occurs with depression. However, benzos do NOT have antidepressant effects with the possible exception of alprazolam 18. On the contrary, benzos might exacerbate depression and cause suicidal behaviour and ideation as they depress the central nervous system.
Dependence
The occasional use of benzos has a relatively low risk of harm. However, when used longer than 3-4 weeks, dependence is likely to develop and stopping the drug suddenly causes withdrawal symptoms. Therefore, it is best not to take benzos for more than 1-2 weeks.
Unlike many other recreational drugs, craving is not a major problem while withdrawing from benzos. It is the physical and psychological symptoms which makes it difficult. Symptoms may take up to 3 weeks to become apparent.
Withdrawal symptoms include anxiety-related symptoms such as panic attacks, insomnia, irritability, aggression, palpitations, nausea, depression and muscle pain.
Other signs include:
- Tremor
- Hypersensitivity to senses
- Abnormal body sensations like pins and needles, tinnitus, metallic taste etc.
- Hallucinations, paranoia, delirium
- Derealisation and depersonalisation
In severe cases, sudden discontinuation can lead to life-threatening seizures or death 19.
Therefore, benzos should never be stopped suddenly. Instead, the dose should be reduced gradually, ideally with a doctor’s supervision.
Gradual dose reduction does not eliminate the withdrawal symptoms. Anxiety management and psychological support is equally important.
A helpful guide about how to withdraw from benzos can be found here.
In the long-term...
Long-term use, even at therapeutic doses, has been shown to cause cognitive impairment, affecting learning, memory and attention and may persist longer than the physical withdrawal symptoms 20.
There is some evidence suggesting that long-term use may increase the risk of dementia 21. However, the evidence is inconclusive.
Dangerous Conditions
Epilepsy
Benzos are first-line treatment for status epilepticus. An increased tolerance due to recreational use can be dangerous in a state of emergency when benzos are needed to control the seizures. Additionally, a history of prolonged use, multiple exposure, and high-dose benzos consumption increases the risk of epilepsy 22. Withdrawal from benzos can also trigger seizures 23.
Depression
Benzos can exacerbate depression and cause suicidal behaviour and ideation because they depress the central nervous system.
Acute angle-closure glaucoma
Benzos can increase the intraocular pressure and can precipitate angle closure-glaucoma in susceptible eyes 24.
References
1 Dassanayake, T., Michie, P., Carter, G. and Jones, A. (2011). Effects of Benzodiazepines, Antidepressants and Opioids on Driving. Drug Safety, 34(2), pp.125-156. DOI: 10.2165/11539050-000000000-00000.
2 Canada, H. (2018). Benzodiazepines - Canada.ca.
3 Benzo.org.uk. (2012). Benzodiazepines: How They Work & How to Withdraw.
4 Cooper, S. (1989). Benzodiazepines and appetite: Recent pre-clinical advances and their clinical implications. Human Psychopharmacology: Clinical and Experimental, 4(2), pp.81-89. DOI: 10.1002/hup.470040203.
5 Hojer, J., Baehrendtz, S. and Gustafsson, L. (1989). Benzodiazepine poisoning: experience of 702 admissions to an intensive care unit during a 14-year period. Journal of Internal Medicine, 226(2), pp.117-122. DOI: 10.1111/j.1365-2796.1989.tb01365.x.
6 Partanen, T., Vikatmaa, P., Tukiainen, E., Lepäntalo, M. and Vuola, J. (2009). Outcome after Injections of Crushed Tablets in Intravenous Drug Abusers in the Helsinki University Central Hospital. European Journal of Vascular and Endovascular Surgery, 37(6), pp.704-711. DOI: doi.org/10.1016/j.ejvs.2009.01.016.
7 Starcevic, B. and Sicaja, M. (2007). Dual intoxication with diazepam and amphetamine: This drug interaction probably potentiates myocardial ischemia. Medical Hypotheses, 69(2), pp.377-380. DOI: 10.1016/j.mehy.2006.12.033.
8 Mattila, M.J. and Nuotto E. (1983). Caffeine and theophylline counteract diazepam effects in man. Medical Biology, 61(6), pp.337-43.
9 Emmanouil, D. and Quock, R. (2007). Advances in Understanding the Actions of Nitrous Oxide. Anesthesia Progress, 54(1), pp.9-18. DOI: 10.2344/0003-3006(2007)54[9:AIUTAO]2.0.CO;2.
10 Jones, J., Mogali, S. and Comer, S. (2012). Polydrug abuse: A review of opioid and benzodiazepine combination use. Drug and Alcohol Dependence, 125(1-2), pp.8-18. DOI: 10.1016/j.drugalcdep.2012.07.004.
11 Kroboth P.D., Smith R.B., Stoehr G.P. and Juhl R.P. (1985). Pharmacodynamic evaluation of the benzodiazepine-oral contraceptive interaction. Clinical pharmacology and therapeutics, 38(5), pp.525-32.
12 D'Arcy P.F. (1986). Drug interactions with oral contraceptives. Drug Intelligence & Clinical Pharmacology, 20(5), pp.353-62.
13 Starcevic, B. and Sicaja, M. (2007). Dual intoxication with diazepam and amphetamine: This drug interaction probably potentiates myocardial ischemia. Medical Hypotheses, 69(2), pp.377-380. DOI: 10.1016/j.mehy.2006.12.033.
14 Parle, M. and Dhingra, D. (2003). Ascorbic Acid: a Promising Memory-Enhancer in Mice. Journal of Pharmacological Sciences, 93(2), pp.129-135. DOI: 10.1254/jphs.93.129.
15 Partanen, T., Vikatmaa, P., Tukiainen, E., Lepäntalo, M. and Vuola, J. (2009). Outcome after Injections of Crushed Tablets in Intravenous Drug Abusers in the Helsinki University Central Hospital. European Journal of Vascular and Endovascular Surgery, 37(6), pp.704-711. DOI: 10.1016/j.ejvs.2009.01.016.
16 Chen, J.P., Barron, C., Lin, K.M., and Chung, H. (2002). Prescribing medication for Asians with mental disorders. Western Journal of Medicine, 176(4), pp.271--275.
17 Volkow, N.D., Wang, G.J., Fowler, J.S., Hitzemann, R., Gatley, S.J., Dewey, S.S., Pappas, N. (1998). Enhanced sensitivity to benzodiazepines in active cocaine-abusing subjects: a PET study. American Journal of Psychiatry, 155(2), pp.200-6.
18 Verster, J. and Volkerts, E. (2006). Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature. CNS Drug Reviews, 10(1), pp.45-76. DOI: 10.1111/j.1527-3458.2004.tb00003.x.
19 Haque, W., Watson, D.J., Bryant, S.G. (1990). Death following suspected alprazolam withdrawal seizures: a case report. Texas Medicine, 86(1), pp.44-7.
20 Barker, M., Greenwood, K., Jackson, M. and Crowe, S. (2004). Cognitive Effects of Long-Term Benzodiazepine Use. CNS Drugs, 18(1), pp.37-48. DOI: 10.2165/00023210-200418010-00004.
21 Takada, M., Fujimoto, M. and Hosomi, K. (2016). Association between Benzodiazepine Use and Dementia: Data Mining of Different Medical Databases. International Journal of Medical Sciences, 13(11), pp.825-834. DOI: 10.7150/ijms.16185.
22 Harnod, T., Wang, Y. and Kao, C. (2015). Association Between Benzodiazepine Use and Epilepsy Occurrence. Medicine, 94(37), p.e1571. DOI: 10.1097/md.0000000000001571.
23 Riss, J., Cloyd, J., Gates, J. and Collins, S. (2008). Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurologica Scandinavica, 118(2), pp.69-86. DOI: 10.1111/j.1600-0404.2008.01004.x.
24 Kadoi, C., Hayasaka, S., Tsukamoto, E., Matsumoto, M., Hayasaka, Y. and Nagaki, Y. (2000). Bilateral Angle Closure Glaucoma and Visual Loss Precipitated by Antidepressant and Antianxiety Agents in a Patient with Depression. Ophthalmologica, 214(5), pp.360-361. DOI: 10.1159/000027521.
25 Begleiter, H. and Kissin, B. (1996). The Pharmacology of Alcohol and Alcohol Dependence. New York: Oxford University Press, p.128.
26 Ramsey-Williams, V., Wu, Y. and Rosenberg, H. (1994). Comparison of anticonvulsant tolerance, crosstolerance, and benzodiazepine receptor binding following chronic treatment with diazepam or midazolam. Pharmacology Biochemistry and Behavior, 48(3), pp.765-772. DOI: 10.1016/0091-3057(94)90344-1.
27 Høiseth, G., Andås, H., Bachs, L. and Mørland, J. (2014). Impairment due to amphetamines and benzodiazepines, alone and in combination. Drug and Alcohol Dependence, 145, pp.174-179. DOI: 10.1016/j.drugalcdep.2014.10.013.