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Benzodiazepines: Difference between revisions

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If hallucinogenic drugs are taken while under the influence of a benzodiazepine, the user many not experience any hallucinations (with few exceptions).
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Revision as of 17:09, 31 July 2017

Fatal overdose may occur when benzodiazepines are combined with other depressants such as opiates, barbiturates, gabapentinoids, thienodiazepines, alcohol or other GABAergic substances.[1]

It is strongly discouraged to combine these substances, particularly in common to heavy doses.

The core structure of benzodiazepines
Xanax (alprazolam) 2 mg tri-score tablets

Benzodiazepines (commonly referred to as benzos) are a class of psychoactive substances that act as central nervous system depressants. These substances work by magnifying the efficiency and effects of the principal inhibitory neurotransmitter gamma-aminobutyric acid (GABA) by binding to and acting on its receptors.[2]

The characteristic effects of benzodiazepines include anxiety suppression, sedation, muscle relaxation, disinhibition, sleepiness and amnesia. In a medical context, short-acting benzodiazepines are typically recommended for treating insomnia or acute anxiety or panic attack disorders while long-acting ones are recommended for the treatment of generalized anxiety disorders.

It is worth noting that the sudden discontinuation of benzodiazepines can be potentially dangerous or life-threatening for individuals that develop a physical dependence on them after using them regularly for extended periods of time, which can result in potentially fatal seizures.[3] For this reason, it is highly recommended to taper one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping one's usage abruptly.[4]

Chemistry

Benzodiazepine is a heterocyclic compound comprised of a benzene ring fused to a seven-member nitrogenous diazepine ring. Benzodiazepine drugs contain an additional substituted phenyl ring bonded at R5, resulting in 5-phenyl-1,4-benzodiazepines with different side groups attached to the structure to create a number of drugs with different strength, duration, and efficacy.

Benzodiazepine drugs commonly contain an aromatic electrophilic substitution such as aromatic halogenation or nitration on R7 of their rings. Benzodiazepines can be subdivided into triazolobenzodiazepines and ketone substituted benzodiazepines. Triazolobenzodiazepines contain a triazole ring bonded to the benzodiazepine structure and are distinguished by the suffix "-zolam." Ketone substituted rings contain a ketone oxygen bond at R2 of their benzodiazepine structure and are distinguished by their suffix "-azepam."

Pharmacology

Benzodiazepines produce a variety of effects by binding to the benzodiazepine receptor site and magnifying the efficiency and effects of the neurotransmitter gamma aminobutyric acid (GABA) by acting on its receptors.[5] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of benzodiazepines on the nervous system.

The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[6]

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠. These effects are listed and defined in detail within their own dedicated articles below:

Physical effects

Paradoxical effects

Cognitive effects

After effects

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Pharmacological classes

Equivalent dosages

The dosages below represent approximate equivalent dosages between various benzodiazepines in comparison to 10mg of diazepam.

The authors of this table specifically state that their equivalents differ from those used by other authors and "are firmly based on clinical experience during switch-over to diazepam at the start of withdrawal programs but may vary between individuals."[14]

Prescription benzodiazepines Half-life (Hours)
[active metabolite]
Approx. equivalent
oral dosage (mg)
Predominant effect
(a= anxiolytic,
c= anticonvulsant,
h= hypnotic)
Alprazolam 6-12 0.5 a
Bromazepam 10-20 5-6 a
Chlordiazapoxide 5-30 [36-200] 25 a
Clobazam 12-60 20 a, c
Clonazepam 18-50 0.5 a, c
Clorazepate 20-179 [36-200] 15 a
Diazepam 20-100 [36-200] 10 a, h, c
Estazolam 10-24 1-2 h
Etizolam 4-12 1 a
Flunitrazepam 18-36 [36-200] 1 h
Flurazepam 40-250 15-30 h
Halazepam 14 [30-200] 20 a
Ketazolam 30-100 [36-200] 15-30 a
Loprazolam 6-12 1-2 h
Lorazepam 10-20 1 a
Lormetazepam 10-12 1-2 h
Medazepam 36-200 10 a
Nitrazepam 15-38 10 h
Nordazepam 36-200 10 a
Oxazepam 4-15 20 a
Prazepam 29-224 [36-200] 10-20 a
Quazepam 25-100 20 h
Temazepam 8-22 20 h
Triazolam 2 0.5 h
Research chemicals Half-life (Hours)
[active metabolite]
Approx. equivalent
oral dosage (mg)
Predominant effect
(a= anxiolytic,
c= anticonvulsant,
h= hypnotic)
Clonazolam ? 0.5 h
Deschloroetizolam ~9-20 6 a
Diclazepam ~120 1 a, h
Flubromazepam 106 4 h
Flubromazolam ? 0.25 h
Nifoxipam 4-6 2 a
Meclonazepam ? 5 a, c
Metizolam ~9-20 2 a
Phenazepam 60 1 a
Pyrazolam 17 1 a
Z-drugs Half-life (Hours)
[active metabolite]
Approx. equivalent
oral dosage (mg)
Predominant effect
(a= anxiolytic,
c= anticonvulsant,
h= hypnotic)
Zaleplon 2 20 h
Zolpidem 2 20 h
Zopiclone 5-6 15 h
Eszopiclone 6 3 h

Toxicity and harm potential

Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[15]

Benzodiazepines have a low toxicity relative to dose.[16] However, they are [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].

It is strongly recommended that one use harm reduction practices when using this class of compounds.

Tolerance and addiction potential

Benzodiazepines are extremely physically and psychologically addictive.

Tolerance will develop to the sedative-hypnotic effects within a couple of days of continuous use.[17] After cessation, the tolerance returns to baseline in 7-14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing one's usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction.[18][19]

Discontinuation

Benzodiazepine discontinuation is notoriously difficult; it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of high blood pressure, seizures, and death.[20] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal. Abrupt discontinuation also causes rebound stimulation which presents as anxiety, insomnia and restlessness.

It is safest to reduce the dose each day by a very small amount, for a couple of weeks until close to abstinence. If using a short half-life benzodiazepine, a longer acting variety such as diazepam can be substituted. Symptoms may still be present, but their severity will be reduced significantly. For more information on tapering from benzodiazepines in a controlled manner, please see this guide. Small amounts of alcohol can also help to reduce the symptoms.

The duration and severity of withdrawal symptoms depends on a number of factors including the half-life of the drug used, tolerance and the duration of abuse. Major symptoms will usually start within just a few days after discontinuation and persist for around a week for shorter lasting benzodiazepines. Benzodiazepines with longer half-lives will exhibit withdrawal symptoms with a slow onset and extended duration.

Preparation methods

  • Volumetric liquid dosing - If one's benzodiazepines are in powder form, they are unlikely to weigh out accurately without the most expensive of scales due to their extreme potency. To avoid this, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial here.

See also

References

  1. Risks of Combining Depressants - TripSit 
  2. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  3. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  4. Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain - Appendix B-6: Benzodiazepine Tapering | http://nationalpaincentre.mcmaster.ca/opioid/cgop_b_app_b06.html
  5. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  6. Benzodiazepines, but not beta-carbolines, limit high-frequency repetitive firing of action potentials of spinal cord neurons in cell culture. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2450203
  7. Henriksen, O. (1998) ‘An overview of Benzodiazepines in seizure management’, Epilepsia, 39(SUPPL. 1), pp. 2–6. doi: 10.1111/j.1528-1157.1998.tb02601.x.
  8. http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
  9. Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
  10. Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
  11. Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
  12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3684331/ | Benzodiazepine Pharmacology and Central Nervous System–Mediated Effects
  13. Goyal, Sarita. "Drugs and Dreams." Indian Journal of Clinical Practice (n.d.): n. pag. Web. | http://medind.nic.in/iaa/t13/i3/iaat13i3p624.pdf
  14. BENZODIAZEPINE EQUIVALENCE TABLE | http://www.benzo.org.uk/bzequiv.htm
  15. Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
  16. Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  17. Principles and Practice of Psychopharmacotherapy | http://books.google.com/books?id=_ePK9wwcQUMC&pg=PA535
  18. Clinical Pharmacology, Clinical Efficacy, and Behavioral Toxicity of Alprazolam: A Review of the Literature | http://onlinelibrary.wiley.com/doi/10.1111/j.1527-3458.2004.tb00003.x/pdf
  19. The American Psychiatric Publishing Textbook of Substance Abuse Treatment | http://books.google.com/books?id=6wdJgejlQzYC&pg=PA222&hl=en#v=onepage&q&f=false
  20. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812