Etizolam

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

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

Summary sheet: Etizolam
Etizolam
Etizolam.svg
Chemical Nomenclature
Common names Etizolam, "Etilaam", "Etizest"
Substitutive name Etizolam
Systematic name 4-(2-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine
Class Membership
Psychoactive class Depressant
Chemical class Thienodiazepine
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold 0.2 - 0.5 mg
Light 0.5 - 1 mg
Common 1 - 2 mg
Strong 2 - 5 mg
Heavy 5 mg +
Duration
Total 5 - 7 hours
Onset 15 - 25 minutes
Come up 30 - 60 minutes
Peak 2 - 3 hours
Offset 1.5 - 2.5 hours
After effects 6 - 24 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Etizolam (also known as Etilaam, Etizest, and many others) is a novel depressant substance of the thienodiazepine class. Etizolam is chemically related to benzodiazepines and acts by binding to GABA receptors in the brain.

Etizolam is not commonly prescribed. It has been sold as a research chemical online and is commonly used as a substitute for pharmaceutical benzodiazepines like alprazolam (Xanax) or diazepam (Valium). Etizolam is commonly found in pellet or pill form, laid on blotter paper, or as a pure powder.

Typical effects of etizolam include anxiety suppression, disinhibition, muscle relaxation, sedation, and euphoria. Etizolam is commonly administered orally and sublingually due to the high bioavailability of these routes.

Users should note that that as with benzodiazepines, the sudden discontinuation of thienodiazepines can be dangerous or even life-threatening for individuals who have been using the substance for extended periods of time. As a result, individuals who are physically dependent on this substance are advised to taper their dose by gradually lowering the amount taken each day over a prolonged period of time instead of stopping use abruptly.[2]

Due to its high abuse and addiction potential, it is highly advised to use proper harm reduction practices if using this substance.

History and culture

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Etizolam first appeared on the online research chemical market in 2011. Since then its popularity has steadily increased. This likely owes itself to both its low cost and its abundance, and the highly dependence-forming and addictive nature that it shares with recreationally-used benzodiazepines.[3]

Etizolam differs from most other research chemicals in that it is approved and actively prescribed as a medical treatment for anxiety in many countries around the world, commonly under brand names like Etilaam and Etizest. Its origins as a medical drug are unclear, although medical papers citing its use in the treatment of anxiety have been documented as early as the 1990s.[4]

Chemistry

Etizolam is a structural relative of benzodiazepines, whereby the benzene ring has been replaced by a thiophene ring, classifying it as a thienodiazepine. Thiophene is a five membered aromatic ring with one sulfur atom. Etizolam contains a thiophene ring fused to a diazepine ring, which is a seven membered ring with the two nitrogen constituents located at R1 and R4. This forms the thienodiazepine core of etizolam. An ethyl chain is bound to this bicyclic structure at R7. Additionally, a R2' chlorine-substituted phenyl ring is bound to this structure at R5.

Etizolam also contains a methylated triazole ring fused to and incorporating R1 and R2 of its diazepine ring. Etizolam shares this fused triazole ring substitution with certain benzodiazepine drugs, called triazolobenzodiazepines, distinguished by the suffix "-zolam".

Pharmacology

Thienodiazepines 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 etizolam on the nervous system.

Subjective effects

Anecdotal reports suggest that in terms of its relative potency, 1 mg of etizolam is approximately equivalent to 0.5 mg of alprazolam (Xanax), 0.5 mg of clonazepam (Klonopin), or 10 mg of diazepam (Valium). It is often compared to a less potent and sedating version of alprazolam in terms of the speed of its onset, total duration, and recreational effect.

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. These effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances of inducing a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Paradoxical effects
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Cognitive effects
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After effects
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Experience reports

There are currently anecdotal reports which describe the effects of this compound within our experience index.

. Additional experience reports can be found here:

Toxicity and harm potential

Blepharospasms (twitching eyelid) can occur with long-term use.[10] Rarely, erythema annulare centrifugum skin lesions have also been reported.[11]

Etizolam likely has a low toxicity relative to dose.[12] However, it is potentially lethal when mixed with depressants like alcohol or opioids.

It is strongly recommended that one use harm reduction practices such as volumetric dosing when using this substance.

Tolerance and addiction potential

Like most benzodiazepines, etizolam is considered to be highly addictive with a high potential for abuse.

In one study in which multiple doses of either etizolam or lorazepam were administered to rat neurons, tolerance to the anticonvulsant effects of lorazepam but not to etizolam was observed.[13] Etizolam therefore has a reduced liability to induce tolerance, and dependence when compared with classic benzodiazepines.[13]

Tolerance will, however, develop to the sedative-hypnotic effects within a couple of days of continuous use. After cessation, the tolerance returns to baseline in 7 - 14 days. However, in certain cases this may take significantly longer in a manner which is proportional to the duration and intensity of one's long-term usage.

Thienodiazepine discontinuation is notoriously difficult and potentially life-threatening for heavy or long-term users. There is an increased risk of seizure following discontinuation of thienodiazepines. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing, and may necessitate a gradual dose reduction. For more information on tapering from thienodiazepines in a controlled manner, please see this guide. Substances which lower the seizure threshold such as tramadol should be avoided during withdrawal.

Etizolam presents cross-tolerance with all benzodiazepines and thienodiazepines, meaning that after its consumption all benzo and thienodiazepines will have a reduced effect.

Overdose

Thienodiazepine overdose may occur when taken in extremely heavy quantities or concurrently with other depressants. This is particularly dangerous with other GABAergic depressants such as barbiturates and alcohol since they work in a similar fashion, but bind to distinct allosteric sites on the GABAA receptor, thus their effects potentiate one another. Thienodiazepine increase the frequency in which the chlorine ion pore opens on the GABAA receptor while barbiturates increase the duration in which they are open, meaning when both are consumed, the ion pore will open more frequently and stay open longer[14]. Thienodiazepine overdose is a medical emergency that may lead to a coma, permanent brain injury or death if not treated promptly and properly.

Symptoms of a thienodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Thienodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Thienodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist[15]. However, care is primarily supportive in nature.

Dangerous interactions

Although many psychoactive substances are safe to use on their own, they can quickly become dangerous or even life-threatening when combined with other substances. The following lists some known dangerous combinations, but may not include all of them. A combination that appears to be safe in low doses can still increase the risk of injury or death. Independent research should always be conducted to ensure that a combination of two or more substances is safe to consume.

  • Depressants (1,4-Butanediol, 2-methyl-2-butanol, alcohol, barbiturates, GHB/GBL, methaqualone, opioids) - This combination can result in dangerous or even fatal levels of respiratory depression. These substances potentiate the muscle relaxation, sedation and amnesia caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
  • Stimulants - It is dangerous to combine thienzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants mask the sedative effect of thienzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of thienzodiazepines will be significantly increased, leading to intensified disinhibition. If combined, one should strictly limit themselves to only dose a certain amount of thienzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal status

  • Canada: Etizolam is not a scheduled substance in Canada, although it is only legal to import for research purposes.[citation needed]
  • Germany: Etizolam is a controlled substance in Germany.[16][17]
  • Poland: Etizolam may be scheduled under the Act on Counteracting Drug Addiction and the State Sanitary Inspection - Article 27c.[citation needed]
  • Switzerland: Etizolam is a controlled substance Switzerland.[18]
  • United Kingdom: Etizolam is a Class C substance in the UK as of May 31st, 2017, making it illegal to possess, produce, or supply.[19]
  • United States: Etizolam is not a scheduled substance in the United States.
  • Arkansas: In August 2014, the state of Arkansas listed etizolam as a Schedule I substance under its substance scheduling guidelines.[20]
  • North Carolina: On March 22, 2017, the General Assembly of North Carolina enacted an addendum to the North Carolina Controlled Substances Act including etizolam as a Schedule I substance.
  • Texas On Jun 9, 2017, the state of Texas listed etizolam as a Penalty Group 3 substance with HB 2671.[21] Contrary to some online reports and conflicting information with the overall Texas controlled substance list website, etizolam became a penalty group 3 substance with the passage of this bill.

See also

External links

Literature

  • Sanna, E., Pau, D., Tuveri, F., Massa, F., Maciocco, E., Acquas, C., ... & Biggio, G. (1999). Molecular and neurochemical evaluation of the effects of etizolam on GABAA receptors under normal and stress conditions. Arzneimittelforschung, 49(02), 88-95. https://doi.org/10.1055/s-0031-1300366
  • Altamura, A. C., Moliterno, D., Paletta, S., Maffini, M., Mauri, M. C., & Bareggi, S. (2013). Understanding the pharmacokinetics of anxiolytic drugs. Expert Opinion on Drug Metabolism & Toxicology, 9(4), 423-440. https://doi.org/10.1517/17425255.2013.759209
  • Fracasso, C., Confalonieri, S., Garattini, S., & Caccia, S. (1991). Single and multiple dose pharmacokinetics of etizolam in healthy subjects. European Journal of Clinical Pharmacology, 40(2), 181-185. https://doi.org/10.1007/BF00280074

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. 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
  3. Tripsit. (n.d.). Etizolam. In TripSit Wiki. Retrieved May 11, 2017, from https://wiki.tripsit.me/wiki/Etizolam
  4. Sanna, E., Pau, D., Tuveri, F., Massa, F., Maciocco, E., Acquas, C., ... & Biggio, G. (1999). Molecular and neurochemical evaluation of the effects of etizolam on GABAA receptors under normal and stress conditions. Arzneimittelforschung, 49(02), 88-95. https://doi.org/10.1055/s-0031-1300366
  5. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  6. http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
  7. Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
  8. Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
  9. Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
  10. Etizolam and benzodiazepine induced blepharospasm. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/14966178
  11. Etizolam-induced superficial erythema annulare centrifugum (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/11952667
  12. Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
  13. 13.0 13.1 Sanna, E; Busonero, F; Talani, G; Mostallino, MC; Mura, ML; Pisu, MG; MacIocco, E; Serra, M; Biggio, G (2005). "Low tolerance and dependence liabilities of etizolam: Molecular, functional, and pharmacological correlates". European Journal of Pharmacology 519 (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16107249
  14. Barbiturates and thienodiazepine effects | https://www.ncbi.nlm.nih.gov/pubmed/2471436
  15. Flumazenil, a benzodiazepine antagonist | https://www.ncbi.nlm.nih.gov/pubmed/8306565
  16. http://www.bundesgesundheitsministerium.de/fileadmin/dateien/Downloads/B/Betaeubungsmittelgesetz/27_BtMAEndV.pdf
  17. http://www.gesetze-im-internet.de/btmg_1981/index.html
  18. http://web.archive.org/web/20170329020935/https://www.admin.ch/opc/de/classified-compilation/20101220/index.html
  19. The Misuse of Drugs (Amendment) (England, Wales and Scotland) Regulations 2017 | http://www.tihs.org.uk/timeline/resources/2017-631.pdf
  20. http://www.healthy.arkansas.gov/aboutADH/RulesRegs/ControlledSubstanceListSummary.pdf
  21. https://capitol.texas.gov/tlodocs/85R/billtext/pdf/HB02671S.pdf