Diclazepam

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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.

Not to be confused with Diazepam.
Summary sheet: Diclazepam
Diclazepam
Diclazepam.svg
Chemical Nomenclature
Common names Diclazepam
Substitutive name Ro5-3448, Chlorodiazepam, 2'-chloro-diazepam
Systematic name 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one
Class Membership
Psychoactive class Depressant
Chemical class Benzodiazepine
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 0.5 mg
Light 0.5 - 1 mg
Common 1 - 3 mg
Strong 3 - 4 mg
Heavy 4 mg +
Duration
Total 8 - 12 hours
Onset 10 - 45 minutes









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.

Interactions

Diclazepam (also known as chlorodiazepam) is a lesser-known novel depressant substance of the benzodiazepine class. It is a structural analog of diazepam (Valium) and is reported to produce similar effects.[2]

Diclazepam was first synthesized by Leo Sternbach and his team at Hoffman-La Roche in 1960.[3] Diclazepam is not currently marketed as a medication, but rather sold online as a research chemical.

Subjective effects are similar to diazepam and include anxiety suppression, disinhibition, anticonvulsant, hypnotic, muscle relaxing, and amnesia. In animal studies, it has a potency of approximately ten times that of diazepam.[citation needed] Its potency has not been systematically tested in humans, but its closest relatives and two main metabolites are lormetazepam[4] with a potency value of x10-12 of delorazepam[5] which is roughly x10 the potency of diazepam.

It should be noted that the sudden discontinuation of benzodiazepines can be potentially dangerous or life-threatening for individuals using regularly for extended periods of time, sometimes resulting in seizures or death.[6] It is highly recommended to taper one's dose by gradually lowering the amount taken each day over a prolonged period of time rather than stopping use abruptly, as this can lead to severe, potentially life-threatening withdrawal symptoms.[7]

Chemistry

Composition

Diclazepam is a drug of the benzodiazepine class. Benzodiazepine drugs contain a benzene ring fused to a diazepine ring, which is a seven-membered ring with the two nitrogen constituents located at R1 and R4. At R1, diclazepam is substituted with methyl group. Further, the benzodiazepine ring is bonded at R5 to a 2-chlorinated phenyl ring. R7 of the benzyl ring is also substituted with a chlorine group. Diclazepam also contains an oxygen group double bonded to R2 of its diazepine ring to form a ketone. This oxygen substitution at R2 is shared with other benzodiazepine drugs with the 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.[8] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of diclazepam on the nervous system.

Diclazepam has an approximate elimination half-life of 42 hours and undergoes N-demethylation to delorazepam, which can be detected in urine for 6 days following administration of the parent compound.[9] Other metabolites detected were lorazepam and lormetazepam which were detectable in urine for 19 and 11 days, respectively, indicating hydroxylation by cytochrome P450 enzymes occurring concurrently with N-demethylation.

The anticonvulsant properties of benzodiazepines may be, in part or entirely, due to binding to voltage-dependent sodium channels rather than benzodiazepine receptors.[10]

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 ☠.

Physical effects
 

    • Muscle relaxation
    • Sedation - In terms of energy level alterations, this drug has the potential to be extremely sedating and often results in an overwhelmingly lethargic state. At higher levels, this causes users to suddenly feel as if they are extremely sleep deprived and have not slept for days, forcing them to sit down and generally feel as if they are constantly on the verge of passing out instead of engaging in physical activities. This sense of sleep deprivation increases proportional to dosage and eventually becomes powerful enough to force a person into complete unconsciousness.
    • Motor control loss
    • Respiratory depression
    • Dizziness

Paradoxical effects
 

  • Paradoxical reactions to benzodiazepines such as increased seizures (in epileptics), aggression, increased anxiety, violent behavior, loss of impulse control, irritability and suicidal behavior sometimes occur (although they are rare in the general population, with an incidence rate below 1%).[11][12]

    These paradoxical effects occur with greater frequency in recreational abusers, individuals with mental disorders, children, and patients on high-dosage regimes.[13][14]

Cognitive effects
 

  • The cognitive effects of diclazepam can be broken down into several components which progressively intensify proportional to dosage. The general head space of diclazepam is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressants cognitive effects. The most prominent of these cognitive effects generally include:

After effects
 

Experience reports

Anecdotal reports which describe the effects of this compound within our experience index include:

Additional experience reports can be found here:

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 non-polar solution such as propylene glycol and dose it accurately based upon the methodological instructions linked within this tutorial.

Toxicity and harm potential

 
Radar plot showing relative physical harm, social harm, and dependence of benzodiazepines in comparison to other drugs.[16]
Further information: Research chemicals § Toxicity and harm potential

Diclazepam likely has a low toxicity relative to dose.[17] 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 to ensure the accurate administration of the intended dose.

Tolerance and addiction potential

Diclazepam is extremely physically and psychologically addictive.

Tolerance will develop to the sedative-hypnotic effects within 3-4 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.

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 benzodiazepines in a controlled manner, please see this guide.

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 hypertension, seizures, and death.[6] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.

Diclazepam presents cross-tolerance with all GABAergics, meaning that after its consumption all benzodiazepines will have a reduced effect.

Overdose

Benzodiazepine overdose may occur when a benzodiazepine is 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. Benzodiazepines 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[18]. Benzodiazepine 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 benzodiazepine overdose may include severe thought deceleration, slurred speech, confusion, delusions, respiratory depression, coma or death. Benzodiazepine overdoses may be treated effectively in a hospital environment, with generally favorable outcomes. Benzodiazepine overdoses are sometimes treated with flumazenil, a GABAA antagonist,[19] however care is primarily supportive in nature.

Dangerous interactions

Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

  • 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 benzodiazepines with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of benzodiazepines, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of benzodiazepines will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of benzodiazepines per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.

Legal status

 

This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • Canada: All benzodiazepines are listed in Schedule IV.[20]
  • Germany: Diclazepam is controlled under Anlage II BtMG (Narcotics Act, Schedule II)[21] as of November 21, 2015.[22] It is illegal to manufacture, possess, import, export, buy, sell, procure or dispense it without a license.[23]
  • Poland: Diclazepam is under the IV-P group as of January 27, 2022.[24] It is illegal to own, possess, and sell in Poland.[25]
  • Russia: Diclazepam is a Schedule III controlled substance since 2017.[26]
  • Switzerland: Diclazepam is a controlled substance specifically named under Verzeichnis E.[27]
  • Turkey: Diclazepam is a classed as drug and is illegal to possess, produce, supply, or import.[28]
  • United Kingdom: Diclazepam is a Class C controlled substance as of May 31, 2017. It is illegal to possess, produce or supply it.[29]
  • United States: Diclazepam is a Schedule I controlled substance as of January 23, 2023.[30]

See also

External links

References

  1. ↑ Risks of Combining Depressants - TripSit 
  2. ↑ Akademii͡a nauk Ukraïnsʹkoï RSR, ed. (1977). Dopovidi Akademiï nauk Ukraïns’koï RSR. Serii͡a B: Heolohii͡a, heofizyka, khimii͡a ta biolohii͡a. Naukova dumka. 
  3. ↑ Earl, R., Henryk, S. L., Amino substituted benzophenone oximes and derivatives thereof 
  4. ↑ benzo.org.uk : Benzodiazepines: How They Work & How to Withdraw, Prof C H Ashton DM, FRCP, 2002 
  5. ↑ Delorazepam 
  6. ↑ 6.0 6.1 Lann, M. A., Molina, D. K. (June 2009). "A fatal case of benzodiazepine withdrawal". The American Journal of Forensic Medicine and Pathology. 30 (2): 177–179. doi:10.1097/PAF.0b013e3181875aa0. ISSN 1533-404X. 
  7. ↑ Kahan, M., Wilson, L., Mailis-Gagnon, A., Srivastava, A. (November 2011). "Canadian guideline for safe and effective use of opioids for chronic noncancer pain. Appendix B-6: Benzodiazepine Tapering". Canadian Family Physician. 57 (11): 1269–1276. ISSN 0008-350X. 
  8. ↑ Haefely, W. (29 June 1984). "Benzodiazepine interactions with GABA receptors". Neuroscience Letters. 47 (3): 201–206. doi:10.1016/0304-3940(84)90514-7. ISSN 0304-3940. 
  9. ↑ Bareggi, S. R., Truci, G., Leva, S., Zecca, L., Pirola, R., Smirne, S. (1988). "Pharmacokinetics and bioavailability of intravenous and oral chlordesmethyldiazepam in humans". European Journal of Clinical Pharmacology. 34 (1): 109–112. doi:10.1007/BF01061430. ISSN 0031-6970. 
  10. ↑ McLean, M. J., Macdonald, R. L. (February 1988). "Benzodiazepines, but not beta carbolines, limit high frequency repetitive firing of action potentials of spinal cord neurons in cell culture". The Journal of Pharmacology and Experimental Therapeutics. 244 (2): 789–795. ISSN 0022-3565. 
  11. ↑ Saïas, T., Gallarda, T. (September 2008). "[Paradoxical aggressive reactions to benzodiazepine use: a review]". L’Encephale. 34 (4): 330–336. doi:10.1016/j.encep.2007.05.005. ISSN 0013-7006. 
  12. ↑ Paton, C. (December 2002). "Benzodiazepines and disinhibition: a review". Psychiatric Bulletin. 26 (12): 460–462. doi:10.1192/pb.26.12.460. ISSN 0955-6036. 
  13. ↑ Bond, A. J. (1 January 1998). "Drug- Induced Behavioural Disinhibition". CNS Drugs. 9 (1): 41–57. doi:10.2165/00023210-199809010-00005. ISSN 1179-1934. 
  14. ↑ Drummer, O. H. (February 2002). "Benzodiazepines - Effects on Human Performance and Behavior". Forensic Science Review. 14 (1–2): 1–14. ISSN 1042-7201. 
  15. ↑ Goyal, S. (14 March 1970). "Drugs and dreams". Canadian Medical Association Journal. 102 (5): 524. ISSN 0008-4409. 
  16. ↑ Nutt, D., King, L. A., Saulsbury, W., Blakemore, C. (24 March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". The Lancet. 369 (9566): 1047–1053. doi:10.1016/S0140-6736(07)60464-4. ISSN 0140-6736. 
  17. ↑ Mandrioli, R., Mercolini, L., Raggi, M. A. (October 2008). "Benzodiazepine metabolism: an analytical perspective". Current Drug Metabolism. 9 (8): 827–844. doi:10.2174/138920008786049258. ISSN 1389-2002. 
  18. ↑ Twyman, R. E., Rogers, C. J., Macdonald, R. L. (March 1989). "Differential regulation of ?-aminobutyric acid receptor channels by diazepam and phenobarbital". Annals of Neurology. 25 (3): 213–220. doi:10.1002/ana.410250302. ISSN 0364-5134. 
  19. ↑ Hoffman, E. J., Warren, E. W. (September 1993). "Flumazenil: a benzodiazepine antagonist". Clinical Pharmacy. 12 (9): 641–656; quiz 699–701. ISSN 0278-2677. 
  20. ↑ Branch, L. S. (2022), Consolidated federal laws of Canada, Controlled Drugs and Substances Act 
  21. ↑ "Anlage II BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 19, 2019. 
  22. ↑ "Dreißigste Verordnung zur Änderung betäubungsmittelrechtlicher Vorschriften" (PDF). Bundesgesetzblatt Jahrgang 2015 Teil I. Nr. 45 (in German). Bundesanzeiger Verlag. November 20, 2015. Retrieved December 29, 2019. 
  23. ↑ "§ 29 BtMG" (in German). Bundesministerium der Justiz und für Verbraucherschutz. Retrieved December 19, 2019. 
  24. ↑ "Rozporządzenie Ministra Zdrowia z dnia 27 stycznia 2022 r. zmieniające rozporządzenie w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych". DZIENNIK USTAW 2022 R. POZ. 274274 (in Polish). 2022-02-04. Archived from the original on 2022-05-07. 
  25. ↑ "Rozporządzenie Ministra Zdrowia z dnia 27 stycznia 2022 r. zmieniające rozporządzenie w sprawie wykazu substancji psychotropowych, środków odurzających oraz nowych substancji psychoaktywnych" (PDF). DZIENNIK USTAW 2022 R. POZ. 274274 (in Polish). 2022-02-04. 
  26. ↑ Постановление Правительства РФ от 12.07.2017 N 827 “О внесении изменений в некоторые акты Правительства Российской Федерации в связи с совершенствованием контроля за оборотом наркотических средств и психотропных веществ” - КонсультантПлюс 
  27. ↑ "Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien" (in German). Bundeskanzlei [Federal Chancellery of Switzerland]. Retrieved January 1, 2020. 
  28. ↑ https://resmigazete.gov.tr/eskiler/2017/01/20170112-8.pdf
  29. ↑ The Misuse of Drugs Act 1971 (Amendment) Order 2017 
  30. ↑ Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule I | https://www.federalregister.gov/documents/2022/12/23/2022-27278/schedules-of-controlled-substances-temporary-placement-of-etizolam-flualprazolam-clonazolam


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