Clonazolam

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Death 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.

Summary sheet: Clonazolam


Clonazolam
Clonazolam.svg
Chemical Nomenclature
Common names Clonazolam, Clonitrazolam
Systematic name 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-s-triazolo- (4,3-a)-(1,4)-benzodiazepine
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 50 - 75 µg
Light 75 - 200 µg
Common 200 - 400 µg
Strong 400 - 1000 µg
Heavy 1000 µg +
Duration
Total 6 - 10 hours
Onset 10 - 30 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.

Clonazolam (also known as Clonitrazolam) is a novel depressant substance of the benzodiazepine chemical class which produces anxiolytic, sedative, muscle relaxant, and amnesic effects when administered. This compound is a novel research chemical derivative of the FDA-approved drugs clonazepam (Klonopin, Rivitrol) and alprazolam (Xanax). Clonazolam is reported to be roughly 2.5x as potent as alprazolam.

The synthesis of clonazolam was first reported in 1971. It was described as the most active compound in the series tested.[2][3] Clonazolam is reputed to be highly potent, and concerns have been raised that it and flubromazolam may pose comparatively higher risks than other designer benzodiazepines due to their ability to produce strong sedation and amnesia at oral doses as low as 0.5 mg, or 500 micrograms (ug).[4] It is reported to have a medium-length onset of action (20 - 60 minutes).

Very little is known about this substance, but it has recently become easily accessible through online research chemical vendors where it is being sold as a designer drug.[5][6] Due to its extremely high potency, it is often found on blotter paper or in volumetrically dosed solutions. Ingestion of raw clonazolam powder is unsafe due to its microgram-range potency and the ease in which it can lead to multi-day blackouts.

The sudden discontinuation of benzodiazepines can lead to life-threatening seizures or death for individuals who have been using them regularly, in heavy doses, or for extended periods of time.[7] For this reason, it is recommended to discontinue use by tapering one's dose by gradually lowering the amount taken each day for a prolonged period of time instead of stopping one's usage abruptly.[8]

Due to the high dependence-forming and addiction potential that this substance shares with other members of the benzodiazepine class, as well as its alcohol-like ability to induce dangerously disinhibited black-out states, it is strongly advised to use proper harm reduction practices if choosing to use this substance.

Chemistry

Clonazolam 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. The benzyl ring of clonazolam is substituted at R8 with a nitro group, NO2-. Further, the diazepine ring is bonded at R6 to a 2-chlorinated phenyl ring.

Clonazolam also contains a 1-methylated triazole ring fused to and incorporating R1 and R2 of its diazepine ring. Clonazolam belongs to a class of benzodiazepines containing this fused triazole ring, called triazolobenzodiazepines, distinguished by the suffix "-zolam." Clonazolam is also a nitrobenzodiazepine, a subclass of benzodiazepines which contain a nitro (NO2-) group. Other nitrobenzodiazepines include clonazepam and flunitrazepam.

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.[9] As this site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming effects) of clonazelam 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.[10]

Subjective effects

Clonazolam is reported to be similar to alprazolam and other benzodiazepines that suppress emotions and produce moderate-strong feelings of relaxation, pleasure and comfort in the body. This seems to present itself more often in those with pre-existing anxiety. Many anecdotal reports from users of this compound have stated it as being one of the most euphoric benzodiazepines.

The cognitive effects of clonazolam are thought to be mainly amnesic, but also include most other typical effects seen with benzodiazepines. Clonazolam is reported to cause "blackouts" at a higher rate than other benzodiazepines.

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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Visual 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 no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:

Common usage

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. Clonazolam is especially important to weigh out and volumetrically dose properly due to it being active in the microgram range. To avoid adverse effects, one can dissolve the benzodiazepine volumetrically into a solution and dose it accurately based upon the methodological instructions linked within this tutorial here.

Toxicity and harm potential

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

Clonazolam likely has a low toxicity relative to dose.[16] 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

Clonazolam is generally considered to be extremely physically and psychologically addictive.

Tolerance will 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.

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

Discontinuation and withdrawal

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.[17] Substances which lower the seizure threshold such as tramadol should be avoided during withdrawal.[citation needed] Abrupt discontinuation also causes rebound stimulation which presents as anxiety, insomnia and restlessness.[citation needed]

If one wishes to discontinue after a period of regular use, 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 such as alprazolam or etizolam, a longer acting variety such as diazepam or clonazepam 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 quantities of alcohol can also help to reduce the symptoms, but otherwise cannot be used as an effective tapering agent.

The duration and severity of withdrawal symptoms depend on a number of factors including the half-life of the substance 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.[citation needed]

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, cross-potentiating each other.[citation needed]

For example, 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] This can result in dangerously disinhibited, total blackout states along with potential lethal respiratory depression.[citation needed]

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 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.

  • Stimulants - It can be dangerous to combine depressants with stimulants due to the risk of accidental excessive intoxication. Stimulants mask the sedative effect of depressants, which is the main factor most people use to gauge their level of intoxication. Once the stimulant effects wear off, the effects of the depressant will significantly increase, leading to intensified disinhibition, motor control loss, and dangerous black-out states. This combination can also potentially result in severe dehydration if one's fluid intake is not closely monitored. If choosing to combine these substances, one should strictly limit themselves to a pre-set schedule of dosing only a certain amount per hour until a maximum threshold has been reached.

Legal status

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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 schedule IV in Canada. [20]
  • United Kingdom: Clonazolam is a class C drug in the UK as of 31st May 2017 and is illegal to possess, produce or supply. [21]

See also

External links

References

  1. Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
  2. 6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines which have central nervous system depressant activity (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/5165540
  3. Triazolobenzazepines, process and intermediates for their preparation and medicines containing them | https://www.google.com/patents/EP0072029B1
  4. Designer benzodiazepines: A new challenge (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/26043347
  5. Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites | http://link.springer.com/article/10.1007%2Fs11419-015-0277-6
  6. Identification of main human urinary metabolites of the designer nitrobenzodiazepines clonazolam, meclonazepam, and nifoxipam by nano-liquid chromatography-high-resolution mass spectrometry for drug testing purposes. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/27071765
  7. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  8. 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
  9. Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
  10. 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
  11. http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
  12. Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
  13. Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
  14. Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
  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. A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
  18. Twyman, R. E., Rogers, C. J., & Macdonald, R. L. (1989). Differential regulation of γ‐aminobutyric acid receptor channels by diazepam and phenobarbital. Annals of Neurology, 25(3), 213-220. https://doi.org/10.1002/ana.410250302
  19. Amrein, R., Leishman, B., Bentzinger, C., & Roncari, G. (1987). Flumazenil in benzodiazepine antagonism. Medical Toxicology and Adverse Drug Experience, 2(6), 411-429. PMID: 8306565
  20. http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-15.html#h-34
  21. The Misuse of Drugs Act 1971 (Amendment) Order 2017 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2017/634/made