Clonazolam |
Death may occur when benzodiazepines are combined with depressants such as opiates, thienodiazepines, alcohol or other GABAergic substances.[1]
It is strongly discouraged to consume moderate to heavy dosages of these substances together.
| Clonazolam | |||||||||||||||||||||||
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| Molecular structure of Clonazolam | |||||||||||||||||||||||
| 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 | |||||||||||||||||||||||
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| Summary sheet: Clonazolam |
Clonazolam (also known as Clonitrazolam) is a medium-duration psychoactive drug of the benzodiazepine class which produces anxiolytic, sedative, hypnotic, muscle relaxant, anticonvulsant, depressant and amnesic effects. This compound is a novel research chemical derivative of the FDA-approved drugs clonazepam (Klonopin, Rivitrol) and alprazolam (Xanax). Clonazolam has a fast onset of action and symptomatic relief. Subjective reports suggest the onset to be between 20 - 60 minutes.
The synthesis of clonazolam was first reported in 1971 and the drug 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 clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg.[4]
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]
It's worth noting 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.[7] 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 abruptly.[8]
Contents
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
The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.
Physical effects 
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- 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.
- Respiratory depression
- Dizziness
- Muscle relaxation
- Motor control loss
Paradoxical effects 
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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 
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- Amnesia
- Disinhibition
- Dizziness
- Delusions of sobriety
- Information processing suppression
- Motor control loss
- Muscle relaxation
- Physical euphoria
- Thought deceleration
- Seizure suppression
- 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.
Toxicity and harm potential
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 when using this drug.
Tolerance and addiction potential
Clonazolam is 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.
Withdrawal symptoms or rebound symptoms may occur after ceasing treatment 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.[17] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Clonazolam presents cross-tolerance with all benzodiazepines, meaning that after its consumption all benzodiazepines will have a reduced effect.
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 issues
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This legality section is a stub. As such, it likely contains incomplete or wrong information. You can help by expanding it. |
- United Kingdom - It is illegal to produce, supply, or import this drug under the Psychoactive Substance Act, which came into effect on May 26th, 2016.[18]
Preparation methods
Preparation methods for this compound within our tutorial index include:
See also
External links
References
- ↑ Risks of Combining Depressants (Tripsit) | https://tripsit.me/combining-depressants/
- ↑ 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
- ↑ Triazolobenzazepines, process and intermediates for their preparation and medicines containing them | https://www.google.com/patents/EP0072029B1
- ↑ Designer benzodiazepines: A new challenge (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/26043347
- ↑ 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
- ↑ 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
- ↑ A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
- ↑ 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
- ↑ Benzodiazepine interactions with GABA receptors (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/6147796
- ↑ 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
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/18922233 | Saïas T, Gallarda T | Paradoxical aggressive reactions to benzodiazepine use: a review
- ↑ Paton C | Benzodiazepines and disinhibition: a review | Psychiatr Bull R Coll Psychiatr | http://pb.rcpsych.org/cgi/reprint/26/12/460.pdf
- ↑ Bond AJ | Drug-induced behavioural disinhibition: incidence, mechanisms and therapeutic implications | CNS Drugs
- ↑ Drummer OH | Benzodiazepines—effects on human performance and behavior | Forensic Sci Rev
- ↑ Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644
- ↑ Benzodiazepine metabolism: an analytical perspective (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18855614
- ↑ A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812
- ↑ Psychoactive Substances Act 2016 (Legislation.gov.uk) | http://www.legislation.gov.uk/ukpga/2016/2/contents/enacted