Clonazolam

Clonazolam is a research chemical (RC) benzodiazepine. Though it was synthesized in the 1970s, it was never brought to market and it has only been used as an RC since the mid-2000s.

It’s a very potent substance, surpassing most benzodiazepines. Due to its potency and strength, it’s often been associated with amnesia and unconsciousness. Those risks exist with all drugs in the class, but the way people use clonazolam makes it more likely they’ll encounter a problem.

Many of the issues with the drug can be blamed on inappropriate dosing. Users believe the common dose is higher than it is and vendors sell products that are too strong. If you stick to a true light/common dose, most of the major concerns won’t apply.

Clonazolam = Clonitrazolam

PubChem: 12317881

Molecular formula: C17H12ClN5O2

Molecular weight: 353.766 g/mol

IUPAC: 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine

Brief Overview Video

Dose

Oral

Light: 100 – 250 μg (0.1 – 0.25 mg)

Common: 250 – 400 μg (0.25 – 0.4 mg)

Strong: 400 – 500 μg (0.4 – 0.5 mg)

Timeline

Oral

Total: 7 – 12 hours

Onset: 00:30 – 00:45

Some users receive no or very light effects until 1-2 hours after administration. Redosing isn’t wise at any point, but it’s especially bad to redose in the first couple hours due to thinking your dose wasn’t strong enough.

Initially keeping it in your mouth for sublingual or buccal administration can shorten the onset to around 00:20. It can work that fast when swallowed, but sublingual/buccal appears more reliable with its speed.

Once it kicks in, the strength builds for at least an hour, sometimes longer. Then the peak is reached. The effects (e.g. sedation vs. anxiolysis being most prominent) can still change over the course of the experience.

The duration is dose-dependent. Strong+ doses can result in effects persisting well over 12 hours, while light doses may be largely gone in about 8 hours.

Experience Reports

Erowid

Effects

Positive

• Anxiety reduction
• Mood lift
• Euphoria
• Muscle relaxation
• Sedation
• Increased talkativeness

Negative

• Amnesia
• Drowsiness
• Dizziness
• Impaired coordination
• Disinhibition
• Unconsciousness
• Cognitive impairment

Benzodiazepines come with some core effects, including anxiolysis, muscle relaxation, sleep-induction, impaired coordination, cognitive impairment, and disinhibition. But the relative strength of those effects can vary between drugs.

Clonazolam is usually considered a strongly sedating benzodiazepine with a higher propensity to cause amnesia and disinhibition. Many people have concerns about amnesia and disinhibition, but those are primarily an issue due to inappropriate dosing. Sticking to light/common amounts greatly lowers the chance of experiencing them.

With the exception of those who consider it “too strong” or “too potent,” users tend to like its effects. Some find it’s one of the most recreational benzodiazepines, though others report it’s only useful for sleep.

Potency

It does stand out from most benzodiazepines due to its potency. The drug can be felt at just 100-200 μg. This has proven to be an issue since some people believe 500+ μg is a common dose and vendors often sell 500 μg products. And there are many reports of people exceeding 1 mg.

VS other benzodiazepines

There’s variation in the reports about how it compares to other benzodiazepines, which is to be expected. Overall, people consider it more recreational than most, but there are reports of the opposite opinion.

Clonazepam

Its general feel is said to be similar to clonazepam, but there are significant differences. Clonazolam appears to be more sedating and more likely to produce recreational effects. While clonazepam can be better for use in functional situations.

Alprazolam

It’s described as stronger than alprazolam with its recreational and amnestic qualities.

Etizolam

Clonazolam is stronger with its positive and negative effects. It feels notably different from etizolam. Because of its greater impact on parameters like memory and energy, some users prefer etizolam for a larger set of situations.

Cognitive and Psychological Effects

Benzodiazepines, clonazolam included, usually produce a relaxed and care-free mental state. The majority of people don’t find they’re very recreational on their own, but they can make social activities more enjoyable and reduce stress when needed. Music enhancement is another potential effect.

For some, just experiencing greatly reduced anxiety and less overthinking can feel liberating and recreational. There are people who notice euphoria, but I wouldn’t go into clonazolam chasing that effect. If you don’t notice it by the time you’re using a strong dose, don’t keep pushing the drug into riskier dosage territory with the hopes of feeling great.

People with anxiety find it’s capable of almost entirely removing their normal anxious thought patterns. Though its muscle relaxing, sedative, and hypnotic properties seem to be stronger per-dose than anxiolysis.

Sedation, Impairment, and Sleep

It’s considered one of the most sedating benzos per dose. This property, along with having an easier time sleeping, is most significant during the first few hours. The sedation can be strong enough to actually make it an annoying quality of the drug, since not everyone is aiming to become tired. You could find yourself doing little more than sitting around or laying down.

After those hours are over the sedation can become less overwhelming.

Depending on the dose and person, a light or common amount might offer an experience with relatively minor sedation and perhaps a slightly energetic, uplifted buzz. But this varies a lot between people.

Cognitive impairment is an issue even at common doses, making it harder to complete tasks or have a conversation. Memory impairment is usually minor at common doses, but it can still make an appearance, particularly with short-term memory. Impairment could become frustrating if it’s getting in the way of an activity you want to accomplish.

Memory issues progress as the dose increases, producing partial blackouts for a portion of the experience and then amnesia for hours worth of time.

If you’re trying to remain functional and not come off as impaired, you’ll want to stick to doses around .1 to .2 mg. Impairment and other issues, like slurring your words, become more prominent after that point.

The hypnotic property of clonazolam makes it useful for natural insomnia or insomnia caused by the after effects of drugs like stimulants and psychedelics.

It has a pretty long duration, so it may be more likely to keep you asleep all night compared to a shorter-acting benzo, which might only be good for inducing sleep. The duration can be an issue due to grogginess and impairment when you wake up. If you need to drive or work less than 12 hours after you take it, avoiding the drug is preferable.

Impairment can last upwards of 12 hours depending on dose and people sometimes wake up still experiencing other effects like anxiolysis and muscle relaxation.

Benzodiazepines impair sleep architecture, but people usually get subjectively good sleep and even impaired sleep is still superior to insomnia.

Some users report vivid dreams when sleeping on clonazolam.

Especially when strong doses are used, an unpleasant hangover can be produced, featuring dizziness, nausea, low motivation, and ongoing sedation.

Physical

Motor coordination is impaired even at typical doses. You might not feel strongly affected in this regard, but you should avoid driving and demanding physical tasks regardless.

It’s common to have “wobbly” legs with common to strong doses, so holding onto things when moving can become a necessity.

Physical euphoria sometimes occurs, including with sensations of warmth and tingling.

Chemistry & Pharmacology

Chemistry

Clonazolam is a benzodiazepine that’s structurally similar to clonazepam.

Both compounds feature a nitro group at the 7 position on the benzodiazepine ring structure, making them both nitrobenzodiazepines, and they also feature a chlorine group at the 2 prime position of each of their respective structures.

Clonazolam differs structurally from clonazepam by the substitution of a triazole ring onto the benzodiazepine ring structure to yield a triazolobenzodiazepine ring structure; therefore, clonazolam can also be referred to as a triazolobenzodiazepie.

(Bergstrand, 2016) – Clonazolam cross-reacts with benzodiazepine immunoassay tests

• It showed strong cross-reactivity on benzodiazepine immunoassay tests when looking for the parent compound. This was true for CEDIA, HEIA, EMIT II Plus, and KIMS II.

Pharmacology

Some pharmacology information exists, but none elucidating its activity at specific receptors. We do know the drug can cause a potent benzodiazepine-like response in animals. Coupled with its known effects in humans and its structure, clonazolam is most likely a benzodiazepine receptor agonist.

If so, that means it’s primarily having an impact by modulating GABA’s activity at GABAA receptors.

(Hester, 1971) – Early study showing benzodiazepine-like activity in animals.

• In a series of triazolobenzodiazepines, it was the most active overall, sometimes proving effective at under 10 μg/kg in mice.

Pharmacokinetics

(Hoiseth, 2016) – Report covering a handful of impaired driving cases in which clonazolam was detected

• Data source
  • Blood taken from suspected drugged drivers and some other criminal offenders in Norway.
• During the study period of July 2013 – May 2016 there were 22,022 cases with blood samples.
• Any of the novel designer benzodiazepines in question (clonazolam, diclazepam, flubromazepam, flubromazolam, pyrazolam, and etizolam) were found in 77 cases, 0.3% of the total.
  • 69 cases represented drugged drivers and in 14/69 there was a traffic accident. The other 8 cases involved other criminal acts, mainly violence.
    • Demographics: 88% male and median age of 27 (17-62 years)
  • In 69 (90%), just one designer benzodiazepine was detected. In the remaining cases, 2 or 3 designer benzodiazepines were detected together.
• Most common novel designer benzodiazepines
  • Flubromazolam (25 cases), flubromazepam (24 cases), diclazepam (15), etizolam (14), clonazolam (7), and pyrazolam (1)
• Clonazolam concentration
  • Median from blood: 0.0053 mg/L
  • Min: 0.0019 mg/L and Max: 0.011 mg/L

(Meyer, 2016) – Investigating the in vivo human urinary metabolite profile of clonazolam

• Sample source: Sweden’s STRIDA project, which collects information related to NPS use.
  • This study used urine samples from STRIDA to look at phase I and II metabolites.
• Clonazolam’s metabolism
  • Evidence supports extensive metabolism in humans.
  • Mainly reduced to the 7-amino benzodiazepine  and then acetylated. Clonazolam was also hydroxylated.
  • Hydroxyclonazolam, 7-aminoclonazolam, and 7-acetaminoclonazolam were then conjugated with glucuronic acid.
  • The most abundant metabolite in urine was 7-aminoclonazolam.

(Huppertz, 2015) – In vitro analysis of its metabolism using human liver microsomes

• Metabolic routes include monohydroxylation and reduction of the nitro group. Hydroxylation position is unknown, but most likely to be at the α- and 4- positions.

History

1971

It was synthesized and studied, as seen in (Hester, 1971). The drug was made by The Upjohn Company, the pharmaceutical company that would eventually bring alprazolam to the market. Though it was studied and covered by patents, it was never marketed.

2013

Reports about its use as a research chemical began to appear online around 2013. It’s one of the more recent RC benzodiazepines and although it’s used by some people, it’s far less popular than prescription benzodiazepines or etizolam.

2010s

Its presence in the market has sometimes been confirmed due to it showing up in drug tests, like with (Hoiseth, 2016).

(Blackberg, 2016) – A couple cases of it showing up alongside 3-FPM, based on data from Sweden’s STRIDA project. Among 19 samples testing positive for 3-FPM, 5 also contained clonazolam, typically alongside other depressant substances.

The EMCDDA says the detection of new benzodiazepines rose “markedly” in Europe in 2016. Over 300,000 tablets containing benzodiazepines (e.g. clonazolam, diclazepam, etizolam, and flubromazolam) were seized in 2015, nearly double the figure from 2014.

The EMCDDA was first notified of clonazolam’s presence in the EU in January 2015 with a report from Sweden.

Legality

United States

Uncontrolled

Other

Australia: Schedule 9

Canada: Schedule 4

Germany: Controlled via an analog law

UK: Class C

Safety

Risks

At common/strong doses, the primary risks are mental impairment (e.g. bad decision making), psychomotor impairment, and unintended unconsciousness.

Overdose

The risk of an accidental overdose is higher than with some of the less potent benzodiazepines. Those without a tolerance should never initially exceed a common dose.

Most benzodiazepine-only overdoses aren’t fatal, but they can still be dangerous due to severe impairment, sudden unconsciousness, disinhibition,  and amnesia.

The greatest risk comes when combining them with other sedatives, like opioids and alcohol, among others. Drugs with a CNS depressant effect shouldn’t be mixed with clonazolam.

Physical Dependence

You’ll build a tolerance to the drug within a week if you’re using higher doses. As physical dependence grows, tolerance becomes more of an issue and the withdrawal symptoms upon cessation become more intense.

Tolerance may build at a different rate for different effects, such as mood lift declining faster than sedation.

Even within a few days of use it can sometimes lead to rebound effects, especially if you’re taking strong+ doses. Those effects include insomnia, anxiety, depression, and agitation. For some people with lower self-control, this can facilitate the start of a physical/psychological dependence.

Rebound symptoms tend to return to pre-benzodiazepine levels within 1-3 weeks of stopping your use. Though that’s not a very long time, the symptoms can still be very frustrating and uncomfortable, which often leads to people resuming their use.

Tapering is recommended. If you have a significant long-term dependence, a supervised detox is worthwhile.

Withdrawal

Common withdrawal symptoms include anxiety, cognitive impairment, insomnia, increased blood pressure, restlessness, shaking, and increased heart rate.

Severe withdrawal sometimes produces psychosis and seizures.

These symptoms likely arise from changes in the GABAA receptor complex that result in less inhibitory control on various neurotransmitter systems.

Risky Combinations

• Other depressants

References

Bäckberg, M., Westerbergh, J., Beck, O., & Helander, A. (2016). Adverse events related to the new psychoactive substance 3-fluorophenmetrazine – results from the Swedish STRIDA project. Clinical Toxicology. https://doi.org/10.1080/15563650.2016.1211288

Drugnet Ireland. (2017). European drug trends 2017, (62). Retrieved from http://www.hrb.ie/uploads/tx_hrbpublications/Drugnet_62_draft3.pdf

EMCDDA. (n.d.). EMCDDA–Europol 2015 Annual Report on the implementation of Council Decision 2005/387/JHA.

Hester, J. (1971). 6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines which have central nervous system depressant activity. Journal of Medicinal Chemistry.

Høiseth, G., Tuv, S. S., & Karinen, R. (2016). Blood concentrations of new designer benzodiazepines in forensic cases. Forensic Science International, 268, 35–38. https://doi.org/10.1016/j.forsciint.2016.09.006

Huppertz, L. M., Bisel, P., Westphal, F., Franz, F., Auwärter, V., & Moosmann, B. (2015). Characterization of the four designer benzodiazepines clonazolam, deschloroetizolam, flubromazolam, and meclonazepam, and identification of their in vitro metabolites. Forensic Toxicology, 33(2), 388–395. https://doi.org/10.1007/s11419-015-0277-6

Meyer, M. R., Bergstrand, M. P., Helander, A., & Beck, O. (2016). 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. Analytical and Bioanalytical Chemistry, 408(13), 3571–3591. https://doi.org/10.1007/s00216-016-9439-6

Moosmann, B., King, L. A., & Auwärter, V. (2015). Designer benzodiazepines: A new challenge. World Psychiatry, 14(2), 248. https://doi.org/10.1002/wps.20236

Pettersson Bergstrand, M., Helander, A., & Beck, O. (2016). Development and application of a multi-component LC–MS/MS method for determination of designer benzodiazepines in urine. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1035, 104–110. https://doi.org/10.1016/j.jchromb.2016.08.047

Pettersson Bergstrand, M., Helander, A., Hansson, T., & Beck, O. (2017). Detectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assays. Drug Testing and Analysis, 9(4), 640–645. https://doi.org/10.1002/dta.2003