Zopiclone

Zopiclone is a hypnotic nonbenzodiazepine drug of the cyclopyrrolone class. Zopiclone and its closely related dextrorotatory S-stereoisomer zopiclone (Lunesta) are the most popular and available cyclopyrrolone drugs. This class of drugs is named for having a pyrrolone core, a five-membered ring with a nitrogen constituent (pyrrole) and a ketone group (-one).

The ketone group found in zopiclone is located at R₅ of the pyrrolone ring. Zopiclone contains four nitrogenous rings including pyrrolone. Fused to the pyrrolone core is a pyrazine ring, a six-membered aromatic ring with two nitrogen substituents. The two rings are fused at R₃ and R₄. This bicylic core is called a pyrollopyrazine. Bound to the nitrogen group of the pyrrolone at R₆ is a substituted pyridine ring. Pyridine is six-membered unsaturated ring with one nitrogen group. The pyridine ring of zopiclone is substituted at R₅ with a chlorine group.

The final ring of zopiclone is a piperazine ring. Piperazine is a six-membered saturated ring with two nitrogen constituents; in this case, it is substituted at R₄ with a methyl group. This piperazine ring is connected to the pyrrolone core of zopiclone at R₇ through a carboxylate group.

Zopiclone may be measured in blood, plasma, or urine by chromatographic methods. Plasma concentrations are typically less than 100 μg/l during therapeutic use, but frequently exceed 100 μg/l in automotive vehicle operators arrested for impaired driving ability and may exceed 1000 μg/l in acutely poisoned patients. Post mortem blood concentrations are usually in a range of 0.4-3.9 mg/l in victims of fatal acute overdose.^[4]

Zopiclone shares an almost identical pharmacological profile to benzodiazepines despite differences in structure. The mechanism of action works by binding to the same site as benzodiazepines and acts as a full agonist, which in turn positively modulates benzodiazepine-sensitive GABA_A receptors and enhances GABA binding at the GABA_A receptors to produce zopiclone's subjective effects.^{[citation needed]}

Since GABA functions as the brain's predominant inhibitory neurotransmitter, this activation of receptors results in the sedative and anxiolytic effects of zopiclone.^{[citation needed]} In addition to zopiclone's benzodiazepine pharmacological properties, it also has some barbiturate-like properties.

Additionally, it (along with desmethylzopiclone) is a noncompetitive antagonist at nicotinic acetylcholine receptor ^[5]. This could be the cause of deliriant like effects.

The metabolite of zopiclone called desmethylzopiclone is also pharmacologically active, although it has predominately anxiolytic properties. One study found some slight selectivity for zopiclone on α1 and α5 subunits,^[6] although it is regarded as being unselective in its binding to α1, α2, α3, and α5 GABA_A benzodiazepine receptor complexes.

Desmethylzopiclone has been found to have partial agonist properties, unlike the parent drug zopiclone, which is a full agonist.^[7] The mechanism of action of zopiclone is similar to benzodiazepines, with similar effects on locomotor activity and on dopamine and serotonin turnover.

In comparison to other substances of a similar nature such as benzodiazepines, zopiclone is commonly reported to present significantly more amnesic and disinhibiting effects in a manner similar to alcohol. 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 ☠.

Experience reports

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

• Experience:Zopiclone (30mg, oral) - DANGER
• Experience:Zopiclone (7.5 mg) + Mirtazapine (7.5 mg) + Cannabis
• Experience:Zopiclone hppd?

Additional experience reports can be found here:

• Erowid Experience Vaults: Zopiclone

Zopiclone is generally thought to have a low toxicity relative to dose. However, it is potentially lethal when mixed with depressants like benzodiazepines, alcohol or opioids. When combined with one or several of these substances the already existing chance of a having a "black-out" is significantly increased, leaving the user with very little to no memory of the events that occurred whilst under the influence of zopiclone alone or combined with most other CNS depressants.

Some users have reported taking zopiclone in combination with alcohol in an attempt to treat hangovers with varying degrees of success.

It is strongly recommended that one use harm reduction practices when using this substance.

Dependence and abuse potential

Zopiclone is extremely physically and psychologically addictive. This compound may have an even greater addictive potential than benzodiazepines. Tolerance will develop to the sedative-hypnotic effects within a couple of weeks of daily use. After cessation, the tolerance returns to baseline in 7 - 14 days. 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.

Zopiclone presents cross-tolerance with all benzodiazepines, meaning that after its consumption benzodiazepines and most other GABAgenic depressants will have a reduced effect.^[8]

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• 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.

• Canada: Zopiclone is available by prescription only in Canada.^[9]
• Germany: Zopiclone is a prescription medicine, according to Anlage 1 AMVV^[10]
• Norway: Zopiclone is available by prescription in Norway.^{[citation needed]}
• Switzerland: Zopiclone is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.^{[citation needed]}

• Responsible use
• Depressants
• Z-drugs
• Benzodiazepines

• Zopiclone (Wikipedia)
• Zopiclone (Erowid Vault)
• Zopiclone (Isomer Design)