Pharmacology
DrugBankDescription
Zopiclone is a novel hypnotic agent used in the treatment of insomnia. Its mechanism of action is based on modulating benzodiazepine receptors. In addition to zopiclone's benzodiazepine pharmacological properties it also has some barbiturate-like properties.
Mechanism of Action
Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABABZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.
Pharmacodynamics
Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABABZ) receptor complex. Subunit modulation of the GABABZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.
Metabolism
Extensively metabolized in the liver via decarboxylation (major pathway), demethylation, and side chain oxidation. Metabolites include an N-oxide derivative (weakly active; approximately 12% of a dose) and an N-desmethyl metabolite (inactive; approximately 16%). Approximately 50% of a dose is converted to other inactive metabolites via decarboxylation. Hepatic microsomal enzymes are apparently not involved in zopiclone clearance.
Absorption
Rapidly absorbed following oral administration.
Toxicity
Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agent. Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing.
Indication
For the short-term treatment of insomnia.
Half-life
Elimination half life is approximately 5 hours (range 3.8 to 6.5 hours) and is prolonged to 11.9 hours in patients with hepatic insufficiency.
Receptor Profile
Receptor Actions
Receptor Binding
History & Culture
Zopiclone was developed by the French pharmaceutical company Rhône-Poulenc S.A. and first introduced to the market in 1986. Rhône-Poulenc has since become part of Sanofi, which remains the primary global manufacturer. Upon its release, zopiclone was marketed as offering improvements over benzodiazepines for treating insomnia, though subsequent meta-analyses have found it comparable to benzodiazepines across all assessed parameters. The substance remained unscheduled in the United States until April 4, 2005, when the Drug Enforcement Administration placed it under Schedule IV of the Controlled Substances Act, citing evidence of addictive properties similar to those of benzodiazepines. Zopiclone as marketed globally is a racemic mixture containing two stereoisomers, of which only one possesses pharmacological activity. In 2005, the same year as federal scheduling, the Massachusetts-based pharmaceutical company Sepracor began marketing the active stereoisomer separately as eszopiclone under the brand name Lunesta in the United States. This development effectively placed what functions as a generic medication in most countries under new patent protection within the American market. In France, zopiclone ranks among the ten most commonly obtained medications through fraudulent prescriptions, indicating significant diversion from legitimate pharmaceutical channels.
Subjective Effect Notes
physical: The physical effects of zopiclone can be broken down into several components which progressively intensify proportional to dosage.
cognitive: The general head space of zopiclone is described by many as one of intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.
Effect Profile
Curated + 44 ReportsStrong anxiolysis, sedation, cognitive impairment, and euphoria
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Hypnotic tolerance to sleep‑inducing effects can develop within days to weeks of daily use; functional tolerance to impairment is incomplete (driving deficits persist despite regular use). Return toward baseline generally occurs over 2–4+ weeks of abstinence but varies widely. Data are a synthesis of clinical guidance for benzodiazepine‑site agonists and limited zopiclone‑specific studies; confidence moderate to low.
Cross-Tolerances
Experience Report Analysis
ErowidDemographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
ErowidEffects aggregated from 44 experience reports (44 Erowid)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 9
Adverse Effects 7
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Heavy (n=13) |
|---|---|
| Stimulation | 61.5% |
| Memory Suppression | 46.2% |
| Sedation | 38.5% |
| Color Enhancement | 30.8% |
| Euphoria | 30.8% |
| Visual Distortions | 30.8% |
| Motor Impairment | 30.8% |
| Tactile Enhancement | 30.8% |
| Auditory Effects | 23.1% |
| Open-Eye Visuals | 23.1% |
| Anxiety Suppression | 23.1% |
| Confusion | 15.4% |
| Nausea | 15.4% |
| Psychosis | 15.4% |
| Introspection | 15.4% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 44 experience reports.
Limited tier coverage — most reports fall within the Heavy range. Effects at other dose levels may not be represented.
| Effect | Heavy (n=13) | |
|---|---|---|
| stimulation | ||
| memory suppression | ||
| sedation | ||
| color enhancement | ||
| euphoria | ||
| visual distortions | ||
| motor impairment | ||
| tactile enhancement | ||
| auditory effects | ||
| open-eye visuals | ||
| anxiety suppression | ||
| confusion | ||
| nausea | ||
| psychosis | ||
| introspection | ||
| empathy |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 62 individual dose entries
Oral (n=47)
Common Combinations
Most co-occurring substances in experience reports
Form / Preparation
Most common forms and preparations reported
Body-Weight Dosing
Dose relative to body weight from reports with weight data
Redose Patterns
Redosing behavior across 35 reports
Legal Status
| Country | Status | Notes |
|---|---|---|
| Canada | Approved prescription medication | Approved for medical use and marketed since the mid-1990s. Multiple brand name products (Imovane, Act Zopiclone, M-zopiclone) and generic formulations (Apo-zopiclone, Ag-zopiclone) are available by prescription. |
| United Kingdom | Prescription only medicine | Available as a prescription medication, commonly dispensed in 3.75mg and 7.5mg tablet formulations for the treatment of insomnia. |
| United States | Scheduled controlled substance | Became a federally scheduled controlled substance in 2005. Prior to scheduling, it was available but not specifically controlled under the Controlled Substances Act. |
Harm Reduction
drugs.wikiZopiclone acts at the benzodiazepine site of the GABAA receptor and should be reserved for short‑term insomnia; longer courses increase tolerance, dependence, and withdrawal risks. Complex sleep‑related behaviors (e.g., sleep‑eating, sleep‑driving) and anterograde amnesia can occur, especially with higher doses, redosing, or use while not immediately going to bed. Residual psychomotor impairment can persist 9–11+ hours; avoid driving or hazardous tasks the next morning and allow a full 8+ hours time in bed. Bitter/metallic taste (dysgeusia) and dry mouth are common and may persist into the next day. Co‑use with other depressants (alcohol, opioids, gabapentinoids, sedating antipsychotics/antihistamines) markedly increases risk of respiratory depression, blackouts, falls, and crashes; avoid such combinations. Hepatic impairment prolongs half‑life and increases next‑day effects; lower doses and extra caution are indicated. Redosing during the same night increases amnesia and disinhibition; due to memory gaps, some users unintentionally redose—pre‑plan a single dose and secure the remainder. If dependence has developed, avoid abrupt cessation; a supervised, gradual taper is safer due to seizure risk. Do not confuse racemic zopiclone dosing (commonly 7.5 mg) with eszopiclone (Lunesta; 1–3 mg)—they are related but not dose‑equivalent.
References
Data Sources
Cited References
Drugs.wiki References
- DrugBank: Zopiclone
- Zopiclone metabolism via CYP3A4/CYP2C8 (DMD 1999)
- EMCDDA/ EUDA: Benzodiazepines drug profile – risks incl. driving/falls and alcohol synergy
- EMCDDA/ EUDA: Non‑medical use of medicines – Z‑drugs with opioids/stimulants in polydrug use
- NCBI Bookshelf: Halcion safety review table citing zopiclone dysgeusia and adverse‑effect profile
- PMCID: Poster Session—Standardized highway driving test; zopiclone 7.5 mg active control shows residual morning impairment
- Drugs‑Forum Wiki: Zopiclone – next‑day impairment, complex behaviors, withdrawal seizures (overview)
- EMCDDA/EUDA: Designer/illicit benzodiazepines – overdose risk, especially with alcohol/sedatives
- DrugWise: Benzodiazepines – harm reduction, driving risk, avoid mixing with alcohol and gabapentinoids (MHRA alert)
- NCBI MeSH: Zopiclone – brand/entry terms