Etizolam Stats & Data
CCc1cc2C(=NCc3nnc(C)n3c2s1)c1ccccc1ClVMZUTJCNQWMAGF-UHFFFAOYSA-NInteraction Warnings
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.
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.
Pharmacology
DrugBankDescription
Etizolam is a thienodiazepine which is chemically related to benzodiazepine (BDZ) drug class; it differs from BDZs in having a benzene ring replaced with a thiophene ring. It is an agonist at GABA-A receptors and possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. Initially introduced in 1983 in Japan as treatment for neurological conditions such as anxiety and sleep disorders, etizolam is marketed in Japan, Italy and India. It is not approved for use by FDA in the US; however it remains unscheduled in several states and is legal for research purposes.
Mechanism of Action
Etizolam is selectively a full agonist at GABA-A receptors to increase GABAergic transmission and enhance GABA-induced Cl- currents . It is reported to bind to the benzodiazepine binding site which is located across the interface between the alpha and gamma subunits. Benzodiazapines are reported to only bind to receptors that contain gamma 2 and alpha 1/2/3/5 subunits . Alpha-1-containing receptors mediate the sedative effects of etizolam whereas alpha-2 and alpha-3 subunit-containing receptors mediate the anxiolytic effect . Etizolam shows high potency and affinity towards GABA-A receptor with alpha 1 beta 2 gamma 2S subunit combination . By binding to the regulatory site of the receptor, etizolam potentiates GABA transmission by facilitating the opening of GABA-induced chloride channels . Etizolam is a specific antagonist at PAFR. It inhibits PAF-induced platelet aggregation by inhibiting PAF binding to the receptors located on the surface of platelets with an IC50 of 22nM .
Pharmacodynamics
Etizolam is a CNS depressant with anxiolytic, anticonvulsant, sedative-hypnotic and muscle relaxant effects. It acts on the benzodiazepine site of the GABA-A receptor as an agonist to increase inhibitory GABAergic transmission throughout the central nervous system. Studies indicate that etizolam mediates its pharmacological actions with 6 to 10 times more potency than that of diazepam. Clinical human studies performed in Italy showed clinical effectiveness of etizolam in relieving symptoms in patients with generalized anxiety disorders with depressive symptoms . Etizolam also mediates imipramine-like neuropharmacological and behavioral effects, as well as minor effects on cognitive functioning. It is shown to substitute the actions of a short-acting barbiturate, pentobarbitol, in a drug discrimination study . Etizolam is an antagonist at platelet-activating-factor (PAF) receptor and attenuates the recurrence of chronic subdural hematoma after neurosurgery in clinical studies . It is shown to inhibit PAF-induced bronchoconstriction and hypotension .
Metabolism
Biotransformation of etizolam is extensive and involves hydroxylation and conjugation . The main metabolite formed via 1'-hydroxylation is α-hydroxyetizolam which retains pharmacological activity comparable to that of the parent drug, indicating that the action of metabolites may contribute to the clinical effects of etizolam . CYP3A4 is predicted to be the main CYP enzyme responsible for mediating etizolam metabolism. CYP2C18 and CYP2C19 are also involved in the metabolic pathways .
Absorption
Etizolam is well absorbed from the intestines with a biological bioavailability of 93% following oral administration. After a single oral dosing of 0.5mg etizolam, it takes approximately 0.9 hours to reach the peak plasma concentration of 8.3 ng/mL .
Toxicity
Major adverse effects include drowsiness, sedation, muscle weakness and incoordination, fainting, headache, confusion, depression, slurred speech, visual disturbances and changes in libido and tremor . Flumazenil is a competitive antagonist of GABA-A receptors and can be also used to reverse the effect of etizolam overdosage. Etizolam demonstrates no effects on fertility, development and teratogenicity . LD50 values of etizolam when delivered orally, intraperitoneally, and subcutaneously are 3509mg/kg, 825mg/kg, and >5000mg/kg in rats, respectively, and 3070mg/kg, 783mg/kg and 5000mg/kg in mice, respectively .
Indication
Indicated for the treatment of generalized anxiety disorder with depression, panic disorder and insomnia.
Half-life
The average elimination half life of etizolam following a single oral dose of 0.5mg is 3.4 hours but may be increased up to 17 hours depending on the rate of metabolism . The main metabolite α-hydroxyetizolam displays a longer elimination half life of 8.2 hours .
Elimination
In a rat study, the amounts of etizolam excreted was 30% in urine was 70% in feces, while the values in a mouse study were 40% in urine and 60% in feces .
Volume of Distribution
Apparent distribution volume was 0.9 ± 0.2 L/kg following a single oral doing of 0.5mg etizolam .
Receptor Profile
Receptor Actions
History & Culture
1972–1984
Etizolam was patented in 1972 and first received approval for medical use in Japan in 1984. Medical literature documenting its therapeutic application for anxiety conditions has appeared since at least the early 1990s. The compound has been prescribed as an anxiolytic in several countries, commonly marketed under brand names such as Etilaam, Etizest, and Depas.
2011–present
Etizolam emerged on online research chemical markets in 2011, and its popularity grew steadily in subsequent years. This rise was likely driven by its low cost, wide availability, and the strongly reinforcing properties it shares with recreational benzodiazepines. Unlike most research chemicals, etizolam occupied an unusual position as a substance with established medical use in some jurisdictions while simultaneously being sold as an unregulated compound in others.
1991–present
Cases of etizolam dependence have been documented in medical literature since 1991, with misuse and addiction reports increasing substantially in subsequent years due to varying levels of accessibility across different regions. The compound has become particularly associated with overdose deaths in Scotland, where drug-related fatalities involving etizolam increased by 107% between 2008 and 2018, reaching 1,187 officially recorded overdoses that year. Women showed a disproportionately greater increase in these deaths compared to men. Counterfeit tablets sold as Xanax or other pharmaceutical benzodiazepines have frequently been found to contain etizolam rather than their labeled ingredients, contributing to unpredictable dosing and increased harm.
Subjective Effect Notes
physical: The physical effects of etizolam can be broken down into several components which progressively intensify proportional to dosage.
cognitive: The cognitive effects of etizolam can be broken down into several components which progressively intensify proportional to dosage. The general head space of etizolam is described by many as one of recreationally intense sedation and decreased inhibition. It contains a large number of typical depressant cognitive effects.
Effect Profile
Curated + 143 ReportsStrong anxiolysis, cognitive impairment, euphoria, and sedation
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Benzodiazepine tolerance develops across the class with frequent use and decays slowly over 2–4 weeks after cessation; time scales vary substantially. Values are heuristic, intended for harm-reduction context, not medical dosing.
Cross-Tolerances
Demographics
Gender Distribution
Age Distribution
Reports Over Time
Effect Analysis
Erowid + BluelightEffects aggregated from 143 experience reports (128 Erowid + 15 Bluelight)
Effect Sentiment Distribution
Confidence Distribution
Positive Effects 23
Adverse Effects 38
Dose-Response Correlation
How effect frequency changes across dose levels
View data table
| Effect | Common (n=14) | Strong (n=30) |
|---|---|---|
| Anxiety Suppression | 71.4% | 63.3% |
| Euphoria | 50.0% | 56.7% |
| Stimulation | 35.7% | 43.3% |
| Music Enhancement | 42.9% | 26.7% |
| Sedation | 35.7% | 40.0% |
| Color Enhancement | 21.4% | 30.0% |
| Memory Suppression | 14.3% | 30.0% |
| Empathy | 21.4% | 26.7% |
| Confusion | 21.4% | 26.7% |
| Body High | 0% | 26.7% |
| Focus Enhancement | 14.3% | 23.3% |
| Visual Distortions | 21.4% | 20.0% |
| Nausea | 21.4% | 20.0% |
| Auditory Effects | 0% | 16.7% |
| Motor Impairment | 0% | 16.7% |
Dose–Effect Mapping
Experience ReportsHow reported effects shift across dose tiers, based on 128 experience reports.
Limited tier coverage — most reports fall within the Common / Strong range. Effects at other dose levels may not be represented.
| Effect | Common (n=14) | Strong (n=30) | |
|---|---|---|---|
| anxiety suppression | → | ||
| euphoria | → | ||
| stimulation | ↑ | ||
| music enhancement | ↓ | ||
| sedation | → | ||
| color enhancement | ↑ | ||
| memory suppression | ↑ | ||
| empathy | ↑ | ||
| confusion | ↑ | ||
| body high | — | → | |
| focus enhancement | ↑ | ||
| visual distortions | → | ||
| nausea | → | ||
| auditory effects | — | → | |
| motor impairment | — | → | |
| jaw clenching | — | → | |
| muscle tension | — | → | |
| increased heart rate | ↓ | ||
| closed-eye visuals | — | → | |
| dissociation | — | → |
Showing top 20 of 24 effects
Risk Escalation
Sentiment AnalysisAverage frequency of positive vs adverse effects across dose tiers
View effect breakdown
Adverse Effects
| Effect | Common (n=14) | Strong (n=30) | Change |
|---|---|---|---|
| Anxiety Suppression | -11% | ||
| Memory Suppression | +109% | ||
| Confusion | +24% | ||
| Nausea | -6% | ||
| Motor Impairment | — | 0% | |
| Jaw Clenching | — | 0% | |
| Muscle Tension | — | 0% | |
| Increased Heart Rate | -53% | ||
| Psychosis | — | 0% | |
| Headache | — | 0% | |
| Pupil Dilation | — | 0% |
Positive Effects
| Effect | Common (n=14) | Strong (n=30) | Change |
|---|---|---|---|
| Euphoria | +13% | ||
| Stimulation | +21% | ||
| Music Enhancement | -37% | ||
| Color Enhancement | +40% | ||
| Empathy | +24% | ||
| Body High | — | 0% | |
| Focus Enhancement | +62% |
Dosage Distribution
Dose distribution from experience reports
Real-World Dose Distribution
62K DosesFrom 213 individual dose entries
Oral (n=166)
Insufflated (n=8)
Sublingual (n=19)
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
Oral
Unknown
Sublingual
Redose Patterns
Redosing behavior across 94 reports
Benzodiazepine Equivalence
Etizolam - 1mg ~=10mg Diazepam.
Legal Status
| Country | Status | Notes |
|---|---|---|
| Australia | Schedule 4 | Listed as Schedule 4 by the Office of Drug Control under Regulation 5 of the Customs (Prohibited Imports) Regulations 1956. License and permit required for import and export. |
| Austria | Illegal (NPSG) | Prohibited since 2012 under the Neue-Psychoaktive-Substanzen-Gesetz (New Psychoactive Substances Act). Possession, production, supply, and import are illegal, though offenders without intent to distribute may not face prosecution. |
| Brazil | Controlled | Illegal since March 23, 2021 following ANVISA Resolution RDC nº 473. Listed on Portaria SVS/MS nº 344, prohibiting possession, production, and sale. |
| Canada | Schedule VI (CDSA) | Captured under section 18 of Schedule VI of the Controlled Drugs and Substances Act as a benzodiazepine derivative and its salts. |
| Finland | Controlled | Classified as a controlled drug since 2016. Not approved for medical use in Finland. |
| Germany | Anlage III BtMG | Controlled under Anlage III of the Betäubungsmittelgesetz (Narcotics Act) since July 17, 2013. Can only be prescribed using a narcotic prescription form (Betäubungsmittelrezept). |
| Japan | Controlled | Regulated under the Narcotics and Psychotropics Control Law. Possession, sale, and manufacture without a prescription are illegal. Approved for medical use with prescription. |
| Netherlands | List II (Opiumwet) | Controlled as a List 2 substance under the Opium Act (Opiumwet). Possession and distribution are illegal. |
| Poland | NPS class | Classified as a New Psychoactive Substance under the Act on Counteracting Drug Addiction. Possession and distribution are prohibited. |
| Russia | Schedule III | Listed as a Schedule III controlled substance since 2017 under Russian drug control legislation. |
| Switzerland | Controlled (Verzeichnis B) | Specifically named as a controlled substance under Verzeichnis B of Swiss narcotics legislation. Medicinal use is permitted with appropriate authorization. |
| Turkey | Illegal | Classified as a controlled drug under Turkish law. Possession, production, supply, and import are prohibited. |
| United Kingdom | Class C | Controlled as a Class C substance under the Misuse of Drugs Act 1971 since May 31, 2017. Possession, production, and supply are criminal offenses. |
| United States | Schedule I (temporary) | Temporarily placed in Schedule I by the DEA effective January 23, 2023, with permanent scheduling likely. Prior to federal action, numerous states independently scheduled etizolam: Alabama (Schedule I, March 2014), Mississippi (Schedule I, April 2014), Arkansas (Schedule I, December 2014), Georgia (Schedule IV, May 2015), Indiana (Schedule I, July 2017), North Carolina (Schedule I, March 2017), Texas (Penalty Group 3, June 2017), Arizona (controlled via House Bill 2033, 2018), and Florida, Louisiana, Ohio, South Carolina, and Virginia (various state controls). |
Harm Reduction
drugs.wikiEtizolam is prescribed in Japan and India under brand names like Depas, Pasaden, Etilaam, Etizola, and Etizest, but is unapproved in many other countries; in unregulated markets it often appears as pressed tablets or powders of uncertain dose. Counterfeit 'benzo' tablets and blister packs may contain etizolam or other designer benzodiazepines; use drug checking services when possible and do not assume branding equals content. Compared dose-for-dose, 1 mg etizolam is commonly estimated around 10 mg diazepam in anxiolytic/sedative effect; individual response varies, so start low to avoid blackouts. Onset is relatively fast (roughly 10–40 minutes), and redosing during the come-up markedly increases the risk of amnesia, disinhibition, accidents, and respiratory depression, especially if other depressants are onboard. As a CYP3A4 substrate, etizolam’s levels can be increased by potent CYP3A4 inhibitors (e.g., some azole antifungals, macrolide antibiotics, fluvoxamine) and reduced by inducers (e.g., carbamazepine); this can unpredictably strengthen or weaken effects. Mixing with opioids, alcohol, GHB/GBL, or Z‑drugs greatly raises overdose risk (compounded sedation, hypoventilation, aspiration); avoid concurrent use and seek help immediately if someone cannot be roused or breathes slowly or irregularly. In several drug checking datasets, benzo-adulterants, including etizolam, appear in expected-fentanyl samples—be vigilant if using opioids, as combined depressants drive severe poisonings. Withdrawal after sustained or high-dose use can produce severe rebound anxiety, insomnia, tremor, and seizures; never abruptly stop after regular use—medical supervision and gradual tapering are strongly advised. Driving or operating machinery is unsafe while under the influence and can remain unsafe the next morning because of residual sedation and psychomotor impairment. Volumetric dosing (diluting a known small mass into a measured volume) reduces dosing error with powders/solutions; avoid eyeballing or 'drops' from unknown-concentration liquids. Intranasal and especially injection routes are discouraged due to poor solubility, binders, infection risk, and unpredictable kinetics—oral or sublingual are the least risky non-medical routes. Packaging and appearance are unreliable indicators of content; use reagent tests and, where available, GC/MS drug checking to verify. Store powders/solutions cool, dry, and protected from light to limit degradation, and keep all benzodiazepines secured to prevent accidental pediatric/naïve exposure.
References
Data Sources
Cited References
- Busardo et al. (2019) - Etizolam safety and psychomotor effects
- DrugBank: Etizolam
- Drug Users Bible: Etizolam
- Fracasso et al. (1991) - Pharmacokinetics of etizolam
- Nielsen & McAuley (2020) - Etizolam pharmacology and harms
- Sanna et al. (2005) - Low tolerance liability of etizolam
- TripSit: Combination Chart
- TripSit Factsheet: Etizolam
- WHO Expert Committee on Drug Dependence - Etizolam Review
- DrugWise: Etizolam Factsheet
- Drug-Do: Benzos
Drugs.wiki References
- Erowid Etizolam Vault (brand names; background)
- Saferparty Zürich: Etizolam (dose, onset, duration, risks, mixing cautions, brand examples)
- DrugWise: Etizolam overview (equivalence, UK context)
- DrugWise: Benzodiazepines (dependence, withdrawal, impairment)
- DrugBank: Etizolam metabolic reaction (alpha-hydroxyetizolam active metabolite)
- DrugBank (Etizolam categories include CYP3A/CYP3A4 substrate)
- Drugs-Forum Wiki: Etizolam (PK notes; metabolite half-life; ROA considerations)
- EUDA/EMCDDA: New benzodiazepines in Europe – review (counterfeits; polydrug risk)
- EUDA/EMCDDA news: Designer benzodiazepines risks (incl. etizolam)
- Toronto Drug Checking Service (reports showing etizolam in fentanyl samples, combined depressant risk)