Diclazepam
Studies and references cited across this article, graded by evidence strength.
Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.
Data points an editor reviewed and accepted for publication.
Value Provenance
Dosing
oraltrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Threshold | 0.5 mg | 0.5 mg | medium |
| Low | 0.5–1 mg | 0.5–1 mg | medium |
| Common | 1–3 mg | 1–3 mg | medium |
| Strong | 3–4 mg | 3–4 mg | medium |
| Heavy | 4+ mg | 4+ mg | medium |
| Editorial | Seed data values (community consensus) corroborated by Abouchedid et al. 2018 which reports recreational range of 1-2.5 mg, consistent with common-to-strong range. No controlled dose-finding study exists. Tablet content variability (0.59-1.39 mg per declared 1 mg) adds dosing uncertainty. All values are safety-critical community consensus, not clinical data. | ||
ReasoningReasoningSeed data values (community consensus) corroborated by Abouchedid et al. 2018 which reports recreational range of 1-2.5 mg, consistent with common-to-strong range. No controlled dose-finding study exists. Tablet content variability (0.59-1.39 mg per declared 1 mg) adds dosing uncertainty. All values are safety-critical community consensus, not clinical data. Evidence basis: community_consensus_large | |||
Duration
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 10–45 minutes | 10–45 minutes | medium |
| Editorial | Seed data value (10-45 minutes). Consistent with benzodiazepine class oral onset. No controlled timing study exists for diclazepam. | ||
ReasoningReasoningSeed data value (10-45 minutes). Consistent with benzodiazepine class oral onset. No controlled timing study exists for diclazepam. Evidence basis: community_consensus_large | |||
| Come uptrace | 15–45 minutes | 15–45 minutes | low |
| Editorial | No diclazepam-specific data. Inferred from benzodiazepine class pharmacology and structural analogy with diazepam. Widened range to account for uncertainty. | ||
ReasoningReasoningNo diclazepam-specific data. Inferred from benzodiazepine class pharmacology and structural analogy with diazepam. Widened range to account for uncertainty. Evidence basis: structural_analogy | |||
| Peaktrace | 2–4 hours | 2–4 hours | low |
| Editorial | No diclazepam-specific data. Inferred from BZD class and long half-life (~42h). Diazepam peak typically 1-2 hours; extended for diclazepam given longer half-life and community reports of broader peak. | ||
ReasoningReasoningNo diclazepam-specific data. Inferred from BZD class and long half-life (~42h). Diazepam peak typically 1-2 hours; extended for diclazepam given longer half-life and community reports of broader peak. Evidence basis: structural_analogy | |||
| Offsettrace | 3–6 hours | 3–6 hours | low |
| Editorial | No diclazepam-specific data. Inferred from BZD class and long parent half-life (~42h). Extended offset reflects slow elimination kinetics. | ||
ReasoningReasoningNo diclazepam-specific data. Inferred from BZD class and long parent half-life (~42h). Extended offset reflects slow elimination kinetics. Evidence basis: structural_analogy | |||
| Totaltrace | 8–12 hours | 8–12 hours | medium |
| Editorial | Seed data value (8-12 hours). Represents subjective experience duration, NOT pharmacological half-life. Active metabolites persist far longer but this captures the user-perceived effect window. | ||
ReasoningReasoningSeed data value (8-12 hours). Represents subjective experience duration, NOT pharmacological half-life. Active metabolites persist far longer but this captures the user-perceived effect window. Evidence basis: community_consensus_large | |||
| After effectstrace | 12–48 hours | 12–48 hours | low |
| Editorial | No diclazepam-specific aftereffects data. Inferred from ~42h parent half-life and active metabolites (delorazepam t½ potentially >100h, lorazepam detectable up to 19 days in urine). Residual impairment persists well beyond subjective effect window per Moosmann 2014. | ||
ReasoningReasoningNo diclazepam-specific aftereffects data. Inferred from ~42h parent half-life and active metabolites (delorazepam t½ potentially >100h, lorazepam detectable up to 19 days in urine). Residual impairment persists well beyond subjective effect window per Moosmann 2014. Evidence basis: structural_analogy | |||
Safety
Toxicity Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Acute | moderate | moderate | low |
| Chronic | moderate | moderate | low |
| Organs Affected | pulmonary, neurological | pulmonary, neurological | low |
| Editorial | Work-notes resolve seed data contradiction (low toxicity note vs high/high ratings) to moderate/moderate based on evidence: monotherapy appears survivable but compound carries real respiratory depression risk. All fatality evidence is polydrug (Partridge 2018, Lehmann 2019). No substance-specific toxicological study exists. Evidence class is case series with structural analogy to diazepam. | ||
ReasoningReasoningWork-notes resolve seed data contradiction (low toxicity note vs high/high ratings) to moderate/moderate based on evidence: monotherapy appears survivable but compound carries real respiratory depression risk. All fatality evidence is polydrug (Partridge 2018, Lehmann 2019). No substance-specific toxicological study exists. Evidence class is case series with structural analogy to diazepam. Evidence basis: published_case_series | |||
Dependence Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Physical | high | high | medium |
| Psychological | high | high | medium |
| Compulsive Redosing | moderate | moderate | medium |
| Dose Escalation | moderate | moderate | medium |
| Editorial | Physical/psychological dependence rated high per work-notes, consistent with benzodiazepine class profile and rodent self-administration data (Lee et al. 2024). Compulsive redosing moderate due to half-life mismatch between perceived and actual duration. No human dependence studies specific to diclazepam; class extrapolation confirmed by rodent behavioral data. | ||
ReasoningReasoningPhysical/psychological dependence rated high per work-notes, consistent with benzodiazepine class profile and rodent self-administration data (Lee et al. 2024). Compulsive redosing moderate due to half-life mismatch between perceived and actual duration. No human dependence studies specific to diclazepam; class extrapolation confirmed by rodent behavioral data. Evidence basis: animal_study | |||
Withdrawal Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Severity | life_threatening | life_threatening | medium |
| Symptoms | rebound anxiety, insomnia, tremor, depersonalization, seizures, psychosis | rebound anxiety, insomnia, tremor, depersonalization, seizures, psychosis | medium |
| Fatal | Yes | Yes | medium |
| Medical Supervision | Required | Required | medium |
| Editorial | Benzodiazepine withdrawal is established as potentially life-threatening (seizures). Onset 1-3 days for long-acting BZDs, duration weeks to months with protracted withdrawal syndrome possible. All values are class-level — no diclazepam-specific withdrawal data exist. Long half-life of diclazepam and delorazepam metabolite may delay withdrawal onset relative to shorter-acting BZDs. | ||
ReasoningReasoningBenzodiazepine withdrawal is established as potentially life-threatening (seizures). Onset 1-3 days for long-acting BZDs, duration weeks to months with protracted withdrawal syndrome possible. All values are class-level — no diclazepam-specific withdrawal data exist. Long half-life of diclazepam and delorazepam metabolite may delay withdrawal onset relative to shorter-acting BZDs. Evidence basis: animal_study | |||
Tolerance Profiletrace
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Buildup | moderate | moderate | low |
| Half-life | 42 hours | 42 hours | low |
| Full Reset | 10.5 days | 10.5 days | low |
| Cross-tolerances | benzodiazepines, alcohol, barbiturates, zolpidem, zopiclone, zaleplon | benzodiazepines, alcohol, barbiturates, zolpidem, zopiclone, zaleplon | low |
| Editorial | Work-notes specify moderate buildup, 10.5-day full reset from seed/community consensus. Mechanism well-established at class level (Engin 2022). Half-life from Moosmann 2014 N=1 self-experiment. No diclazepam-specific tolerance timeline studies exist — values are community consensus extrapolated from general BZD pharmacology. | ||
ReasoningReasoningWork-notes specify moderate buildup, 10.5-day full reset from seed/community consensus. Mechanism well-established at class level (Engin 2022). Half-life from Moosmann 2014 N=1 self-experiment. No diclazepam-specific tolerance timeline studies exist — values are community consensus extrapolated from general BZD pharmacology. Evidence basis: community_consensus_large | |||
Effects & Profile
Contraindications
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| respiratory Concurrent opioid usetrace | absolute | absolute | high |
| Editorial | Documented fatalities in polydrug contexts with opioids; pharmacodynamic and metabolic interaction confirmed by Lawson et al. 2023. | ||
ReasoningReasoningDocumented fatalities in polydrug contexts with opioids; pharmacodynamic and metabolic interaction confirmed by Lawson et al. 2023. | |||
| respiratory Severe respiratory insufficiencytrace | absolute | absolute | high |
| Editorial | Class-level benzodiazepine contraindication; respiratory depression is the primary lethal mechanism in benzodiazepine toxicity. | ||
ReasoningReasoningClass-level benzodiazepine contraindication; respiratory depression is the primary lethal mechanism in benzodiazepine toxicity. | |||
| other Acute alcohol intoxicationtrace | absolute | absolute | high |
| Editorial | Class-level benzodiazepine contraindication; shared GABA-A potentiation mechanism with alcohol is well-established. | ||
ReasoningReasoningClass-level benzodiazepine contraindication; shared GABA-A potentiation mechanism with alcohol is well-established. | |||
| immunological Known benzodiazepine hypersensitivitytrace | absolute | absolute | high |
| Editorial | Standard pharmaceutical contraindication for any drug class with documented hypersensitivity reactions. | ||
ReasoningReasoningStandard pharmaceutical contraindication for any drug class with documented hypersensitivity reactions. | |||
| hepatic Hepatic impairmenttrace | relative | relative | medium |
| Editorial | Class-level benzodiazepine contraindication; CYP metabolism pathway inferred from structural analogy with diazepam. No diclazepam-specific hepatic impairment data. | ||
ReasoningReasoningClass-level benzodiazepine contraindication; CYP metabolism pathway inferred from structural analogy with diazepam. No diclazepam-specific hepatic impairment data. | |||
| psychiatric History of substance use disordertrace | relative | relative | medium |
| Editorial | Reinforcing properties confirmed in rodent models (Lee et al. 2024); high self-medication use documented in user communities (Abouchedid et al. 2018). | ||
ReasoningReasoningReinforcing properties confirmed in rodent models (Lee et al. 2024); high self-medication use documented in user communities (Abouchedid et al. 2018). | |||
| pregnancy breastfeeding Pregnancytrace | relative | relative | medium |
| Editorial | Class-level benzodiazepine contraindication via structural analogy. No diclazepam-specific reproductive data. | ||
ReasoningReasoningClass-level benzodiazepine contraindication via structural analogy. No diclazepam-specific reproductive data. | |||
| neurological Myasthenia gravistrace | relative | relative | medium |
| Editorial | Class-level benzodiazepine contraindication; muscle relaxation is a confirmed effect of diclazepam from user reports and class pharmacology. | ||
ReasoningReasoningClass-level benzodiazepine contraindication; muscle relaxation is a confirmed effect of diclazepam from user reports and class pharmacology. | |||
| respiratory Sleep apneatrace | relative | relative | medium |
| Editorial | Class-level benzodiazepine contraindication via structural analogy. No diclazepam-specific sleep apnea data. | ||
ReasoningReasoningClass-level benzodiazepine contraindication via structural analogy. No diclazepam-specific sleep apnea data. | |||
Timeline Phases
oral
| Field | Published | AI Proposed | Confidence |
|---|---|---|---|
| Onsettrace | 600–2700 sec(i=0.15) | 600–2700 sec(i=0.15) | low |
| Editorial | Onset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. | ||
ReasoningReasoningOnset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. Evidence basis: community_consensus_large | |||
| Come uptrace | 900–2700 sec(i=0.40) | 900–2700 sec(i=0.40) | low |
| Editorial | Onset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. | ||
ReasoningReasoningOnset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. Evidence basis: community_consensus_large | |||
| Peaktrace | 7200–14400 sec(i=1.00) | 7200–14400 sec(i=1.00) | low |
| Editorial | Onset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. | ||
ReasoningReasoningOnset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. Evidence basis: community_consensus_large | |||
| Plateautrace | 10800–21600 sec(i=0.50) | 10800–21600 sec(i=0.50) | low |
| Editorial | Onset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. | ||
ReasoningReasoningOnset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. Evidence basis: community_consensus_large | |||
| Afterglowtrace | 43200–172800 sec(i=0.15) | 43200–172800 sec(i=0.15) | low |
| Editorial | Onset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. | ||
ReasoningReasoningOnset and total duration from seed data (community consensus). Come_up, peak, and offset (mapped to plateau here) phases inferred from structural analogy with diazepam and general long-acting benzodiazepine pharmacology. Afterglow duration reflects active metabolite persistence (delorazepam t½ potentially >100h) from Moosmann 2014. No controlled human pharmacokinetic timing study exists for diclazepam beyond N=1. Evidence basis: community_consensus_large | |||
Dose Tier Summaries
Barely perceptible anxiolysis at 0.5 mg oral. A subtle reduction in baseline anxiety emerges without overt sedation or cognitive impairment. Most users report minimal awareness of drug effects at this level — a slight loosening of tension that could easily be attributed to placebo. Physical effects are negligible. No meaningful muscle relaxation, motor impairment, or sedation is expected. The body feels essentially unchanged. Active metabolites (delorazepam, lorazepam, lormetazepam) will persist in the body far longer than any perceived effect at this dose. Tablet content variability (0.59–1.39 mg per declared 1 mg tablet) means even a "half tablet" may deliver an unpredictable dose.
Work-notes threshold summary expanded with substance-specific metabolite and tablet variability context from research output (Moosmann 2014, Abouchedid 2018). Dose from seed data community consensus.
ReasoningReasoning
Work-notes threshold summary expanded with substance-specific metabolite and tablet variability context from research output (Moosmann 2014, Abouchedid 2018). Dose from seed data community consensus.
Evidence basis: community_consensus_large
Mild anxiety suppression and slight muscle relaxation at 0.5–1 mg. Functional capacity is largely preserved. Some users report improved social ease and a general sense of calm without feeling intoxicated. Sedation is minimal unless the user is already sleep-deprived. Physical effects include gentle muscle relaxation and mild bodily heaviness. Motor coordination remains largely intact. No significant respiratory effects at this dose range. The slow onset (10–45 minutes) may tempt redosing before full effects establish. Delusions of sobriety can begin even at this level — users may not recognize subtle cognitive slowing that is apparent to observers.
Work-notes light tier expanded with onset timing from seed data and delusions-of-sobriety warning from Phase 1 effects assessment. Community consensus dose ranges.
ReasoningReasoning
Work-notes light tier expanded with onset timing from seed data and delusions-of-sobriety warning from Phase 1 effects assessment. Community consensus dose ranges.
Evidence basis: community_consensus_large
Clear anxiety suppression and moderate sedation at 1–3 mg. The anxiolytic effect is now unambiguous — worry and tension dissolve noticeably. Thought deceleration becomes apparent: information processing slows, and concentration narrows. Emotional suppression flattens both positive and negative affect. Some anterograde amnesia is possible at the upper end of this range. Muscle relaxation becomes pronounced. Motor control impairment is mild but measurable — fine motor tasks and balance are affected. Sedation may produce drowsiness, especially in the evening. Dizziness is possible. Disinhibition and delusions of sobriety are significant risks at common doses. Users may believe themselves fully functional while exhibiting slurred speech, impaired judgment, and ataxia visible to others. The 8–12 hour subjective duration understates true pharmacological exposure due to active metabolites persisting for days.
Work-notes common tier expanded with effects profile details (amnesia, disinhibition, delusions of sobriety) from Phase 1 assessment. Metabolite persistence from Moosmann 2014.
ReasoningReasoning
Work-notes common tier expanded with effects profile details (amnesia, disinhibition, delusions of sobriety) from Phase 1 assessment. Metabolite persistence from Moosmann 2014.
Evidence basis: community_consensus_large
Pronounced sedation and substantial anxiety suppression at 3–4 mg. Cognitive slowing is now dominant — thought deceleration, analysis suppression, and thought disorganization are all apparent. Anterograde amnesia is likely: events during this period may not be encoded into long-term memory. Emotional suppression is marked. Significant motor control impairment makes walking unsteady and fine motor tasks difficult. Muscle relaxation is deep. Sleep induction is common, particularly if the user is reclined or in a quiet environment. Respiratory depression remains mild in healthy individuals at this dose but risk increases with any co-intoxicant. Disinhibition and delusions of sobriety become prominent hazards. Users may engage in compulsive redosing, unaware they are already heavily impaired. Blackout behavior — acting without subsequent memory — is a documented risk at strong benzodiazepine doses.
Work-notes strong tier expanded with amnesia, disinhibition, and compulsive redosing detail from Phase 1 effects and safety sections. Respiratory depression context from article prose.
ReasoningReasoning
Work-notes strong tier expanded with amnesia, disinhibition, and compulsive redosing detail from Phase 1 effects and safety sections. Respiratory depression context from article prose.
Evidence basis: community_consensus_large
Overwhelming sedation at 4+ mg. Dense anterograde amnesia is expected — hours or entire days may be lost from memory. Cognitive function is severely impaired: thought disorganization, confusion, and complete analysis suppression dominate. Communication becomes slurred and incoherent. Severe motor impairment makes standing and walking hazardous. Respiratory depression risk increases substantially, especially with any co-intoxicant — all published diclazepam-associated fatalities involve polydrug combinations at elevated doses. Muscle relaxation is maximal. Blackout behavior is the defining risk at heavy doses. Users may make phone calls, drive vehicles, or engage in other complex activities with zero subsequent recall. Active metabolites (delorazepam t½ potentially >100 hours) mean pharmacological impairment persists for days after a single heavy dose. Do not drive or operate machinery for at least 48 hours after ingestion at this level.
Work-notes heavy tier expanded with blackout behavior, polydrug fatality context from research output (Partridge 2018, Lehmann 2019), and metabolite duration from Moosmann 2014.
ReasoningReasoning
Work-notes heavy tier expanded with blackout behavior, polydrug fatality context from research output (Partridge 2018, Lehmann 2019), and metabolite duration from Moosmann 2014.
Evidence basis: community_consensus_large
History
backfill Jun 4, 2026
Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.
Sources
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- [3]strongDesigner drugs: mechanism of action and adverse effectsLuethi D, Liechti ME · 2020 · Archives of Toxicology
- [4]moderateCharacterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics.Moosmann B, Bisel P, Auwärter V · 2014 · Drug Testing and Analysis
- [5]moderateDiscriminative stimulus and reinforcing effects of diclazepam in rodents.Lee W, Lee JW, Kim S, Kim JM, Youn DH, Park SH, Kwon CH, Choi SO · 2024 · Pharmacology, Biochemistry, and Behavior
- [6]moderateDesigner Benzodiazepines: A Review of Published Data and Public Health SignificanceGreenblatt HK, Greenblatt DJ · 2019 · Clinical Pharmacology in Drug Development
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- [9]weakCouncil Decision (EU) 2024/832 of 4 March 2024 - EU scheduling of diclazepamCouncil of the European Union · 2024linkno claims checked
- [10]weakFederal Register: Schedules of Controlled Substances: Placement of Clonazolam, Diclazepam, Etizolam, Flualprazolam, and Flubromazolam in Schedule I of the Controlled Substances ActDEA · 2026linkno claims checked
- [11]moderateCharacterization and in vitro phase I microsomal metabolism of designer benzodiazepines: An update comprising flunitrazolam, norflurazepam, and 4'-chlorodiazepam (Ro5-4864)Moosmann B, Bisel P, Westphal F, Wilde M, Kempf J, Angerer V, Auwärter V · 2019 · Drug Testing and Analysis
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- [14]moderateThe Psychonauts' Benzodiazepines; Quantitative Structure-Activity Relationship (QSAR) Analysis and Docking Prediction of Their Biological Activity.Catalani V, Botha M, Corkery JM, Guirguis A, Vento A, Scherbaum N, Schifano F · 2021 · Pharmaceuticals
- [15]moderateThe blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepinesManchester KR, Waters L, Haider S, Maskell PD · 2022 · Forensic Toxicology
- [16]strongGABA-A receptor subtypes and benzodiazepine use, misuse, and abuseEngin E · 2022 · Frontiers in Psychiatry
- [17]weakOrgan distribution of diclazepam, pyrazolam and 3-fluorophenmetrazineLehmann S, Sczyslo A, Froch-Cortis J, Rothschild MA, Thevis M, Andresen-Streichert H, Mercer-Chalmers-Bender K · 2019 · Forensic Science International
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- [19]moderateDetectability of designer benzodiazepines in CEDIA, EMIT II Plus, HEIA, and KIMS II immunochemical screening assaysPettersson Bergstrand M, Helander A, Hansson T, Beck O · 2017 · Drug Testing and Analysis
- [20]moderateValidation of an LC-MS/MS Method for the Quantification of 13 Designer Benzodiazepines in Blood.Mei V, Concheiro M, Pardi J, Cooper G · 2019 · Journal of Analytical Toxicology
- [21]moderateUrine analysis of 28 designer benzodiazepines by liquid chromatography-high-resolution mass spectrometryPettersson Bergstrand M, Beck O, Helander A · 2018 · Clinical Mass Spectrometry
- [22]moderateFast and Sensitive Method for the Determination of 17 Designer Benzodiazepines in Hair by Liquid Chromatography-Tandem Mass SpectrometryDeFreitas L, Fonseca Pego AM, Kronstrand R, Lendoiro E, de Castro-Rios A, Concheiro M · 2022 · Journal of Analytical Toxicology
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- [24]weakOverdose from designer benzodiazepine Diclazepam.Runnstrom M, Kalra SS, Lascano J, Patel DC · 2020 · QJM: Monthly Journal of the Association of Physicians
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- [26]strongClinical Management of Designer Benzodiazepine Intoxication: A Systematic Review.Noe G, McDuffee N, Li K, Munjal S · 2025 · Journal of Clinical Psychopharmacology
- [27]moderateProbe Electrospray Ionization Tandem Mass Spectrometry for the Detection and Quantification of BenzodiazepinesGriffeuille P, El Balkhi S, Dulaurent S, Saint-Marcoux F · 2024 · Therapeutic Drug Monitoring
- [28]moderateBenzodiazepines and Related Sedatives.Peng L, Morford KL, Levander XA · 2022 · Medical Clinics of North America
- [29]weakChallenges of Diagnosing and Managing Designer Benzodiazepine Dependence and Withdrawal: A Case Report.Peng L, Lawrence D, Levander XA · 2021 · Journal of Addiction Medicine
- [30]weakDesigner benzodiazepine dependence and the difficulties of outpatient management; a case report.Reeves JJ, Brown AD, Collier BS · 2024 · Journal of Addictive Diseases
- [31]moderateFlumazenil: a benzodiazepine antagonist.Hoffman EJ, Warren EW · 1993 · Clinical pharmacypubmed 83065651 claim checked1 verified
- [32]weakFederal Register: Schedules of Controlled Substances: Temporary Placement of Etizolam, Flualprazolam, Clonazolam, Flubromazolam, and Diclazepam in Schedule IDEA · 2022linkno claims checked
Claim Verification
Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.
summary8 claims5verified3inconclusive
verifiedDiclazepam (7-chloro-5-(2-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one, also 2-chlorodiazepam, chlorodiazepam) is a 1,4-benzodiazepine derivative and positive allosteric modulator of the GABA-A receptor[2]model confidence 85%
The comprehensive review covers pharmacodynamics of designer benzodiazepines including diclazepam. GABA-A PAM activity is within the stated scope of pharmacodynamics.
Comprehensive review of designer benzodiazepines including diclazepam — pharmacokinetics, pharmacodynamics, analytical approaches, history, and market context.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedIt differs from diazepam by a single chlorine substitution at the 2′-position of the pendant phenyl ring — a modification yielding substantially altered pharmacological activity despite minimal structural distance[1]model confidence 97%
Abstract directly states diclazepam differs from diazepam by addition of one chlorine atom at the 2-chloro position, resulting in substantial activity differences.
Notes diclazepam differs from diazepam by addition of one chlorine atom (2-chloro position), resulting in substantial activity differences.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveSynthesized at Hoffmann-La Roche circa 1960 as compound Ro 5-3448 during systematic benzodiazepine structure-activity exploration, diclazepam was never advanced to clinical development and has never been marketed as a pharmaceutical[4]model confidence 65%
Abstract confirms the Ro 5-3448 designation and 2012 research-chemical market appearance (implying no pharmaceutical history), but does not explicitly state Hoffmann-La Roche, circa 1960, or never advanced to clinical development. These details are likely in the full text.
Diclazepam (other names: 2-chlorodiazepam, Ro 5-3448 or 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one) emerged as a new compound in this class of drugs.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveSynthesized at Hoffmann-La Roche circa 1960 as compound Ro 5-3448 during systematic benzodiazepine structure-activity exploration, diclazepam was never advanced to clinical development and has never been marketed as a pharmaceutical[2]model confidence 60%
Review scope includes market history and structure-activity relationships, so the historical claims may be covered, but the abstract itself does not confirm Hoffmann-La Roche, circa 1960, or clinical development status.
Comprehensive review of designer benzodiazepines including diclazepam — pharmacokinetics, pharmacodynamics, analytical approaches, history, and market context.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedAs a classical benzodiazepine, diclazepam potentiates GABA-mediated chloride conductance at the α/γ subunit interface of the GABA-A receptor without directly gating the channel[3]model confidence 80%
Abstract confirms benzodiazepines act as GABA-A positive allosteric modulators, which is consistent with the claim. The chloride conductance and non-direct gating are properties of GABA-A PAMs that the review covers under mechanism of action.
Benzodiazepines act as GABA-A positive allosteric modulators.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedPublished fatalities involve exclusively polydrug combinations — typically with opioids or other CNS depressants[6]model confidence 95%
Abstract directly states mortality occurs almost exclusively in polysubstance contexts.
Mortality occurs almost exclusively in polysubstance contexts.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveAll three primary metabolites (delorazepam, lorazepam, lormetazepam) are pharmacologically active, creating cumulative CNS depression extending well beyond perceived effect duration[4]model confidence 60%
Abstract confirms the three metabolites by name but does not characterize them as pharmacologically active or discuss cumulative CNS depression extending beyond perceived effects. These details would be in the full text.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedReinforcing properties have been confirmed in rodent self-administration paradigms[5]model confidence 97%
Abstract directly confirms mice self-administering IV diclazepam showed significantly higher infusion and active lever responses versus vehicle.
Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
history8 claims3verified5inconclusive
inconclusiveAnalysis of tablets sold as 1 mg diclazepam revealed content ranging from 0.59 to 1.39 mg, indicating significant quality control failures in the unregulated supply.[8]model confidence 50%
Abstract covers UK internet availability, motivations, and legal status, but contains no data on tablet content analysis or the 0.59–1.39 mg range. This specific finding may be in the full text.
UK internet availability: 49 sites selling in Nov 2014, 55 by Mar 2016.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveDiclazepam was first synthesized by Leo Sternbach and colleagues at Hoffmann-La Roche circa 1960, as part of the systematic structure-activity relationship program that produced diazepam, chlordiazepoxide, and dozens of related 1,4-benzodiazepin-2-one analogs[4]model confidence 50%
Abstract confirms the Ro 5-3448 designation (a Roche internal compound number) and 2012 NPS market appearance, but does not mention Leo Sternbach, Hoffmann-La Roche, circa 1960, or the SAR program that produced diazepam/chlordiazepoxide. These historical details would be in the full text.
Diclazepam (other names: 2-chlorodiazepam, Ro 5-3448).
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveDiclazepam was first synthesized by Leo Sternbach and colleagues at Hoffmann-La Roche circa 1960, as part of the systematic structure-activity relationship program that produced diazepam, chlordiazepoxide, and dozens of related 1,4-benzodiazepin-2-one analogs[2]model confidence 55%
Review scope includes market history and structure-activity relationships, making it plausible that Leo Sternbach/1960/SAR program details are covered, but the abstract does not confirm these specific historical claims.
Comprehensive review of designer benzodiazepines including diclazepam — pharmacokinetics, pharmacodynamics, analytical approaches, history, and market context.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThe compound was assigned the internal designation Ro 5-3448[4]model confidence 99%
Abstract directly lists Ro 5-3448 as an alternate name for diclazepam.
Diclazepam (other names: 2-chlorodiazepam, Ro 5-3448 or 7-chloro-5-(2-chlorophenyl)-1-methyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one).
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveDespite being patented alongside numerous analogs, diclazepam was never advanced through clinical development — no pharmacological characterization beyond the initial synthesis was published by Roche, and the compound was never marketed as a pharmaceutical product in any jurisdiction.[2]model confidence 55%
Review scope includes history and market context, potentially covering these claims. However, the abstract does not confirm patenting, lack of clinical development, or absence of pharmaceutical marketing.
Comprehensive review of designer benzodiazepines including diclazepam — pharmacokinetics, pharmacodynamics, analytical approaches, history, and market context.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedDiclazepam first appeared on online research chemical vendor sites in 2012, constituting one of the earliest designer benzodiazepines to enter the NPS market[4]model confidence 97%
Abstract directly states designer benzodiazepines were first offered in online shops selling 'research chemicals' in 2012.
Designer benzodiazepines, first offered in online shops selling 'research chemicals' in 2012.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThe broader designer benzodiazepine phenomenon emerged between approximately 2007 and 2012, with diclazepam among the first wave.[7]model confidence 92%
Abstract directly states first designer BZDs appeared as NPS around 2007, with 29 designer BZDs subsequently notified to EMCDDA — consistent with the 2007–2012 emergence claim.
First designer BZDs appeared as NPS around 2007. 29 designer BZDs notified to EMCDDA.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThe first scientific characterization was published in 2014 by Moosmann, Bisel, and Auwärter at the University of Freiburg, who performed NMR, GC-MS, and LC-MS/MS spectroscopic analysis alongside a self-experiment providing the only published human pharmacokinetic data.[4]model confidence 50%
This is the characterization paper itself, so the content is correct, but the abstract does not mention 2014, Moosmann/Bisel/Auwärter, University of Freiburg, NMR/GC-MS/LC-MS/MS methods, or the self-experiment methodology.
Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics.
checked by claude-sonnet-4-6 · May 9, 2026
chemistry2 claims2verified
verifiedDiclazepam is the 2′-chloro analog of diazepam: the two compounds share identical substitution at N-1 (methyl), C-5 (phenyl), and C-7 (chloro), differing only by the addition of a chlorine atom at the ortho position (2′) of the C-5 pendant phenyl ring[1]model confidence 92%
Abstract directly states diclazepam differs from diazepam by addition of one chlorine atom at the 2-chloro position, consistent with the structural claim.
Notes diclazepam differs from diazepam by addition of one chlorine atom (2-chloro position).
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThis single halogen addition produces measurably different pharmacological activity despite minimal structural modification.[1]model confidence 97%
Abstract directly states the addition of one chlorine atom results in substantial activity differences.
Notes diclazepam differs from diazepam by addition of one chlorine atom (2-chloro position), resulting in substantial activity differences.
checked by claude-sonnet-4-6 · May 9, 2026
pharmacology10 claims5verified5inconclusive
inconclusiveDiclazepam is a positive allosteric modulator (PAM) of the γ-aminobutyric acid type A (GABA-A) receptor, binding at the classical benzodiazepine site located at the interface between α and γ₂ subunits[2]model confidence 65%
Review covers pharmacodynamics of designer benzodiazepines, but the abstract does not specifically confirm the α/γ₂ subunit interface binding site. This level of mechanistic detail may be in the full review.
Comprehensive review of designer benzodiazepines including diclazepam — pharmacokinetics, pharmacodynamics, analytical approaches, history, and market context.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveDiclazepam is a positive allosteric modulator (PAM) of the γ-aminobutyric acid type A (GABA-A) receptor, binding at the classical benzodiazepine site located at the interface between α and γ₂ subunits[3]model confidence 65%
Abstract confirms benzodiazepines are GABA-A PAMs, but the specific α/γ₂ subunit interface is not mentioned. The mechanism of action section likely covers this in the full text.
Benzodiazepines act as GABA-A positive allosteric modulators.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedNo published radioligand competition binding studies (Ki values) or functional efficacy measurements (EC50) for diclazepam at individual GABA-A receptor subunit configurations (α1β2γ2, α2β3γ2, α3β3γ2, α5β3γ2) have been identified. Pharmacodynamic potency is inferred from computational approaches: Waters and colleagues applied quantitative structure-activity relationship models predicting GABA-A binding affinity consistent with potent benzodiazepine activity, Manchester and colleagues generated predicted binding affinity and blood-to-plasma ratio data, and Catalani and colleagues docked 101 designer benzodiazepines against crystallized GABA-A receptor structures (PDB: 6HUO, 6HUP), finding 41% exhibited high predicted biological activity; diclazepam's structural features — the halogen at R7 and electronegative 2′-chlorophenyl — are consistent with high affinity at the benzodiazepine site.[13]model confidence 90%
Abstract directly describes the Waters QSAR model for GABA-A binding affinity of NPS benzodiazepines, supporting the relevant portion of this compound claim.
QSAR model predicting GABA-A receptor binding affinity of NPS benzodiazepines.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedNo published radioligand competition binding studies (Ki values) or functional efficacy measurements (EC50) for diclazepam at individual GABA-A receptor subunit configurations (α1β2γ2, α2β3γ2, α3β3γ2, α5β3γ2) have been identified. Pharmacodynamic potency is inferred from computational approaches: Waters and colleagues applied quantitative structure-activity relationship models predicting GABA-A binding affinity consistent with potent benzodiazepine activity, Manchester and colleagues generated predicted binding affinity and blood-to-plasma ratio data, and Catalani and colleagues docked 101 designer benzodiazepines against crystallized GABA-A receptor structures (PDB: 6HUO, 6HUP), finding 41% exhibited high predicted biological activity; diclazepam's structural features — the halogen at R7 and electronegative 2′-chlorophenyl — are consistent with high affinity at the benzodiazepine site.[15]model confidence 90%
Abstract directly confirms the Manchester blood-to-plasma ratio and QSAR-predicted GABA-A binding affinity study for multiple designer BZDs including diclazepam.
QSAR-modelled GABA-A receptor binding affinity and blood-to-plasma ratio for multiple designer BZDs including diclazepam.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedNo published radioligand competition binding studies (Ki values) or functional efficacy measurements (EC50) for diclazepam at individual GABA-A receptor subunit configurations (α1β2γ2, α2β3γ2, α3β3γ2, α5β3γ2) have been identified. Pharmacodynamic potency is inferred from computational approaches: Waters and colleagues applied quantitative structure-activity relationship models predicting GABA-A binding affinity consistent with potent benzodiazepine activity, Manchester and colleagues generated predicted binding affinity and blood-to-plasma ratio data, and Catalani and colleagues docked 101 designer benzodiazepines against crystallized GABA-A receptor structures (PDB: 6HUO, 6HUP), finding 41% exhibited high predicted biological activity; diclazepam's structural features — the halogen at R7 and electronegative 2′-chlorophenyl — are consistent with high affinity at the benzodiazepine site.[14]model confidence 95%
Abstract directly confirms 101 designer BZDs, 41% with high predicted biological activity, and GABA-A receptor structures 6HUO and 6HUP — precisely matching the Catalani portion of the compound claim.
QSAR and molecular docking study of 101 designer BZDs. High biological activity predicted for 41% of compounds. Binding affinity at GABA-A receptors (6HUO, 6HUP) evaluated by docking.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedNo published radioligand competition binding studies (Ki values) or functional efficacy measurements (EC50) for diclazepam at individual GABA-A receptor subunit configurations (α1β2γ2, α2β3γ2, α3β3γ2, α5β3γ2) have been identified. Pharmacodynamic potency is inferred from computational approaches: Waters and colleagues applied quantitative structure-activity relationship models predicting GABA-A binding affinity consistent with potent benzodiazepine activity, Manchester and colleagues generated predicted binding affinity and blood-to-plasma ratio data, and Catalani and colleagues docked 101 designer benzodiazepines against crystallized GABA-A receptor structures (PDB: 6HUO, 6HUP), finding 41% exhibited high predicted biological activity; diclazepam's structural features — the halogen at R7 and electronegative 2′-chlorophenyl — are consistent with high affinity at the benzodiazepine site.[6]model confidence 92%
Abstract directly states 'No systematic pharmacodynamic or receptor binding data exists for designer BZDs,' directly supporting the claim that no published radioligand binding studies have been identified.
No systematic pharmacodynamic or receptor binding data exists for designer BZDs.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThe elimination half-life is approximately 42 hours, derived from a single self-experiment in which one researcher ingested a 1 mg oral tablet and provided serum and urine samples over 14 and 21 days respectively[4]model confidence 60%
Abstract confirms the ~42h half-life figure, but the specific study design details — single self-experiment, 1 mg oral tablet, 14-day serum and 21-day urine sampling — are not in the abstract. These are likely in the full text.
Approximate elimination half-life of 42 h.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedAn independent review cites the estimate at approximately 46 hours; the discrepancy reflects measurement variability within the same N=1 dataset.[6]model confidence 88%
Abstract directly states 'Diclazepam estimated half-life 46 hours,' confirming the independent review's figure. The interpretive conclusion about N=1 variability is reasonable synthesis.
Diclazepam estimated half-life 46 hours.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThree pharmacologically active metabolites have been identified in vivo: delorazepam (the primary and highest-concentration metabolite, itself a long-acting benzodiazepine), lorazepam, and lormetazepam[4]model confidence 55%
Abstract confirms the three metabolites by name but does not characterize delorazepam as the primary or highest-concentration metabolite, nor describe any of them as pharmacologically active or long-acting.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThe parent compound was detectable in serum up to 99 hours post-intake; delorazepam in serum up to 10 days; lorazepam in urine up to 19 days; and lormetazepam in urine up to 11 days.[4]model confidence 50%
Abstract confirms the existence of these metabolites but contains no detection window data. Specific detection timelines would be in the full text of this characterization study.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
receptor pharmacology5 claims5verified
verifiedAlpha-1-containing receptors appear integral to benzodiazepine-induced plasticity in reward circuits and to tolerance and dependence development.[16]model confidence 97%
Abstract directly states 'Alpha-1-containing GABA-A receptors play key role in benzodiazepine-induced plasticity in reward circuits and tolerance/dependence development.'
Alpha-1-containing GABA-A receptors play key role in benzodiazepine-induced plasticity in reward circuits and tolerance/dependence development.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedQSAR modeling — Waters and colleagues developed a quantitative structure-activity relationship model for GABA-A binding affinity of emerging benzodiazepines, with predictions for diclazepam consistent with potent activity at the benzodiazepine site.[13]model confidence 90%
Abstract directly describes a QSAR model predicting GABA-A receptor binding affinity of NPS benzodiazepines, consistent with the claim.
QSAR model predicting GABA-A receptor binding affinity of NPS benzodiazepines.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedMolecular docking — Catalani and colleagues docked 101 designer benzodiazepines against crystallized GABA-A receptor structures (PDB: 6HUO and 6HUP) and found that 41% showed high predicted biological activity. Diclazepam's 7-chloro and 2′-chlorophenyl substitutions are structural features associated with high binding affinity at the classical benzodiazepine site.[14]model confidence 95%
Abstract directly confirms the study of 101 designer BZDs, 41% with high predicted biological activity, and GABA-A receptor structures 6HUO and 6HUP — all key numerical and methodological claims are confirmed.
QSAR and molecular docking study of 101 designer BZDs. High biological activity predicted for 41% of compounds. Binding affinity at GABA-A receptors (6HUO, 6HUP) evaluated by docking.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedBlood-to-plasma ratio and predicted affinity — Manchester and colleagues reported QSAR-predicted GABA-A binding affinity data alongside blood-to-plasma partitioning ratios for designer benzodiazepines including diclazepam.[15]model confidence 97%
Abstract directly confirms QSAR-modelled GABA-A receptor binding affinity and blood-to-plasma ratio for multiple designer BZDs including diclazepam.
QSAR-modelled GABA-A receptor binding affinity and blood-to-plasma ratio for multiple designer BZDs including diclazepam.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedLee and colleagues conducted the only published substance-specific pharmacological study of diclazepam in rodent models:[5]model confidence 88%
Abstract confirms this is a rodent pharmacological study of diclazepam covering discriminative stimulus and reinforcing effects.
Diclazepam fully elicited alprazolam-appropriate dose-dependent lever responses (>80%) similar to those of alprazolam. Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
neuroscience4 claims3verified1inconclusive
verifiedThis is consistent with the prominent anxiolytic motivation reported by diclazepam users (23.9% of coded forum motivations).[8]model confidence 97%
Abstract directly states anxiety relief was a motivation for 23.9% of users.
Motivations for use: anxiety relief 23.9%.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveMesolimbic dopaminergic reward pathway involvement in benzodiazepine reinforcement occurs via disinhibition: GABA-A receptor activation on GABAergic interneurons in the ventral tegmental area (VTA) reduces tonic inhibition of dopaminergic projection neurons, increasing dopamine release in the nucleus accumbens[16]model confidence 55%
Abstract confirms the review covers GABA-A subtypes and reward circuit plasticity, making it plausible this mechanism is discussed in the full text. However, the abstract does not specifically describe the VTA/nucleus accumbens/dopaminergic disinhibition mechanism.
Alpha-1-containing GABA-A receptors play key role in benzodiazepine-induced plasticity in reward circuits and tolerance/dependence development.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedAlpha-1-containing GABA-A receptors appear integral to benzodiazepine-induced plasticity in reward circuits.[16]model confidence 97%
Abstract directly states alpha-1-containing GABA-A receptors play a key role in benzodiazepine-induced plasticity in reward circuits.
Alpha-1-containing GABA-A receptors play key role in benzodiazepine-induced plasticity in reward circuits.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThe reinforcing properties of diclazepam, confirmed by self-administration but not by conditioned place preference, suggest the compound engages wanting (instrumental responding for drug access) more robustly than liking (hedonic conditioning)[5]model confidence 88%
Abstract directly confirms positive self-administration results alongside negative CPP findings, supporting the wanting-vs-liking interpretation as reasonable synthesis from the empirical data.
Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle. No significant rewarding effects in CPP paradigm.
checked by claude-sonnet-4-6 · May 9, 2026
pharmacokinetic detail10 claims4verified6inconclusive
inconclusiveThe sole published human pharmacokinetic data derive from a single-volunteer self-experiment by Moosmann and colleagues, in which one author ingested a single 1 mg oral tablet of diclazepam and provided serial serum and urine samples for 14 and 21 days respectively.[4]model confidence 55%
Abstract confirms this is the characterization paper providing preliminary PK data, but does not mention Moosmann, the single-volunteer self-experiment design, 1 mg dose, or 14/21-day sampling windows.
Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusive<div class="compact-kv"> <table> <tbody> <tr><td>Route</td><td>Oral (single 1 mg dose)</td></tr> <tr><td>Elimination half-life (parent)</td><td>~42 hours (cited as ~46 hours in independent review)</td></tr> <tr><td>Parent detection in serum</td><td>Up to 99 hours post-dose</td></tr> <tr><td>Delorazepam detection in serum</td><td>Up to 10 days post-dose</td></tr> <tr><td>Lorazepam detection in urine</td><td>Up to 19 days post-dose</td></tr> <tr><td>Lormetazepam detection in urine</td><td>Up to 11 days post-dose</td></tr> <tr><td>Oral bioavailability</td><td>Not published</td></tr> <tr><td>Tmax</td><td>Not published</td></tr> <tr><td>Protein binding</td><td>Not published</td></tr> <tr><td>Volume of distribution</td><td>Not published</td></tr> </tbody> </table> </div>[4]model confidence 55%
Abstract confirms ~42h half-life and the three metabolites, but specific detection window data (99h, 10 days, 19 days, 11 days) and route/dose details are not in the abstract. Full text required to verify the table entries.
Approximate elimination half-life of 42 h; metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusive<div class="compact-kv"> <table> <tbody> <tr><td>Route</td><td>Oral (single 1 mg dose)</td></tr> <tr><td>Elimination half-life (parent)</td><td>~42 hours (cited as ~46 hours in independent review)</td></tr> <tr><td>Parent detection in serum</td><td>Up to 99 hours post-dose</td></tr> <tr><td>Delorazepam detection in serum</td><td>Up to 10 days post-dose</td></tr> <tr><td>Lorazepam detection in urine</td><td>Up to 19 days post-dose</td></tr> <tr><td>Lormetazepam detection in urine</td><td>Up to 11 days post-dose</td></tr> <tr><td>Oral bioavailability</td><td>Not published</td></tr> <tr><td>Tmax</td><td>Not published</td></tr> <tr><td>Protein binding</td><td>Not published</td></tr> <tr><td>Volume of distribution</td><td>Not published</td></tr> </tbody> </table> </div>[6]model confidence 55%
Abstract confirms the 46h half-life estimate from this independent review, which is one table entry. Other specific detection window data are not in this abstract.
Diclazepam estimated half-life 46 hours.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedLawson and colleagues investigated metabolic interactions between diclazepam and oxycodone using ex vivo, in vivo, and in silico approaches, demonstrating both pharmacodynamic and metabolic interactions with direct clinical implications for polydrug overdose scenarios.[18]model confidence 90%
Abstract directly states it 'Investigates metabolic interactions between oxycodone, diazepam and diclazepam in abuse/overdose conditions through ex vivo, in vivo and in silico approaches,' matching all methodological claims.
Investigates metabolic interactions between oxycodone, diazepam and diclazepam in abuse/overdose conditions through ex vivo, in vivo and in silico approaches.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveHowever, at a single 1 mg oral dose, only one tested immunoassay detected intake, and only in high-creatinine urine specimens[4]model confidence 50%
Abstract does not mention immunoassay testing or creatinine. This specific finding would be in the full text of the characterization study.
Approximate elimination half-life of 42 h; metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThe three primary metabolites — delorazepam (N-demethylation), lorazepam (3-hydroxylation of delorazepam), and lormetazepam (3-hydroxylation of parent) — are all pharmacologically active benzodiazepines[4]model confidence 50%
Abstract confirms the three metabolites by name but does not describe their metabolic pathways (N-demethylation, 3-hydroxylation) or characterize them as pharmacologically active. These details are in the full text.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedPostmortem organ distribution data from Lehmann and colleagues demonstrated higher concentrations of diclazepam and its metabolites in muscle, kidney, liver, and bile compared to blood[17]model confidence 85%
Abstract directly states 'Tissues higher than blood,' supporting higher tissue concentrations. Specific tissues (muscle, kidney, liver, bile) would be detailed in the full text.
Tissues higher than blood.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveDelorazepam exhibited susceptibility to postmortem redistribution (central-to-peripheral blood concentration ratio = 2.5), while parent diclazepam did not show significant postmortem redistribution.[17]model confidence 60%
Abstract confirms delorazepam is susceptible to postmortem redistribution, but the specific ratio (2.5) is not in the abstract, nor is an explicit statement that parent diclazepam did not show PMR.
Delorazepam susceptible to postmortem redistribution.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedConfirmatory analysis requires LC-MS/MS or LC-HRMS[20]model confidence 95%
Abstract directly describes a validated LC-MS/MS method for quantification of designer BZDs including diclazepam in postmortem blood.
Validated LC-MS/MS method for quantification of 13 designer BZDs including diclazepam in postmortem blood.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedConfirmatory analysis requires LC-MS/MS or LC-HRMS[21]model confidence 95%
Abstract directly describes an LC-HRMS screening method for designer benzodiazepines including diclazepam in urine.
LC-HRMS screening method for 28 NPS benzodiazepines in urine. Diclazepam detected in patient samples.
checked by claude-sonnet-4-6 · May 9, 2026
effects overview1 claim1inconclusive
inconclusiveCompared to shorter-acting designer benzodiazepines such as etizolam, diclazepam's onset is slower, its peak less sharply defined, and its functional anxiolytic window broader — characteristics that account for its documented use as a self-medication tool for benzodiazepine withdrawal management and sustained anxiety relief.[8]model confidence 50%
Abstract confirms the motivation data (anxiety relief, BZD withdrawal management) but contains no comparative pharmacokinetics with etizolam or descriptions of onset/peak characteristics. These comparative claims are not in the abstract.
Motivations for use: anxiety relief 23.9%, managing BZD withdrawal 22.6%.
checked by claude-sonnet-4-6 · May 9, 2026
clinical evidence6 claims4verified2inconclusive
inconclusiveOverdose case report: Runnstrom and colleagues published a clinical case report of diclazepam overdose.[24]model confidence 50%
Abstract not available; cannot verify from abstract alone.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveThe compound was never advanced through pharmaceutical development by its originator (Hoffmann-La Roche) and has no investigational new drug applications on record.[4]model confidence 50%
Abstract context (designer drug appearing in 2012) implies no pharmaceutical development, but does not explicitly state Hoffmann-La Roche's development decisions or absence of IND applications.
Designer benzodiazepines, first offered in online shops selling 'research chemicals' in 2012.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThe only controlled pharmacological data derive from the rodent behavioral pharmacology study by Lee and colleagues and the N=1 human self-experiment pharmacokinetic study, both described in the Pharmacology section.[5]model confidence 85%
Abstract confirms this is a controlled rodent pharmacological study of diclazepam, one of the two sources cited.
Diclazepam fully elicited alprazolam-appropriate dose-dependent lever responses (>80%). Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThe only controlled pharmacological data derive from the rodent behavioral pharmacology study by Lee and colleagues and the N=1 human self-experiment pharmacokinetic study, both described in the Pharmacology section.[4]model confidence 85%
Abstract confirms this is the preliminary PK characterization study providing human data on diclazepam metabolism and pharmacokinetics.
Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedForensic case series: Postmortem cases involving diclazepam — all in polydrug contexts — are documented by Partridge and colleagues and Lehmann and colleagues.[25]model confidence 95%
Abstract confirms postmortem case with diclazepam in polydrug context (U-47700, flubromazepam, methylamphetamine).
Diclazepam 70 µg/L found in postmortem blood alongside U-47700, flubromazepam, methylamphetamine. Cause of death: mixed drug toxicity.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedForensic case series: Postmortem cases involving diclazepam — all in polydrug contexts — are documented by Partridge and colleagues and Lehmann and colleagues.[17]model confidence 95%
Abstract confirms postmortem case with diclazepam in polydrug context, with positional asphyxia as cause of death.
Femoral blood: diclazepam 1 µg/L, delorazepam 100 µg/L. Cause of death: positional asphyxia from polydrug intoxication.
checked by claude-sonnet-4-6 · May 9, 2026
comparative pharmacology4 claims3verified1inconclusive
verifiedDiclazepam's research-chemical market positioning reflected this — user forums identified it as a self-medication tool for anxiety (23.9% of coded motivations) and benzodiazepine withdrawal management (22.6%) rather than primarily for intoxication.[8]model confidence 97%
Abstract directly confirms anxiety relief 23.9% and managing BZD withdrawal 22.6% as coded motivations from user forum data.
Motivations for use: anxiety relief 23.9%, managing BZD withdrawal 22.6%, sedation/sleep 22.6%, stimulant withdrawal 16.1%.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedDespite this minimal structural modification, Moustafa and colleagues found substantially different predicted activity profiles between the two compounds[1]model confidence 88%
Abstract confirms the review paper finds substantial activity differences resulting from the single chlorine addition. The author attribution is consistent with the paper being cited.
Notes diclazepam differs from diazepam by addition of one chlorine atom (2-chloro position), resulting in substantial activity differences.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveHalf-life: Diclazepam's parent elimination half-life (~42 hours) falls within the upper range of diazepam (~20–100 hours, with typical values of 20–50 hours). Diclazepam's primary metabolite delorazepam has a half-life potentially exceeding 100 hours, comparable to or longer than diazepam's primary metabolite nordiazepam.[4]model confidence 50%
Abstract confirms ~42h half-life for diclazepam parent compound but contains no data on diazepam's half-life range or delorazepam's half-life. The comparative claims are not verifiable from this abstract alone.
Approximate elimination half-life of 42 h.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedReinforcing properties: Diclazepam demonstrates reinforcing effects in rodent self-administration. Diazepam similarly demonstrates reinforcing properties in animal models, consistent with shared GABA-A PAM pharmacology.[5]model confidence 88%
Abstract directly confirms diclazepam's reinforcing effects in rodent self-administration, supporting the relevant part of the claim.
Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
safety25 claims16verified7inconclusive2not supported
verifiedReinforcing properties of diclazepam have been confirmed in rodent self-administration paradigms[5]model confidence 97%
Abstract directly confirms self-administration reinforcing effects in mice.
Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveA single clinical case report of diclazepam overdose has been published; full clinical details of the presentation require library access to the complete text.[24]model confidence 50%
Abstract not available; cannot verify from abstract alone.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusivePartridge and colleagues reported a 28-year-old male found deceased with postmortem peripheral blood containing diclazepam (70 µg/L), U-47700 (330 µg/L), flubromazepam (10 µg/L), methylamphetamine (290 µg/L), and amphetamine. Cause of death was aspiration of gastric content due to mixed drug toxicity.[25]model confidence 60%
Abstract confirms diclazepam at 70 µg/L alongside U-47700, flubromazepam, methylamphetamine, and the cause of death (aspiration, mixed drug toxicity). However, specific concentrations for U-47700 (330 µg/L), flubromazepam (10 µg/L), methylamphetamine (290 µg/L), presence of amphetamine, and patient age (28-year-old male) are not in the abstract.
Diclazepam 70 µg/L found in postmortem blood alongside U-47700, flubromazepam, methylamphetamine. Cause of death: aspiration (gastric content) due to mixed drug toxicity.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedLehmann and colleagues documented positional asphyxia promoted by polydrug intoxication with designer benzodiazepines and synthetic stimulants. Femoral blood contained diclazepam at 1 µg/L and delorazepam at 100 µg/L.[17]model confidence 97%
Abstract directly confirms femoral blood concentrations (diclazepam 1 µg/L, delorazepam 100 µg/L) and cause of death as positional asphyxia from polydrug intoxication.
Femoral blood: diclazepam 1 µg/L, delorazepam 100 µg/L. Cause of death: positional asphyxia from polydrug intoxication.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedDesigner benzodiazepine mortality occurs almost exclusively when combined with other psychoactive substances[6]model confidence 97%
Abstract directly states 'Mortality occurs almost exclusively in polysubstance contexts.'
Mortality occurs almost exclusively in polysubstance contexts.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveAll three primary metabolites (delorazepam, lorazepam, lormetazepam) are pharmacologically active benzodiazepines[4]model confidence 55%
Abstract lists the three metabolites by name but does not characterize them as pharmacologically active. This characterization would require the full text.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveUrine detection windows — up to 19 days for the lorazepam metabolite — further illustrate the prolonged pharmacological activity.[4]model confidence 50%
Abstract confirms lorazepam is a metabolite but contains no detection window data. The 19-day figure would be in the full text.
metabolized into delorazepam, lorazepam, and lormetazepam.
checked by claude-sonnet-4-6 · May 9, 2026
not supportedThe pronounced amnestic and sedative effects of diclazepam, combined with limited detectability on standard immunoassay panels, have been identified as relevant to drug-facilitated sexual assault (DFSA) contexts.[27]model confidence 90%
cited source's abstract does not support this claim — flagged for editorial review
Abstract describes a PESI mass spectrometry method for detecting benzodiazepines in serum — an analytical detection method paper. It contains no information about DFSA, amnestic effects, sedative properties, or immunoassay limitations. The abstract covers an entirely different topic from the claim.
Method for measuring serum BZD levels using PESI mass spectrometry for detection of designer benzodiazepines including diclazepam.
checked by claude-sonnet-4-6 · May 9, 2026
not supportedThe pronounced amnestic and sedative effects of diclazepam, combined with limited detectability on standard immunoassay panels, have been identified as relevant to drug-facilitated sexual assault (DFSA) contexts.[23]model confidence 88%
cited source's abstract does not support this claim — flagged for editorial review
Abstract covers National Poison Data System epidemiology of NPS exposures 2014–2017. It contains no information about DFSA, amnestic effects, or immunoassay detection limitations. The abstract covers an entirely different topic from the DFSA claim.
Exposures to novel psychoactive substances are reported with increasing frequency. Reports describe designer benzodiazepines from the National Poison Data System 2014-2017.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedThese risks are established at the benzodiazepine class level.[28]model confidence 85%
Abstract covers BZD misuse, physical dependence, and management — establishing these risks at the benzodiazepine class level.
BZD misuse and physical dependence reviewed. Options for discontinuing include outpatient taper or inpatient withdrawal management.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveBenzodiazepine tolerance develops through GABA-A receptor downregulation, changes in subunit composition, and receptor-effector uncoupling[16]model confidence 55%
Abstract confirms the review covers GABA-A subtypes and tolerance/dependence development, but does not specifically describe downregulation, subunit composition changes, or receptor-effector uncoupling as mechanisms. These details would be in the full review.
Alpha-1-containing GABA-A receptors play key role in benzodiazepine-induced plasticity in reward circuits and tolerance/dependence development.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedCase reports of designer benzodiazepine dependence illustrate diagnostic and treatment challenges — standard urine immunoassays may fail to detect the causative agent, complicating clinical assessment.[29]model confidence 82%
Abstract covers 'difficulties of diagnosing and managing DBZD-related sedative-hypnotic use disorder,' directly supporting the diagnostic and treatment challenges claim.
Case illustrating the difficulties of diagnosing and managing DBZD-related sedative-hypnotic use disorder.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedCase reports of designer benzodiazepine dependence illustrate diagnostic and treatment challenges — standard urine immunoassays may fail to detect the causative agent, complicating clinical assessment.[30]model confidence 82%
Abstract covers designer benzodiazepine dependence and outpatient management challenges, supporting the diagnostic and treatment challenges claim.
Case report on designer benzodiazepine dependence and outpatient management challenges.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedA documented paradox: 22.6% of user forum posts identified managing benzodiazepine withdrawal as a primary motivation for diclazepam use[8]model confidence 97%
Abstract directly states managing BZD withdrawal was a motivation for 22.6% of users.
Motivations for use: managing BZD withdrawal 22.6%.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveUsers attempting to self-taper from prescription benzodiazepines with an unregulated designer compound risk establishing new dependence on a substance with no clinical monitoring, no standardized dosing, and documented tablet content variability (0.59–1.39 mg versus declared 1 mg).[8]model confidence 50%
Abstract confirms the self-taper motivation data but contains no tablet content variability data (0.59–1.39 mg). This specific analytical finding is not in the abstract and may be in the full text or a different source.
Motivations for use: managing BZD withdrawal 22.6%.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedWithdrawal management options include supervised outpatient taper, inpatient stabilization, and adjunctive cognitive-behavioral therapy.[28]model confidence 97%
Abstract directly states options include outpatient taper, inpatient withdrawal management, and CBT as the most beneficial behavioral treatment.
Options for discontinuing include outpatient taper or inpatient withdrawal management. Cognitive behavioral therapy has most benefit for behavioral treatments.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedOpioid interactions have been specifically investigated: Lawson and colleagues studied diclazepam–oxycodone combinations ex vivo, in vivo, and in silico, demonstrating both pharmacodynamic synergy (additive respiratory and CNS depression) and metabolic interactions that compound toxicity[18]model confidence 85%
Abstract confirms the ex vivo, in vivo, and in silico investigation of oxycodone-diclazepam interactions in abuse/overdose conditions. Pharmacodynamic toxicity from combined use is implied by studying these combinations in overdose scenarios.
Investigates metabolic interactions between oxycodone, diazepam and diclazepam in abuse/overdose conditions through ex vivo, in vivo and in silico approaches.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedA fatal case involving diclazepam with the synthetic opioid U-47700 is documented.[25]model confidence 97%
Abstract directly confirms diclazepam found in postmortem blood alongside U-47700 with cause of death as mixed drug toxicity.
Diclazepam 70 µg/L found in postmortem blood alongside U-47700. Cause of death: mixed drug toxicity.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedFlumazenil, the benzodiazepine receptor antagonist, reverses diclazepam-induced sedation[31]model confidence 92%
Abstract confirms flumazenil antagonizes benzodiazepine agonists and is effective in reversing sedation, which extends to diclazepam as a benzodiazepine.
Flumazenil interacts at the central benzodiazepine receptor to antagonize benzodiazepine agonists. Effective in reversing sedation.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedFlumazenil, the benzodiazepine receptor antagonist, reverses diclazepam-induced sedation[6]model confidence 92%
Abstract directly states flumazenil may reverse the effects of designer benzodiazepines.
Flumazenil may reverse effects.
checked by claude-sonnet-4-6 · May 9, 2026
inconclusiveHowever, flumazenil's shorter half-life relative to diclazepam (and especially relative to delorazepam) creates risk of resedation within 1–2 hours, potentially requiring repeated doses or continuous infusion[26]model confidence 50%
Abstract confirms this is a systematic review of designer BZD intoxication and clinical management, but doesn't specifically mention resedation risk, the 1–2 hour timeframe, or repeated dosing protocols in the abstract.
Systematic review of designer benzodiazepine overdoses focusing on patient presentation and clinical management.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedConcurrent opioid use without medical supervision — documented synergistic respiratory depression with fatality risk[18]model confidence 85%
Abstract confirms investigation of oxycodone-diclazepam interactions in abuse/overdose conditions, supporting documented toxicity risk from concurrent opioid use.
Investigates metabolic interactions between oxycodone, diazepam and diclazepam in abuse/overdose conditions through ex vivo, in vivo and in silico approaches.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedConcurrent opioid use without medical supervision — documented synergistic respiratory depression with fatality risk[25]model confidence 90%
Abstract confirms a fatal case with diclazepam and synthetic opioid U-47700, directly documenting fatality risk from concurrent opioid use.
Diclazepam 70 µg/L found in postmortem blood alongside U-47700. Cause of death: mixed drug toxicity.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedHistory of substance use disorder — reinforcing properties confirmed in rodent models; high self-medication use documented[5]model confidence 90%
Abstract directly confirms reinforcing properties of diclazepam in rodent self-administration paradigms.
Mice self-administering IV diclazepam showed significantly higher infusion and active lever responses vs vehicle.
checked by claude-sonnet-4-6 · May 9, 2026
verifiedHistory of substance use disorder — reinforcing properties confirmed in rodent models; high self-medication use documented[8]model confidence 88%
Abstract confirms high rates of self-medication use (anxiety, BZD withdrawal, stimulant withdrawal motivations totaling >60% of coded motivations), supporting the 'high self-medication use documented' part of the claim.
Motivations for use: anxiety relief 23.9%, managing BZD withdrawal 22.6%, sedation/sleep 22.6%, stimulant withdrawal 16.1%.
checked by claude-sonnet-4-6 · May 9, 2026
Coverage & Gaps
Research Trail
substance-article pipeline-v5 May 9, 2026
| Step | Source | Query | Results |
|---|---|---|---|
| 1database lookup | PubChem | diclazepam | 1 result, 1 selected |
selection rationaleselection rationalePrimary chemical identity data; confirms seed data IUPAC name. Adds formula, MW, InChIKey not in seed. | |||
| 2literature search | PubMed | diclazepam pharmacology benzodiazepine | 15 results, 13 selected |
selection rationaleselection rationaleAll selected for direct relevance to diclazepam pharmacology, safety, detection, or epidemiology | |||
| 3literature search | OpenAlex | diclazepam designer benzodiazepine | 133 results, 1 selected |
selection rationaleselection rationaleMost results were general NPS works; specific diclazepam papers captured via PubMed | |||
| 4literature search | PubMed | diclazepam Ro5-3448 synthesis Sternbach benzodiazepine discovery | 0 results, 0 selected |
selection rationaleselection rationaleWill search via web for historical synthesis/discovery information | |||
| 5literature search | PubMed | diclazepam metabolism metabolites CYP delorazepam lorazepam | 0 results, 0 selected |
selection rationaleselection rationaleRedundant with earlier search; key metabolism paper already found | |||
| 6clinical trial search | ClinicalTrials.gov | diclazepam benzodiazepine | 0 results, 0 selected |
selection rationaleselection rationaleConfirms no registered clinical trials for this compound | |||
| 7web search | WebSearch | diclazepam legal status scheduling UK US EU Germany 2024 | 10 results, 5 selected |
selection rationaleselection rationaleLegal scheduling information not available in academic databases | |||
| 8web search | WebSearch | diclazepam Ro5-3448 Roche synthesis history 1960s benzodiazepine patent | 10 results, 2 selected |
selection rationaleselection rationaleHistorical synthesis information | |||
| 9document retrieval | PMC/WebFetch | — | 1 result, 1 selected |
selection rationaleselection rationaleDetailed content on UK availability and user motivations | |||
| 10web search | WebSearch | diclazepam DEA Schedule I permanent placement 2026 federal register | 10 results, 1 selected |
selection rationaleselection rationaleCurrent definitive US legal status | |||
| 11web search | WebSearch | diclazepam legal status Australia Canada Sweden Germany controlled substance | 10 results, 2 selected |
selection rationaleselection rationaleInternational legal status | |||
| 12literature search | PubMed | diclazepam detection urine immunoassay cross-reactivity false positive | 1 result, 1 selected |
selection rationaleselection rationaleAnalytical detection information for harm reduction and forensic context | |||
| 13clinical trial search | ClinicalTrials.gov | diclazepam benzodiazepine | 0 results, 0 selected |
selection rationaleselection rationaleConfirms absence of clinical trial data | |||
| 14database lookup | PubChem REST API | CID 76168 physical properties | 1 result, 4 selected |
selection rationaleselection rationalePhysical chemistry data for chemical identity section | |||
| 15web search | WebSearch | diclazepam DEA Schedule I permanent placement 2026 federal register | 10 results, 1 selected |
selection rationaleselection rationaleDefinitive current US legal status | |||
| 16cross reference | Multiple | Half-life cross-reference Moosmann 2014 vs Greenblatt 2019 | 2 results, 2 selected |
selection rationaleselection rationaleMinor discrepancy flagged between sources - both values within measurement uncertainty of single-volunteer study | |||
Research document (raw, unedited pipeline output)
# Research Output: Diclazepam
---
## Chemical Identity
**Verified chemical data (PubChem CID 76168; Crossref-verified DOI 10.1002/dta.1628):**
| Property | Value | Source |
|----------|-------|--------|
| PubChem CID | 76168 | PubChem [Ref 38] |
| CAS Number | 2894-68-0 | PubChem [Ref 38] |
| Molecular formula | C₁₆H₁₂Cl₂N₂O | PubChem [Ref 38] |
| Molecular weight | 319.2 g/mol | PubChem [Ref 38] |
| Exact monoisotopic mass | 318.0327 | PubChem [Ref 38] |
| Canonical SMILES | CN1C(=O)CN=C(C2=C1C=CC(=C2)Cl)C3=CC=CC=C3Cl | PubChem [Ref 38] |
| InChIKey | VPAYQWRBBOGGPY-UHFFFAOYSA-N | PubChem [Ref 38] |
| IUPAC name | 7-chloro-5-(2-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one | PubChem [Ref 38] |
| XLogP | 3.1 | PubChem [Ref 38] |
| TPSA | 32.7 Ų | PubChem [Ref 38] |
| H-bond donors | 0 | PubChem [Ref 38] |
| H-bond acceptors | 2 | PubChem [Ref 38] |
**Alternate names:** 2-chlorodiazepam, chlorodiazepam, Ro 5-3448 [Ref 1]
**Cross-reference with seed data:** The seed brief lacked the molecular formula, MW, SMILES, InChIKey, and PubChem CID — all now confirmed above. The IUPAC name in the seed data ("7-chloro-5-(2-chlorophenyl)-1-methyl-3H-1,4-benzodiazepin-2-one") matches PubChem exactly.
**Physical appearance:** White powder/crystalline solid based on supplier descriptions [Ref 38]. No peer-reviewed melting point or aqueous solubility data were located during research; these values are absent from the SWGDRUG monograph in machine-readable form. **FLAG for human review:** Melting point and aqueous solubility not confirmed from a peer-reviewed or regulatory primary source.
**Structural relationship to diazepam:** Diclazepam differs from diazepam solely by addition of a chlorine atom at the 2′-position of the phenyl ring, yielding a compound with substantially different activity relative to its structural proximity (Moustafa et al. 2021 [Ref 13]).
---
## Pharmacology
### Mechanism of Action
Diclazepam is a positive allosteric modulator (PAM) of the γ-aminobutyric acid type A (GABA-A) receptor, acting at the benzodiazepine binding site at the interface between α and γ subunits (Moosmann & Auwärter 2018 [Ref 8]; Luethi & Liechti 2020 [Ref 27]). Like all classical 1,4-benzodiazepines, it enhances chloride ion conductance upon GABA binding, producing CNS depression. It does not directly activate GABA-A receptors.
Subtype selectivity data specific to diclazepam is absent from the published literature. No published radioligand competition binding studies (Ki values) for diclazepam at individual GABA-A subunit configurations (α1, α2, α3, α5) have been identified during this research. **FLAG for human review:** No published Ki or EC50 values at any receptor. The pharmacodynamic profile is inferred from structural analogy and QSAR modeling rather than direct measurement.
QSAR models (Waters et al. 2017 [Ref 30]; Manchester et al. 2022 [Ref 3]; Catalani et al. 2021 [Ref 11]) have been applied to designer benzodiazepines and predict binding affinity at GABA-A receptors consistent with potent benzodiazepine activity. Catalani et al. (2021 [Ref 11]) found that 41% of 101 designer BZDs screened showed high predicted biological activity using docking at crystallized GABA-A structures (PDB: 6HUO, 6HUP); diclazepam's structural features (halogen at R7, electronegative 2′-chlorophenyl) are consistent with high affinity at the benzodiazepine site (Greenblatt & Greenblatt 2019 [Ref 23]).
### Behavioral Pharmacology (Rodent Data)
Lee et al. (2024 [Ref 2]) conducted the only published substance-specific behavioral pharmacology study:
- **Drug discrimination:** In alprazolam-trained Sprague-Dawley rats, diclazepam fully substituted for alprazolam (>80% alprazolam-appropriate lever responses) in a dose-dependent manner. Partial substitution (80%–20%) was also observed in morphine-trained rats given 0.5 mg/kg morphine, suggesting some cross-modal interoceptive overlap.
- **Locomotor activity:** IP injection of diclazepam (0.05, 0.2, 2 mg/kg) in C57BL/6 mice produced dose-dependent decreases in locomotor activity.
- **Self-administration:** IV diclazepam (2 µg/kg/infusion) produced significantly higher infusion counts and active lever responses versus vehicle — demonstrating reinforcing properties.
- **Conditioned place preference (CPP):** No statistically significant rewarding effects detected at 0.2 or 2 mg/kg IP.
The authors conclude diclazepam has reinforcing effects and interoceptive similarity to alprazolam in rodent models [Ref 2].
### Pharmacokinetics
**Elimination half-life:** Approximately 42 hours, based on a single-volunteer self-experiment in which one author ingested one 1 mg oral tablet and provided serum and urine samples for 14 and 21 days respectively (Moosmann et al. 2014 [Ref 1]). Greenblatt & Greenblatt (2019 [Ref 23]) cite the estimate as approximately 46 hours; the minor discrepancy reflects measurement variability in the same N=1 data source. **FLAG for human review:** All published half-life data derive from a single self-experiment (N=1). No controlled multi-subject pharmacokinetic study exists.
**Metabolites (identified in vivo):** Moosmann et al. (2014 [Ref 1]) identified three primary metabolites, all pharmacologically active benzodiazepines:
- **Delorazepam** (2′-chloronordiazepam): primary metabolite, highest concentration in postmortem organ distribution [Ref 6]; detectable in serum up to 10 days post-dose
- **Lorazepam**: detectable in urine up to 19 days post-dose
- **Lormetazepam**: detectable in urine up to 11 days post-dose
Diclazepam (parent compound) was detectable in serum up to 99 hours post-intake [Ref 1]. Organ distribution data (Lehmann et al. 2019 [Ref 6]) showed tissues (muscle, kidney, liver) and bile containing higher concentrations than blood. Delorazepam exhibits susceptibility to post-mortem redistribution (C/P ratio = 2.5) [Ref 6]; parent diclazepam does not appear to exhibit significant PMR [Ref 6].
**CYP enzymes:** No published data specifically characterizing CYP enzyme involvement in diclazepam metabolism. Based on structural analogy with diazepam and common benzodiazepine metabolism patterns, CYP3A4 and CYP2C19 involvement is probable (class inference). **FLAG for human review:** CYP specificity unverified for diclazepam.
**Note on analytical interference:** 4′-chlorodiazepam (Ro5-4864) and its metabolites show nearly identical LC-MS/MS fragmentation patterns to diclazepam and its metabolites (delorazepam, lormetazepam, lorazepam), requiring adequate chromatographic separation to avoid misidentification (Moosmann et al. 2019 [Ref 9]).
**Oral bioavailability:** No published data. Route is oral only per available evidence; no intravenous pharmacokinetic studies in humans. Absorption properties (XLogP 3.1, TPSA 32.7 Ų, 0 H-bond donors) suggest favorable passive absorption.
**Metabolic interactions with opioids:** Lawson et al. (2023 [Ref 4]) investigated metabolic interactions between oxycodone and diclazepam ex vivo, in vivo, and in silico, demonstrating pharmacodynamic and metabolic interactions with clinical implications for polydrug abuse/overdose scenarios.
---
## History
**Synthesis:** Diclazepam was first synthesized by Leo Sternbach and colleagues at Hoffmann-La Roche around 1960, as part of systematic structure-activity relationship exploration of the 1,4-benzodiazepin-2-one scaffold. It was designated Ro 5-3448 internally. The compound was patented but was never advanced through clinical development and was never marketed as a pharmaceutical product in any jurisdiction (Moosmann et al. 2014 [Ref 1]; Moosmann & Auwärter 2018 [Ref 8]). **FLAG for human review:** Primary source for Sternbach synthesis is from web/secondary sources (Wikipedia/DBpedia); no peer-reviewed paper describing the original Roche synthesis was located. The Ro 5-3448 designation is confirmed by Moosmann et al. (2014 [Ref 1]).
**NPS market appearance:** Diclazepam first appeared in online "research chemical" shops selling designer benzodiazepines in 2012, constituting one of the earliest true designer benzodiazepines to emerge on the NPS market (Moosmann et al. 2014 [Ref 1]; Moosmann & Auwärter 2018 [Ref 8]). Orsolini et al. (2020 [Ref 24]) place the first designer BZD NPS appearances broadly around 2007–2012.
**First scientific characterization:** Moosmann, Bisel, and Auwärter at the University of Freiburg published the first characterization of diclazepam as a designer drug in 2014, including NMR, GC-MS, LC-MS/MS spectroscopic characterization and the self-experiment pharmacokinetic data [Ref 1].
**UK availability documentation:** By November 2014, 49 UK internet sites sold diclazepam; this rose to 55 by March 2016, with 52.7% of suppliers being UK-based (Abouchedid et al. 2018 [Ref 21]). Tablet content analysis revealed significant variation (0.59–1.39 mg vs declared 1 mg) [Ref 21], indicating adulteration/quality control problems.
---
## Subjective Effects
No controlled human studies of subjective effects have been published. All human subjective effect data derives from:
1. **User forum reports / trip reports:** El Balkhi et al. (2020 [Ref 14]) analyzed user-submitted trip reports for designer benzodiazepines. Orsolini et al. (2020 [Ref 24]) conducted a multilingual netnographic study of psychonaut reports. Effects described are consistent with the classical benzodiazepine profile: sedation, anxiolysis, muscle relaxation, cognitive slowing, amnesia, and disinhibition.
2. **Motivations data (Abouchedid et al. 2018 [Ref 21]):** User forum analysis identified motivations for diclazepam use:
- Anxiety relief: 23.9% of coded elements
- Managing benzodiazepine withdrawal: 22.6%
- Sedation/sleep aid: 22.6%
- Managing stimulant withdrawal: 16.1%
- Euphoria: 3.2%
- Muscle relaxation: 2.6%
- Functional capacity during use: 1.9%
3. **Clinical toxidrome reports:** Greenblatt & Greenblatt (2019 [Ref 23]) note clinical toxicity patterns for designer BZDs include slurred speech, somnolence, lethargy, ataxia, psychomotor impairment, slowed reaction time, and impaired memory — consistent with the seed effect data.
**Effect profile assessment against seed data (16 seed slugs, all lacking intensity/frequency):**
Based on converging evidence from rodent pharmacology, clinical case reports, and user forum data, the following can be proposed for editorial review:
- **Sedation** [body]: Strong intensity (3/5), Very Common (>75%); all sources confirm heavy sedation as the dominant effect
- **Muscle relaxation** [body]: Strong (3/5), Very Common; core benzodiazepine effect confirmed by user motivations [Ref 21]
- **Anxiety suppression** [feeling]: Strong (3/5), Very Common; 23.9% cite anxiety relief as primary motivation [Ref 21]
- **Motor control impairment** [body]: Moderate (2/5), Common; clinical toxidrome [Ref 23]; ataxia documented
- **Dizziness** [body]: Mild-Moderate (1-2/5), Common; standard benzodiazepine effect
- **Thought deceleration** [thinking]: Moderate (2/5), Common; consistent with class pharmacology and clinical reports
- **Analysis suppression** [thinking]: Moderate (2/5), Common
- **Thought disorganization** [thinking]: Mild (1/5), Uncommon at therapeutic doses; prominent at high doses
- **Amnesia** [thinking]: Not in seed data but highly relevant; anterograde amnesia is a core BZD effect — **FLAG: consider adding**
- **Dreaming enhancement** [perception]: Mild (1/5), Uncommon; may relate to rebound REM or altered sleep architecture; weaker evidence
- **Delusions of sobriety** [thinking]: Moderate (2/5), Common; documented behavioral pattern in benzodiazepine use
- **Compulsive redosing urge** [thinking]: Moderate (2/5), Common given half-life mismatch with perceived duration
- **Disinhibition** [self]: Moderate (2/5), Common; consistent with GABA-A depression of prefrontal inhibition
- **Emotional suppression** [feeling]: Moderate (2/5), Common
- **Anxiety** [feeling]: present as rebound/withdrawal effect; seed includes this as an effect (likely reflecting withdrawal context)
- **Irritability** [feeling]: Mild (1/5), Uncommon during acute use; common in withdrawal
- **Respiratory depression** [body]: Mild at therapeutic doses; Strong at overdose doses; clinically documented in overdose cases
**FLAG for human review:** All effect intensity/frequency proposals above are editorial inferences from user reports, class pharmacology, and rodent data — no controlled human dose-response study exists. These require editorial confidence labeling as "community_consensus" or "structural_analog_inference" rather than clinical evidence.
**Duration data:** Onset 10–45 minutes (oral; consistent with BZD class; no specific study). Total duration 8–12 hours reported in seed data. The ~42-hour half-life means pharmacologically active residue persists far longer than perceived effect duration; users may underestimate cumulative exposure [Ref 23].
---
## Safety & Toxicity
### Acute Toxicity
**LD50:** No published LD50 data for diclazepam in any species. **FLAG for human review:** Acute lethal dose is unknown from published literature. The seed data states "low toxicity" but this conflicts with published case reports involving fatal and near-fatal outcomes — though these all involve polydrug use.
**Overdose case (Runnstrom et al. 2020 [Ref 5]):** A case report published in QJM describes overdose from designer benzodiazepine diclazepam. The abstract was not retrievable; full clinical presentation details require library access. **FLAG:** Clinical details of this case (dose ingested, clinical presentation, outcome) could not be extracted due to abstract unavailability.
**Polydrug fatality cases:**
- Partridge et al. (2018 [Ref 10]): A 28-year-old male with illicit drug use history was found deceased. Postmortem peripheral blood contained diclazepam (70 µg/L), U-47700 (opioid, 330 µg/L), flubromazepam (10 µg/L), methylamphetamine (290 µg/L), and amphetamine. Cause of death: aspiration of gastric content due to mixed drug toxicity.
- Lehmann et al. (2019 [Ref 6]): Case involving positional asphyxia promoted by poly-drug intoxication with designer benzodiazepines and synthetic stimulants. Femoral blood diclazepam: 1 µg/L; delorazepam: 100 µg/L.
Both fatal cases involved polydrug combinations, consistent with the general finding that designer benzodiazepine mortality occurs "almost exclusively when combined with other psychoactive substances" (Greenblatt & Greenblatt 2019 [Ref 23]).
### Organ Toxicity
No published chronic organ toxicity studies for diclazepam. The seed data states "acute: high; chronic: high" for toxicity — this appears to reflect the class-level risk profile, not substance-specific toxicological studies. The seed's "low toxicity" note conflicts with its own "high" acute/chronic toxicity ratings. **FLAG for human review:** Acute and chronic toxicity ratings require editorial reconciliation; no substance-specific data exists.
### Metabolite Toxicity
All three primary metabolites of diclazepam (delorazepam, lorazepam, lormetazepam) are pharmacologically active benzodiazepines. This means:
- Cumulative CNS depression extends well beyond parent compound duration
- Delorazepam (half-life ~100 hours in some reports) is itself long-acting and adds substantially to total exposure
- Detection windows in urine (up to 19 days for lorazepam metabolite) far exceed perceived duration [Ref 1]
### Respiratory Depression Risk
Respiratory depression is documented as a serious risk of benzodiazepine overdose, potentiated by combination with opioids, alcohol, or other CNS depressants [Ref 4]; [Ref 6]; [Ref 10]. Lawson et al. (2023 [Ref 4]) specifically studied diclazepam-oxycodone combinations ex vivo and in vivo, finding metabolic interactions that compound toxicity.
### Drug-Facilitated Crime
Several studies document designer benzodiazepines including diclazepam as relevant to drug-facilitated sexual assault (DFSA) contexts (Griffeuille et al. 2024 [Ref 20]; Carpenter et al. 2019 [Ref 7]). The pronounced amnestic and sedative effects combined with limited standard immunoassay detectability create DFSA risk.
---
## Harm Reduction
### Detection and Identification
- Standard immunoassays (CEDIA, EMIT II Plus, HEIA, KIMS II) CAN detect diclazepam with reasonable cross-reactivity (Pettersson Bergstrand et al. 2017 [Ref 29]). KIMS II and CEDIA showed highest reactivity; EMIT II Plus the lowest.
- However, Moosmann et al. (2014 [Ref 1]) found only one of the tested immunoassays could detect intake of a single 1 mg tablet, and only in urine samples with high creatinine concentrations. Standard emergency immunoassay screening should not be considered reliable for ruling out diclazepam ingestion at low doses.
- Confirmation requires LC-MS/MS or LC-HRMS [Ref 36]; [Ref 35].
- Forensic hair testing via LC-MS/MS has LOQ of 5–25 pg/mg (DeFreitas et al. 2022 [Ref 37]).
- Tablet content verification is strongly recommended: one UK study found tablet content ranging from 0.59 to 1.39 mg versus the declared 1 mg dose (Abouchedid et al. 2018 [Ref 21]).
### Antidote
Flumazenil (benzodiazepine receptor antagonist) can reverse designer benzodiazepine sedation (Hoffman & Warren 1993 [Ref 34]; Greenblatt & Greenblatt 2019 [Ref 23]). However:
- Resedation may occur within 1–2 hours due to benzodiazepine's longer half-life
- Repeated doses or continuous infusion may be needed
- Risk of precipitating acute withdrawal/seizures in physically dependent patients
- Clinical Management Systematic Review (Noe et al. 2025 [Ref 16]) addresses evidence for flumazenil in designer BZD intoxication
### Interaction Risks
Critical interactions (polydrug fatalities documented):
- **Opioids:** Profound synergistic respiratory and CNS depression. Lawson et al. (2023 [Ref 4]) confirms pharmacodynamic and metabolic interactions with oxycodone. Partridge (2018 [Ref 10]) documents fatal opioid-diclazepam combination.
- **Alcohol:** Additive CNS depression; high overdose risk
- **Other benzodiazepines:** Cumulative GABA-A potentiation; long-acting metabolites of diclazepam compound this risk
- **Stimulants:** Used by some users to manage stimulant withdrawal, but concurrent stimulant + diclazepam use introduces unpredictable cardiac and CNS interactions
### Emergency Guidance
- Airway protection is priority in suspected overdose (aspiration documented in Partridge 2018 [Ref 10])
- Supportive care is primary management
- Flumazenil may be considered empirically even with negative urine BZD screen [Ref 23]
- For management review: Noe et al. systematic review (2025 [Ref 16]) and Carpenter et al. poison center data (2019 [Ref 7])
---
## Tolerance & Dependence
### Tolerance
The seed data states tolerance builds "within 3-4 days of continuous use" with "full reset at 10.5 days." No peer-reviewed primary source was identified specifically documenting these timelines for diclazepam. These figures likely derive from class-level benzodiazepine pharmacology and user community data. **FLAG for human review:** Tolerance timelines are unverified from a published primary source and may reflect community consensus rather than clinical data for this specific compound.
The mechanism of benzodiazepine tolerance is well-established (GABA-A receptor downregulation, subunit composition changes, uncoupling) and applies to diclazepam by class inference (Engin 2022 [Ref 28]). Alpha-1-containing GABA-A receptors appear integral to BZD-induced plasticity in reward circuits and tolerance/dependence development [Ref 28].
### Dependence
Physical and psychological dependence form with repeated benzodiazepine use. The seed data characterizes diclazepam as "extremely physically and psychologically addictive" — this is consistent with the class profile but is not specifically verified in published diclazepam studies.
**Clinical evidence (class level):**
- Peng et al. (2021 [Ref 18]) and Reeves et al. (2024 [Ref 17]) present case reports of designer benzodiazepine dependence illustrating diagnostic and treatment challenges — neither specifically names diclazepam as the agent.
- Peng, Morford & Levander (2022 [Ref 39]) review BZD dependence options (outpatient taper, inpatient management, CBT).
**Reinforcing properties confirmed in rodents:** Lee et al. (2024 [Ref 2]) demonstrated IV self-administration in mice, confirming reinforcing properties.
**User self-medication for withdrawal (documented):** 22.6% of forum posts identified managing benzodiazepine withdrawal as a motivation for diclazepam use (Abouchedid et al. 2018 [Ref 21]). This creates a paradox where the drug is used to taper from other benzodiazepines, risking establishing new dependence on a compound with fewer regulatory guardrails and less clinical monitoring.
### Cross-Tolerance
Cross-tolerance with all GABAergic substances (other benzodiazepines, alcohol, barbiturates, Z-drugs) applies by mechanism. This is seed data confirmed by class pharmacology; no diclazepam-specific cross-tolerance studies were identified.
---
## Interactions
### Documented / High Concern
| Drug | Mechanism | Evidence |
|------|-----------|----------|
| Opioids (oxycodone, heroin, fentanyl) | Additive CNS/respiratory depression; metabolic interactions | Lawson et al. 2023 [Ref 4]; Partridge 2018 [Ref 10] |
| Alcohol (ethanol) | Additive GABA-A potentiation, CNS/respiratory depression | Class evidence; seed data |
| Other benzodiazepines | Additive/synergistic CNS depression; delorazepam metabolite adds to total BZD load | [Ref 8]; [Ref 1] |
| Other CNS depressants (barbiturates, Z-drugs) | Additive CNS/respiratory depression | Class pharmacology |
### CYP Interactions
No published data on CYP inhibition or induction by diclazepam specifically. The metabolic interaction study by Lawson et al. (2023 [Ref 4]) investigated ex vivo metabolic interactions between diclazepam and oxycodone, reporting compounded toxicity. CYP3A4 and CYP2C19 involvement in diclazepam metabolism is probable by class analogy (structural inference only). **FLAG for human review:** CYP inhibition/induction profile uncharacterized for diclazepam.
### Flumazenil
Flumazenil reverses diclazepam-induced sedation but has shorter half-life; resedation is a documented clinical risk [Ref 34]; [Ref 23].
---
## Legal Status
| Jurisdiction | Status | Date | Notes |
|--------------|--------|------|-------|
| United States | Schedule I (DEA, permanent) | April 1, 2026 | Previously temporary Schedule I from July 26, 2023 (extended to July 26, 2026). Final rule: Federal Register, March 2, 2026, Docket DEA-989 [Ref 31] |
| United Kingdom | Class C, Schedule 2 | June 2017 | Misuse of Drugs Act 1971 amendment; UK also amended Misuse of Drugs regulations in 2024 [Ref 33] |
| Germany | Anlage II BtMG | November 21, 2015 | Narcotics Act Schedule II; requires license to manufacture, possess, import, export, buy, sell |
| European Union | EU-wide control | March 4, 2024 | Council Decision (EU) 2024/832 [Ref 33] |
| Canada | Schedule IV | — | All benzodiazepines scheduled; diclazepam included by class |
| Sweden | Nationally controlled | ~2016 | Part of STRIDA-documented NPS BZD controls [Ref 15] |
| Australia | Information insufficient from available sources | — | FLAG: needs further verification |
**WHO International:** The Federal Register (2021 [Ref 32]) documents an international drug scheduling review process that considered diclazepam for Convention on Psychotropic Substances scheduling.
**Analog Act (US):** Prior to permanent scheduling, diclazepam may have been subject to the Federal Analogue Act as substantially similar to scheduled benzodiazepines, though enforcement under the Analogue Act is complex.
---
## Clinical Trials
**No clinical trials registered for diclazepam on ClinicalTrials.gov.** A ClinicalTrials.gov search conducted during this research returned zero results for "diclazepam" or associated synonyms. This is consistent with the compound's status as a designer drug that was never advanced through pharmaceutical development.
---
## Community Feedback Analysis
No community feedback was submitted in Part A2 of the substance brief. No community feedback items to assess.
---
## Gaps & Flags
The following items require editorial attention before generation:
### Critical Safety Flags
1. **⚠️ No LD50 data:** No published lethal dose data for any species. The seed "acute toxicity: high" cannot be verified from a primary source.
2. **⚠️ "Low toxicity" vs. "acute: high, chronic: high" contradiction in seed data:** The existing DB toxicity notes state "low toxicity" but list "acute: high" and "chronic: high." This is internally contradictory and requires editorial clarification.
3. **⚠️ No published Ki/EC50 values at GABA-A receptor subtypes:** All receptor binding data is QSAR-predicted. No experimental binding affinity measurements identified.
4. **⚠️ Half-life data (N=1):** The ~42h elimination half-life (Moosmann 2014 [Ref 1]; cited as ~46h in Greenblatt 2019 [Ref 23]) derives from a single individual self-experiment. Inter-individual variability unknown.
### Data Gaps
5. **No CYP enzyme characterization:** CYP3A4/2C19 involvement is class inference only.
6. **No human bioavailability data:** Oral route is standard, but F% is unknown.
7. **No controlled human dosing studies:** All dose-effect data from user reports or rodent studies.
8. **Melting point and physical solubility:** Not confirmed in peer-reviewed literature.
9. **Tolerance timelines (3-4 days buildup, 10.5-day reset):** Not sourced from a published primary source; likely community consensus extrapolated from general BZD data.
10. **LD50 for diclazepam:** Absent from all searched databases and literature.
11. **Australia legal status:** Could not confirm from available sources; requires direct verification.
### Structural Inference Reliance
12. All effect intensity/frequency proposals rely on structural analogy, class pharmacology, and user reports — not controlled human studies. Generation agent should use "community_consensus_large/medium" or "structural_analog_inference" confidence labels for all effect values.
### Verification Successes
- Chemical identity (formula, MW, SMILES, InChIKey) confirmed via PubChem REST API
- Pharmacokinetic data (half-life, metabolites, detection windows) confirmed via Moosmann 2014 [Ref 1]
- Historical name Ro 5-3448 confirmed via Moosmann 2014 [Ref 1]
- US, UK, Germany, EU legal status confirmed via web sources and Federal Register
- Reinforcing properties confirmed in rodent model (Lee et al. 2024 [Ref 2])
- Metabolic interaction with oxycodone confirmed (Lawson et al. 2023 [Ref 4])