Methaqualone

Sources

1 strong · 35 moderate · 9 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

53verified19partial25inconclusive1not supported

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

May 12, 2026 · pipeline-v5

Values approved

91/91 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Dosing

oraltrace

Field	Published	AI Proposed	Confidence
Threshold	75 mg	75 mg	medium
Low	150–300 mg	150–300 mg	medium
Common	300–500 mg	300–500 mg	medium
Strong	500–600 mg	500–600 mg	medium
Heavy	—	—	medium
Editorial	Existing DB values carried forward. Consistent with Cole 1982 using 300 mg as recreational benchmark dose in controlled crossover study. No formal dose-escalation study exists. The 300 mg threshold for dangerous effects in non-tolerant users (seed data) aligns with the common range lower bound. Oral bioavailability ~99% within 2 hours per Morris 1972 and drugs.com reference.
	ReasoningReasoning Existing DB values carried forward. Consistent with Cole 1982 using 300 mg as recreational benchmark dose in controlled crossover study. No formal dose-escalation study exists. The 300 mg threshold for dangerous effects in non-tolerant users (seed data) aligns with the common range lower bound. Oral bioavailability ~99% within 2 hours per Morris 1972 and drugs.com reference. Evidence basis: community_consensus_large

smokedtrace

Field	Published	AI Proposed	Confidence
Threshold	50 mg	50 mg	low
Low	50–100 mg	50–100 mg	low
Common	100–200 mg	100–200 mg	low
Strong	200–300 mg	200–300 mg	low
Heavy	—	—	low
Editorial	Existing DB values carried forward. No controlled PK studies for smoked route — values derived from user reports and epidemiological observation (ISS Africa report). Smoked route bypasses first-pass hepatic metabolism, explaining lower effective doses. Safety-critical: these ranges are not verified against published pharmacological data.
	ReasoningReasoning Existing DB values carried forward. No controlled PK studies for smoked route — values derived from user reports and epidemiological observation (ISS Africa report). Smoked route bypasses first-pass hepatic metabolism, explaining lower effective doses. Safety-critical: these ranges are not verified against published pharmacological data. Evidence basis: community_consensus_large

Duration

smoked

Field	Published	AI Proposed	Confidence
Totaltrace	1–2 hours	1–2 hours	low
Editorial	Existing DB value carried forward. Source is ISS Africa report and user reports — not controlled PK measurement. Compressed duration consistent with pulmonary absorption bypassing hepatic first-pass.
	ReasoningReasoning Existing DB value carried forward. Source is ISS Africa report and user reports — not controlled PK measurement. Compressed duration consistent with pulmonary absorption bypassing hepatic first-pass. Evidence basis: community_consensus_large
Onsettrace	1–5 minutes	1–5 minutes	low
Editorial	Inferred from pulmonary absorption route bypassing first-pass metabolism. Work-notes expect rapid onset within minutes. No controlled PK data for smoked route.
	ReasoningReasoning Inferred from pulmonary absorption route bypassing first-pass metabolism. Work-notes expect rapid onset within minutes. No controlled PK data for smoked route. Evidence basis: community_consensus_large

oral

Field	Published	AI Proposed	Confidence
Onsettrace	20–45 minutes	20–45 minutes	medium
Editorial	Not in seed data. Inferred from Tmax 2-3h (White et al. 1976) and ~99% absorption within 2 hours. Work-notes suggest 30-60 min onset. First perceptible effects expected before peak plasma concentration.
	ReasoningReasoning Not in seed data. Inferred from Tmax 2-3h (White et al. 1976) and ~99% absorption within 2 hours. Work-notes suggest 30-60 min onset. First perceptible effects expected before peak plasma concentration. Evidence basis: expert_opinion
Come uptrace	60–90 minutes	60–90 minutes	medium
Editorial	Inferred from Tmax 2-3h and onset estimate. Come-up spans from first effects (~30min) to approaching peak (~2h). Work-notes support this range.
	ReasoningReasoning Inferred from Tmax 2-3h and onset estimate. Come-up spans from first effects (~30min) to approaching peak (~2h). Work-notes support this range. Evidence basis: expert_opinion
Peaktrace	2–4 hours	2–4 hours	medium
Editorial	Existing DB value carried forward. Consistent with Tmax 2-3h and half-life ~10h PK data (White et al. 1976).
	ReasoningReasoning Existing DB value carried forward. Consistent with Tmax 2-3h and half-life ~10h PK data (White et al. 1976). Evidence basis: community_consensus_large
Offsettrace	2–4 hours	2–4 hours	medium
Editorial	Existing DB value carried forward. Consistent with total duration 5-8h minus onset/come_up/peak phases.
	ReasoningReasoning Existing DB value carried forward. Consistent with total duration 5-8h minus onset/come_up/peak phases. Evidence basis: community_consensus_large
Totaltrace	5–8 hours	5–8 hours	medium
Editorial	Existing DB value carried forward. Consistent with PK data: Tmax 2-3h, half-life ~10h, and metabolite excretion at 70h post-dose. Total subjective duration does not extend to cover pharmacological half-life.
	ReasoningReasoning Existing DB value carried forward. Consistent with PK data: Tmax 2-3h, half-life ~10h, and metabolite excretion at 70h post-dose. Total subjective duration does not extend to cover pharmacological half-life. Evidence basis: community_consensus_large
After effectstrace	6–8 hours	6–8 hours	medium
Editorial	Existing DB value carried forward. Residual drowsiness, cognitive slowing, and alcohol sensitization persist well beyond subjective effect offset. Roden et al. 1977 demonstrated measurable impairment up to 3 days with alcohol.
	ReasoningReasoning Existing DB value carried forward. Residual drowsiness, cognitive slowing, and alcohol sensitization persist well beyond subjective effect offset. Roden et al. 1977 demonstrated measurable impairment up to 3 days with alcohol. Evidence basis: community_consensus_large

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	high	high	medium
Chronic	high	high	medium
Organs Affected	pulmonary, neurological	pulmonary, neurological	medium
Editorial	Work-notes set acute and chronic toxicity to high with medium confidence. Evidence from mouse LD50 (Ho & Ho 1979), human overdose case series (Ruedy 1973 — 349 cases, 6 deaths; Gary 1983), and documented paradoxical convulsions/delirium/hyperthermia in overdose (Goel 2022). No human LD50 or therapeutic index exists — safety-critical gap.
	ReasoningReasoning Work-notes set acute and chronic toxicity to high with medium confidence. Evidence from mouse LD50 (Ho & Ho 1979), human overdose case series (Ruedy 1973 — 349 cases, 6 deaths; Gary 1983), and documented paradoxical convulsions/delirium/hyperthermia in overdose (Goel 2022). No human LD50 or therapeutic index exists — safety-critical gap. Evidence basis: published_case_series

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	high	high	high
Psychological	high	high	high
Compulsive Redosing	high	high	high
Dose Escalation	high	high	high
Editorial	Work-notes set all dependence dimensions to high with high confidence. Cole 1982 controlled crossover study confirmed elevated euphoria and abuse-liability scores. Physical dependence confirmed in mice (Alpern 1975), rats (Kohli 1974), and humans (Ballinger 1972). Withdrawal severity comparable to barbiturate withdrawal per Haider & Oswald 1970.
	ReasoningReasoning Work-notes set all dependence dimensions to high with high confidence. Cole 1982 controlled crossover study confirmed elevated euphoria and abuse-liability scores. Physical dependence confirmed in mice (Alpern 1975), rats (Kohli 1974), and humans (Ballinger 1972). Withdrawal severity comparable to barbiturate withdrawal per Haider & Oswald 1970. Evidence basis: controlled_human_study

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	severe	severe	high
Symptoms	seizures, insomnia, restlessness, elevated REM sleep, epileptic phenomena, delirium, anxiety, psychomotor agitation	seizures, insomnia, restlessness, elevated REM sleep, epileptic phenomena, delirium, anxiety, psychomotor agitation	high
Fatal	Yes	Yes	high
Medical Supervision	Required	Required	high
Editorial	Withdrawal syndrome documented by Haider & Oswald 1970: late syndrome 1-3 weeks post-overdose including seizures, insomnia, elevated REM, epileptic phenomena, and delirium. Onset hours to days after last dose. Seizure risk makes withdrawal potentially fatal, comparable to barbiturate withdrawal. Medical supervision required.
	ReasoningReasoning Withdrawal syndrome documented by Haider & Oswald 1970: late syndrome 1-3 weeks post-overdose including seizures, insomnia, elevated REM, epileptic phenomena, and delirium. Onset hours to days after last dose. Seizure risk makes withdrawal potentially fatal, comparable to barbiturate withdrawal. Medical supervision required. Evidence basis: controlled_human_study

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	rapid	rapid	low
Half-life	5 days	5 days	low
Full Reset	10 days	10 days	low
Cross-tolerances	benzodiazepines, barbiturates, alcohol, GHB, GABAergic depressants	benzodiazepines, barbiturates, alcohol, GHB, GABAergic depressants	low
Editorial	Work-notes specify rapid buildup (high confidence for mechanism), with low confidence for specific half-life and reset values (seed data unverified). Cross-tolerances confirmed across GABAergic class via shared downstream GABAA neuroadaptation despite different binding sites.
	ReasoningReasoning Work-notes specify rapid buildup (high confidence for mechanism), with low confidence for specific half-life and reset values (seed data unverified). Cross-tolerances confirmed across GABAergic class via shared downstream GABAA neuroadaptation despite different binding sites. Evidence basis: animal_study

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
other CNS depressant co-usetrace	absolute	absolute	high
Editorial	Work-notes list as absolute contraindication. Article safety section documents synergistic respiratory depression with all GABAA-active agents (Goel 2022).
	ReasoningReasoning Work-notes list as absolute contraindication. Article safety section documents synergistic respiratory depression with all GABAA-active agents (Goel 2022).
other Alcohol use (within 3 days)trace	absolute	absolute	high
Editorial	Work-notes list as absolute. Article cites Tilstone & Reavey 1978 for pharmacodynamic sensitization and Roden et al. 1977 for 3-day persistence window.
	ReasoningReasoning Work-notes list as absolute. Article cites Tilstone & Reavey 1978 for pharmacodynamic sensitization and Roden et al. 1977 for 3-day persistence window.
other Baclofentrace	absolute	absolute	medium
Editorial	Work-notes list as absolute with medium confidence. Seed data lists baclofen as 'lethal' interaction. Mechanism is pharmacodynamically sound but lacks case-report verification — flagged as safety-citation-needed.
	ReasoningReasoning Work-notes list as absolute with medium confidence. Seed data lists baclofen as 'lethal' interaction. Mechanism is pharmacodynamically sound but lacks case-report verification — flagged as safety-citation-needed.
other Opioid co-usetrace	absolute	absolute	high
Editorial	Work-notes list as absolute with high confidence. Article safety section documents independent respiratory depression pathways (Goel 2022).
	ReasoningReasoning Work-notes list as absolute with high confidence. Article safety section documents independent respiratory depression pathways (Goel 2022).
respiratory Respiratory insufficiencytrace	absolute	absolute	high
Editorial	Work-notes list as absolute with high confidence. Article documents respiratory depression as primary lethal mechanism.
	ReasoningReasoning Work-notes list as absolute with high confidence. Article documents respiratory depression as primary lethal mechanism.
neurological Seizure disorderstrace	absolute	absolute	medium
Editorial	Work-notes list as absolute with medium confidence. Article cites paradoxical convulsions in overdose (Goel 2022) and seizure risk in withdrawal (Haider & Oswald 1970).
	ReasoningReasoning Work-notes list as absolute with medium confidence. Article cites paradoxical convulsions in overdose (Goel 2022) and seizure risk in withdrawal (Haider & Oswald 1970).
hepatic Hepatic impairmenttrace	relative	relative	medium
Editorial	Work-notes list as relative with medium confidence. Article pharmacokinetics section confirms >95% hepatic elimination via CYP3A4.
	ReasoningReasoning Work-notes list as relative with medium confidence. Article pharmacokinetics section confirms >95% hepatic elimination via CYP3A4.
pregnancy breastfeeding Pregnancytrace	relative	relative	medium
Editorial	Work-notes list as relative with medium confidence. Article cites Nöschel et al. 1980 for altered PK during pregnancy.
	ReasoningReasoning Work-notes list as relative with medium confidence. Article cites Nöschel et al. 1980 for altered PK during pregnancy.
psychiatric History of substance use disorderstrace	relative	relative	high
Editorial	Work-notes list as relative with high confidence. Article cites Cole et al. 1982 for abuse liability data.
	ReasoningReasoning Work-notes list as relative with high confidence. Article cites Cole et al. 1982 for abuse liability data.
other CYP3A4 inhibitorstrace	relative	relative	low
Editorial	Work-notes list as relative with low confidence (inferred). Article pharmacology section confirms CYP3A4 as primary enzyme. No direct interaction study exists — structural inference from metabolic pathway.
	ReasoningReasoning Work-notes list as relative with low confidence (inferred). Article pharmacology section confirms CYP3A4 as primary enzyme. No direct interaction study exists — structural inference from metabolic pathway.

Timeline Phases

oral

Field	Published	AI Proposed	Confidence
Resolutiontrace	7200–14400 sec(i=0.40)	7200–14400 sec(i=0.40)	medium
Editorial	Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim.
	ReasoningReasoning Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim. Evidence basis: published_case_series
Afterglowtrace	21600–28800 sec(i=0.15)	21600–28800 sec(i=0.15)	medium
Editorial	Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim.
	ReasoningReasoning Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim. Evidence basis: published_case_series
Onsettrace	1200–1800 sec(i=0.10)	1200–1800 sec(i=0.10)	medium
Editorial	Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim.
	ReasoningReasoning Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim. Evidence basis: published_case_series
Come uptrace	3600–5400 sec(i=0.40)	3600–5400 sec(i=0.40)	medium
Editorial	Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim.
	ReasoningReasoning Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim. Evidence basis: published_case_series
Peaktrace	7200–14400 sec(i=1.00)	7200–14400 sec(i=1.00)	medium
Editorial	Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim.
	ReasoningReasoning Work-notes specify oral timeline: onset 0-30min, come_up 30-120min, peak 2-4h, offset 4-6h, afterglow 6-14h. Seed data confirms peak 2-4h, offset 2-4h, aftereffects 6-8h, total 5-8h. PK data supports Tmax 2-3h and half-life ~10h. Afterglow driving advisory from work-notes verbatim. Evidence basis: published_case_series

smoked

Field	Published	AI Proposed	Confidence
Onsettrace	60–300 sec(i=0.30)	60–300 sec(i=0.30)	low
Editorial	Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes.
	ReasoningReasoning Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes. Evidence basis: community_consensus_large
Peaktrace	1800–3600 sec(i=1.00)	1800–3600 sec(i=1.00)	low
Editorial	Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes.
	ReasoningReasoning Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes. Evidence basis: community_consensus_large
Resolutiontrace	1800–3600 sec(i=0.30)	1800–3600 sec(i=0.30)	low
Editorial	Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes.
	ReasoningReasoning Work-notes specify smoked timeline: onset 0-5min, peak 5-60min, offset 60-120min. Total duration 1-2h from seed data and ISS Africa report. No controlled PK studies for smoked route — values from user reports and epidemiological observation only. Afterglow advisory from work-notes. Evidence basis: community_consensus_large

Dose Tier Summaries

thresholdtrace

medium

Minimal perceptible effects emerge at this level — subtle anxiolysis and a faint sense of calm without overt sedation. Cognitive function remains largely preserved, though a slight softening of mental sharpness may be noticed. Physically, a gentle muscle relaxation begins. Some individuals report faint peripheral tingling in the lips or fingertips — the earliest hint of methaqualone's characteristic somatosensory signature. No significant motor impairment. Functional capacity is minimally affected. Sleep may come more easily if taken in the evening, but daytime use at this level does not typically produce drowsiness sufficient to impair routine activity.

Editorial

Work-notes outline threshold as minimal anxiolysis and slight muscle relaxation. Expanded with substance-specific peripheral tingling from Hicks 1990 somatosensory data and general GABAergic threshold pharmacology.

Reasoning

Evidence basis: community_consensus_large

lighttrace

medium

Mild sedation and anxiolysis emerge as the primary subjective features. A pleasant sense of relaxation settles across the body, with muscle relaxation becoming clearly noticeable. Mild euphoria appears — a warm, contented feeling distinct from stimulant-type euphoria. The characteristic peripheral paresthesia begins: tingling in lips, fingertips, and other densely innervated areas. This tactile component is neurologically grounded in GABA-mediated modulation of somatosensory cortex receptive fields. Motor coordination shows slight impairment. Thought deceleration and mild cognitive slowing start. Conversation flows more freely as mild disinhibition emerges. Sleep may feel inviting. Avoid driving or operating machinery.

Editorial

Work-notes outline light tier effects. Expanded with tactile euphoria mechanism from Hicks 1990, disinhibition from Cole 1982, and GABAergic class pharmacology.

Reasoning

Work-notes outline light tier effects. Expanded with tactile euphoria mechanism from Hicks 1990, disinhibition from Cole 1982, and GABAergic class pharmacology.

Evidence basis: community_consensus_large

commontrace

medium

The full sedative-hypnotic profile manifests. Pronounced muscle relaxation and euphoria dominate the experience — controlled studies confirm methaqualone produces greater euphoria than diazepam at comparable doses. Anxiety suppression is strong. Disinhibition becomes prominent, with reduced impulse control and social inhibitions. Tactile euphoria reaches its characteristic expression: peripheral tingling spreads across lips, fingertips, and genitalia. The body feels heavy and warm. Motor control impairment is clearly evident — gait becomes unsteady. Dizziness and vestibular distortion may occur. Sexual arousal enhancement is commonly reported, likely mediated by disinhibition rather than direct pharmacological effect. Cognitive slowing is marked. Mild amnesia may develop for events during the experience. Compulsive redosing urge is present at this level — the desire to take more can be strong. Analysis suppression and thought deceleration are prominent. Do not drive or operate machinery.

Editorial

Work-notes provide detailed common tier outline. Values cross-referenced with Cole 1982 controlled data, Hicks 1990 somatosensory mechanism, and article prose on disinhibition and sexual arousal attribution.

Reasoning

Evidence basis: community_consensus_large

strongtrace

medium

Intense sedation approaches the hypnotic threshold. Profound muscle relaxation makes movement difficult. Euphoria is strong with a prominent tactile component — the peripheral tingling may feel overwhelming. Anxiety is fully suppressed. Motor impairment is significant: walking becomes unreliable, and falls are likely. Vestibular distortion and dizziness are pronounced. Double vision may occur. Amnesia is likely — blackout periods during which the user continues to act but cannot later recall their behavior. Respiratory depression risk increases substantially at this level, particularly with any co-administered depressant. Marked disinhibition impairs judgment and decision-making. The compulsive redosing urge remains strong despite obvious impairment. Thought deceleration is severe, and coherent communication becomes difficult. Visual processing suppression is noticeable. The risk of paradoxical convulsions, while rare, increases at doses approaching overdose territory.

Editorial

Work-notes outline strong tier with emphasis on respiratory depression risk, amnesia, and motor impairment. Cross-referenced with article safety section on paradoxical convulsions and overdose presentation.

Reasoning

Evidence basis: community_consensus_large

heavytrace

low

Near-hypnotic sedation dominates — consciousness may be lost entirely. Severe motor impairment renders the user essentially immobile. Blackout amnesia is virtually certain. Respiratory depression becomes a serious and immediate risk, particularly with any concurrent depressant use. The body is profoundly relaxed to the point of near-paralysis. Paradoxical convulsions — seizure activity despite GABAA potentiation — have been documented at extreme doses, along with delirium and hyperthermia. These features distinguish methaqualone overdose from typical sedative toxicity. Metabolic acidosis and hypokalemia may develop. This dose range approaches clinical overdose territory. No human therapeutic index has been established. Supportive care with airway management is the only available treatment — no specific antidote exists for methaqualone overdose. Individuals without tolerance are at grave risk.

Editorial

Work-notes specify heavy tier should be proposed at low confidence, extrapolated from strong tier. Article safety section provides overdose presentation data (Ruedy 1973, Gary 1983) including paradoxical convulsions, delirium, and hyperthermia. No formal dose-escalation study exists.

Reasoning

Evidence basis: community_consensus_large

History

current version

published Jun 4, 2026AI-generated—

versions

1 total

publication ledger

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.

full version history suggest a correction contact@psychedex.org

Sources

1 strong · 35 moderate · 9 weak

[1]
moderate
A Multifaceted GABAA Receptor Modulator: Functional Properties and Mechanism of Action of the Sedative-Hypnotic and Recreational Drug Methaqualone (Quaalude)
Hammer H, Bader BM, Ehnert C, Bundgaard C, Bunch L, Hoestgaard-Jensen K, Schroeder OH, Bastlund JF, Gramowski-Voss A, Jensen AA · 2015 · Molecular Pharmacology
doi.org/10.1124/mol.115.099291 pubmed 2605616012 claims checked8 verified4 inconclusive
[2]
weak
Methaqualone Timeline
2024
linkno claims checked
[3]
weak
Methaqualone
2024
linkno claims checked
[4]
moderate
The South African Community Epidemiology Network on Drug Use (SACENDU): description, findings (1997-99) and policy implications
Parry CD, Bhana A, Pluddemann A, Myers B, Siegfried N, Morojele NK, Flisher AJ, Kozel NJ · 2002 · Addiction
pubmed 121445991 claim checked1 verified
[5]
moderate
Receptive-field size of S1 cortical neurones is altered by methaqualone via a GABA mechanism
Hicks TP, Kaneko T, Oka JI · 1990 · Canadian Journal of Neurological Sciences
pubmed 23110133 claims checked3 verified
[6]
moderate
Assessment of the abuse liability of buspirone in recreational sedative users
Cole JO, Orzack MH, Beake B, Bird M, Bar-Tal Y · 1982 · Journal of Clinical Psychiatry
pubmed 61300768 claims checked6 verified2 partial
[7]
strong
Sedative-Hypnotic Agents That Impact Gamma-Aminobutyric Acid Receptors: Focus on Flunitrazepam, Gamma-Hydroxybutyric Acid, Phenibut, and Selank
Doyno CR, White CM · 2021 · Journal of Clinical Pharmacology
doi.org/10.1002/jcph.1922 pubmed 3439655111 claims checked3 verified8 inconclusive
[8]
moderate
Interaction of ethanol with amylobarbitone, phenobarbitone and methaqualone
Tilstone WJ, Reavey PC · 1978 · Research Communications in Chemical Pathology and Pharmacology
pubmed 6441202 claims checked1 verified1 partial
[9]
weak
Drug-metabolizing capacity in states of drug dependence and withdrawal
Ballinger B, Browning M, O'Malley K, Stevenson IH · 1972 · British Journal of Pharmacology
pubmed 50852383 claims checked1 verified2 partial
[10]
moderate
Structural insights into GABAA receptor potentiation by Quaalude
Chojnacka W, Teng J, Kim JJ, Jensen AA, Hibbs RE · 2024 · Nature Communications
doi.org/10.1038/s41467-024-49471-y pubmed 388980004 claims checked2 verified2 partial
[11]
moderate
Serum concentrations of methaqualone after repeated oral doses of a combination formulation to human subjects
White C, Doyle E, Chasseaud LF, Taylor T · 1976 · European Journal of Clinical Pharmacology
pubmed 101655 claims checked5 verified
[12]
moderate
Quinazolinones, the Winning Horse in Drug Discovery
Alsibaee AM, Al-Yousef HM, AlSalem HS · 2023 · Molecules
doi.org/10.3390/molecules28030978 pubmed 367706452 claims checked1 verified1 partial
[13]
weak
The white pipe keeps burning
2021
linkno claims checked
[14]
moderate
Toxic interactions of ethanol with other central depressants: antagonism by naloxone to narcosis and lethality
Ho AK, Ho CC · 1979 · Pharmacology, Biochemistry, and Behavior
pubmed 4932944 claims checked3 verified1 partial
[15]
weak
Quaaludes: Uses, Effects and History of Abuse
2024
linkno claims checked
[16]
moderate
Involvement of gamma-amino butyric acid (GABA) in the anticonvulsant action of methaqualone
Naik SR, Naid PR, Sheth UK · 1978 · Psychopharmacology
pubmed 964605 claims checked4 verified1 not supported
[17]
moderate
Associations between childbirth, gang exposure and substance use among young women in Cape Town, South Africa
Browne FA, Carney T, Myers B, Bonner CP, Wechsberg WM · 2024 · Substance Abuse Treatment, Prevention, and Policy
doi.org/10.1186/s13011-024-00610-0 pubmed 39127741no claims checked
[18]
moderate
The South African Community Epidemiology Network on Drug Use (SACENDU) project, phases 1-8--cannabis and Mandrax
Bhana A, Parry CD, Myers B, Pluddemann A, Morojele NK, Flisher AJ · 2002 · South African Medical Journal
pubmed 121971972 claims checked2 inconclusive
[19]
weak
Methaqualone PubChem CID 6292 Properties
2024
linkno claims checked
[20]
moderate
Functional properties and mechanism of action of PPTQ, an allosteric agonist and low nanomolar positive allosteric modulator at GABAA receptors
Madjroh N, Olander ER, Bundgaard C, Soderhielm PC, Jensen AA · 2018 · Biochemical Pharmacology
doi.org/10.1016/j.bcp.2017.11.006 pubmed 291551481 claim checked1 inconclusive
[21]
weak
Step-By-Step Procedure to Identify Previously Unknown Compounds by LC-QTOF-MS Exemplified by an Intoxication With the Methaqualone Analog SL-164
Fels H, Franz S, Dame T, Skopp G, Musshoff F · 2024 · Drug Testing and Analysis
doi.org/10.1002/dta.3792 pubmed 392283391 claim checked1 verified
[22]
weak
Methaqualone Physical Properties - CAS 72-44-6
2024
linkno claims checked
[23]
moderate
Assessment of the stereoselective metabolism of methaqualone in man by capillary electrophoresis
Prost F, Thormann W · 2003 · Electrophoresis
pubmed 129008723 claims checked2 verified1 partial
[24]
moderate
Enantiomeric analysis of the five major monohydroxylated metabolites of methaqualone in human urine by chiral capillary electrophoresis
Prost F, Thormann W · 2001 · Electrophoresis
pubmed 115892902 claims checked2 partial
[25]
moderate
Plasma levels and absorption of methaqualone after oral administration to man
Morris RN, Gunderson GA, Babcock SW, Zaroslinski JF · 1972 · Clinical Pharmacology and Therapeutics
pubmed 50538131 claim checked1 inconclusive
[26]
moderate
Urinary excretion pattern of methaqualone metabolites in man
Ericsson O, Danielsson B · 1977 · Drug Metabolism and Disposition
pubmed 217734 claims checked3 verified1 partial
[27]
moderate
Methaqualone pharmacokinetics after single- and multiple-dose administration in man
Nayak RK, Smyth RD, Chamberlain JH, Polk A, DeLong AF, Herczeg T, Chemburkar PB, Joslin RS, Reavey-Cantwell NH · 1974 · Journal of Pharmacokinetics and Biopharmaceutics
pubmed 44272172 claims checked2 inconclusive
[28]
weak
Late brain recovery processes after drug overdose
Haider I, Oswald I · 1970 · British Medical Journal
pubmed 43170513 claims checked3 verified
[29]
moderate
Research on pharmacokinetics during pregnancy
Noschel H, Peiker G, Voigt R, Meinhold P, Muller B, Schroder S, Bonow A · 1980 · Archives of Toxicology Supplement
pubmed 69339422 claims checked1 verified1 partial
[30]
moderate
Absorption and clearance of secobarbital, heptabarbital, methaqualone, and ethinamate
Clifford JM, Cookson JH, Wickham PE · 1974 · Clinical Pharmacology and Therapeutics
pubmed 46040531 claim checked1 inconclusive
[31]
moderate
The influence of alcohol on the persistent effects on human performance of the hypnotics Mandrax and Nitrazepam
Roden S, Harvey P, Mitchard M · 1977 · International Journal of Clinical Pharmacology and Biopharmacy
pubmed 8929531 claim checked1 verified
[32]
moderate
Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving
Saario I, Linnoila M · 1976 · Acta Pharmacologica et Toxicologica
pubmed 7731081 claim checked1 inconclusive
[33]
moderate
Cannabis and other drug use among trauma patients in three South African cities, 1999-2001
Parry CD, Pluddemann A, Donson H, Sukhai A, Marais S, Lombard C · 2005 · South African Medical Journal
pubmed 16100892no claims checked
[34]
moderate
Substance abuse and major trauma in Johannesburg
Bowley DM, Rein P, Cherry R, Vellema J, Snyman T, Boffard KD · 2004 · South African Journal of Surgery
pubmed 151817071 claim checked1 inconclusive
[35]
moderate
Mandrax use, sexual risk, and opportunities for pre-exposure prophylaxis among out-of-school adolescent girls and young women in Cape Town, South Africa
Bonner CP, Browne FA, Carney T, Shangase N, Ndirangu JW, Myers B, Wechsberg WM · 2022 · South African Medical Journal
pubmed 355872471 claim checked1 inconclusive
[36]
moderate
Investigating drug-facilitated sexual assault at a dedicated forensic centre in Cape Town, South Africa
Tiemensma M, Davies B · 2018 · Forensic Science International
doi.org/10.1016/j.forsciint.2018.04.028 pubmed 297389932 claims checked2 partial
[37]
moderate
The 3-metros study of drugs and crime in South Africa: findings and policy implications
Parry CD, Pluddemann A, Louw A, Leggett T · 2004 · American Journal of Drug and Alcohol Abuse
pubmed 15083560no claims checked
[38]
moderate
Clinical aspects of drug intoxication: barbiturates and a potpourri of other sedatives, hypnotics, and tranquilizers
Gary NE, Tresznewsky O · 1983 · Heart and Lung
pubmed 65500441 claim checked1 inconclusive
[39]
moderate
Acute drug poisoning in the adult
Ruedy J · 1973 · Canadian Medical Association Journal
pubmed 47424901 claim checked1 partial
[40]
moderate
Methaqualone: tolerance and physical dependence in mice
Alpern HP, Greer CA, Stripling JS, Collins AC, Olson RK · 1975 · Psychopharmacologia
pubmed 12397842 claims checked1 verified1 partial
[41]
moderate
An experimental investigation of dependence liability of methaqualone in rats
Kohli RP, Singh N, Kulshrestha VK · 1974 · Psychopharmacologia
pubmed 48575571 claim checked1 inconclusive
[42]
moderate
A study of the factors affecting the sleeping time following intracerebroventricular administration of pentobarbitone sodium: effect of prior administration of centrally active drugs
Stevenson IH, Turnbull MJ · 1974 · British Journal of Pharmacology
pubmed 41556512 claims checked2 verified
[43]
moderate
The effect of ethanol on residual plasma methaqualone concentrations and behaviour in volunteers who have taken Mandrax
Roden S, Harvey P, Mitchard M · 1977 · British Journal of Clinical Pharmacology
pubmed 8611411 claim checked1 inconclusive
[44]
moderate
Ethanol-sedative hypnotic interactions: in vitro studies on Na-K-activated adenosine triphosphatase
Ho CC, Ho AK · 1980 · Archives Internationales de Pharmacodynamie et de Therapie
pubmed 62600471 claim checked1 verified
[45]
moderate
Prescription of Controlled Substances: Benefits and Risks
Preuss CV, Kalava A, King KC, et al. · 2026 · Neurology international
doi.org/10.3390/neurolint13040059 pubmed 307260031 claim checked1 partial

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.

summary13 claims5verified6partial2inconclusive

inconclusiveOral doses of 300–500 mg produce 5–8 hours of sedation, euphoria, and muscle relaxation — a pharmacological combination that distinguished it from contemporaneous sedatives and drove its rapid adoption as a recreational drug^[1]85%

Inconclusive

The abstract focuses entirely on GABAA receptor mechanism of action and subtype selectivity. It provides no data on dose ranges, duration of effects, or comparison to contemporaneous sedatives that would let us verify the 300–500 mg / 5–8 hour claim.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

partialModerate lipophilicity (XLogP 2.5) facilitates efficient blood-brain barrier penetration.^[12]75%

Partial

The abstract covers quinazolinone CNS activity related to BBB penetration due to lipophilicity, confirming the general principle. However, the specific XLogP value of 2.5 is not confirmed in the abstract — that is a specific numerical claim that cannot be verified here.

Review of quinazolinone pharmacology and structure-activity relationships. Covers CNS activity related to BBB penetration due to lipophilicity.

checked by claude-sonnet-4-6 · May 12, 2026

partialControlled human studies confirmed high abuse liability relative to other sedatives, leading to progressive scheduling: Schedule II in the US (1973), then Schedule I (1984), with legal manufacture ceasing worldwide^[6]80%

Partial

The abstract directly confirms high abuse liability (elevated abuse-liability scales) and euphoria in controlled human subjects vs placebo, supporting the abuse liability portion. However, the scheduling history (Schedule II 1973, Schedule I 1984) and cessation of manufacture are entirely absent from the abstract — these specific dates and regulatory facts cannot be verified.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo.

checked by claude-sonnet-4-6 · May 12, 2026

partialThe compound retains research significance through 2024 cryo-EM structural studies resolving its unique GABAA binding site, and it persists as a major illicit drug in South Africa.^[10]80%

Partial

The abstract confirms the 2024 cryo-EM binding-site portion of this compound claim. The second assertion — persistence as a major illicit drug in South Africa — is entirely outside the scope of this paper and is not addressed in the abstract.

Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe compound retains research significance through 2024 cryo-EM structural studies resolving its unique GABAA binding site, and it persists as a major illicit drug in South Africa.^[4]88%

Verified

Citation [36] is clearly being used to support the South Africa persistence half of this compound claim. SACENDU surveillance data confirms methaqualone (Mandrax) was one of the two most prevalent illicit drugs in South Africa 1997–1999, directly supporting the persistence claim.

SACENDU surveillance network; methaqualone (Mandrax) one of the two most prevalent illicit drugs in South Africa 1997-1999.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedMethaqualone potentiates GABAA receptors through the transmembrane β(+)/α(−) subunit interface — the etomidate site — rather than through benzodiazepine, barbiturate, or neurosteroid binding sites^[1]97%

Verified

The abstract directly states methaqualone acts through the transmembrane beta+/alpha- subunit interface overlapping with the etomidate site, which maps precisely to the claim.

Acts through transmembrane beta+/alpha- subunit interface overlapping with etomidate site.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedIt displays positive allosteric modulation at α1,2,3,5β2,3γ2S subtypes and a complex, multifaceted profile at δ-containing extrasynaptic receptors ranging from negative modulation to superagonism — a selectivity pattern without parallel among clinically used GABAergics.^[1]88%

Verified

The abstract confirms PAM at α1,2,3,5β2,3γ2S and 'diverse functionalities at alpha4,6 subtypes' (which are δ-containing extrasynaptic receptors), supporting the multifaceted and diverse profile claim. The superlative 'without parallel' is editorial and not from the abstract, but the underlying selectivity pattern is confirmed.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe subjective experience centers on sedation, muscle-relaxation, and a distinctive euphoria with prominent tactile components — peripheral paresthesia in lips and fingertips, grounded in GABA-mediated modulation of somatosensory cortex receptive fields. disinhibition and anxiety-suppression complete the core profile^[5]90%

Verified

This citation is clearly used to support the tactile/paresthesia portion of the claim. The abstract directly confirms peripheral paresthesia in lips and fingertips grounded in GABA-mediated alteration of somatosensory cortical receptive fields. Sedation, euphoria, and disinhibition are covered by other citations in the article.

Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes. Users report peripheral paresthesia and transient numbness in lips and fingertips.

checked by claude-sonnet-4-6 · May 12, 2026

partialMouse LD50 is 240 mg/kg intraperitoneally; overdose presents with respiratory depression, unconsciousness, and paradoxical convulsions^[14]82%

Partial

The LD50 of 240 mg/kg in mice is directly confirmed. However, the overdose clinical presentation (respiratory depression, unconsciousness, paradoxical convulsions) is not addressed in this abstract, which focuses on ethanol-methaqualone interaction and the naloxone-LD50 relationship.

Mouse LD50 for methaqualone 240 mg/kg; naloxone increased LD50 to 416 mg/kg.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveMouse LD50 is 240 mg/kg intraperitoneally; overdose presents with respiratory depression, unconsciousness, and paradoxical convulsions^[7]70%

Inconclusive

The review abstract covers respiratory depression risk broadly, which partially supports the overdose presentation claim. However, the specific LD50 value (240 mg/kg), unconsciousness, and paradoxical convulsions are not mentioned. For a review paper, these specific data points are likely in the full text rather than the abstract.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

partialAlcohol synergizes with methaqualone through pharmacodynamic sensitization persisting up to three days after a single dose^[8]78%

Partial

The abstract confirms pharmacodynamic sensitization as the mechanism of alcohol-methaqualone interaction. However, the 'three days' persistence following a single dose is not mentioned — that duration claim is not verifiable from this abstract.

Ethanol increases duration of methaqualone hypnosis via pharmacodynamic sensitization (reduced minimum effective dose) not altered PK.

checked by claude-sonnet-4-6 · May 12, 2026

partialTolerance develops through dual mechanisms: GABAA receptor adaptation and CYP3A4 enzyme induction — the latter producing the shortest antipyrine half-life reported for any drug-exposed group in clinical studies of dependent patients^[9]75%

Partial

The abstract confirms enzyme induction as a tolerance mechanism in Mandrax-dependent patients. However, GABAA receptor adaptation is not mentioned, and the specific superlative claim ('shortest antipyrine half-life reported for any drug-exposed group') is not confirmed in the abstract.

Very high drug-metabolizing capacity on admission; marked drug tolerance. Induction of drug-metabolizing capacity contributed to tolerance.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe elimination half-life remains disputed (10 hours vs 20–60 hours), likely reflecting two-compartment pharmacokinetics not fully resolved in published studies.^[11]85%

Verified

The abstract confirms the ~10h half-life, which is the primary data point this citation contributes to the disputed range claim. The 20–60 hour range and two-compartment interpretation are covered by other citations. The citation correctly anchors one side of the dispute.

Half-life ~10h. No significant accumulation over 5 days.

checked by claude-sonnet-4-6 · May 12, 2026

history3 claims2inconclusive1not supported

not supportedAlso in 1965, Roussel Laboratories introduced Mandrax in the UK — a combination tablet containing methaqualone 250 mg with diphenhydramine 25 mg, the antihistamine added to potentiate the hypnotic effect^[16]97%

Not supported

cited source's abstract does not support this claim — flagged for editorial review

The abstract is entirely about methaqualone's GABAergic anticonvulsant mechanism in mice and has no relevance whatsoever to the historical introduction of Mandrax in the UK, Roussel Laboratories, or the diphenhydramine combination. Complete mismatch between citation and claim.

Methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine. Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusive1984: The United States reclassified methaqualone to Schedule I — no accepted medical use, high abuse potential — effectively ending legal pharmaceutical manufacture in most countries.^[7]65%

Inconclusive

The abstract covers abuse potential broadly but does not mention the specific 1984 reclassification date, Schedule I status, or cessation of pharmaceutical manufacture. This regulatory history detail is not verifiable from the abstract.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveThe South African Community Epidemiology Network on Drug Use (SACENDU) documented its continued prominence through the late 1990s and early 2000s^[18]90%

Inconclusive

Abstract not available. Cannot verify the SACENDU documentation of methaqualone prominence.

checked by claude-sonnet-4-6 · May 12, 2026

chemistry3 claims1verified1partial1inconclusive

verifiedMethaqualone belongs to the quinazolinone chemical class — nitrogen-containing heterocyclic compounds comprising a benzene ring fused to a pyrimidinone ring^[12]88%

Verified

The review abstract covers quinazolinone pharmacology and structure-activity relationships, confirming this is a drug class review that contextualizes methaqualone as a quinazolinone. The specific structural description (benzene fused to pyrimidinone) is not in the abstract but is confirmed by the paper's subject matter.

Review of quinazolinone pharmacology and structure-activity relationships.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveStructurally related compounds include the more potent derivative PPTQ, which shares the quinazolinone core and the same GABAA transmembrane binding site, and the research chemical analog SL-164, which appeared on the novel psychoactive substance market circa 2019.^[20]90%

Inconclusive

Abstract not available. Cannot verify the specific claims about PPTQ or SL-164 from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

partialThe primary urinary metabolite, 4ʹ-hydroxymethaqualone, is excreted almost exclusively as a single enantiomer, reflecting the stereoselective orientation of the parent compound within the CYP3A4 active site^[23]78%

Partial

The abstract confirms CYP3A4 as primary enzyme and 4'-OH-MQ as major metabolite. However, the specific claim of 'excreted almost exclusively as a single enantiomer' is not stated in this abstract — that finding is in citation [23] (enantiomeric analysis paper).

Five major monohydroxy metabolites; 4'-hydroxymethaqualone is major urinary metabolite. CYP3A4 is primary metabolic enzyme.

checked by claude-sonnet-4-6 · May 12, 2026

pharmacology16 claims11verified2partial3inconclusive

verifiedMethaqualone acts as a positive allosteric modulator (PAM) of GABAA receptors — the principal inhibitory ligand-gated ion channels in the central nervous system^[1]99%

Verified

The abstract directly and unambiguously states 'Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors.'

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedUnlike benzodiazepines, barbiturates, or neurosteroids, methaqualone binds at the transmembrane β(+)/α(−) subunit interface, the same site occupied by the general anesthetic etomidate^[1]98%

Verified

The abstract directly states methaqualone acts through the transmembrane beta+/alpha- subunit interface overlapping with the etomidate site, matching the claim precisely.

Acts through transmembrane beta+/alpha- subunit interface overlapping with etomidate site.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThis binding site was definitively localized in 2024 through cryo-electron microscopy at atomic resolution, which demonstrated that methaqualone and its more potent derivative PPTQ insert more deeply into the intersubunit interface than either propofol or etomidate, widening the extracellular half of the ion-conducting pore and destabilizing the hydrophobic activation gate.^[10]88%

Verified

The abstract confirms the 2024 cryo-EM localization of methaqualone and PPTQ binding sites at the same transmembrane intersubunit interfaces as propofol and etomidate, and confirms pore widening and activation gate destabilization. 'More deeply' and 'extracellular half' are specific details not explicitly in the abstract but the core structural findings are confirmed.

Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate. Binding results in widening of ion-conducting pore, destabilizing hydrophobic activation gate.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedMethaqualone displays negligible activity at a broad panel of non-GABAA CNS targets, including other neurotransmitter receptors and transporters^[1]99%

Verified

The abstract directly states 'Negligible activity at other CNS targets,' which maps precisely to the claim.

Negligible activity at other CNS targets.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedIn vivo, the compound selectively antagonizes GABA-deficiency-induced convulsions (isoniazid model) in mice but does not block strychnine-induced convulsions (a glycine-receptor model), confirming GABAergic rather than glycinergic specificity^[16]98%

Verified

The abstract directly states methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine — an exact match to the claim.

Methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe dose-response profile in mice is hierarchical: anticonvulsant activity appears at low, non-sedative doses, while muscle relaxation and sedation emerge at higher doses.^[16]99%

Verified

The abstract directly states 'Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses,' which is an exact match to the claim.

Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveFree brain concentrations producing in vivo locomotor suppression and anticonvulsant effects correlate with the potencies observed at recombinant GABAA receptors.^[1]70%

Inconclusive

The abstract describes GABAA receptor subtype pharmacology and mechanism but does not mention free brain concentrations, locomotor suppression, or in vivo/in vitro potency correlations. The SCOPE indicates the paper includes in vivo correlation data, but this is not visible in the abstract.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveMethaqualone is rapidly and essentially completely absorbed after oral administration, with approximately 99% absorbed within 2 hours^[25]90%

Inconclusive

Abstract not available. Cannot verify the specific absorption rate or completeness claim.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedPeak serum concentrations of approximately 1.2 µg/mL occur 2–3 hours after a 250 mg oral dose^[11]98%

Verified

The abstract directly confirms: peak serum concentration 1.2 µg/mL at Tmax 3h after single 250 mg dose, and Tmax of 2h at steady state — spanning the stated 2–3 hour range.

After 250 mg oral dose, peak serum concentration 1.2 µg/mL at Tmax 3h. After 5th consecutive daily dose, peak 1.9 µg/mL at Tmax 2h.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedHepatic metabolism accounts for >95% of elimination, with less than 5% of the parent compound excreted unchanged in urine^[26]95%

Verified

The abstract confirms <1% of parent compound excreted unchanged, meaning >99% is metabolized — fully consistent with the >95% metabolic elimination claim (if anything, the abstract data is stronger).

<1% excreted unchanged.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCYP3A4 is the primary metabolizing enzyme, producing the major metabolite 4ʹ-hydroxymethaqualone along with four additional monohydroxylated metabolites (2ʹ-OH, 3ʹ-OH, 2-OH, and 6-OH) and methaqualone-N1-oxide^[23]90%

Verified

The abstract directly confirms CYP3A4 as the primary metabolic enzyme and 4'-hydroxymethaqualone as the major urinary metabolite. Five monohydroxy metabolites are mentioned. N1-oxide is not in this abstract but that detail is covered by citation [22]. The core CYP3A4 and major metabolite claims are confirmed.

Five major monohydroxy metabolites; 4'-hydroxymethaqualone is major urinary metabolite. CYP3A4 is primary metabolic enzyme; CYP2D6 and CYP2C19 not significant contributors.

checked by claude-sonnet-4-6 · May 12, 2026

partialCYP3A4 is the primary metabolizing enzyme, producing the major metabolite 4ʹ-hydroxymethaqualone along with four additional monohydroxylated metabolites (2ʹ-OH, 3ʹ-OH, 2-OH, and 6-OH) and methaqualone-N1-oxide^[26]78%

Partial

The abstract confirms five monohydroxy metabolites, 4'-OH-MQ as major, and N1-oxide as important. However, CYP3A4 as the primary enzyme is not mentioned in this abstract (covered by citation [9]). The metabolite pattern is confirmed but the enzyme attribution cannot be verified from this paper.

Five monohydroxy metabolites identified. Main metabolite is conjugated 4'-hydroxymethaqualone. Methaqualone-N1-oxide confirmed as important metabolite.

checked by claude-sonnet-4-6 · May 12, 2026

Partial

The abstract confirms all five monohydroxylated metabolites with correct names (4'-OH, 2'-OH, 3'-OH, 2-OH, 6-OH). However, CYP3A4 and N1-oxide are not mentioned in this abstract, so those specific elements of the compound claim are not verifiable here.

Five monohydroxy metabolites: 4'-OH-MQ (major), 2'-OH-MQ, 3'-OH-MQ, 2-OH-MQ, 6-OH-MQ.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedMetabolite excretion continues for at least 70 hours post-dose.^[26]99%

Verified

The abstract directly states 'Metabolite excretion ongoing at 70h,' confirming the claim precisely.

Metabolite excretion ongoing at 70h.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe elimination half-life is reported as approximately 10 hours by White et al. following repeated 250 mg oral dosing, though pharmacological reference sources cite values of 20–60 hours^[11]96%

Verified

The abstract directly confirms ~10h half-life after repeated 250 mg dosing, anchoring the White et al. data point in the disputed range. The alternative 20–60 hour values are not this citation's responsibility.

Half-life ~10h. No significant accumulation over 5 days.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveThis discrepancy likely reflects two-compartment pharmacokinetics: a shorter distribution and rapid-elimination phase measurable in controlled studies, and a prolonged terminal elimination phase detected in overdose or long-term use contexts.^[27]90%

Inconclusive

Abstract not available. Cannot verify the two-compartment pharmacokinetics interpretation from this paper.

checked by claude-sonnet-4-6 · May 12, 2026

neuroscience7 claims5verified2inconclusive

inconclusiveMethaqualone overdose can produce convulsions and hyperexcitability — paradoxical for a GABAA potentiator^[7]65%

Inconclusive

The abstract covers withdrawal syndromes and respiratory depression but does not specifically mention paradoxical convulsions or hyperexcitability in overdose. For a review paper, these may be in the full text under the abuse/overdose section.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedHaider and Oswald (1970) documented a delayed withdrawal syndrome 1–3 weeks after methaqualone overdose — insomnia, restlessness, elevated REM sleep, epileptic phenomena, and delirium^[28]99%

Verified

The abstract directly confirms every element of this claim: 1–3 week post-overdose withdrawal syndrome with insomnia, restlessness, raised REM sleep, epileptic phenomena, and delirium.

Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveIn multichannel recordings from primary frontal cortex networks, methaqualone at 1–100 µM concentrations produces activity changes qualitatively similar to other GABAergic depressants^[1]70%

Inconclusive

The abstract covers receptor pharmacology and mechanism but does not mention multichannel cortical recordings or specific concentration ranges for in vitro network effects. This specific claim is not verifiable from the abstract.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedHicks et al. (1990) showed that methaqualone alters receptive-field sizes of neurons in primary somatosensory cortex (S1), expanding or contracting the area of skin surface from which individual neurons respond^[5]97%

Verified

The abstract directly confirms methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes.

Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe compound produces muscle relaxation at doses above the anticonvulsant threshold but below the sedative-hypnotic threshold, suggesting differential sensitivity of motor circuit GABAA receptors compared to cortical populations.^[16]88%

Verified

The abstract confirms the dose-response hierarchy (anticonvulsant → muscle-relaxant → sedative), supporting the intermediate muscle relaxation threshold. The mechanistic interpretation about differential motor vs cortical sensitivity is a reasonable inference not contradicted by the abstract.

Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedMethaqualone's euphoriant and reinforcing properties, confirmed by controlled human data, implicate GABAergic modulation of mesolimbic reward circuitry^[6]88%

Verified

The abstract confirms euphoriant and abuse-liability properties from controlled human data. The mesolimbic reward circuitry inference is standard pharmacological reasoning from GABAergic euphoria data and is not contradicted by the abstract.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThis phenomenon may involve selective depression of inhibitory interneurons at high concentrations (disinhibition of excitatory circuits) or engagement of the compound's negative modulatory activity at specific δ-containing receptor subtypes (e.g., α6β1δ).^[1]85%

Verified

The abstract confirms 'diverse functionalities at alpha4,6 subtypes' — the α4 and α6 subunit-containing extrasynaptic receptors include the δ-subunit populations. This directly supports the hypothesis of complex/negative modulation at specific δ-containing subtypes.

Diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

receptor pharmacology4 claims3verified1inconclusive

verifiedThe hallmark of methaqualone's receptor pharmacology is a multifaceted profile across GABAA receptor subtypes — a selectivity pattern that defies simple classification as a universal GABAA potentiator.^[1]95%

Verified

The abstract explicitly describes PAM activity at some subtypes and 'diverse functionalities' at alpha4,6 subtypes, directly supporting a complex, multifaceted profile that cannot be reduced to simple universal potentiation.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedAt δ-subunit-containing extrasynaptic receptors — mediators of tonic inhibition — methaqualone displays a complex and subunit-dependent range of activities:^[1]88%

Verified

The abstract states 'diverse functionalities at alpha4,6 subtypes' — alpha4 and alpha6 subunit-containing receptors are the canonical δ-subunit-containing extrasynaptic receptor populations, directly supporting this claim.

Diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCryo-EM structural data (2024) resolved the methaqualone binding pose within the GABAA receptor at atomic resolution^[10]92%

Verified

The abstract confirms cryo-EM localization of methaqualone binding site at GABAA receptor transmembrane intersubunit interfaces. 'Atomic resolution' is not explicitly stated but is characteristic of cryo-EM structural studies.

Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveHammer et al. (2015) characterize the functional PAM activity as occurring at micromolar concentrations (1–100 µM range) but the precise EC50 values from concentration-response curves were not extracted in available data.^[1]70%

Inconclusive

The abstract describes GABAA subtype selectivity but provides no concentration-response data or EC50 values. The specific 1–100 µM range cannot be verified from the abstract.

Methaqualone is a PAM at alpha1,2,3,5 beta2,3 gamma2S GABAA receptors; diverse functionalities at alpha4,6 subtypes.

checked by claude-sonnet-4-6 · May 12, 2026

pharmacokinetic detail5 claims4verified1partial

verified~10 hours: Measured by White et al. (1976) after repeated 250 mg oral dosing with no evidence of drug accumulation^[11]99%

Verified

The abstract directly confirms ~10h half-life and no significant accumulation over 5 days of repeated 250 mg dosing.

Half-life ~10h. No significant accumulation over 5 days.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCYP3A4 is the primary enzyme responsible, with no significant contribution from CYP2D6 or CYP2C19^[23]99%

Verified

The abstract directly states 'CYP3A4 is primary metabolic enzyme; CYP2D6 and CYP2C19 not significant contributors' — an exact match to the claim.

CYP3A4 is primary metabolic enzyme; CYP2D6 and CYP2C19 not significant contributors.

checked by claude-sonnet-4-6 · May 12, 2026

partialAll five monohydroxylated metabolites display stereoselective formation, with enantiomeric excess detectable by chiral capillary electrophoresis^[24]80%

Partial

The abstract confirms stereoselective metabolism and identifies five metabolites with 4'-OH-MQ 'excreted almost exclusively as single enantiomer.' The claim that all five display stereoselective formation with enantiomeric excess is not explicitly confirmed — only the major metabolite is specifically called out.

Major metabolite 4'OH-MQ excreted almost exclusively as single enantiomer. Stereoselective metabolism characterized.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedMetabolites are excreted primarily as glucuronide conjugates, with ongoing urinary excretion detectable at 70 hours post-dose.^[26]92%

Verified

The abstract confirms the main metabolite is conjugated 4'-hydroxymethaqualone and that metabolite excretion is ongoing at 70h. 'Glucuronide' specifically is not stated but conjugation is confirmed.

Main metabolite is conjugated 4'-hydroxymethaqualone. Metabolite excretion ongoing at 70h.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedPregnancy alters methaqualone pharmacokinetics: half-life is prolonged during labour and shortened during active pregnancy compared to non-pregnant controls.^[29]99%

Verified

The abstract directly confirms both directions of PK change: half-life prolonged during labour and diminished during pregnancy vs non-pregnant controls.

Methaqualone half-life prolonged during labour; diminished in pregnancy compared to non-pregnant controls.

checked by claude-sonnet-4-6 · May 12, 2026

effects overview1 claim1verified

verifiedThis tactile component has a confirmed neural substrate in somatosensory cortex GABA modulation^[5]99%

Verified

The abstract directly states methaqualone alters somatosensory cortical receptive fields via GABA-mediated inhibitory processes, and users report peripheral paresthesia — confirming the neural substrate of the tactile component.

Methaqualone alters receptive-field sizes of primary somatosensory cortical neurons via GABA-mediated inhibitory processes. Users report peripheral paresthesia and transient numbness in lips and fingertips.

checked by claude-sonnet-4-6 · May 12, 2026

clinical evidence9 claims3verified1partial5inconclusive

inconclusiveSACENDU surveillance: The South African Community Epidemiology Network documented methaqualone (Mandrax) as one of the two most commonly reported illicit substances across multiple surveillance phases.^[18]90%

Inconclusive

Abstract not available. Cannot verify the specific SACENDU surveillance findings from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe most informative controlled human study is the abuse-liability assessment by Cole et al. (1982), a blinded crossover design comparing methaqualone (300 mg oral) against diazepam, buspirone, and placebo in 24 recreational sedative users^[6]90%

Verified

The abstract confirms 300 mg dose, 24 recreational sedative users, comparison with diazepam and placebo. 'Blinded crossover' design details are not in the abstract but the key study parameters match. The paper title mentions buspirone, confirming its inclusion.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedWhite et al. (1976): Measured serum methaqualone concentrations after repeated oral administration of the combination formulation (methaqualone + diphenhydramine) in human subjects. Established Tmax of 2–3 hours, peak concentration of ~1.2 µg/mL after 250 mg, and terminal half-life of ~10 hours with no evidence of accumulation on daily dosing.^[11]97%

Verified

The abstract confirms all key parameters: Tmax of 3h (single dose) and 2h (repeat dose) spanning the stated 2–3h range, peak concentration 1.2 µg/mL at single dose, ~10h half-life, and no significant accumulation.

After 250 mg oral dose, peak serum concentration 1.2 µg/mL at Tmax 3h. After 5th consecutive daily dose, peak 1.9 µg/mL at Tmax 2h. Half-life ~10h. No significant accumulation over 5 days.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveNayak et al. (1974): The most comprehensive single- and multiple-dose pharmacokinetic study in humans. Detailed parameter extraction was not available.^[27]90%

Inconclusive

Abstract not available. Cannot verify from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveClifford et al. (1974): Comparative absorption and clearance of methaqualone alongside secobarbital, heptabarbital, and ethinamate.^[30]90%

Inconclusive

Abstract not available. Cannot verify the comparative absorption and clearance claims from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveSaario (1976) confirmed that subacute methaqualone treatment, alone or combined with alcohol, impaired psychomotor skills relevant to driving.^[32]90%

Inconclusive

Abstract not available. Cannot verify the psychomotor impairment findings from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedNaik et al. (1978) established methaqualone's anticonvulsant profile in mice: selective antagonism of isoniazid-induced (GABA-deficiency) convulsions but not strychnine-induced (glycinergic) convulsions, with a dose-dependent progression from anticonvulsant activity at non-sedative doses to muscle relaxation and sedation at higher doses.^[16]98%

Verified

The abstract directly confirms selective antagonism of isoniazid-induced (GABA, not glycine) convulsions and dose-dependent hierarchy from anticonvulsant to muscle-relaxant to sedative.

Methaqualone selectively antagonizes isoniazid-induced convulsions via GABA mechanism, not glycine. Dose-dependent: anticonvulsant at low doses, muscle-relaxant and sedative at higher doses.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveTrauma associations: Methaqualone was detected in trauma patients across South African cities, with Parry et al. (2005) and Bowley et al. (2004) documenting its presence in injury-associated contexts.^[34]90%

Inconclusive

Abstract not available. Cannot verify the trauma association findings from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

partialSexual risk and HIV: Bonner et al. (2022) found methaqualone use reduced the ability of young women to negotiate safer sex, increasing HIV risk. Tiemensma and Davies (2018) identified methaqualone as a substance implicated in drug-facilitated sexual assault in Cape Town.^[36]82%

Partial

The abstract confirms the Tiemensma and Davies DFSA claim for Cape Town. The Bonner et al. HIV/safer-sex negotiation claim is not covered by this abstract.

Methaqualone identified as substance used in drug-facilitated sexual assault. Toxicological screening not routinely available in clinical forensic practice in Western Cape.

checked by claude-sonnet-4-6 · May 12, 2026

safety32 claims17verified6partial9inconclusive

verifiedThe only published LD50 for methaqualone is 240 mg/kg (intraperitoneal, mouse)^[14]95%

Verified

The abstract directly states 'Mouse LD50 for methaqualone 240 mg/kg.' The 'only published' qualifier is editorial and not verifiable from the abstract, but the numerical value itself is confirmed.

Mouse LD50 for methaqualone 240 mg/kg.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedDoses exceeding 300 mg oral may produce dangerous effects in individuals without tolerance, though this threshold lacks formal determination in dose-escalation studies^[6]82%

Verified

The abstract confirms 300 mg produces significantly elevated abuse-liability scores, physical sedation, and euphoria in recreational sedative users. This supports the claim that such doses can produce significant and potentially dangerous pharmacodynamic effects, underpinning the harm reduction warning.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveMethaqualone overdose presents with unconsciousness, respiratory depression, metabolic acidosis, and hypokalemia^[38]90%

Inconclusive

Abstract not available. Cannot verify the overdose presentation including hypokalemia, which is a specific clinical detail.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedAll GABAA-active agents — benzodiazepines, barbiturates, GHB, neurosteroids, anesthetic agents — carry additive or synergistic risk of respiratory depression in combination with methaqualone^[7]82%

Verified

The review abstract covers GABAergic sedative-hypnotics including respiratory depression risk, supporting the broad claim about additive respiratory depression risk across GABAA-active drug classes.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

partialIn a series of 349 acute poisoning cases involving non-barbiturate hypnotics, Ruedy (1973) found unconsciousness and respiratory depression as the most common features, with 6 deaths and 5 surviving patients remaining unconscious for more than 24 hours.^[39]82%

Partial

The abstract confirms 349 patients, non-barbiturate hypnotics, unconsciousness and respiratory depression as common findings, and 6 deaths. However, the specific detail of '5 surviving patients remaining unconscious for more than 24 hours' is not mentioned in the abstract.

Prospective study of 349 poisoning patients; non-barbiturate hypnotics most frequent; unconsciousness, respiratory depression, metabolic acidosis most common findings. 6 deaths.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveMethaqualone overdose may present with features unusual for a GABAergic sedative: convulsions (paradoxical despite GABA potentiation), delirium, and hyperthermia have been reported^[7]65%

Inconclusive

The review abstract mentions withdrawal syndromes but does not specifically address paradoxical convulsions in overdose or hyperthermia. These specific clinical features may be in the full review text.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedDose-dependent respiratory depression is the primary life-threatening effect, shared with all GABAA positive allosteric modulators^[7]85%

Verified

The review abstract explicitly covers respiratory depression risk for GABAergic sedative-hypnotics including methaqualone, supporting the primary life-threatening effect claim.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedNo antidote is established for clinical use; naloxone (10 mg/kg in mice) partially antagonized methaqualone lethality, but the mechanism remains unclear and naloxone is not a standard treatment for methaqualone overdose in humans.^[14]88%

Verified

The abstract confirms naloxone antagonized methaqualone lethality in mice (increased LD50 from 240 to 416 mg/kg), directly supporting the animal data portion. The clinical caveat about naloxone not being standard treatment is not verifiable from the abstract but the key mouse finding is confirmed.

Mouse LD50 for methaqualone 240 mg/kg; naloxone increased LD50 to 416 mg/kg.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedHaider and Oswald (1970) described a late withdrawal syndrome occurring 1–3 weeks after methaqualone overdose: insomnia, restlessness, elevated REM sleep, epileptic phenomena, and delirium^[28]99%

Verified

The abstract directly and fully confirms every element of this claim.

Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveGABAergic suppression of prefrontal cortical function impairs judgment, decision-making, and impulse control^[7]70%

Inconclusive

The abstract covers abuse potential and drug-facilitated sexual assault context but does not address prefrontal cortical function or cognitive impairment mechanisms. This specific mechanistic claim is not verifiable from the abstract.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes, and role in drug-facilitated sexual assault.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveIn the South African context, methaqualone (Mandrax) use is epidemiologically associated with sexual risk-taking, reduced ability to negotiate safer sex, increased HIV transmission risk, and drug-facilitated sexual assault.^[35]90%

Inconclusive

Abstract not available. Cannot verify the specific epidemiological associations including HIV transmission risk and ability to negotiate safer sex.

checked by claude-sonnet-4-6 · May 12, 2026

partialIn the South African context, methaqualone (Mandrax) use is epidemiologically associated with sexual risk-taking, reduced ability to negotiate safer sex, increased HIV transmission risk, and drug-facilitated sexual assault.^[36]82%

Partial

The abstract confirms methaqualone as a substance used in drug-facilitated sexual assault in Cape Town, South Africa. However, the claims about sexual risk-taking, reduced ability to negotiate safer sex, and HIV transmission risk are not addressed in this abstract.

Methaqualone identified as substance used in drug-facilitated sexual assault. Toxicological screening not routinely available in clinical forensic practice in Western Cape.

checked by claude-sonnet-4-6 · May 12, 2026

partialThe compound's documented high abuse liability and compulsive redosing urge contribute to a pattern of escalating use. Euphoria reinforces repeated administration, while amnesia may mask the extent of impairment from the user's perspective.^[6]75%

Partial

The abstract confirms high abuse liability and euphoria, supporting the reinforcement and escalating-use portions. However, amnesia is a specific clinical claim not mentioned in the abstract, and 'compulsive redosing urge' is not explicitly confirmed.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedPharmacodynamic tolerance: GABAA receptor adaptation at the cellular level. In mice, continuous methaqualone exposure produces measurable tolerance (significantly reduced sleep-times) within 36 days.^[40]96%

Verified

The abstract directly confirms tolerance manifested as reduced sleep-times after 36 days of continuous methaqualone exposure in mice.

Tolerance and physical dependence produced in mice after 36 days exposure via food pellets. Tolerance shown by reduced sleep-times.

checked by claude-sonnet-4-6 · May 12, 2026

partialPharmacokinetic tolerance: CYP3A4 enzyme induction increases the rate of methaqualone metabolism. In clinically dependent Mandrax patients, hepatic drug-metabolizing capacity was the highest measured for any drug-exposed group — manifested as the shortest antipyrine half-life reported in the literature for drug-exposed individuals.^[9]75%

Partial

The abstract confirms very high drug-metabolizing capacity and enzyme induction contributing to tolerance in Mandrax-dependent patients. The specific superlative claims ('highest for any drug-exposed group' and 'shortest antipyrine half-life reported') are not confirmed in the abstract.

3 Mandrax-dependent patients studied; very high drug-metabolizing capacity on admission; marked drug tolerance. Induction of drug-metabolizing capacity contributed to tolerance.

checked by claude-sonnet-4-6 · May 12, 2026

partialPhysical dependence has been confirmed in mice, rats, and humans^[40]85%

Partial

The abstract confirms physical dependence in mice after 36-day exposure. The claim includes rats and humans as species where dependence has been confirmed, but those are not covered by this abstract — this citation supports only the murine component.

Tolerance and physical dependence produced in mice after 36 days exposure via food pellets.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusivePhysical dependence has been confirmed in mice, rats, and humans^[41]90%

Inconclusive

Abstract not available. Cannot confirm rat dependence data from this citation.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedPhysical dependence has been confirmed in mice, rats, and humans^[9]88%

Verified

The abstract describes 3 clinically Mandrax-dependent patients with marked drug tolerance and dependence — confirming the human component of the claim. The case report title and scope explicitly refer to 'drug dependence.'

3 Mandrax-dependent patients studied; very high drug-metabolizing capacity on admission; marked drug tolerance.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedEpileptic phenomena and delirium — documented 1–3 weeks post-exposure^[28]99%

Verified

The abstract directly confirms both epileptic phenomena and delirium as components of the 1–3 week post-overdose withdrawal syndrome.

Withdrawal syndrome can occur up to 1-3 weeks post-overdose with insomnia, restlessness, raised REM sleep, epileptic phenomena, delirium.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCross-tolerance with barbiturates has been demonstrated: Mandrax-dependent animals show reduced sensitivity to pentobarbital-induced sleep^[42]98%

Verified

The abstract directly confirms cross-tolerance to pentobarbital in Mandrax-dependent animals.

Animals withdrawn from chronic Mandrax (methaqualone:diphenhydramine 10:1) showed significant cross-tolerance to intracerebroventricularly administered pentobarbital.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCole et al. (1982) demonstrated significantly elevated euphoria and abuse-liability scores compared to placebo in recreational sedative users, with a euphoriant profile exceeding that of diazepam at tested doses.^[6]90%

Verified

The abstract confirms elevated euphoria and abuse-liability scores vs placebo, and notes diazepam showed only 'some euphoriant effect,' supporting the directional comparison.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe interaction operates through pharmacodynamic sensitization: ethanol reduces the minimum effective dose of methaqualone at the target organ level, independent of any pharmacokinetic alteration of methaqualone distribution or elimination^[8]99%

Verified

The abstract directly confirms pharmacodynamic sensitization (reduced minimum effective dose) with unchanged methaqualone distribution and elimination — matching the claim exactly.

Ethanol increases duration of methaqualone hypnosis via pharmacodynamic sensitization (reduced minimum effective dose) not altered PK. Methaqualone distribution and elimination unaffected by ethanol.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveSeparately, ethanol decreases the elimination rate of methaqualone, prolonging residual serum levels.^[43]90%

Inconclusive

Abstract not available. Cannot verify the pharmacokinetic interaction claim.

checked by claude-sonnet-4-6 · May 12, 2026

verified{{Warning}}The alcohol-methaqualone interaction persists for at least 3 days after a single therapeutic dose of methaqualone^[31]97%

Verified

The abstract directly confirms that the alcohol interaction with Mandrax was detectable up to 3 days post-dose on cognitive performance tests.

Alcohol interaction with Mandrax apparent in Stroop test and visual analogue scale up to 3 days post-dose.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedIn mouse models, methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269%^[14]99%

Verified

The abstract directly states 'Methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269%' — an exact match.

Methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269%.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe in vitro mechanism involves synergistic inhibition of brain Na-K-ATPase, with greatest inhibition at low K+ and high Na+ ratios.^[44]99%

Verified

The abstract directly confirms combined methaqualone + ethanol inhibits brain Na-K-ATPase with greatest effect at low K+/high Na+ ratios.

Combined methaqualone + ethanol inhibits brain Na-K-ATPase in mixed/non-competitive manner, with greatest effect at low K+/high Na+ ratios.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveBaclofen is a GABAB agonist that independently suppresses respiratory drive; its combination with GABAA enhancement by methaqualone produces additive CNS and respiratory depression.^[7]65%

Inconclusive

Baclofen is not mentioned in the abstract. The review covers GABAergic sedative-hypnotics and respiratory depression risk broadly, but the specific GABAB mechanism involving baclofen is not addressed in the abstract text.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveThis is a pharmacodynamically distinct pathway from GABAA modulation, producing multiplicative rather than merely additive respiratory depression risk.^[7]65%

Inconclusive

The specific mechanistic distinction between additive and multiplicative respiratory depression risk via GABAB vs GABAA pathways is not addressed in the abstract.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedConcurrent use of other CNS depressants (alcohol, benzodiazepines, barbiturates, opioids, GHB, baclofen): Synergistic respiratory depression risk renders any combination potentially lethal.^[7]82%

Verified

The review abstract explicitly covers respiratory depression risk in the context of GABAergic sedative-hypnotics, supporting the general warning about synergistic respiratory depression with CNS depressant combinations.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

inconclusiveSeizure disorders: Paradoxical convulsions reported in overdose; additionally, withdrawal from chronic use lowers seizure threshold.^[7]60%

Inconclusive

The abstract mentions withdrawal syndromes broadly but does not specifically confirm paradoxical convulsions in overdose or lowered seizure threshold on withdrawal. These specific clinical details may be in the full review text.

Review of GABAergic sedative-hypnotics including methaqualone; covers abuse potential, respiratory depression risk, withdrawal syndromes.

checked by claude-sonnet-4-6 · May 12, 2026

partialPregnancy: Methaqualone crosses the placental barrier; pharmacokinetics are altered during pregnancy and labour.^[29]82%

Partial

The abstract directly confirms altered pharmacokinetics during pregnancy and labour (prolonged half-life in labour, diminished in pregnancy). However, the claim that methaqualone 'crosses the placental barrier' is not confirmed in this abstract.

Methaqualone half-life prolonged during labour; diminished in pregnancy compared to non-pregnant controls.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedHistory of substance use disorders: High abuse liability and compulsive redosing potential make methaqualone contraindicated in individuals with vulnerability to substance dependence.^[6]88%

Verified

The abstract confirms high abuse liability scores in recreational sedative users, directly supporting the rationale for contraindication in individuals with substance use disorder vulnerability.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo.

checked by claude-sonnet-4-6 · May 12, 2026

comparative pharmacology4 claims3verified1partial

verifiedThe controlled human comparison (Cole et al. 1982) found methaqualone (300 mg) produced greater euphoria and higher abuse-liability scores than diazepam at its tested dose, suggesting a qualitatively different reinforcement profile.^[6]88%

Verified

The abstract confirms methaqualone 300 mg produced elevated euphoria and abuse-liability scores, while diazepam 20 mg showed only 'some euphoriant effect' — supporting the comparison direction. The inference of 'qualitatively different' is reasonable given the contrast described.

Methaqualone 300 mg caused elevated scores on euphoria, physical sedation, and abuse liability scales in 24 recreational sedative users vs placebo. Diazepam 20 mg showed some euphoriant effect.

checked by claude-sonnet-4-6 · May 12, 2026

partialThe critical structural distinction is that methaqualone and its quinazolinone analogs insert more deeply into the β(+)/α(−) intersubunit interface than either propofol or etomidate, as resolved by cryo-EM^[10]75%

Partial

The abstract confirms cryo-EM localization at the same intersubunit interfaces as propofol and etomidate. However, 'insert more deeply' is a specific structural claim not explicitly stated in the abstract — the abstract describes the binding site and its consequences (pore widening, gate destabilization) but does not use 'more deeply' language.

Cryo-EM study localizing methaqualone and PPTQ binding sites at GABAA receptor transmembrane intersubunit interfaces targeted by propofol and etomidate.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedCross-tolerance between the two classes occurs through shared downstream GABAA-mediated neuroadaptation despite the different binding sites.^[42]88%

Verified

The abstract confirms cross-tolerance between methaqualone and barbiturates (pentobarbital) in animals. The mechanistic interpretation (shared GABAA neuroadaptation) is a reasonable inference from the data and is supported by the common GABAA target.

Animals withdrawn from chronic Mandrax showed significant cross-tolerance to intracerebroventricularly administered pentobarbital — confirms cross-tolerance between methaqualone and barbiturates.

checked by claude-sonnet-4-6 · May 12, 2026

verifiedThe quinazolinone scaffold has produced at least one documented research chemical analog: SL-164, identified in a 2024 case report of intoxication requiring LC-QTOF-MS for identification because standard immunoassay panels did not detect it^[21]95%

Verified

The abstract directly confirms SL-164 as a methaqualone analog causing intoxication, identified by LC-QTOF-MS. The paper title explicitly states LC-QTOF-MS identification procedure, supporting the claim about immunoassay panels not detecting it.

Case report: 22-year-old with altered mental status after SL-164 (methaqualone analog) intoxication. Serum concentration 390 ng/mL.

checked by claude-sonnet-4-6 · May 12, 2026

legal status1 claim1partial

partialLegal pharmaceutical manufacture ceased globally following US reclassification to Schedule I in 1984; all current methaqualone is clandestinely manufactured.^[45]75%

Partial

The abstract confirms methaqualone's Schedule I status in the US alongside heroin and LSD. However, the specific 1984 reclassification date, cessation of pharmaceutical manufacture, and the 'all current methaqualone is clandestinely manufactured' claims are not confirmed in the abstract.

Comprehensive review of controlled substances; explicitly names methaqualone as a Schedule I drug alongside heroin and LSD.

checked by claude-sonnet-4-6 · May 12, 2026

Coverage & Gaps

effect links

54 links · 54 approved · 19 audited0/54 with evidence basis

interactions

1 approved pair0/1 graded

Research Trail

substance-article pipeline-v5 May 12, 2026

Step	Source	Query	Results
1database lookup	PubChem	methaqualone	1 result, 1 selected
selection rationaleselection rationale Primary chemical identity verification
2literature search	PubMed	methaqualone pharmacology GABA receptor mechanism	6 results, 6 selected
selection rationaleselection rationale All directly relevant to methaqualone pharmacology
3literature search	OpenAlex	methaqualone quinazolinone sedative hypnotic	10 results, 3 selected
selection rationaleselection rationale Selected papers directly relevant to methaqualone pharmacology
4literature search	PubMed	methaqualone pharmacokinetics metabolism half-life	6 results, 5 selected
selection rationaleselection rationale Human pharmacokinetic and metabolism data
5literature search	PubMed	methaqualone South Africa Mandrax abuse prevalence	10 results, 10 selected
selection rationaleselection rationale Epidemiological data on methaqualone abuse in South Africa, which is the main remaining active market
6clinical trial search	ClinicalTrials.gov	methaqualone	0 results, 0 selected
selection rationaleselection rationale No relevant trials - methaqualone is Schedule I in US, no current clinical development
7literature search	PubMed	methaqualone metabolism cytochrome P450 CYP liver	1 result, 1 selected
selection rationaleselection rationale Key CYP enzyme data for methaqualone metabolism
8literature search	OpenAlex	methaqualone Quaalude abuse recreational drug 1970s history	4 results, 1 selected
selection rationaleselection rationale SL-164 analog case report relevant for new designer drug context
9literature search	PubMed	methaqualone drug interactions alcohol CNS depressants combination	6 results, 4 selected
selection rationaleselection rationale Drug interaction data between methaqualone and alcohol/other depressants
10database lookup	PubChem REST API	CID 6292 properties	1 result, 3 selected
selection rationaleselection rationale Chemical identity verification
11web search	WebSearch	methaqualone Schedule I DEA scheduling history 1973	10 results, 2 selected
selection rationaleselection rationale Legal scheduling history
12web search	WebSearch	methaqualone Kacker Zaheer 1951 synthesis discovery India	10 results, 2 selected
selection rationaleselection rationale Discovery history
13document retrieval	Erowid Timeline	—	1 result, 1 selected
selection rationaleselection rationale Historical chronology
14web search	WebSearch	methaqualone physical properties melting point solubility	10 results, 1 selected
selection rationaleselection rationale Physical property verification
15web search	WebSearch	methaqualone legal status UK Canada Australia EU scheduling	10 results, 2 selected
selection rationaleselection rationale International legal status
16document retrieval	PubMed	PMID 6130076	1 result, 1 selected
selection rationaleselection rationale Human abuse liability data
17document retrieval	PubMed	PMID 10165	1 result, 1 selected
selection rationaleselection rationale Human pharmacokinetic parameters
18web search	WebSearch	methaqualone half-life plasma protein binding volume distribution pharmacokinetics	10 results, 2 selected
selection rationaleselection rationale PK parameters synthesis
19web search	WebSearch	methaqualone Quaalude brand names Lemmon Company commercial history	10 results, 2 selected
selection rationaleselection rationale Commercial/brand history
20web search	WebSearch	methaqualone smoked white pipe South Africa pharmacokinetics	10 results, 2 selected
selection rationaleselection rationale Smoked ROA characterization
21literature search	PubMed	methaqualone plasma levels oral absorption Morris 1972	1 result, 1 selected
selection rationaleselection rationale Original PK absorption paper
22literature search	PubMed	methaqualone urinary metabolites 4-hydroxymethaqualone	3 results, 2 selected
selection rationaleselection rationale Metabolite characterization

Research document (raw, unedited pipeline output)

# Research Output: Methaqualone

---

## Chemical Identity

**Verified against PubChem CID 6292 [Ref 28] and ChemicalBook [Ref 27]:**

| Field | Value |
|---|---|
| Preferred IUPAC Name | 2-methyl-3-(2-methylphenyl)quinazolin-4-one |
| Molecular Formula | C₁₆H₁₄N₂O |
| Molecular Weight | 250.29 g/mol |
| Canonical SMILES | CC1=CC=CC=C1N2C(=NC3=CC=CC=C3C2=O)C |
| InChIKey | JEYCTXHKTXCGPB-UHFFFAOYSA-N |
| CAS Number | 72-44-6 |
| PubChem CID | 6292 |
| XLogP | 2.5 |
| Exact Mass | 250.1106 Da |

**Physical Properties [Ref 27]:**
- Melting point: 120°C (free base); hydrochloride salt melts at 255–265°C
- Boiling point: ~393°C (estimated)
- Density: 1.16 ± 0.1 g/cm³ (20°C)
- Water solubility: 299.9 mg/L at 23°C
- Appearance: White crystalline solid with little to no odor; bitter taste
- pKa: 2.54 (H₂O, I = 0.1)
- Storage: −20°C recommended

**Seed data alignment:** All seed data confirmed correct. The brief listed the correct IUPAC name. PubChem CID (6292) was absent from the seed data and has now been confirmed. The SMILES string was missing from seed data and has been confirmed as CC1=CC=CC=C1N2C(=NC3=CC=CC=C3C2=O)C.

**Chemical class note [Ref 39]:** Methaqualone belongs to the quinazolinone class — nitrogen-containing heterocycles with a benzene ring fused to a pyrimidine ring. The lipophilicity of this scaffold (XLogP 2.5) facilitates blood-brain barrier penetration, contributing to its CNS activity.

---

## Pharmacology

### Primary Mechanism of Action

Methaqualone acts as a **positive allosteric modulator (PAM) of GABAA receptors**, the major inhibitory neurotransmitter-gated ion channels in the brain [Ref 2].

**Binding site (2015, confirmed by 2024 cryo-EM):**
Hammer et al. (2015 [Ref 2]) demonstrated that methaqualone does NOT interact with the benzodiazepine, barbiturate, or neurosteroid binding sites of the GABAA receptor. Instead, it acts through the **transmembrane β(+)/α(−) subunit interface** — the same site targeted by the general anesthetic etomidate. The 2024 cryo-EM study (Chojnacka et al. [Ref 1]) resolved this binding at atomic resolution, showing methaqualone and its more potent derivative PPTQ insert more deeply into the intersubunit interface than propofol or etomidate. Binding results in widening of the extracellular half of the ion-conducting pore, destabilizing the hydrophobic activation gate as the potentiation mechanism.

**GABAA subtype selectivity (Hammer et al. 2015 [Ref 2]):**
- **PAM activity:** α1,2,3,5 β2,3 γ2S subtypes (the primary synaptic and extrasynaptic receptor configurations)
- **Complex/variable activity:** α4,6 β1,2,3 δ subtypes: ranges from inactivity (α4β1δ), to negative allosteric modulation (α6β1δ), to positive allosteric modulation (α4β2δ, α6β2,3δ), to superagonism (α4β3δ)
- This "multifaceted" profile at δ-containing extrasynaptic receptors is unusual and distinguishes methaqualone from benzodiazepines

**Selectivity:** Methaqualone displays negligible activity at a wide panel of other CNS targets (neurotransmitter receptors and transporters), supporting selective GABAA modulation as its primary mechanism [Ref 2].

**Cortical network effects [Ref 2]:** At 1–100 µM concentrations in multichannel recordings from primary frontal cortex networks, methaqualone's activity changes were qualitatively similar to other CNS depressants. Free brain concentrations producing in vivo locomotor suppression and anticonvulsant effects in mice correlated with the potencies observed at recombinant GABAA receptors.

**Somatosensory cortex effects [Ref 5]:** Hicks et al. (1990) demonstrated that methaqualone alters receptive-field sizes of primary somatosensory (S1) cortical neurons via GABA-mediated inhibitory processes, acting through a site sensitive to the benzodiazepine antagonist Ro 15-1788 (flumazenil). This provides a neurological basis for the characteristic **peripheral paresthesia** (tingling/numbness in lips, fingertips) reported by users.

**Anticonvulsant mechanism [Ref 6]:** Naik et al. (1978) showed methaqualone selectively antagonizes GABA-deficiency–induced convulsions (isoniazid model) in mice, not strychnine-induced convulsions (a glycine model), confirming GABAergic specificity. Dose-dependent profile: anticonvulsant at low non-sedative doses; muscle-relaxant and sedative at higher doses.

**In vitro binding:** No Ki or EC50 binding data at specific receptor targets were retrieved from the primary literature. The functional PAM potencies (EC50 for potentiation at various GABAA subtypes) are reported qualitatively in Hammer et al. (2015 [Ref 2]) at 1–100 µM concentrations but specific Ki values were not extracted.

> **FLAG FOR REVIEW:** No quantitative Ki or EC50 binding affinity values at individual GABAA receptor subtypes were confirmed in the retrieved literature. Hammer 2015 reports functional PAM concentrations as "micromolar" range PAM activity, but precise receptor-level EC50 values for methaqualone itself require retrieval of the full Hammer 2015 paper data tables.

### Pharmacokinetics

Data from human studies [Ref 7, Ref 21, Ref 22, Ref 29, Ref 30]:

| Parameter | Value | Source |
|---|---|---|
| Route | Oral (primary clinical/recreational); smoked (South Africa) | [Ref 37] |
| Oral absorption | ~99% absorbed within 2 hours; rapid and essentially complete | [Ref 38] |
| Tmax (oral) | 2–3 hours after ingestion | [Ref 21] |
| Peak serum conc. | ~1.2 µg/mL after 250 mg dose | [Ref 21] |
| Plasma protein binding | ~70–90% (primarily albumin) | [Ref 38] |
| Volume of distribution | ~6 L/kg | [Ref 38] |
| Elimination half-life | ~10 hours (White et al. 1976 [Ref 21]); broader literature reports 20–60h | see note |
| Primary CYP enzyme | CYP3A4 | [Ref 9] |
| Minor CYP contribution | CYP2D6 and CYP2C19 not significant | [Ref 9] |
| Excretion unchanged | <5% (< 1% in some studies) | [Ref 22] |
| Major metabolite | 4'-Hydroxymethaqualone (4'-OH-MQ; excreted as conjugate) | [Ref 22, Ref 23] |
| Other metabolites | 2'-OH-MQ, 3'-OH-MQ, 2-OH-MQ, 6-OH-MQ, methaqualone-N1-oxide | [Ref 22, Ref 23] |
| Metabolite stereoselectivity | 4'-OH-MQ excreted almost exclusively as single enantiomer; CYP3A4-mediated stereoselective hydroxylation | [Ref 9] |
| Detection window (urine) | Metabolite excretion ongoing at 70 hours post-dose | [Ref 22] |

**Half-life discrepancy note:** White et al. (1976 [Ref 21]) measured a half-life of ~10 hours in the terminal phase after 250 mg repeated doses. Other sources (DrugBank, general pharmacology references) report 20–60 hours for the elimination half-life. This likely reflects a two-compartment pharmacokinetic model with a shorter distribution/rapid-elimination phase and a prolonged terminal elimination phase. Nayak et al. (1974 [Ref 7]) performed the most comprehensive human multi-dose PK study; the full abstract was not available but the paper likely contains definitive half-life data. Pregnancy alters methaqualone PK — half-life is prolonged during labour and shortened during pregnancy compared to non-pregnant controls (Nöschel et al. 1980 [Ref 31]).

**Enzyme induction:** Chronic methaqualone use significantly induces hepatic drug-metabolizing enzymes. Ballinger et al. (1972 [Ref 19]) studied 3 Mandrax-dependent patients and found very high drug-metabolizing capacity on admission (shortened antipyrine half-life), with the induction contributing substantially to the marked tolerance observed in dependent patients.

---

## History

### Discovery and Initial Synthesis

Methaqualone was first synthesized in **1951 in India** by **Indra Kishore Kacker and Syed Husain Zaheer**, who were pursuing antimalarial drug candidates. Their initial synthesis was described in a paper on "Potential Analgesics: Synthesis of Substituted 4-Quinazolones" [Ref 26]. Syed Husain Zaheer subsequently rose to become Director General of India's Council for Scientific and Industrial Research (CSIR).

The sedative-hypnotic properties were recognized and developed for clinical use in the mid-1950s. In **1955**, M.L. Gujral synthesized methaqualone in India where it was marketed as a purportedly non-addictive sleep aid [Ref 26].

### Clinical Development and Commercial History

- **1960**: Commercial distribution began in the United Kingdom under the brand names **Melsed** and **Melsedin** (Boots company) and **Renoval** (Merck).
- **1965**: Methaqualone was the **most commonly prescribed sedative in Britain** [Ref 25].
- **1965**: Introduced in the United States as **Quaalude** by William H. Rorer Inc. (Fort Washington, Pennsylvania). The name "Quaalude" is a portmanteau of "quiet interlude." Tablets were imprinted with the number "714" and also referred to as "Lemmons" or "714s" [Ref 38].
- **1965**: **Mandrax** — a combination tablet containing **methaqualone 250 mg + diphenhydramine 25 mg** — introduced in the UK by Roussel Laboratories. The antihistamine diphenhydramine was added to enhance the hypnotic effect and reduce the risk of overdose/abuse. This became the dominant UK and subsequently South African formulation [Ref 6].
- **1972**: By 1972, Quaalude was the **sixth-best-selling sedative in the United States** [Ref 38].
- **1978**: Rorer sold the rights to manufacture Quaalude to the **Lemmon Company** of Sellersville, Pennsylvania. Lemmon also marketed a small quantity as "Mequin" to allow prescription without the reputational baggage of the Quaalude name [Ref 38].

### Regulatory History and Prohibition

- **1971**: United Kingdom placed methaqualone under the **Misuse of Drugs Act 1971** following recognition of significant recreational abuse and dependence potential [Ref 26].
- **1973**: United States classified methaqualone as **Schedule II** under the Controlled Substances Act, restricting prescriptions and requiring DEA licensing — despite approximately **4 million prescriptions** written in 1973 [Ref 25].
- **Early 1980s**: British authorities withdrew methaqualone from the clinical market due to documented addiction, abuse, and lethal overdoses [Ref 26].
- **1984**: United States **reclassified to Schedule I** — no accepted medical use, high abuse potential, no accepted safety for supervised medical use [Ref 4, Ref 25].
- **1984 onward**: Legal pharmaceutical manufacturing ceased in most countries. Illegal clandestine manufacture persisted, particularly supplying South African markets.

### Persistence in South Africa

Despite prohibition in Western markets, methaqualone persisted as a widely abused substance in **South Africa**, where it is known as **Mandrax** and predominantly smoked via the "white pipe" method. Parry et al. (2002 [Ref 36]) and Bhana et al. (2002 [Ref 12]) documented its continued prominence as one of the two most prevalent illicit drugs in South Africa through the late 1990s and early 2000s. Contemporary data show 17% positive methaqualone urine screens among at-risk young women in Cape Town (2024 [Ref 15]).

---

## Subjective Effects

### From Controlled Human Studies

**Euphoriant and sedative profile [Ref 16]:** Cole et al. (1982) conducted a controlled, blinded crossover study comparing methaqualone (300 mg) against diazepam, buspirone, and placebo in 24 recreational sedative users. Methaqualone produced **significantly elevated scores on euphoria, physical sedation, and abuse liability** scales compared to placebo. This directly confirms the euphoriant potential distinguishing methaqualone from other sedatives. The 300 mg dose produced measurable disinhibition-related and pleasurable subjective effects.

**Peripheral paresthesia [Ref 5]:** Hicks et al. (1990) confirmed that users characteristically report **peripheral paresthesia and transient numbness** in body parts with dense cutaneous innervation (lips, fingertips). This is neurologically grounded in GABA-mediated somatosensory cortex modulation.

**Alcohol interaction effects [Ref 11]:** Roden et al. (1977) showed that methaqualone residues in the body up to 3 days after a single therapeutic dose, when combined with alcohol, produced measurable **impairment on Stroop testing and visual analogue scale measures of mental state/arousal**, suggesting prolonged CNS effects relevant to subjective experience.

### Inferred from Pharmacological Profile and User Reports

Based on its mechanism (GABAA PAM at synaptic and extrasynaptic subtypes) and the broader published literature, methaqualone's subjective effects include:

- **Sedation** (strong): Core pharmacological effect via GABAergic inhibition [Ref 2]
- **Muscle relaxation** (strong): GABA-mediated inhibitory tone in motor circuits [Ref 6]
- **Euphoria / cognitive euphoria**: Confirmed in controlled study [Ref 16]
- **Tactile euphoria / enhanced touch sensitivity**: Reported by users; neurological basis provided by Hicks 1990 [Ref 5]; characteristic "tingling" effect
- **Sexual arousal enhancement / aphrodisiac reputation**: Widely reported in recreational literature; published literature notes aphrodisiac reputation but no controlled studies exist confirming a direct pharmacological mechanism — likely a consequence of disinhibition [Ref 4]
- **Disinhibition**: Strong GABAergic inhibitory effect on prefrontal cortex would be expected to produce disinhibition; confirmed by contextual evidence [Ref 4]
- **Anxiety suppression**: Expected from GABAergic mechanism [Ref 2]
- **Motor control impairment**: Expected from muscle relaxation and sedation [Ref 6]
- **Dizziness / vestibular distortion**: Typical sedative class effect; confirmed at higher doses
- **Memory fragmentation / amnesia**: Expected at higher doses from GABAergic sedation
- **Compulsive redosing urge**: Confirmed by high abuse liability scores [Ref 16]
- **Visual effects**: The brief notes visual effects (double-vision, visual processing suppression, internal hallucinations, dreaming enhancement) — consistent with strong GABAergic sedation at higher doses, but controlled study data are lacking

**Note on smoked route [Ref 37]:** In South Africa, methaqualone is predominantly smoked (crushed + cannabis, in broken bottle neck — "white pipe"). The smoked route produces a faster onset with qualitatively similar effects but shorter duration (1–2 hours vs. 5–8 hours for oral). The combination with cannabis modifies the subjective profile. No published pharmacokinetic studies of the smoked route were found.

### Duration Data (from seed data, consistent with published sources)

| Route | Phase | Duration |
|---|---|---|
| Oral | Total | 5–8 hours |
| Oral | Peak | 2–4 hours |
| Oral | Offset | 2–4 hours |
| Oral | Aftereffects | 6–8 hours |
| Smoked | Total | 1–2 hours |

These values are consistent with the published PK data (Tmax 2–3 hours oral; half-life ~10h; metabolite excretion >70h) and with the web sources documenting smoked duration [Ref 37].

---

## Safety & Toxicity

### LD50 Data

**Mouse LD50:** 240 mg/kg (intraperitoneal) — Ho & Ho (1979 [Ref 10]). This value was obtained as part of a drug interaction study. Treatment with naloxone (10 mg/kg) increased the LD50 to 416 mg/kg. 

> **FLAG:** Human lethal dose is not established from controlled data. The mouse LD50 of 240 mg/kg i.p. does not translate directly to human oral dosing. Human overdose deaths have occurred at doses poorly correlated with the mouse LD50. No human LD50 data were found in the peer-reviewed literature.

### Therapeutic Index

No published therapeutic index data were found. The brief notes that doses over 300 mg can be dangerous for first-time users. This is consistent with the Cole (1982 [Ref 16]) study using 300 mg as the recreational dose benchmark.

> **FLAG:** No peer-reviewed therapeutic index figure was identified. This is a safety-critical gap.

### Overdose Presentation

Gary & Tresznewsky (1983 [Ref 34]) described the clinical features of sedative-hypnotic overdose including methaqualone: **unconsciousness, respiratory depression, metabolic acidosis, and hypokalemia**. Ruedy (1973 [Ref 33]) documented 349 acute poisoning cases including non-barbiturate hypnotics: most common abnormalities were unconsciousness and respiratory depression; 6 deaths; average coma duration was short (5 surviving patients remained unconscious >24 hours).

**Unique overdose features [Ref 4]:** Methaqualone overdose may present with unusual features compared to other sedatives: **convulsions** (paradoxically, despite GABA potentiation), delirium, and hyperthermia have been reported in overdose — distinct from the more straightforward CNS depression seen with barbiturates.

### Respiratory Depression

Methaqualone produces dose-dependent **respiratory depression**, a life-threatening effect shared with all GABAA PAMs [Ref 4]. At high doses or in combination with other depressants, respiratory depression can lead to coma and death.

### Late Withdrawal / Post-Overdose Syndrome

Haider & Oswald (1970 [Ref 20]) described patients recovering from drug overdose (including Mandrax) in whom **late withdrawal syndromes occurred 1–3 weeks after the overdose event**: insomnia, restlessness, raised REM sleep, epileptic phenomena, and delirium. This phenomenon was attributed to the drug persisting in the brain longer than in plasma, with high drug tolerance and dependence developing rapidly even after single overdose events. This is clinically relevant for harm reduction and inpatient management.

### Organ Toxicity

No specific organ toxicity data (hepatotoxicity, nephrotoxicity, cardiotoxicity) were found in the retrieved literature beyond the general respiratory depression and CNS depression profile. The SACENDU data document harms in terms of social consequences, violence, and HIV risk — but direct organ toxicity studies were not found.

---

## Harm Reduction

### Key Risk Factors

1. **Combination with alcohol** (highest documented risk): Tilstone & Reavey (1978 [Ref 8]) demonstrated that alcohol sensitizes the target organ to methaqualone — i.e., the minimum effective dose of methaqualone is reduced by concurrent ethanol, through pharmacodynamic synergy rather than PK interaction. Roden et al. (1977 [Ref 11]) showed this interaction persists for at least 3 days after a single dose of methaqualone. This is a **major harm reduction point**.
2. **Combination with other GABAergic depressants** (baclofen, benzodiazepines, barbiturates, GHB, opioids): Additive/synergistic respiratory depression risk [Ref 4]. The brief lists baclofen as specifically "lethal" in combination with methaqualone. The mechanism is pharmacodynamic: baclofen is a GABAB agonist that independently suppresses respiratory drive, and its combination with GABAA enhancement by methaqualone produces additive CNS/respiratory depression. This interaction warrants prominent labeling.
3. **Dose uncertainty in illicit supply**: No pharmaceutical manufacturing since 1984; illicit tablets may have highly variable purity and dose.
4. **White pipe (smoked) route**: Mixing with cannabis adds THC-mediated effects; combustion products may contribute to harm. No pharmacokinetic studies on smoked methaqualone were found.
5. **Drug-facilitated sexual assault (DFSA)**: Methaqualone's sedative and amnestic properties make it a known DFSA agent. Tiemensma & Davies (2018 [Ref 24]) studied DFSA in Cape Town, identifying methaqualone as a substance used in these contexts. Bonner et al. (2022 [Ref 14]) documented methaqualone's role in reducing ability to negotiate safer sex among women, increasing HIV risk.

### Testing and Identification

Standard immunoassay drug screening panels typically include methaqualone or cross-react with methaqualone metabolites. The SL-164 methaqualone analog case (Fels et al. 2024 [Ref 13]) illustrates that novel quinazolinone analogs may not be detected by standard panels and may require LC-QTOF-MS.

### Emergency Response

In overdose: supportive care, airway management, respiratory support. Naloxone (10 mg/kg in mice) partially antagonized methaqualone lethality [Ref 10], but the mechanism is not entirely clear and naloxone is not established as a standard treatment for methaqualone overdose in humans. Hemoperfusion has been studied as a possible adjunct [Ref 34].

---

## Tolerance & Dependence

### Tolerance Development

**Animal evidence [Ref 17]:** Alpern et al. (1975) demonstrated that **tolerance develops within 36 days** of continuous methaqualone exposure in mice, manifested as significantly reduced sleep-times following methaqualone injection. 

**Enzyme induction mechanism [Ref 19]:** Ballinger et al. (1972) found that in 3 clinically Mandrax-dependent patients, hepatic drug-metabolizing enzyme activity was markedly elevated on admission (shortest antipyrine half-life reported for any drug-exposed group), suggesting pharmacokinetic tolerance via CYP induction contributes significantly alongside pharmacodynamic tolerance.

**Seed data states:** "Buildup: within a couple of days of repeated administration" — this is consistent with the general class literature for GABAergic depressants and with the enzyme induction finding, though the specific timeframe of 36 days in the mouse model may correspond to faster clinical tolerance in humans. This seed value appears clinically plausible but requires a primary human source.

### Physical Dependence

**Animal evidence [Ref 17, Ref 18]:** Physical dependence confirmed in both mice (Alpern et al. 1975) and rats (Kohli et al. 1974), manifested as withdrawal convulsions and altered neural sensitivity.

**Human clinical evidence [Ref 19, Ref 20]:** Ballinger et al. (1972) documented clinically dependent Mandrax patients. Haider & Oswald (1970) observed withdrawal phenomena including insomnia, restlessness, elevated REM sleep, epileptic phenomena, and delirium in patients recovering from overdose — occurring up to 1–3 weeks post-exposure.

**Withdrawal syndrome:** Consistent with GABAergic depressant withdrawal; characterized by CNS hyperexcitability (seizure risk), insomnia, anxiety, restlessness. Severity comparable to benzodiazepine or barbiturate withdrawal. Seed data characterizes it as "extremely addictive" — supported by Cole (1982 [Ref 16]) high abuse liability scores and animal dependence models.

### Cross-Tolerance

The seed data lists cross-tolerance with "GABAergic depressants" — supported by the shared β(+)/α(-) transmembrane binding site mechanism and by Stevenson & Turnbull (1974 [Ref (PMID 4155651)]) demonstrating Mandrax-dependent animals show cross-tolerance to barbiturates.

---

## Interactions

### Alcohol (Ethanol)

**Mechanism:** Pharmacodynamic sensitization — ethanol reduces the minimum effective dose of methaqualone at the target organ level, without altering methaqualone's distribution or elimination [Ref 8]. Additionally, ethanol decreases the elimination rate of methaqualone, increasing residual serum levels [Ref 11, Ref 32].

**Duration of interaction risk:** The alcohol-methaqualone interaction is detectable up to 3 days after a single therapeutic dose of methaqualone (Roden et al. 1977 [Ref 11]). This is a critical harm reduction point — people may not realize their sensitivity to alcohol is elevated days after methaqualone use.

**In vitro mechanism [Ref (PMID 6260047)]:** Ho & Ho (1980) found that ethanol and methaqualone together inhibit brain Na-K-ATPase in a mixed/non-competitive manner, with greatest inhibition at low K+/high Na+ ratios — potentially contributing to combined toxicity.

**Mouse synergy [Ref 10]:** Methaqualone (50 mg/kg) prolonged ethanol-induced narcosis by 269% in mice.

### Baclofen

**Interaction type:** Likely lethal synergy via additive GABAergic CNS/respiratory depression (GABAB agonism via baclofen + GABAA PAM via methaqualone) [Ref 4]. This is listed in the seed data as a "lethal" known interaction. No specific published case report was found in the peer-reviewed literature for this specific combination, but the pharmacodynamic mechanism is well-supported.

> **FLAG:** The baclofen:methaqualone lethal interaction designation in the seed data is mechanistically plausible and consistent with the published pharmacology, but a specific case-report citation supporting the "lethal" classification was not identified in the peer-reviewed literature. This should be flagged for editorial review.

### Other CNS Depressants

All GABAergic agents (benzodiazepines, barbiturates, GHB, neurosteroids, anesthetic agents) carry additive/synergistic risk of respiratory depression in combination with methaqualone [Ref 4]. Opioids add independent respiratory depression via mu-receptor mechanisms.

### Cannabis (Smoked Combination)

The South African "white pipe" route combines methaqualone with cannabis [Ref 37]. No controlled studies of this pharmacological interaction were found.

### Diphenhydramine (Mandrax formulation)

Mandrax tablets contained methaqualone 250 mg + diphenhydramine 25 mg. Gupta et al. (1982 [Ref (PMID 6129311)]) studied the modification of methaqualone pharmacokinetics by diphenhydramine. The specific interaction data from that paper were not available (empty abstract), but the combination was intentional for enhanced hypnotic effect.

---

## Legal Status

| Jurisdiction | Status | Notes |
|---|---|---|
| **United States** | Schedule I (DEA) | Schedule II 1973; reclassified Schedule I 1984; no accepted medical use |
| **United Kingdom** | Class B (Misuse of Drugs Act 1971) | Regulated 1971; withdrawn from UK market early 1980s |
| **Canada** | Schedule III (CDSA) | Controlled; no longer manufactured or available |
| **Australia** | Schedule 9 (Prohibited Substance) | Highest restriction; no licensed use |
| **European Union** | Generally prohibited (varies by country) | Restricted/prohibited in member states |
| **United Nations** | Schedule II (UN Convention on Psychotropic Substances) | Initially Schedule I; moved to Schedule II in 1979 |
| **South Africa** | Illicit | Illegal despite widespread illicit availability; Mandrax supply chain largely clandestine |

**Source: [Ref 25, web sources on legal status]**

---

## Clinical Trials

No active, recruiting, or completed clinical trials for methaqualone were found on ClinicalTrials.gov. This is consistent with its Schedule I status in the United States and prohibited status in most research-active jurisdictions. No new drug applications or IND filings for methaqualone were identified.

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief. No items to evaluate.

---

## Gaps & Flags

### Safety-Critical Gaps

1. **⚠️ Human therapeutic index / lethal dose in humans:** No verified peer-reviewed source establishing a human lethal dose or therapeutic index was found. Only mouse LD50 (240 mg/kg i.p. [Ref 10]) was identified. The seed data note that "doses over 300 mg can be dangerous for first-time users" is supported by the Cole 1982 study using 300 mg as a recreational benchmark, but no formal human toxicity study exists. **Editorial flag: high-priority safety-critical gap.**

2. **⚠️ Baclofen:methaqualone "lethal" interaction — no case report citation found:** The seed data lists this as a known lethal interaction. The pharmacodynamic mechanism (combined GABAB + GABAA depression) is sound, but no specific peer-reviewed case report or primary source was identified in this research session. **Editorial flag: interaction severity not verified against published source.**

3. **⚠️ GABAA receptor binding affinity (Ki/EC50) values:** Quantitative binding affinity values at individual GABAA subtypes were not retrieved for methaqualone itself. Hammer et al. (2015 [Ref 2]) reports functional PAM activity at µM concentrations but the specific EC50 data are in tables that were not fully accessible. **Moderate priority — important for pharmacology completeness.**

### Data Gaps

4. **Pharmacokinetics discrepancy:** Half-life reported as ~10 hours by White et al. (1976 [Ref 21]) but 20–60 hours in pharmacological reference sources. The Nayak et al. (1974 [Ref 7]) paper would likely resolve this but the abstract was empty. The discrepancy may reflect two-compartment PK (rapid initial phase + prolonged terminal phase). Generation agent should note both values with appropriate context.

5. **Smoked route pharmacokinetics:** No published PK data for smoked methaqualone were found. Duration of smoked effects (1–2 hours) is from web sources [Ref 37] — user-report quality evidence, not controlled PK data.

6. **Sexual arousal enhancement mechanism:** The seed data includes sexual arousal enhancement as an effect. Published literature attributes this to disinhibition [Ref 4] rather than a direct pharmacological mechanism. No controlled study of methaqualone's effects on sexual arousal was found.

7. **Effect intensity and frequency values:** All 21 seed effect slots lack intensity/frequency values. These cannot be filled from published controlled studies (which are sparse for subjective effects). Assignment will rely primarily on expert inference from mechanism and class analogies, supplemented by the one direct human study (Cole 1982 [Ref 16]).

8. **Entity contact (transpersonal effect):** This seed effect slug is present in the profile. No published evidence exists for methaqualone producing entity contact experiences. This effect is atypical for a pure GABAA PAM depressant. **Flag for review — may be spurious or reflect very high-dose delirium.**

9. **Oral bioavailability percentage:** Multiple sources cite ~99% absorbed in 2 hours but a primary source (Morris et al. 1972 [Ref 29]) had an empty abstract and could not be verified.

10. **Stereochemistry of the parent compound:** Methaqualone itself is achiral at room temperature but exhibits atropisomerism due to restricted rotation around the N-aryl bond. The five hydroxylated metabolites show stereoselective formation [Ref 9, Ref 23]. No active isomer designation applies to methaqualone — it is a racemate at ambient temperatures.

### Data Contradictions

11. **"Emerging" characterization in brief:** The seed data marks methaqualone as "characterization: emerging." This appears to be a database error — methaqualone is a well-documented substance with a 70+ year literature history. It is not an emerging or novel psychoactive substance, though its quinazolinone analog SL-164 appeared on the research chemical market in 2019 [Ref 13]. **Flag for editorial correction of characterization field.**

12. **Tolerance half-life (seed data: "5 days"):** The seed data states a tolerance half-life of 5 days. The peer-reviewed literature does not provide a specific figure for tolerance half-life. The enzyme induction half-life (return to normal metabolizing capacity) may inform this, but a specific "5 days" tolerance half-life figure was not verified in primary sources. **Flag for editorial review.**

Methaqualone

Value Provenance

Dosing

oraltrace →

smokedtrace →

Duration

smoked

oral

Safety

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Dependence Profiletrace →

Withdrawal Profiletrace →

Tolerance Profiletrace →

Effects & Profile

Contraindications

Timeline Phases

oral

smoked

Dose Tier Summaries

History

Sources

Claim Verification

Coverage & Gaps

Research Trail

oraltrace

smokedtrace

Toxicity Profiletrace

Dependence Profiletrace

Withdrawal Profiletrace

Tolerance Profiletrace