Most readers know this drug by its old American brand name, Quaaludes. Methaqualone is a quinazolinone sedative-hypnotic that acts on GABA-A receptors, it sits in Schedule II of the 1971 Convention on Psychotropic Substances and in Schedule I in the United States, and it has not disappeared. It is still used, mainly as mandrax in southern Africa.
The brand, the 1970s and the story of how the drug left pharmacy shelves are covered on our separate page about quaaludes. This page deals with the pharmacology, the withdrawal picture, the scheduling record and where the drug is now.
What class of drug methaqualone actually is
The WHO Expert Committee on Drug Dependence information repository identifies methaqualone (INN, CAS 72-44-6) as 2-methyl-3-o-tolyl-4(3H)-quinazolinone, notes that no stereoisomeric forms exist, and describes it as a “depressant of the central nervous system similar in its actions and effects to the barbiturates”.
That comparison describes what the drug does. It does not describe where it acts, and the difference matters more than the older literature suggests.
Work published in Molecular Pharmacology in 2015 found methaqualone to be a positive allosteric modulator at human α1,2,3,5β2,3γ2S GABA-A receptors, with what the authors called “highly diverse functionalities” at α4,6β1,2,3δ subtypes, ranging from inactivity through negative or positive modulation to superagonism. The same study reported that methaqualone “did not interact with the benzodiazepine, barbiturate, or neurosteroid binding sites in the GABAAR”, acting instead through the transmembrane β(+)/α(-) subunit interface.
A 2024 cryo-electron microscopy study in Nature Communications located that site precisely, reporting that methaqualone binds the same intersubunit transmembrane sites targeted by the general anaesthetics propofol and etomidate, and that it inserts more deeply into the subunit interfaces than previously characterised modulators.
Our reading of those two papers together is that methaqualone is not a chemical cousin of the barbiturates at all. It reaches the same receptor by a different door. That is our synthesis of the two findings rather than a claim either paper makes in those words.
How it sits against barbiturates and benzodiazepines
| Methaqualone | Barbiturates | Benzodiazepines | |
|---|---|---|---|
| Target | GABA-A receptor | GABA-A receptor | GABA-A receptor |
| Binding site | Transmembrane subunit interface, shared with propofol and etomidate | Distinct barbiturate site | Distinct benzodiazepine site |
| Current medical use | None accepted in the US | Limited, narrow indications | Widely prescribed |
| International control | Schedule II, 1971 Convention | Varies by substance | Varies by substance |
The row that does the most work is the second one. The 2015 study’s finding that methaqualone does not touch the barbiturate or benzodiazepine sites means that the familiar shorthand “it is basically a barbiturate” is a statement about effect, not about mechanism.
The safer alternative that was not
Methaqualone was introduced as a non-barbiturate hypnotic and promoted on that basis. A 2023 review in ACS Chemical Neuroscience describes it as “a sedative-hypnotic medication, with effects resembling barbiturates and other downers, that exerts its effects through modulation of γ-aminobutyric acid type A receptors”, and traces how a drug marketed as a safe sleeping option came to be recognised as addictive after widespread recreational use, overdoses and dependence.
Our observation is that the original safety claim rested on the drug not being a barbiturate chemically, at a time when nobody knew that both classes converge on the same receptor. Being structurally novel was mistaken for being pharmacologically safer. That is our reading of the sequence rather than a conclusion stated in the sources.
The 2024 Nature Communications paper puts the outcome plainly: “Due to its high abuse potential, medical use of methaqualone was eventually prohibited, yet it persists as a globally abused substance.”
Withdrawal, and why sedative withdrawal is the medically serious kind
This is the part of the page that carries the most weight.
The WHO repository records that methaqualone produces tolerance and physical dependence of the barbiturate type. A 1986 case report in Neurology states it directly: “Methaqualone is a sedative hypnotic that is often abused. Tolerance and habituation may develop, and the withdrawal syndrome may include seizures.” The reported case involved myoclonic and tonic-clonic seizures in a person with no prior seizure history, with the abnormalities resolving after withdrawal.
That places methaqualone in the same category as alcohol and the benzodiazepines, where stopping suddenly after sustained heavy use is the dangerous part rather than the drug itself. Opioid withdrawal is miserable and rarely lethal in itself. Sedative withdrawal can involve seizures. If methaqualone or mandrax has been part of daily use, stopping abruptly and alone is not the safe option, and a clinician should be involved before anything changes. What that looks like in practice is closest to benzodiazepine withdrawal and detox and medically supervised drug detox.
We also looked for a current, published protocol for managing methaqualone withdrawal specifically. We could not verify one. Our reading is that clinicians treat it as a sedative-hypnotic withdrawal and manage it accordingly, but that is an inference on our part and not something a guideline we could check says in those terms.
The scheduling record
Legal status is quoted here from control bodies rather than asserted, and readers should check the position in their own country.
Internationally, methaqualone is listed in Schedule II of the 1971 Convention on Psychotropic Substances, per the WHO repository above. The placement dates from 1979. The same record shows a critical review by the twenty-fifth Expert Committee on Drug Dependence in 1989.
In the United States, the DEA’s chronological record of scheduling actions shows methaqualone placed in Schedule II with effect from 4 October 1973 at 38 FR 27516, then transferred from Schedule II to Schedule I with effect from 27 August 1984 at 49 FR 33870. The DEA defines Schedule I as covering substances with “no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse”.
The DEA’s alphabetical list of controlled substances carries methaqualone at drug code 2565 in Schedule I as a non-narcotic, and lists its other names as “Quaalude; Parest; Somnafac; Opitimil; Mandrax”. The presence of Mandrax in a current American federal list is the clearest single sign that this is not a closed historical file.
Where the drug still is
Southern Africa is the answer, and the evidence is recent.
The South African Community Epidemiology Network on Drug Use, run by the South African Medical Research Council, monitors treatment admissions across all nine provinces. Its update covering July to December 2025 records methaqualone, or mandrax, as the primary substance of use for 7 per cent of admissions in the Western Cape, and between 1 and 4 per cent across the other five reporting regions. The report describes the figure as covering “the cannabis/mandrax (methaqualone) also known as ‘white-pipe’ combination”, so the number counts the combination rather than mandrax used alone. Our reading is that this makes the surveillance figure a floor rather than a ceiling for mandrax involvement, but the report does not say that.
The clinical consequences show up in unrelated research. A 2024 pharmacokinetic study of people being treated for tuberculosis found that methaqualone use reduced rifampicin bioavailability by 19 per cent. The same study found no significant effect of alcohol use on those medicines other than faster ethambutol clearance in heavy drinkers, so the finding is specific to the drug rather than to substance use in general. A 2026 study in the Journal of Infectious Diseases recruited 750 people who smoke drugs, tested for methamphetamine and methaqualone, and found a sampling-adjusted tuberculosis prevalence of 10.4 per cent. A 2024 study of young women in Cape Town reported around 17 per cent screening positive for methaqualone.
There is also a newer complication. A 2026 review in Forensic Toxicology identified five designer methaqualone analogues on the illicit market and described them as roughly a hundred times more potent than methaqualone itself, calling them a serious and underrecognised threat. Published case reports of one such analogue, SL-164, describe prolonged agitated delirium and, in a separate case, hypoxia, hyperreflexia and myoclonus in someone who believed they had taken methaqualone. Our observation is the obvious one: a substance sold today as methaqualone may not be methaqualone, and may be far stronger.
Getting help with sedative use
The Orchid Recovery is a residential addiction and mental health treatment centre in Hang Dong District, Chiang Mai, Thailand, for international English speaking adults. If sedative use has become difficult to stop, our pages on residential treatment, medically supervised drug detox and polysubstance use explain what care involves, our clinical team is listed here, and you can contact us if it would help.
If someone is unresponsive, having a seizure or in immediate danger, that is an emergency. Outside the UK, use your local emergency number.
Sources
- WHO Expert Committee on Drug Dependence Information Repository, Methaqualone
- DEA Diversion Control Division, Scheduling Actions, Chronological Order
- DEA Diversion Control Division, Controlled Substances, Alphabetical Order
- DEA Diversion Control Division, Controlled Substance Schedules
- Hammer et al, A Multifaceted GABAA Receptor Modulator, Molecular Pharmacology 2015
- Chojnacka et al, Structural insights into GABAA receptor potentiation by Quaalude, Nature Communications 2024
- Inger et al, DARK Classics in Chemical Neuroscience: Methaqualone, ACS Chemical Neuroscience 2023
- Faught, Methaqualone withdrawal syndrome with photoparoxysmal responses, Neurology 1986
- South African Medical Research Council, SACENDU
- SACENDU Update, July to December 2025, via the SAMRC SACENDU page
- Wijk et al, The impact of alcohol and illicit substance use on the pharmacokinetics of first-line TB drugs, Journal of Antimicrobial Chemotherapy 2024
- Malatesta et al, Tuberculosis Disease Prevalence Among People Who Smoke Illicit Drugs, Journal of Infectious Diseases 2026
- Browne et al, Associations between childbirth, gang exposure and substance use among young women in Cape Town, 2024
- Wachełko et al, Reinventing quaaludes: a comprehensive review of designer methaqualone analogs, Forensic Toxicology 2026
- Romanek et al, Return of the Quaaludes? Prolonged agitated delirium after intentional ingestion of the methaqualone analog SL-164, Substance Abuse 2021
- Lund et al, Qua-Alluding to the Past: A Case of Methaqualone Analog Ingestion, Journal of Analytical Toxicology 2021
Frequently Asked Questions
What type of drug is methaqualone?
It is a quinazolinone sedative-hypnotic that acts as a positive allosteric modulator at GABA-A receptors. The WHO Expert Committee repository describes it as a central nervous system depressant similar in its actions and effects to the barbiturates. Its binding site, however, is not the barbiturate site. A 2024 structural study placed it at the same transmembrane interface used by propofol and etomidate.
Is methaqualone the same as quaaludes?
Yes. Quaalude was an American brand name for methaqualone, and Mandrax is the name used in southern Africa and parts of Asia. The DEA´s own list of controlled substances gives Quaalude, Parest, Somnafac, Opitimil and Mandrax as other names for the same substance.
Is methaqualone withdrawal dangerous?
It should be treated as potentially dangerous. Methaqualone produces tolerance and physical dependence, and a 1986 Neurology report states that the withdrawal syndrome may include seizures. Sedative withdrawal is the category where abrupt stopping after sustained heavy use carries real medical risk. Anyone using it daily should speak to a clinician before stopping rather than stopping alone.
What schedule is methaqualone in?
It is listed in Schedule II of the 1971 Convention on Psychotropic Substances. In the United States it was placed in Schedule II of the Controlled Substances Act with effect from 4 October 1973 and moved to Schedule I with effect from 27 August 1984. National law varies, so check the position where you live rather than relying on a summary.
Is methaqualone still used anywhere?
Yes, mainly as mandrax in southern Africa. South African treatment surveillance for July to December 2025 recorded methaqualone or mandrax as the primary substance for 7 per cent of admissions in the Western Cape, usually as the cannabis and mandrax combination known as white pipe, and between 1 and 4 per cent in the other reporting regions.
Why was methaqualone marketed as safer than barbiturates?
Because it was chemically a different class of compound, at a time when its receptor action was not understood. Later work showed that methaqualone and the barbiturates both act as positive modulators at the GABA-A receptor, though at different sites. Our reading is that structural novelty was mistaken for pharmacological safety, which the drug´s subsequent history did not support.
What are designer methaqualone analogues?
They are newer compounds built on the methaqualone structure and sold online. A 2026 review in Forensic Toxicology identified five and described them as roughly a hundred times more potent than methaqualone, calling them a serious and underrecognised threat. Case reports of one analogue, SL-164, describe prolonged agitated delirium and marked neurological signs in people who thought they had taken methaqualone.
How would someone start treatment for sedative dependence?
With a conversation and a medical assessment, not with stopping. Admissions at The Orchid Recovery takes a history of what is being used and for how long, and our on-site psychiatrist then decides whether a supervised detox inside a residential admission is appropriate. Stays run four, eight or twelve weeks. We admit international adults residentially and do not offer detox on its own.
