The HIV antiretroviral drug efavirenz has LSD-like properties.
Michael B. Gatch, Alexey Kozlenkov, Ren-Qi Huang, Wenjuan Yang, Jacques D. Nguyen, Javier González-Maeso, Kenner C Rice, Charles P France, Glenn H Dillon, Michael J Forster, John A Schetz
Neuropsychopharmacology May 24, 2013 DOI: 10.1038/npp.2013.135 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rodents (rats and mice) |
| Interventions | efavirenz LSD cocaine |
| Topics | LSD |
| Keywords | Animals Mice Rats, sprague-dawley Alkynes Cyclopropanes Benzoxazines Receptors, cell surface Receptor, serotonin, 5-ht2a Hallucinogens Anti-hiv agents Behavior, animal Male Conditioning, psychological Discrimination, psychological |
| Key findings | Efavirenz's prevailing behavioral effect in rodents is LSD-like activity mediated via the 5-HT(2A) receptor, despite its multifarious molecular pharmacology. |
Abstract
Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABAA and 5-HT(2A) receptors. In rodents, interaction with the 5-HT(2A) receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT(2A) receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT(2A)-knockout, mice. Despite having GABAA-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT(2A) receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 7
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- Efavirenz exposure, alone and in combination with known drugs of abuse, engenders addictive-like bio-behavioural changes in rats Scientific Reports August 21, 2018
- Novel Phenethylamines and Their Potential Interactions With Prescription Drugs: A Systematic Critical Review. Therapeutic Drug Monitoring April 1, 2020
- Mind the gap! Addressing unresolved aspects of abuse potential evaluation and scheduling of classic and novel psychedelic drugs Journal of Psychopharmacology October 16, 2025
- Snapshot IP 1 Detection Following 5-HT 2 A Receptor Stimulation in the Mouse Brain ACS Chemical Neuroscience January 2, 2026
and 2 more in the library
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