Gatch MB, Gonzalez Maeso J, Huang RQ, Yang W, Kozlenkov A, Nguyen JD, Rice KC, France CP, Dillon GH, Forster MJ, Schetz JA.
“The HIV antiretroviral drug efavirenz has LSD-like properties”.
Neuropsychopharmacology. 2013 May 24.
Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz 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-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz depress open field activity in a novel environment. In rats trained to discriminate LSD from saline, efavirenz substitutes for LSD, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild type, but not 5-HT2A-knockout mice. Despite having GABAA potentiating effects, like benzodiazepines and barbiturates, and interactions with DAT, SERT and VMAT2, like cocaine and methamphetamine, efavirenz fails to maintain self-administration responding in rats that maintain cocaine self-administration responding, and it fails to produce a conditioned place preference. Though its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A 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.Neuropsychopharmacology accepted article preview online, 24 May 2013; doi:10.1038/npp.2013.135.