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 Schetz

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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 GABA A 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 GABA A-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.

Original languageEnglish
Pages (from-to)2373-2384
Number of pages12
JournalNeuropsychopharmacology
Volume38
Issue number12
DOIs
StatePublished - 1 Nov 2013

Fingerprint

efavirenz
Lysergic Acid
HIV
Receptor, Serotonin, 5-HT2A
Pharmaceutical Preparations
Cocaine
Rodentia
Night Terrors
Vesicular Monoamine Transport Proteins
GABA Plasma Membrane Transport Proteins
Pharmacology
diethylamine
Serotonin Plasma Membrane Transport Proteins
Dopamine Plasma Membrane Transport Proteins
HIV-2
Barbiturates
Methamphetamine
Hallucinations
Street Drugs

Keywords

  • AIDS
  • adverse neuropsychiatric events
  • hallucinogen
  • side effects

Cite this

Gatch, M. B., Kozlenkov, A., Huang, R-Q., Yang, W., Nguyen, J. D., González-Maeso, J., ... Schetz, J. (2013). The HIV antiretroviral drug efavirenz has LSD-like properties. Neuropsychopharmacology, 38(12), 2373-2384. https://doi.org/10.1038/npp.2013.135
Gatch, Michael B. ; Kozlenkov, Alexey ; Huang, Ren-Qi ; Yang, Wenjuan ; Nguyen, Jacques D. ; González-Maeso, Javier ; Rice, Kenner C. ; France, Charles P. ; Dillon, Glenn H. ; Forster, Michael J. ; Schetz, John. / The HIV antiretroviral drug efavirenz has LSD-like properties. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 12. pp. 2373-2384.
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Gatch, MB, Kozlenkov, A, Huang, R-Q, Yang, W, Nguyen, JD, González-Maeso, J, Rice, KC, France, CP, Dillon, GH, Forster, MJ & Schetz, J 2013, 'The HIV antiretroviral drug efavirenz has LSD-like properties', Neuropsychopharmacology, vol. 38, no. 12, pp. 2373-2384. https://doi.org/10.1038/npp.2013.135

The HIV antiretroviral drug efavirenz has LSD-like properties. / Gatch, Michael B.; Kozlenkov, Alexey; Huang, Ren-Qi; Yang, Wenjuan; Nguyen, Jacques D.; González-Maeso, Javier; Rice, Kenner C.; France, Charles P.; Dillon, Glenn H.; Forster, Michael J.; Schetz, John.

In: Neuropsychopharmacology, Vol. 38, No. 12, 01.11.2013, p. 2373-2384.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Yang, Wenjuan

AU - Nguyen, Jacques D.

AU - González-Maeso, Javier

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