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Scientists explore mystery of a psychedelic HIV/AIDS drug

April 22, 2013|By Melissa Healy

For those taking antiretroviral medications for HIV/AIDS, there is one drug in the mix that can put a particular kick in the cocktail: the drug efavirenz, marketed under the commercial names Sustiva and Stocrin, appears to have an "LSD-like interaction" with the receptors in the brain that govern the activity of serotonin, says a study presented in Boston today.

That may explain why roughly half of patients taking efavirenz at the prescribed dose have reported neuropsychiatric side effects that include suicidal depression, night terrors, hallucinations, paranoia, psychosis and delusions. And it may also explain why efavirenz tablets are reportedly being ground up and smoked by drug abusers looking for a hallucinogenic high.

Working with mice, a team led by Dr. John A. Schetz, a pharmacologist from the University of North Texas Health Science Center in Fort Worth, found that efavirenz activates the serotonin 5-HT 2A receptor in the brain, the same molecular site on which lysergic acid diethylamide (LSD) works. Mice that were given efavirenz responded with the same distinctive head-twitching behavior seen when they are given LSD, and mice bred without the serotonin 5-HT 2A receptor do not. And just as they are when under the influence of LSD, mice given efavirenz also were far less bold than would be expected normally when they were allowed to explore an environment filled with unfamiliar sights, smells and objects.

While efavirenz is highly effective in helping suppress the human immunodeficiency virus, its psychoactive potency is weak compared with  that of LSD, Schetz said. But if the medication's abuse potential results in increased diversion of the medication to drug abusers, the result could not only be shortages for patients who need it, but the medication's more widespread use could encourage the emergence of strains of HIV that are resistant to efavirenz.

The findings of Schetz's team will be presented this week in Boston at the annual meeting of the Federation of American Societies for Experimental Biology.

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