Popular antiretroviral drug has same effect on brain as LSD
Antiretroviral drugs are vital for those trying to keep HIV and AIDS at bay, but the psychedelic side effects of one common drug might take some users by surprise.
Efavirenz, a drug that is usually used in conjunction with other drugs as a cocktail to fight type one HIV (HIV-1), has a range of side effects that includes feelings of terror, severe depression, paranoia, psychosis and delusional hallucinations. Much to the surprise of researchers investigating these side effects, it turns out that efevirenz has a similar effect on the brain as lysergic acid diethylamide — known to most as LSD.
The recreational side effects of efavirenz are not something new — for years in South Africa people have been smoking crushed efavirenz pills (sometimes with marijuana or other drugs) for an easy high in a mixture known as "wunga". A terrible side effect of this is that, in a country where 17.8 percent of adults are carrying the HIV virus (the fourth-highest rate in the world), people are training their bodies to be immune to antiretroviral drugs.
The psychedelic side effects of efavirenz are also seen in people who take it as medically prescribed, however, with some people developing adverse psychiatric conditions as a result. This known side effect history, along with the reports of its use in South Africa, attracted the attention of neuropharmacologist John Schetz from the University of North Texas Health Science Centre.
Schetz said: “I saw an ABC News Nightline Report by Jim E Sciutto a few years ago where he detailed the practice of people crushing the efavirenz pills and smoking them for a high. I was curious to see if I could gather any scientific data that might confirm or refute the idea that efavirenz might be an attractive recreational drug. During this process I came across literature describing adverse neuropsychiatric side effects of efavirenz, which, in some cases, seemed to dovetail with behaviours observed in the new report in those who were smoking the medicine.”
Clearly, efavirenz has neuropsychiatric effects that both users and abusers are experiencing. When Schetz and his team tested efavirenz on mice, it gave intriguing results — according to molecular profiling of the receptor pharmacology of efavirenz, the 5-HT2A serotonin receptor was the site most affected by the drug. That’s the area of the brain that is specifically activated by hallucinogenic and psychedelic drugs like LSD.
While efavirenz’s potency was nowhere near that of LSD, the behavioural effects on the mice (most easily seen in terms of wild, uncontrollable twitching) were demonstrably similar under the influence of both drugs. Put simply, the mice were tripping balls, dude.
However, as to whether it’s accurate to say the effects of LSD and efavirenz feel the same for humans, it’s not possible to say, Schetz said: “Based upon pre-clinical receptor profiling and behavioural measures we expect there would be some similarities, [however] controlled studies in humans simulating the practice of those who abuse efavirenz have not yet been performed. Further, most drugs have multiple sites of action leading to multiple, mixed effects, which might influence the overall subjective effect experienced by a user.”
Psilocybin, the active ingredient in magic mushrooms, also acts on the 5-HT2A receptor, so just as different hallucinogens give different experiences, so might efavirenz feel different to LSD. Schetz cautions against anyone thinking this research makes efavirenz a fun new drug to try: “It is reasonable to expect that the dangers associated with the recreational use of the efavirenz would be at least as great as for LSD. However, there are likely to be even greater dangers as there may be more than one effect and efavirenz was developed for oral consumption as a medicine to treat HIV-1. I would strongly caution against even experimenting with efavirenz and emphasise that it would be extremely reckless for anyone to use it for anything other than its intended use.”
Schetz presented the results of the study to the annual conference of the Federation of American Societies for Experimental Biology on 22 April, and the paper is currently undergoing peer review as part of its submission to the Journal of the Federation of American Societies for Experimental Biology. While waiting for that Schetz and his team are now “devising ways to prevent both adverse neuropsychiatric side effects and abuse potential for a very efficacious HIV antiretroviral drug”.
He said: “We have ideas for both shorter term and longer term solutions. Because this is the first scientific report concerning the mechanism of efavirenz’s psychoactivity, there are literally countless other avenues of research related directly or indirectly to this topic that should be of interest to the medical community and to public health in general.”