Can Hallucinogens Treat Anxiety and Depression?

Hallucinogens have quite the tangled past in Western cultures, especially in the United States. On the one hand, drugs such as lysergic acid diethylamide (LSD) and psilocybin (psychedelic mushrooms) were a prominent feature of the rock-n-roll scene and countercultural movements of the 1960s¹. They were seen as a way to rebel against the system and achieve a more open mindset², and a number of prominent thinkers of the time, such as Aldous Huxley³, even actively advocated for their consumption.

On the other hand, these drugs have a much darker side. For instance, in the 1950s under the infamous project MKULTRA, the CIA conducted experiments attempting to use LSD as a mind-controlling agent⁴. They even went as far as administering the drug to unknowing and/or unwilling participants to determine the drug’s effectiveness.

Given this mixed history, it could be hard to think of hallucinogens as a potential treatment for mental disorders. However, these drugs initially received a great deal of attention from psychiatrists interested in their therapeutic effects. During the 1960s and 1970s, these early researchers reported a number of promising findings.

Specifically, hallucinogens seemed to reduce symptoms of anxiety, depression, and, surprisingly, even addiction^5-8. Unfortunately, though, such work was soon cut short. Government officials were alarmed by the increasing number of recreational users of hallucinogens and were uneasy about the strong connection between these drugs and countercultural movements⁹. Thus, most hallucinogens were banned in many countries, making effective human research almost impossible for many years.

Due to shifting regulations, the 1990s saw a resurgence of human research on hallucinogens as a means of treating psychiatric disorders, and since then a number of earlier findings appear to have been supported. For instance, there is growing evidence that both LSD and psilocybin can help with anxiety and depression^10-11.

In particular, work at John Hopkins University has found the psilocybin can help treat severe cases of depression¹², and research has found similar evidence for ketamine (MDMA or “ecstasy”)^13-14, which also has hallucinogenic effects. With these promising findings, there has been a renewed interest in adequately investigating hallucinogens, and there are now even organizations, such as the Multidisciplinary Association for Psychedelic Studies (MAPS)¹⁵, which count a number of prominent scientists amongst its members, calling for relaxing restrictions on such drugs.

In a paper published this summer, Dr. Rafael dos Santos from the University of São Paulo in Brazil, along with his colleagues, sought to analyze and compile the research done on these drugs. Given the legal restrictions still placed on them, one difficulty in this area of research is identifying clinical trials conducted with the proper experimental methods and controls. Thus, of the 144 studies that the researcher found, only 6 made the cut for their analyses.

Despite their small number, these studies reported consistent positive effects among their participants. For instance, psilocybin was found to improve symptoms of obsessive-compulsive disorder (OCD)^16-17, reduce symptoms of anxiety and depression among terminally ill cancer patients¹¹, and decrease both alcohol¹⁸ and tobacco¹⁹ dependence among addicts. Likewise, LSD was reported to decrease anxiety symptoms associated with life-threatening diseases^19-21 as well as help in the treatment of alcoholism²². Crucially, the reported improvements lasted over the course of several days and, in some cases, months.

To be clear, though, these findings do not mean that anyone should rush to self-medicate with hallucinogens. For starters, despite including studies from the past 15 years, the current paper found only 6 that adequately tested the effects of their target drugs, and even these studies included extremely small sample sizes.

Consequently, we are still not sure if the positive effects they report will generalize to the larger population, and even if they do, much work still needs to be done in order to determine the best means of administering each drug. In this vein, it remains unclear how these drugs actually function. A great deal of research must still be done to localize and understand their effects in the brain so as to improve their efficacy and ensure they are not interfering with other important processes.

Furthermore, and perhaps most importantly, these drugs are still illegal in many Western countries. Attempting to purchase or being caught in possession of most hallucinogens are grounds for criminal prosecution and can result in fines, loss of employment, and possibly prison sentences. In short, we still aren’t sure that these drugs work, and they certainly aren’t worth the legal risks of trying them on your own.

All of that aside, this research is immensely promising. Disorders such as anxiety, depression, and addiction are notoriously difficult to treat, and many of the drugs available have negative side effects that can rival symptoms of the disorders they intend to treat. In all of the studies reported by dos Santos and colleagues, though, participants reported few, if any, negative side effects of the drugs, making them a potentially appealing avenue of treatment.

Hopefully, these findings will spur government agencies to relax restrictions on human testing with hallucinogens and provide funding so that adequate clinical trials can begin. Despite being once associated with rebellious youth and dark government conspiracies, hallucinogens may one day play a pivotal role in the treatment of mental disorders.

Samuel Hunley, Ph.D.

Program Analyst, U.S. Department of Agriculture at Emory University

Sam Hunley received his doctorate from Emory University in cognitive psychology. He received his Bachelor of Science in psychology from Furman University in 2012 and his master’s in psychology from Emory in 2014. Working with Dr. Stella Lourenco, Sam studies how humans think about and perceive the space immediately surrounding the body, and he is specifically interested in how anxiety and phobic fears affect the way we see the space around us. Sam and Dr. Lourenco collaborate to write articles for Anxiety.org. After graduating, Sam accepted a position as a Presidential Management Fellow.