Classic psychedelic drugs include psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT). These drugs cause hallucinatory and mystical/spiritual experiences. They have also been associated with significant risks and abuse. Recent studies performed at academic medical centers in North America and Europe suggest that these drugs may have therapeutic value in treating a variety of conditions including addictions. This work was reviewed in a 2015 article in the Canadian Medical Association Journal and has appeared in several high profile journals. How strong is the evidence?
Psychedelic mushrooms and plant-based ayahuasca brew have been used in religious and shaman-based ceremonies for centuries. Psilocybin is the active ingredient in “magic” mushrooms, and DMT is an active ingredient in ayahuasca.
LSD was synthesized by Albert Hofman in 1938. Hofman was a chemist working for Sandoz Laboratories, a pharmaceutical company. While he was examining respiratory and circulatory properties of chemicals derived from various plants and fungi, he discovered that one of the compounds, LSD, had psychedelic properties when he absorbed a very small amount accidentally. It turns out that LSD is extremely potent and a minuscule amount has strong psychedelic effects. By the late 1960s, tens of thousands of individuals had participated in inadequately designed studies of LSD for the treatment of a variety of conditions including alcohol addiction. In addition, LSD was used by the military in human experimentation. It also became a popular street drug and a staple of the 1960s’ counterculture.
Eventually, these psychedelic drugs were classified as dangerous drugs without therapeutic value (DEA schedule 1 drugs). When drugs are classified as schedule 1 agents, research regarding their actions is greatly inhibited because of increased regulations and difficulty in obtaining research funding.
Interestingly, the brain mechanisms underlying the psychedelic effects of these three very different drugs are similar, and a small group of individuals maintained a strong belief that these drugs had unique therapeutic properties. Some of these individuals formed an organization called the Multidisciplinary Association for Psychedelic Research (MAPS). In addition, a few persistent scientists were able to perform laboratory studies. Partly because of these individuals, an increasing number of clinical scientists have started to study these drugs.
Results from a number of recent studies suggest the possibility that carefully administered exposure to a few doses of hallucinogens may be effective in the treatment of addictions, including alcohol and nicotine addiction. It is important to emphasize that these studies involved very small numbers of participants and were of limited duration. Also, it is difficult to include an appropriate placebo control when studying drugs that may induce a mystical experience in order to be therapeutic. Because these studies suggested the possibility of benefit, there are now ongoing phase 2 medication trials of these drugs for the treatment of alcoholism and other disorders. (Phase 2 studies examine safety and possible benefit.) If phase 2 trials are successful, then some of these drugs may enter into much larger, phase 3 clinical trials.
Some question whether studies involving psychedelic drugs should be done at all, even when carefully designed and closely supervised, given known problems associated with prior use of these agents. Certainly, drug addictions are devastating, and the possibility of a new group of therapeutic agents should be carefully pursued. But studies of these agents are complicated by their history, reputation, political issues surrounding their use, and public opinion. Also, these drugs are available on the black market. One must ask whether their clinical use would lead to increased illegal use, something that has a significant probability given what we know about current misuse of therapeutic opiates and other prescribed drugs.
Currently, ketamine, another drug with hallucinogenic properties, is receiving a lot of attention for its ability to rapidly reverse severe depressive symptoms and suicidality. Because this drug is already approved for use as a dissociative anesthetic, ketamine clinics targeting the treatment of depression are opening around the country. Ketamine also is a street drug with similar effects as PCP (angel dust). Little is known about the clinical use of ketamine in treating depression, although studies of ketamine are much further along than studies with other hallucinogens. Although this is an area of active investigation, ketamine’s off-label clinical use in these clinics may be premature. Problems with this drug will likely show up in the increasing number of patients being treated with it in non-research settings.
Unlike ketamine, psilocybin, DMT, and LSD are not approved for any medical conditions and, therefore, cannot be prescribed legally in the US. However, psychedelic drugs may be used increasingly in “clinics” outside the US.
Because addictions and other psychiatric illnesses are so devastating and so common, it is important to evaluate all potential treatment approaches in carefully designed clinical studies. Until this happens, we are concerned that there will be a growing demand and black market for “therapeutic uses” of psychedelics.
This column was written by Eugene Rubin MD, PhD and Charles Zorumski MD.