Don’t Have an Unsafe Trip

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Psychedelics (“hallucinogens”) are substances that produce unfamiliar changes in thinking, perception and mood. Effects can include hallucinations, distortions in time and space, and intensified sensory experiences (sound, colors etc.). Examples include LSD, psilocybin (“magic mushrooms”), MDMA (Molly, Ecstasy), mescaline, ayahuasca, and ketamine.

The study of psychedelics for mental health has received much attention recently, with an explosion of research at well-respected institutions (Johns Hopkins, NYU and others) for conditions such as: depression, PTSD, addiction, anorexia, existential anxiety in people facing death, social anxiety in autism, and quitting smoking. 

Psychedelics may also have benefits in healthy people. Users report intense feelings such as connectedness with others, connectedness with the universe, expansion of consciousness, sense of awe, calmness, and mystical experiences. These experiences can result in long-lasting positive changes in perspective, mood and fulfillment.

It’s important to temper the promise of these drugs with caution and to understand the very real risks of experimenting with powerful psychoactive substances without structures in place to reduce the chances of a negative reaction.

Unpredictable effects can include profound negative moods, such as despair and intense anxiety; suicidal thinking; accidents caused by changes in perception when intoxicated; long-term persistence of flashbacks, psychosis or paranoia; cardiovascular changes; and toxicity when mixed with other drugs, including prescribed medications.

Some history:

LSD (lysergic acid diethylamide) was first synthesized in 1938 by Albert Hofmann, a Swiss chemist looking for a medication to stimulate circulation. But the drug did not work as hoped. One day he had a strange reaction: “…. I perceived an uninterrupted stream of fantastic pictures, extraordinary shapes with intense, kaleidoscopic play of colors.” He later realized he had inadvertently ingested a trace amount of the LSD. He went on to experiment on himself with higher doses, resulting in some beautiful mystical experiences and also some very frightening “trips.” He later said “The unpredictability of effects is the major danger of LSD.” 

In the 1950s and 1960s, the CIA conducted experiments with LSD, hoping it could be used as a psychological weapon in the Cold War. These top-secret Project MK-Ultra mind-control experiments included dosing people without their knowledge or consent (and other forms of physical and psychological torture). Ironically, author Ken Kesey first took LSD as a volunteer subject in this CIA project. Ultimately the effects of LSD were too unpredictable to be useful, and the experiment was shut down.

Psychedelics such as LSD and psilocybin were also studied for therapeutic effects during the 1940s-1960s at Harvard and other institutions. The idea was that the mystical experiences induced by these compounds could have transformative healing effects for people struggling with illnesses such as depression and alcoholism. 

The Harvard psychologists Timothy Leary and Richard Alpert were fired under a cloud of scandal for sloppy work and ethics violations, including taking the drugs along with their student volunteers. Leary went on to become an iconic figure in the counterculture movement of the 1970s. He was a divisive figure who famously urged young people to “turn on, tune in, drop out.” Some blame Leary’s hedonism and ego for the backlash against psychedelics (especially LSD), and the criminalization movement that essentially halted studies for several decades. 

That is beginning to change.

Currently, there is a LOT of enthusiastic press attention as research into psychedelics is again moving forward. This excitement is natural, given the limits of traditional psychiatric medications—in effectiveness, side-effects, and acceptability (such as having to take a medication daily and ongoing). 

While it is not known how different psychedelic compounds might work to relieve mental suffering, one theory posits an increase in neuroplasticity, the ability of the brain to form new connections and reorganize. Also, loosening the hold of our “ego” may open us up to new insights.

Hoped-for benefits of psychedelics, in addition to effectiveness, include quick action, sustained response, only needing a few doses, and better tolerability. 

For example, a study was published in the August 24, 2022 issue of JAMA Psychiatry in which a combination of psilocybin (2 doses, given 4 weeks apart) plus psychotherapy (12 weeks) was significantly more effective than placebo plus psychotherapy in reducing alcohol use in people with alcohol dependence. Headaches, anxiety and nausea were some of the more common side-effects of the psilocybin treatment. There were no serious side-effects.

However, while there is reason to be excited, the studies are ongoing and not yet conclusive. The clinical research is tricky; it is difficult to separate effects of the psychotherapy from the influence of volunteers’ positive expectations. Also, a true placebo control is hard to achieve; the psychedelic reaction often makes it obvious to the volunteer if they received the active compound. And, many “real world” patients are screened out due to potential risks (such as people with other mental health disorders, drug use disorders, significant medical illnesses, family histories of psychosis, and people on other psychiatric medications). We need larger clinical trials with more diversity to better understand benefits and risks. 

Also, it is important to emphasize that in these studies psychedelics are administered as a component of Psychedelic-Assisted Therapy. The doses are carefully controlled. And they are not given alone, but are accompanied by support and structure. Psychedelic-Assisted Therapy includes sessions for preparation ahead of the “trip,” taking the drug in a controlled environment with trained therapists, and an “integration” session afterwards to process the experience. “Set” and “setting” are considered crucial to the outcome of a psychedelic experience: “set” being one’s mindset going into the session, and the “setting” being a safe and soothing environment.

As noted above, there are risks to ingesting psychedelics, especially in vulnerable people. These include disturbing psychotic experiences (a “bad trip”); development of persistent hallucinogenic perceptions or an ongoing psychotic syndrome similar to schizophrenia; panic attacks; intense negative mood; and changes in blood pressure and pulse. Bad outcomes are more likely in people with a personal or family history of psychosis, who take other drugs or certain medications, or have cardiovascular disease. 

The abuse potential of psychedelics is unclear, with the exception of ketamine. Ketamine is known to carry abuse liability. For other psychedelic drugs, there is some known risk for abuse and misuse, based on their use as street drugs, but this needs more study. (Interestingly, some psychedelics are being studied as potential treatments for substance use disorders.)

We do need more effective and tolerable treatments for many of the disabling and common mental illnesses. And this is an exciting time for psychedelic research. However, it is important to give the clinical trials time to better understand how these substances might safely fit into our treatment options. 

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