In 1960s Harvard University housed a very noteworthy entity. It is not possible to talk about the history of psychedelic research without talking about the 'The Harvard Psychedelic Club' or Timothy Leary (1). Timothy Leary, Richard Alpert (who became Ram Dass afterward), Huston Smith, and Andrew Weil were four researchers who conducted research at Harvard University studying the effects of psychedelic drugs. The studies were quite different from what we are used to nowadays. There was no clear distinction between the experimenter and the participant; the roles could change. They drew a lot of media attention and became the subject of controversy. Timothy Leary, in particular, did not live a boring life. From being a Harvard professor to being a fugitive, being well respected by many but also getting the title of "the most dangerous man in America," he definitely made his mark (1,2). Was there a basis for the fear created by psychedelic research in that era?
Original mage by Pixabay
Before I talk about psychedelic research, I would like to mention its general use. The history of psychedelic use is long, starting from spiritual and ceremonial use by indigenous communities from ancient, even prehistoric times (3). The study of psychedelics in the research context is also not new. A simple search in PubMed, a database of life sciences scientific publications, shows an increasing number of studies focusing on psychedelics starting 1950s (4).
Image generated by using PubMed data (4). The number of articles is displayed on a logarithmic scale.
Other than the research done at Harvard University, there were other studies across the globe in those years. After the first synthesis of LSD by Albert Hofmann in 1938 (5), studies focusing on LSD and other similar substances followed. In the 1950s, Bill Wilson, the founder of Alcoholics Anonymous, was a strong believer that the use of LSD could be beneficial in treating alcohol addiction (2). Humphry Osmond and Abram Hoffer used LSD to treat alcohol addiction with successful results even six months after the psychedelic experience (6). During the same years, in Canada, LSD and mescaline were studied as possible treatments for schizophrenia (2).
There was a peak in psychedelic research in the 1970s, which lost its momentum for many decades following. The "War on Drugs" started by Richard Nixon in the '60s is generally assumed to be the break in clinical research on such substances (6). However, digging into this made me realize that things were much more complicated.
The widespread use of psychedelics in the '60s caused stricter regulations, which seems to have a definite effect (5). Despite the positive reports from researchers, the negative incidents seem to take more focus by the media (6). The negative media effects caused some companies and organizations to distance themselves from such studies, including a pharmaceutical company that provided the drugs to researchers (6). That seems to be a major blow to the research arena.
It is also possible that the main contributor to the halt of psychedelic research can be something else (6). If you look at the graph, you can notice that the number of clinical trials is absent in the first couple of decades. The number of clinical trials, in general, is so low compared to the number of articles published that I had to plot the graph on a logarithmic scale. Otherwise, the red dots looked like a flat line at zero. An unrelated tragedy (see thalidomide disaster) in 1963 seems to cause a shift in how clinical research is done for good (6). Stricter regulations were introduced on using unapproved drugs (6). With these regulations, research that did not include safety and efficacy studies came to a halt.
The lack of standardization of the studies pre '70s shed doubt on their results as well. Many controlled studies done after the new regulations did not show as positive results as previous studies (6). For example, Osmond and Hoffer’s six-month success story did not continue up to 12 months (6). It is possible that the researchers who were advocates of psychedelics may have lost their objectivity and been biased in perceiving and sharing their study results. Their beliefs were so strong that they went to the level of organizing their own religion (League for Spiritual Discovery) to be able to use the drugs legally (2). That does mean that the benefits were not there, to begin with? Not at all!
Moving forward to today: The Multidisciplinary Association for Psychedelic Studies (MAPS) is currently conducting phase 3 trials on MDMA-assisted psychotherapy (7). There are clinical trials for the use of psilocybin for alcohol use disorder or major depression (5,8). Ketamine is a legal substance currently used for anesthesia as well as for major depression as part of ketamine-assisted psychotherapy (KAP) (5,8). The potentials of psychedelics are very apparent, and there has been a vast momentum in research in the last decade. So, what was the issue in the first place?
Psychedelics are quite different than any other drug we use for medicinal purposes. Pretty much every article I read about the use of psychedelics for treatment or recreational purposes talks about the "context," which includes the "set" and "setting" (3). Set is the mental state and expectations of the person using the drug, which is highly impacted by the culture, the stigma, or the support the person is getting. The "setting," on the other hand, is the environment they are in. The setting is shown to be important not only in the short term outcomes but also in the long term outcomes (3).
A common theme in many articles I read is the inclusion of pre-drug training, proper setting, and inclusion of therapy sessions. Psychedelics are a different type of drug, not something to take from the pharmacy and use regularly, but rather help your mind to heal itself by providing openness. For example, it is shown that for ketamine to show long-term effects, it needs to accompany psychotherapy (5). William Richards, a researcher who has spent 25 years on psychedelics psychotherapy, highlights the importance of integration sessions, the drug-free sessions after drug exposure (9). He also points to the role of the set, the training before, the patient taking responsibility, as well as the proper usage of knowledge as the important aspects of successful psychotherapy (9).
There are many difficulties in running successful controlled studies on psychedelics. The most obvious one is that having a placebo group is quite difficult when the impacts of the drug are so apparent. Another is the experimental setup affecting the "setting" of the experience, which is crucial (3). For example, being observed by the experimenter or having some cables around to take certain measurements while experiencing a “trip” would probably be a mood killer for the participant. Finally, in terms of testing the impacts of different settings, an ethical dilemma arises in creating a sub-optimal setting for participants (3). The lack of clinical research in the first few decades does not necessarily show the presence of a different perspective in conducting research. It just isn't easy to run such trials.
The effects of psychedelics are also, in a way, “unworldly.” Psychedelics change our perception, and this state of open-mindedness causes people to have mystical experiences (5,8,9). However, it also causes them to be vulnerable. That is why the setting is so crucial; the “sitter” who guides such a session needs to be ethical and knowledgeable. During the panel we attended a couple of weeks ago, on which Tanisse wrote a great review, the importance of ethics and training of the therapist who would provide the treatment was discussed. Psychedelics are considered non-addictive; however, their misuse is possible (3). The misuse does not have to be by the user either. A very dramatic example is Charles Manson's abuse of the power of LSD to form a cult and provoke its members to commit horrible crimes (6). This is a very extraordinary example but is a good reminder of psychedelics' power in the wrong hands.
Timothy Leary has famously said, "LSD is a drug that produces fear in people who don't take it" (2). Many examples of contradictions show that the attitudes towards certain drugs are not objective. Alcohol and nicotine are amongst the most addictive drugs, and still, they are widely available. In fact, the stigma against drugs works just the opposite way when it comes to alcohol. Its consumption is promoted in many ways, and non-drinkers would be questioned on "why?" at a party (thanks to the excuse of "I’m driving"!). The most common psychedelics, MDMA (also known as ecstasy), LSD, mescaline, and psilocybin, find themselves among the schedule 1 drugs in US, right beside heroin and, hard-to-believe, marijuana (10). As a reminder, schedule 1 drugs are drugs that are highly addictive and have no clinical usage. Many studies mentioned above show that is not the case. It is also interesting that these psychedelics are listed as schedule 3 drugs on Canada’s Controlled Drug and Substances Act (11) rather than schedule 1. Marijuana being legal in many US states and Canada is also another conflicting fact. Another contradiction is that US FDA accepted MDMA-assisted therapy for alcoholism and PTSD, psilocybin for addiction and depression as breakthrough therapies (5). The rules and regulations do not always follow the scientific findings; there is a lot of politics behind them.
According to 2010 statistics, the number of people in the US who has at least one psychedelic experience in their lifetime exceeds 30 million (8). With such a wide acceptance and use by the public, it is important to understand better what psychedelics are and are not.
It is also important to consider the possible negative outcomes not to jeopardize the current momentum in psychedelic research, not to revert slowly dissolving stigma. I will end my post with Timothy Leary's answer to Nancy Reagan's "Just Say No": "Just Say Know" (2). Rather than labeling psychedelics as good or bad, we just have to continue learning.
Blog by Emine Topcu
References:
1. Lattin D. The Harvard Psychedelic Club: How Timothy Leary, Ram Dass, Huston Smith, and Andrew Weil Killed the Fifties and Ushered in a New Age for America [Internet]. HarperCollins; 2011. Available from: https://books.google.ca/books?id=yNylsx9HD28C
2. Ulrich J, Leary Z, Horowitz M. The Timothy Leary Project: Inside the Great Counterculture Experiment [Internet]. ABRAMS; 2018. Available from: https://books.google.ca/books?id=Ks1FDwAAQBAJ
3. Carhart-Harris RL, Roseman L, Haijen E, Erritzoe D, Watts R, Branchi I, et al. Psychedelics and the essential importance of context. J Psychopharmacol. 2018;32(7):725–31.
4. NIH. PubMed. Available from: https://pubmed.ncbi.nlm.nih.gov/?term=psychedelics. Accessed on 2022-03-26.
5. Doblin RE, Christiansen M, Jerome L, Burge B. The Past and Future of Psychedelic Science: An Introduction to This Issue. J Psychoactive Drugs [Internet]. 2019;51(2):93–7. Available from: https://doi.org/10.1080/02791072.2019.1606472
6. Hall W. Why was early therapeutic research on psychedelic drugs abandoned? Psychol Med. 2022;52(1):26–31.
7. Sessa B, Higbed L, Nutt D. A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. Front Psychiatry. 2019;10(MAR):1–7.
8. Gorman I, Nielson EM, Molinar A, Cassidy K, Sabbagh J. Psychedelic Harm Reduction and Integration: A Transtheoretical Model for Clinical Practice. Front Psychol. 2021;12(March):1–16.
9. Richards WA. Psychedelic Psychotherapy: Insights From 25 Years of Research. J Humanist Psychol. 2017;57(4):323–37.
10. DEA. Drug Enforcement Administration [Internet]. Available from: https://www.dea.gov/drug-information/drug-scheduling. Accessed on 2022-03-26.
11. Canada G of. Controlled Drugs and Substances Act [Internet]. Available from: https://laws-lois.justice.gc.ca/eng/acts/C-38.8/. Accessed on 2022-03-26.
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