by Clara Raithel
This is the first post in our series on the consequences of outside influences on the performance and communication of science.
More than fifty years after the criminalization of psychedelic drugs, psychedelic research is experiencing what many call a “renaissance” [1,2]. Researchers across the world conduct clinical trials testing the efficacy of psychedelic drugs, such as ecstasy (MDMA), mescaline, lysergic acid diethylamide (LSD), and psilocybin, as a form of treatment against various mental diseases, with some pointing towards therapeutic potential [3,4]. This increase in scientific interest is not a first: in the 1950s and 1960s, researchers first got their hands on psychedelics and saw great potential in these compounds to allow for a breakthrough in mental health science. However, instead of describing a breakthrough, psychedelic drugs gained a bad reputation and were effectively banned in 1970 when the US government initiated its “war on drugs”. How did the perception of psychedelic drugs change so drastically? Contemporary psychedelic scientists often put the blame on counterculture figures. The most prominent scapegoat is Dr. Timothy Leary, a Harvard psychologist who lightheartedly shared the drug at parties, evoking a bulk of negative press surrounding LSD that ultimately justified the “war on drugs” in the public eye. But explaining the bad reputation of past psychedelic research takes more than just pointing fingers at “bad scientists”.
Let’s focus on the example of LSD. The compound was first synthesized in a laboratory by Dr. Albert Hofmann in 1938, who at the time was an employee at Sandoz pharmaceuticals. The drug’s hallucinogenic properties were discovered in 1943, when Hofmann ingested LSD and first described its mind-altering effects. These effects soon caught the attention of psychiatrists - initially because they mimicked the symptoms of psychosis and schizophrenia. Researchers believed that artificially inducing these symptoms could help them understand the underlying neurobiological mechanisms, which in turn may highlight ways to reverse them and find a cure for these disorders. However, it did not take long for researchers to recognize the therapeutic potential of LSD itself, and soon the drug was widely distributed to scientists and psychiatrists to test its effects on alcoholics, schizophrenics, people diagnosed with obsessive-compulsive disorder, patients suffering from depression, as well as terminal cancer patients.
Of note, the widespread distribution of LSD occurred in the absence of much empirical data on the drug’s safety or efficacy in the treatment of any of the above medical conditions. This practice was enabled through loose regulations specified in the 1938 Food Drug and Cosmetic Act (FDCA). Under the FDCA, a new drug was only allowed on the market if proven safe; however, pharmaceutical companies were authorized to hand out drug samples prior to such proof, if they were exclusively intended for “investigational use by experts qualified by scientific training and experience to investigate the safety of drugs” (FDCA, Sec. 505 (i), 21 U.S.C. § 355(d)). This meant that anyone who was a medical doctor could request samples and test them on their own patients despite there not being any formal approval of the drug.
In this context, a proliferation of scientific research was observed, with many researchers incorporating LSD into the treatment of their patients and reporting vastly positive outcomes. To provide an example, LSD-aided psychotherapy, or “psychedelic therapy”, showed great potential in helping alcoholics get sober [5,6]. However, the loose regulations regarding LSD also meant that academics had free reign in administering the drugs to all sorts of populations, including vulnerable subjects who were often lacking legal protection and/or the ability to consent.
To understand these research practices and their impact on the perception of psychedelic science, I spoke to Andrew Jones, a PhD candidate at the Institute for the History of Philosophy of Science and Technology at the University of Toronto. As part of his dissertation, he studies the history of LSD research on autistic children and the structural conditions under which this research took place. Jones explained that autistic children back in the 1950s and 1960s were often institutionalized. In the absence of a universally accepted theory of autism, effective behavioral strategies to manage these children at home were lacking, often leaving parents feeling overwhelmed and helpless. Accordingly, parents were encouraged to admit their children to in-patient facilities - thereby handing over responsibility for their children’s lives.
Jones explained that this institutionalization, and the fact that these children were often labeled as “lost souls”, or “hopeless cases”, allowed for psychiatric researchers to - perhaps not explicitly, but implicitly - devalue these children’s lives. Often, research studies on children with autism were initiated out of sheer convenience - simply because these children were “available” and “should not be wasted”, as Jones pointed out. Viewing these children as “experimental materials” rather than human beings (as had previously been done with members of Aboriginal communities in Canada) likely made it easier to perform some of their research. Said research was often centered on the premise that LSD could increase interpersonal communication skills in autistic children, but the experimental approaches chosen to achieve this goal varied widely across institutions. Dr. Lauretta Bender, for example, gave LSD to children daily for up to 3 years as a form of pharmacotherapy. Dr. Ivar Lovaas and his group at UCLA administered LSD to children while measuring their behavior in a “Human Skinner Box”, a playroom with two-sided mirrors, in what they named “Applied Behavioral Analysis”. Another approach used by Dr. Gary Fisher consisted of combining large doses of LSD with a form of psychotherapy and was largely inspired by the previously mentioned “psychedelic therapy” used in alcoholics. Notes taken during these LSD sessions reveal the great anguish these children were experiencing, many of them crying, hyperventilating, or even having seizures. While Bender and Fisher apparently claimed to have obtained consent from the children’s parents, this alone does not make the research ethical or unproblematic.
From today’s perspective, it is difficult to fathom how such research was even possible. The loose regulations regarding investigational drugs can only partially explain these practices, as in 1962, the FDCA was amended to incorporate stricter rules and thereby increase patient safety. Importantly, all of the investigators mentioned above obtained approval to continue their research programs even after these amendments were implemented in 1963. Jones emphasized that it is important to see the research, and the scientists associated with this research, in the context of their time. While many contemporary scientists and journalists like to label these early psychedelic researchers “mad scientists” who mindlessly violated ethical codes in pursuit of academic excellence, these researchers were not the metaphorical bad apples. Many scientists at the time engaged in what we now deem unethical practices; however, the research community back then had no issue with the approaches taken.
As another example, consider Blewett and Chwelos’ LSD research in imprisoned populations, as described in Jones, 2023. Leaning on their earlier findings of psychedelic therapy helping alcoholics become sober, they decided to apply the very same methods in convicts, hypothesizing that the psychedelic experience may provide them with critical insight about their lives and future paths. Despite their intentions, using LSD as a correctional tool within prison populations proved difficult, at least partially due to the disregard for set and setting: as it turns out, being in a prison cell alongside other convicts is not the most conducive environment for having a pleasant trip. Subjects of similar research projects later filed complaints on the basis of not having volunteered or consented to part of this research.
Who is responsible for these lapses in research ethics? It’s a tricky subject. Obviously, we do not want to excuse the scientists involved in these research projects from their individual responsibility. Nonetheless, it appears that the institutional setting in which they operated - be it in-patient facilities or prisons - provided an environment that enabled the abuse of human research subjects. In other words, the structural and sociocultural context that these scientists were acting in heavily influenced their research.
The effect of sociocultural context becomes particularly clear when looking at MK-Ultra, a human experimentation program initiated by the US Central Intelligence Agency (CIA) with the ultimate goal to find drugs allowing for the control of the mind. The initiation of this project was heavily influenced by cold war propaganda and the fear of “brainwashing” - a term coined by anticommunist journalist Edward Hunter in an attempt to describe how communist governments appeared to make people cooperate. Even though the use of mind control by the Soviets was never confirmed, the officials involved in MK-Ultra became obsessed by this idea - so much so that any experiment that might have enabled the US to close the perceived gap was justified, no matter how unethical. Dr. Sidney Gottlieb, head of MK-Ultra and a described patriot, engaged a global network of researchers to give mind-altering drugs to unwitting subjects, often “people who could not fight back”. In a particularly appalling experiment, described in Dr. Ido Hartogsohn’s “American Trip” (p.55), Canadian psychiatrist Dr. Duncan Ewen Cameron, notably head of the American Psychiatric Association from 1952 to 1953, administered a combination of sleeping pills, LSD and electroshocks to vulnerable subject populations (e.g., women with postnatal depression) for months on end, repeatedly playing them recorded messages up to 250,000 times. This procedure had little, if any, empirical basis and more closely resembled torture than scientific research.
Whereas Gottlieb and Cameron might have been extreme cases, receiving considerable attention in the press [7,8], their stories nonetheless have certain commonalities with the somewhat “milder” cases of unethical research mentioned above. Ultimately, the failure of these mid-twentieth century scientists provides a microcosm of how we failed as a society. By endorsing and blindly trusting the involved institutions we failed to protect the human rights of those who were most vulnerable. What are we willing to risk for a chance of scientific breakthrough and heroic discovery? If we want to turn psychedelic science around and harvest the benefits these compounds undoubtedly hold in stock, we must not forget its complicated history. That means that we need to protect those who have fallen victim in the past. And it means that we need to stay attuned to the outside influences on psychedelic research moving forward, be it pressure from concerned parents, financial investors, political stakeholders, the headline-hungry media, or an overly enthusiastic general public. Clinical trials that stay immune to such influences will offer an objective assessment regarding the therapeutic value of psychedelics and the mechanism by which they achieve their effects. The resulting knowledge can then inform our decisions on how to ethically research and use these drugs in highly vulnerable populations. Taking such precaution will ultimately increase the safety and benefit for all, ensuring that history does not repeat itself.