For decades, one of the most standardized practices in medical and scientific research has been the use of placebos. No, we’re not talking about the 2000s alt-rock band. We’re talking about a method that, despite its admitted flaws, has for years allowed researchers to study the effects of various substances.
However, today this practice faces a challenge that is forcing science to rethink its mechanisms: psychedelic-assisted therapy.
How a Placebo Works (and How It Doesn’t)
Basically, a placebo is a little deception in pill form. In clinical trials, patients are divided into two groups: one is given the drug under investigation and the other a placebo (which could be, for example, a sugar pill). The catch? The patient doesn’t know which group they belong to. This way, the effectiveness of the drug is compared with a control group.
But things do get complicated: sometimes, patients who have received a placebo, experience effects or improvements whose cause can only be explained psychologically, where expectation plays a role that transcends the mental and produces tangible effects in the physical realm. This is the famous placebo effect.
Now, this methodology opens a Pandora’s box of ethical dilemmas, intensely debated in the scientific community. Is it right to deceive patients this way when they may be expecting to receive a potentially life-saving medicine? Are patient autonomy and rights, not to mention their safety, being ignored? Doesn’t this practice damage trust in medicine as an institution?
All these questions have been circulating in academic circles for years, extending beyond the field of traditional medicine to become relevant in the field of psychedelics. Clinical research with these substances tends to follow the same format as studies of traditional drugs, including randomized placebo trials. If you’re familiar with psychedelics, you’ll automatically understand the problem.
One of the basic characteristics of psychedelic substances is their powerful impact on perception. The visual, mental, and emotional effects can range from mild to overwhelming, but they are definitely noticeable. In other words, it’s extremely easy for a person to distinguish whether they’ve received, say, a dose of LSD instead of a sugar pill.
So: how does the use of placebos work in the context of psychedelic-assisted therapy? Pretty badly, according to a new study published in The British Journal of Psychiatry.
Psychedelics and Placebo: Plenty of Problems and Proposals
The research raises the same ethical and moral dilemmas already familiar in the history of medicine, mentioned above, and questions the effectiveness of these methods: “Placebo-controlled trials often fail to reflect the realities of clinical practice, in which the key questions are about a treatment’s relative effectiveness, safety and suitability for different patient populations.” These patients often have delicate psychiatric conditions, requiring the utmost care and commensurate responsibility.
But the study goes further, declaring that it is unrealistic to propose a placebo for a psychedelic substance: “The profound and unmistakable changes in mood, perception and consciousness they create result in near-universal functional unblinding.” Lower doses have been proposed instead of placebos, but such a path would present more problems than solutions.
The study also shows that it is not really possible to use placebos in the context of psychotherapy. A placebo is sometimes defined as an “inert substance,” and a “double-blind” method (where there is no contact or knowledge between professionals and patients) is used for trials. There is nothing inert or blind about psychotherapy: standard methods simply do not work in these cases.
This is even less feasible in psychedelic-assisted therapy: “Most critical is the integrative and synergistic nature of psychedelic therapies, in which psychedelics are theorized to catalyze an unfolding psychotherapeutic process,” the research states. “The power of the treatment is understood to be more than the sum of its parts, which cannot be separated and isolated.”
So. How can we generate knowledge in this field with placebo as a tool? For the professionals in this study, it is not possible, and we should stop insisting.
How do we move forward, then? Fortunately, the research does not limit itself to criticizing the existing method, but rather adds proposals for its improvement.
The study proposes prioritizing “clinically relevant data that address real-world needs, while maintaining a high degree of scientific rigor.” That is, studying the effects of psychotherapy directly, without comparing them to a placebo group. Instead, historical data can be included to complement or directly replace the control groups, using benchmark studies or established treatments to compare outcomes.
The use of adaptive trials is also proposed, allowing for modifications “on the basis of interim data to improve efficiency and personalization.” Plainly speaking: we make the path as we go.
Likewise, emphasis is placed on interdisciplinary articulation with other methodologies, such as statistics, epidemiology, computer science, behavioral sciences, and public policy.
On the other hand, the researchers propose leveraging expectations instead of ignoring them or considering it an “error,” and instead reframing it as another valid variable.
“The default faith in placebo control is a doomed attempt to reduce a complex treatment and mislabel that reduction as rigor,” the study concludes, bluntly. “Chaining the future of complex treatments to traditional placebo-controlled trials will not only lead to irrelevant information but will also impede the application of methodological rigor required to determine whether these interventions are safe and effective enough for therapeutic application.”
Thus, these professionals call on the psychedelic scientific community to innovate instead of continuing to try to make one piece fit when, clearly, the solution lies elsewhere.
