Date:
Author: Florian Naudet, Professeur en thérapeutique, Université de Rennes 1 - Université de Rennes
Original article: https://theconversation.com/hallucinogens-approved-for-treating-psychiatric-disorders-what-does-the-science-say-245303
Once sidelined in the 1970s, psychedelic substances – ranging from esketamine (a ketamine derivative) and psilocybin (the active ingredient in hallucinogenic mushrooms) to MDMA – are being reintroduced as potential therapies for severe psychiatric disorders.
Psychedelic antidepressants approved
Esketamine-based antidepressants have been approved in countries such as France and the United States, where dextromethorphan is also used. Australia has gone a step further, granting regulatory approval for MDMA and psilocybin to treat certain psychiatric conditions.
Yet, an analysis led by researchers at the University of Rennes suggests that the scientific evidence supporting these treatments is weak. These substances also carry significant risks, including misuse and vulnerabilities associated with the patient’s mental state.
Not new, but making a comeback
Hallucinogens are now being presented as a breakthrough in the treatment of severe psychiatric disorders, such as depression or post-traumatic stress disorder, sometimes in combination with psychotherapy).
Despite being presented as innovations, the therapeutic potential of psychedelics is not a new discovery. In the 1960s and 70s, these substances were explored for medical use but quickly fell out of favour due to regulatory restrictions.
Now, in 2024, the question remains: Are psychedelics genuinely effective for treating psychiatric disorders? An international panel of experts – two psychiatrists, one addiction specialist, and three psychologists, supported by researchers from the University of Rennes – reviewed clinical trials to provide insights.
Challenges of evaluating psychedelics in clinical trials
Psychedelics such as MDMA and psilocybin have already gained approval in regions such as the U.S., Europe, and Australia. However, assessing their effectiveness presents unique challenges, particularly within the rigorous framework of double-blind trials.
In traditional drug testing, two groups of patients are compared: one receives the drug, while the other receives a placebo or standard treatment. To ensure unbiased results, neither the patients nor the clinicians know who is receiving which treatment.
With psychedelics, this method falters. Their unmistakable effects – hallucinations, altered perceptions, and dissociation – make it nearly impossible to maintain the “blindness” of the study groups, potentially skewing results.
Accelerated approvals compromise scientific rigour
Psychedelics are often considered treatments of last resort for patients unresponsive to conventional therapies. As a result, regulatory bodies frequently rely on accelerated approval pathways to fast-track their availability. Unfortunately, such pathways typically require less robust scientific evidence than traditional approval processes – a trend that raises concerns.
Some flaws in scientific articles
The analysis identified several shortcomings in studies on psychedelic treatments:
-
Errors were frequently noted, sometimes in the titles of published articles.
-
The benefits of psychedelics were often exaggerated.
-
Trials generally involved small patient samples and were conducted over brief periods, limiting their relevance even in late-stage trials.
-
Researchers failed to adequately address the limitations of double-blind protocols for psychedelics.
Underestimated risks
According to the authors of the article, these gaps have serious consequences: they hinder a thorough evaluation not only of the long-term effects of these compounds but also of the safety risks, particularly those related to severe side effects that may occur in patients during treatment.
Indeed, hallucinogens, due to their varied and still poorly understood mechanisms of action, present significant potential risks that must be carefully evaluated. Using them in psychotherapy introduces additional risks of abuse and coercion, as hallucinogen use can heighten patients’ vulnerability.
Notably, there have been reports of concerning psychiatric side effects (such as dissociation and suicidal thoughts) in individuals treated with esketamine for treatment-resistant depression. Chronic use of ketamine and its derivatives can also lead to urinary disorders. Substances such as psilocybin and MDMA may also cause severe cardiovascular side effects, especially through their metabolites.
Recommendations for safer practices
The authors of the study emphasise the need for stricter regulation and improved clinical trial protocols. They urge health authorities to move away from expedited approval processes and adopt more stringent measures to ensure that the benefits of psychedelics outweigh their risks.
By addressing these concerns, researchers and regulators can better safeguard patients while exploring the therapeutic potential of these powerful substances.