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The promise of psychedelic medicine

Updated: Jan 5

At what many see as a pivotal moment in modern psychiatry, some herald a paradigm shift, even a revolution... What is it that's captivating the minds of leading experts in the field? It's psychedelic medicine, offering novel treatments that hold promise for effectively treating patients unresponsive to current therapies. This rapidly evolving field could fundamentally transform our approach to psychiatric care. How has this field developed, and why is it igniting such passion now? Read on to discover more!


LSD remains illegal in France today, and any use outside a therapeutic framework is potentially dangerous.


Entering the realm of psychedelic medicine is to step into a world where science, philosophy, and psychiatry converge amidst a storm of hope and controversy. The intrigue and debates surrounding this practice stem from a straightforward reason: proponents believe that psychedelics, under certain conditions, could effectively treat devastating mental health issues like severe depression, addictions, and end-of-life anxiety – conditions notoriously difficult to manage with current treatments. In this context, the advocates of psychedelic medicine are heralding an era of unprecedented progress, backed by an ever-growing number of clinical trials conducted around the globe.

How did this field evolve, and are the results of psychedelic therapies truly promising? To address these questions, we'll take you on a journey through the history of psychedelic research in the Western world and introduce you to the latest scientific breakthroughs in this fascinating area.



A Brief History of Psychedelic Research in the West


The story of human use of psychedelics is an ancient one, so ancient that some historians consider it futile to pinpoint its origins. Historian Mike Jay suggests that their consumption predates even Homo Sapiens Sapiens:


The plants containing these substances evolved alongside our animal ancestors, developing chemicals impactful on creatures like us. We were taking drugs long before we were human.

(Jay 2010, p. 13) (6)


Jay proposes that psychotropics and our physiological responses to them are the result of an intricate evolutionary dance between the animal and plant kingdoms, dating back over 300 million years. Beyond this speculative evolutionary theory, one certainty remains: before their laboratory synthesis, psychedelics were deeply embedded in the cultural practices of certain civilizations for spiritual rites and therapeutic purposes. For instance, as early as 1451 A.D., Mazatec ceremonies (indigenous people of Mexico) involved Psilocybes (the scientific name for magic or hallucinoegnic mushrooms).

However, it wasn't until much later that these substances caught the attention of the Western world. From the 17th century, but particularly from the 19th, various psychotropic substances were either rediscovered or synthesized in Europe (like cocaine, nitrous oxide, cannabis, morphine, ether, opium, chloroform) and used to explore altered states of consciousness or for healing. The next century would usher in the era of psychedelics. In 1938, Albert Hofmann accidentally synthesized LSD and discovered its hallucinogenic properties a few years later, in 1943. Psilocybin, the active ingredient of magic mushrooms, was popularized by married mycologists the Wassons in the 1950s after their trip to Mexico. This marked the beginning of modern psychedelic research in the West.


Soon, researchers and psychiatrists began exploring the therapeutic potential of these substances, leading to the emergence of three main uses.


The Psychotomimetic Paradigm


In the 1950s, LSD was initially thought to induce symptoms resembling a psychotic episode (synesthesia, delusions, hallucinations, depersonalization, etc.) Psychiatrists used psychedelics to simulate mental illnesses in healthy individuals to study psychosis symptoms, particularly schizophrenia. It was also common, and even considered good practice, for psychiatrists to take psychedelics themselves to better understand their patients.

However, this usage was soon questioned as most LSD experiences didn't align with psychotic crisis. This led to the development of two other approaches.


The Psycholytic Paradigm


The psycholytic approach used psychedelics to tackle psychoanalysis's big challenge:accessing the unconscious, traditionally thought accessible only through free association or dreams. English psychiatrist Ronald Sandison suggested that low doses of LSD or psilocybin could offer a third, more reliable path. This method gained immense popularity, especially after 1959, following Cary Grant's interview about how the therapy transformed him (Pollan, 2019)(1)


The Psychedelic Paradigm


The final use was "psychedelic therapy" proper, combining psychotherapy with high doses of psychedelics. In mid-1950s America, this involved one to three sessions where patients took large doses of LSD or psilocybin, lay on a couch in a comfortable environment with a blindfold, and listened to music in the presence of one or two therapists. The goal was to create a transformative experience, akin to a revelation, that could help overcome traumas.


It was in this context that psychiatrist Humphry Osmond, during a letter exchange with writer Aldous Huxley, coined the term 'psychedelic:


To make this trivial world sublime, Take a half a gramme of phanerothyme.

Aldous Huxley, letter dated March 30, 1956 (Huxley and Osmond 2018)(7)


To fathom Hell or soar angelic, Just take a pinch of psychedelic.


Humphry Osmond, letter from early April 1956(7)


Promising initial results were achieved with these therapies within the psychedelic paradigm, notably in treating alcoholic patients. However, in the 1960s, the medical potential of these substances was quickly overshadowed for political reasons. Psychedelics' growing popularity and recreational use outside medical settings led to their association with counter-culture. The "War on Drugs", initiated mainly under the Nixon administration in the United States, was the final blow to psychedelic research. In the 1970s, psychedelics were made illegal in most countries, making research funding and authorization a significant hurdle. As a result, research gradually ceased.

During this period, many unfounded rumors circulated about the dangers of these substances. For instance, in France, historian Zoë Dubus describes how a series of articles in Le Monde portrayed nightmarish, often fictionalized accounts of LSD users.


Renaissance of Psychedelic Research in the West and Promising Results


It wasn't until the late 1980s that research could resume, first in Switzerland, where LSD was rediscovered. Researchers obtained the necessary approval to conduct clinical studies, often with private funding. This sudden and rapid resurgence of research, referred to as a "renaissance" in scientific literature, is attributed to several factors, such as a relative legislative easing, renewed interest from the scientific community due to the development of new brain imaging techniques, and the therapeutic failure of available treatments for a portion of patients suffering from certain disorders, like depression.

In various countries, numerous studies gradually highlighted the effectiveness of psychedelics in treating a variety of psychiatric disorders. The case of addiction treatment is particularly illustrative of the therapeutic capacity of psychedelics. There are now many serious studies on this topic, but we'll cite just one: published in 2014 and conducted by researchers at the prestigious Johns Hopkins University, it shows impressive results in treating tobacco addiction with psilocybin (Johnson et al., 2014)(14). Participants who received a series of psilocybin doses in a therapeutic setting showed an 80% abstinence rate over a six-month follow-up period. By comparison, current treatment methods generally do not achieve more than a 25% effectiveness rate (Rigotti et al., 2022) (8) Furthermore, recent research indicates psilocybin has low abuse and no physical dependence potential (see for example : Johnson et al., 2018) (14) Other studies are underway for different forms of addiction, such as alcoholism or opioid dependence.

This study is just one example among many: dozens of other clinical studies are ongoing, not only to verify and validate these results but also to broaden the application to other pathologies. From enthusiastic converts to cautious optimists, there are also fervent critics who rightly point out that there is still much to be done to improve study methodologies, to understand the occurrence of such effects, and to explain the psychological, physiological, and cognitive factors they depend on. Whatever side one chooses, it now seems difficult to ignore these therapeutic effects, demonstrated by an ever-increasing number of studies (Doblin et al., 2019)


How Does It Work? The Mystery Unfolds…


While the clinical results are promising, understanding the underlying mechanisms of the therapeutic effects of psychedelics remains a major challenge in this research. Several explanatory hypotheses coexist, but a comprehensive explanation integrating all data regarding the effects of psychedelics at psychological, cognitive, and pharmacological levels has yet to be achieved.

Today, one of the controversial debates in the field concerns the possibility of dissociating the biological (neural and physiological) effects from the subjective psychedelic experience. The question is whether it's possible to achieve therapeutic benefits without undergoing a psychedelic experience. Promising recent preclinical trials focus on new non-hallucinogenic psychedelics (e.g., Cameron et al., 2021)(10) In these studies, scientists are working to synthesize chemical analogues of psychedelics that are non-hallucinogenic. Their idea is that these could yield equivalent therapeutic benefits by inducing physiological effects similar to psychedelics, but without producing psychotropic effects. The goal is to develop safer molecules that do not induce a psychedelic state, thereby reducing the risks associated with these therapies, such as feelings of anxiety or hallucinations akin to nightmares ( often referred to as ‘bad trips’) and making them more accessible.

Research is ongoing to determine if these molecules are as effective as classic psychedelics. For proponents of the psychedelic paradigm, the answer is not straightforward: they argue that the intensity of the subjective experience during therapy may predict the degree of therapeutic benefits. Neuroscientists like David Olson caution that correlation does not imply causation, and it's uncertain whether physiological effects might be necessary for therapeutic outcomes. In short, the debate remains open.




As we await the resolution of this debate, psychedelic research continues to advance, and therapeutic successes are multiplying. We might currently be at a turning point in modern psychiatry. Though still in an exploratory phase, psychedelic medicine already suggests promising therapeutic approaches for treatment-resistant pathologies, based on serious studies. The time has come to take these efforts seriously and to see how far they can lead us.


References


Introductive bibliography:


1. Pollan, M., 2019, How to Change Your Mind: The New Science of Psychedelics. London: Penguin Books, 2019.


2. Chayet S., 2020, Phantastica: ces substances interdites qui guérissent. Paris: Bernard Grasset.


3. Nutt D. et Carhart-Harris, R., 2021, “The Current Status of Psychedelics in Psychiatry.” JAMA Psychiatry, doi: 10.1001/jamapsychiatry.2020.2171


Historical bibliography:


4. Zoë Dubus Z., 2023, « L’émergence des psychothérapies assistées au LSD (1950-1970) », Annales Médico-Psychologiques, doi: 10.1016/j.amp.2022.11.002



5. Dubus Z., 2022, « Le traitement médiatique du LSD en France en 1966 : de la panique morale à la fin des études cliniques ». Cygne noir, doi: 10.7202/1091460ar.


6. Jay M., 2023, Psychonauts: drugs and the making of the modern mind. New Haven: Yale University Press.


7. Huxley A. et Osmond H., 2018, Psychedelic Prophets: The Letters of Aldous Huxley and Humphry Osmond. Montreal Kingston London Chicago: McGill-Queen’s University Press.


Experimental research:

8. Rigotti NA et al., 2022, “Treatment of Tobacco Smoking: A Review.”, JAMA, doi: 10.1001/jama.2022.0395. PMID: 35133411.


9. Johnson MW, Garcia-Romeu A, Griffiths RR., 2017, “Long-term follow-up of psilocybin-facilitated smoking cessation.” Am J Drug Alcohol Abuse, doi: 10.3109/00952990.2016.1170135.


10. Cameron et al., 2020, “A Non-Hallucinogenic Psychedelic Analogue with Therapeutic Potential”, Nature, doi: 10.1038/s41586-020-3008-z.


11. Hadar et al., 2023, “The Psychedelic Renaissance in Clinical Research: A Bibliometric Analysis of Three Decades of Human Studies with Psychedelics”, J Psychoactive Drugs, doi: 10.1080/02791072.2021.2022254.


12. Morgan et al., 2017, “Tripping up addiction: the use of psychedelic drugs in the treatment of problematic drug and alcohol use”, Current Opinion in Behavioral Sciences, doi: 10.1016/j.cobeha.2016.10.009


13. Ross et al., 2016, “Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial”, Journal of Psychopharmacology, doi: 10.1177/0269881116675512


14. Johson et al., 2018, “The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act”, Neuropharmacology, doi: 10.1016/j.neuropharm.2018.05.012



This article was specialist edited by Zoë Dubus and copy edited by Amandine Maire



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