The first-ever randomized clinical trial of psilocybin-assisted therapy for people with a diagnosis of major depressive disorder was published in the peer-reviewed JAMA (Journal of the American Medical Association) Psychiatry on November 4—the day after voters in Oregon approved Measure 109, legalizing psilocybin for medical purposes.
The study was conducted at the Center of Psychedelic and Consciousness Research, Johns Hopkins Bayview Medical Center in Baltimore, Maryland. The team has previously investigated psilocybin treatments for anxiety and depression in patients with life-threatening cancer and tobacco addiction, among other uses.
Globally, over 264 million people suffer from depression, and with no end in sight to COVID-19, rates of mental health conditions have been exceptionally high in the US—particularly for people who are younger, Hispanic, Black or essential workers.
Seventeen participants showed a 50 percent or more reduction in depression symptoms—including 13 who met the criteria for remission.
The randomized study recruited 27 participants, all of whom had experienced persisting symptoms of depression for at least two years before enrollment. Of the 24 participants who completed the treatment, 13 were randomly assigned to begin treatment immediately, while 11 received the treatment after an eight-week delay. The treatment consisted of two five-hour psilocybin sessions which patients lay on a couch, wearing eye shades with headphones playing mostly-classical music, to facilitate inward reflection, according to the study. The psilocybin doses used were 20 mg per 70 kg of body weight in the first session, and 30 mg/70 kg in the second.
The researchers found that 17 participants showed a 50 percent or more reduction in depression symptoms four weeks after treatment—including 13 participants who met the criteria for remission. Those in the delayed group showed no difference in symptoms before receiving the psilocybin treatment.
The participants received pure synthetic psilocybin, as an alternative to psilocybin-containing mushrooms. When compared to ketamine, a dissociative psychedelic that has been the subject of similar research, the researchers noted, “the therapeutic effects are different: ketamine effects typically last for a few days to 2 weeks, whereas the current study showed that clinically significant antidepressant response to psilocybin therapy persisted for at least 4 weeks.”
Alongside the study’s highly encouraging results, its limitations should also be acknowledged. For example, there’s the small sample size. And the study had only white non-Hispanic participants (16 women and eight men), meaning it was in no way representative of the wider US population.
There is a long history of people of color being either excluded from, or harmed by, scientific research. One study, for example, found that mistrust and racism were the primary reasons cited by Black adults for not participating in research studies.
Clinically, too, the participants in the new study were limited, consisting of people considered to have low risk of suicide and moderately severe depression. Ideally, future research would include larger and more diverse cohorts, longer-term follow-up and a placebo group, as noted by the researchers themselves.
We must continue to advocate for the accessibility of breakthrough therapies.
Nonetheless, the study points to an important potential alternative to pharmaceutical antidepressants. Antidepressants are life-savers or life-changers for millions of people who have access to healthcare, making daily functioning possible. But for many others, they have limited effectiveness in treating depression and unpleasant side effects.
Existing medication-based treatments for depression focus on reducing symptoms, unlike therapy, which attempts to address the root causes of depression. Psychedelic-assisted therapies are aimed at enhanced openness and emergence of unresolved issues, to speed the progression of therapy. Traditional non-drug therapy often requires years of commitment and the money or health insurance to pay for many sessions, making access inherently inequitable. Psychedelics could therefore represent a valuable additional tool and a way of making treatment accessible to more people.
It is extremely welcome that psychedelic research is experiencing a resurgence, having long been blocked by the federal government. However, we must continue to investigate and advocate for the accessibility of breakthrough therapies for those most affected by mental health issues and the War on Drugs.
Researching Synthesized Versus Plant Substances
There is something of a controversy around the use of synthesized or lab-made psychedelic compounds in research like the new study, despite the potential of such manufacturing to spread the healing properties of psychedelics without endangering the longevity and sustainability of psychedelic plants like peyote and ibogaine.
Mainstream medicine asserts that the use of pure or synthesized drugs is necessary for safety and standardization reasons; one strain of mushrooms may contain more or less psilocybin than another, for example. But other researchers and advocates assert that using the whole plant is not only more accessible but also more effective, due to the “entourage effect.” Framing this debate, Brazilian neuroscientist Sidarta Ribeiro wrote that the entourage effect “refers to the synergistic effects of the multiple compounds present in whole organisms, which may potentiate clinical efficacy while attenuating side effects.”
It is therefore unfortunate that the investigation of full-spectrum compounds, such as psilocybin-containing mushrooms, is heavily restricted in medical research. The effects of cannabis, for example, vary from strain to strain due to their different mixtures of hundreds of chemicals besides THC and CBD. Much like cannabis, psilocybin-containing mushrooms may contain chemicals such as psilocin, baeocystin, norbaeocystin, and aeruginascin in different ratios, which may account for differences between strains.
The use of full-spectrum compounds in research would reflect that most people discover the benefits of psychedelics through personal experimentation, obtaining the drug illegally and without guidance. The only other ways, apart from legally permitted religious exceptions, are through admittance into research studies with strict exclusionary criteria and requiring medical insurance, or through overpriced psychedelic ceremonies that appeal to the white and wealthy.
Yet Maria Sabina, the first contemporary Mazatec curandera (healer) to allow outsiders to participate in the Indigenous Mexican culture’s mushroom healing rituals, once said (according to Albert Hoffmann’s LSD—My Problem Child) that “the [psilocybin] pills had the same power as the mushrooms, that there was no difference.” The book comments, “This was a confirmation from the most competent authority, that the synthetic psilocybin is identical with the natural product.”
Photo by Nik Shuliahin on Unsplash
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