Probing expectancy effects; EU to spend big on psilocybin trial; MDMA-assisted therapy may improve self-compassion
Plus: Nevada holds psychedelic therapy hearing and Australia’s first MDMA prescription?
Happy Friday and welcome back to The Microdose, an independent journalism newsletter brought to you by the U.C. Berkeley Center for the Science of Psychedelics.
Probing expectancy effects
In psychedelic clinical trials, it can be tricky to disentangle what drives outcomes. For instance, if patients in a psilocybin study show improvement in their depression symptoms, how much of that can be attributed to the psilocybin itself, versus the role of therapy or the power of participants’ hopes and expectations about the treatment?
In a new study published in Psychological Medicine, researchers at Imperial College London and the University of California, San Francisco re-analyzed data from Compass’s 2021 phase 2 clinical trial to further probe the role of these expectancy effects in patient outcomes. In that 2021 study, researchers followed 59 participants for six weeks. Half received two 25 mg doses of psilocybin three weeks apart, plus a daily placebo pill; the other half received two 1 mg doses of psilocybin three weeks apart — a tiny, imperceptible dose — plus a daily dose of the antidepressant escitalopram. Overall, they found that participants in both groups showed improvement in their depression symptoms.
In their analysis of expectancy effects, the researchers report that while participants had higher hopes for the efficacy of psilocybin over the antidepressant (escitalopram), those expectations predicted outcomes only for participants in the escitalopram group and not for those in the psilocybin group. In other words, people in the escitalopram group who believed escitalopram would help them reported fewer depressive symptoms after treatment, but this pattern did not hold for the people in the psilocybin group; for them, higher expectations that psilocybin treatment would help them did not correlate with a greater improvement in symptoms. “If anything, there is some ‘negative expectancy,’ i.e. higher expectancy tends to be associated with worse outcomes,” lead author Balázs Szigeti wrote in a thread on X about the new paper. The results, the authors conclude, “suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected.”
EU to spend €6.5 million on psilocybin trial
For the first time, the European Union is funding psychedelics research. This week, the Psychedelic Access and Research European Alliance (PAREA) announced that the EU’s Horizon Europe program is awarding € 6.5 million Euros for a multi-site clinical study investigating psilocybin-assisted therapy’s efficacy in treating psychological distress associated with chronic illness. Each of the study’s four sites will study a different progressive disease: multiple sclerosis (Czech Republic), amyotrophic lateral sclerosis or ALS (Denmark), chronic obstructive pulmonary disorder, or COPD (the Netherlands), and atypical Parkinson’s disease (Portugal).
“This new EU-funded project is thrilling for many reasons: it's a pioneering EU investment in this field, it promises to generate important evidence for these therapies, and it lends further legitimacy to the field, especially considering the prestige of the Horizon Europe programme,” says PAREA founder Tadeusz Hawrot. “The focus on palliative care, a field in significant need of better therapeutic options, is particularly important.”
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MDMA-assisted therapy may improve self-compassion and “self-experience”
It’s common for survivors of trauma to lack feelings of self-worth and self-compassion. In a new study sponsored by Lykos Therapeutics (formerly known as MAPS Public Benefit Corporation), researchers studied the effect of MDMA-assisted therapy on 90 PTSD patients. They assessed the patients based on questionnaires measuring self-compassion, the ability to notice internal mental states, and the ability to maintain a stable sense of personal identity and self-awareness.
In the study, half the participants underwent three sessions of MDMA-assisted therapy over 12 weeks, while the other half received a placebo during therapy sessions. After the study, those in the MDMA-assisted therapy condition showed more improvement on all measures. “MDMA may be particularly effective for enhancing treatment efficacy by improving a range of problems with self-experience that are associated with treatment resistance,” the authors conclude. “Therapy alone may not sufficiently compensate for the debilitating effects of deficient self-experience on being able to deal with traumatic material.”
The State of Psychedelics: Nevada holds psychedelic therapy hearing
Last Friday, Nevada’s Joint Interim Standing Committee on the Judiciary heard testimony about the potential of psychedelic therapy. Last year, the legislature passed Senate Bill 242, which established a working group to study psychedelic medicines. The committee heard from researchers about the latest in psychedelic science, as well as veterans and first responders with stories of how psychedelics helped them. But some raised concerns as well; Detective Joshua Garber from the Las Vegas Metro Police Department’s narcotics unit said that the LVPD was against any initiative to legalize or decriminalize “psilocybin or other hallucinogens.” “While therapeutic benefits may be seen when facilitated by medical teams with science-based research that meets federal grant standards, our concerns are for the individual and community at whole if a person taking psychedelics outside of a medical facility experiences violence outbursts, hallucinations, states of agitation, psychosis, or a loss of reality,” he said.
Australia’s first MDMA prescription?
In July 2023, Australia became the first country in the world to allow licensed psychiatrists to prescribe psilocybin and MDMA as medicine, and this week, an Australian psychiatrist claims to have written the country’s first prescription for a patient with PTSD. Ted Cassidy, a psychiatrist who founded a clinic called Monarch Mental Health Group, posted a photo of the script on LinkedIn, writing that it was “the very first regular normal script that any doctor has written for a psychedelic medicine in the world.” (The Microdose reached out to Australia’s Therapeutic Goods Administration for confirmation that Cassidy’s script is the first, and for more info about how many psychiatrists have received clearance to write such scripts, but did not receive a reply.)
Nature reports on an AI tool called AlphaFold, developed by Google DeepMind, which they say has identified “hundreds of thousands of potential new psychedelic molecules.”
Vogue asks: Are psychedelics retreats the future of wellness travel?
Lucid News interviews Stephen N. Xenakis, a psychiatrist, a former U.S. Army general, and a co-founder of veteran group Reason for Hope, about his new role as executive director of the American Psychedelic Practitioners Association.
University of Virginia’s publication UVA Today profiles the researchers studying whether psilocybin could help treat chronic back pain.
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