Massachusetts psychedelics ballot measure race heats up; Psychedelic study designs affect the magnitude of antidepressant effects; Is New Jersey next?

Plus: Psilocybin as an “anti-distressant” and using AI to study psychedelics

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.

Massachusetts psychedelics ballot measure race heats up 

In a few weeks, Bay Staters will vote on Question 4, a ballot initiative that would create a state-regulated program providing supervised use of certain psychedelics, similar to programs in Oregon and Colorado. Question 4 would also allow adults in the state 21 and over to cultivate, possess, process, use, test, and non-commercially gift “personal use quantities” of DMT, mescaline, ibogaine, psilocybin, and psilocin. 

In polling released this week by the University of Massachusetts at Amherst and Boston’s ABC affiliate WCVB, the 700 poll respondents were split on how to vote on the question. 43% of respondents said they approved of the initiative, and 43% said they were opposed; the other 14% said they were unsure. 

“This ballot question only enjoys majoritarian support among a small number of demographic and political groups in the state that include young people, Democrats, liberals and Biden voters,” says the poll’s director Tatishe Nteta, who is also a provost professor of political science at UMass Amherst. “Older voters, independents, Republicans and parents are particularly opposed to this ballot question, and given the high turnout among these groups in particular, this does not bode well for those who seek to make Massachusetts the third state in the nation to make these substances legal.” 

The voices publicly endorsing or opposing Question 4 are similarly split. Last week, The Boston Globe’s editorial board published an op-ed opposing the measure, writing that allowing people to grow and consume creates “a free for all.” This could “carry real health risks,” they write, citing DMT’s potential to cause bad trips and ibogaine’s association with cardiac issues. But supporters say it is possible to mitigate those risks, and that a regulated program can provide safer alternatives than individuals trying to navigate the illicit psychedelics space. “Unregulated use of magic mushrooms is already widespread,” Boston University counselor Karen Bouhard wrote in an opinion piece for BU’s website that supports the measure. “Decriminalizing isn’t about unleashing a flood of psychedelics—it’s about acknowledging reality. Adopting a harm-reduction approach, which prioritizes education and the creation of safer conditions for those seeking these experiences, would do more to protect the public than continued prohibition ever could.”

Some veterans groups have also rallied to support the measure, including Heroic Hearts Project, which paid for a TV ad. 

Psychedelic study designs affect the magnitude of antidepressant effects

The classic design of any pharmacological research study with human subjects involves giving some participants a drug, while other participants — in a control condition — receive an inactive substance or no intervention at all. In psychedelics studies, the make-up of that control condition can vary widely or be omitted entirely. A new study, published in the Journal of Affective Disorders and led by researchers in Taiwan, analyzed the relationship between study design and outcomes in depression clinical trials that used psychedelics. They found that study design appears to significantly influence the antidepressant effects of a psychedelic intervention.

For their analysis, the researchers examined 21 studies that used MDMA, ayahuasca, LSD, or psilocybin to treat depression or PTSD. Those studies included five types of study designs: non-active-drug as placebo (participants in the control condition received an inert capsule); an active drug as placebo (participants received a small amount of a psychedelic)*; waitlist as control (researchers added some participants to a waitlist for psychedelic treatment, and compared those waitlisters’ depression scores with the scores of people who received the psychedelic); pre-post single-arm design (there was no control group, and a single group of participants’ symptoms were compared before and after a study); and fixed-order (all participants first received a placebo, then the psychedelic drug). Their major finding was that psilocybin, MDMA, and LSD all seem to produce strong antidepressant effects in studies when they were compared to a non-active placebo, but those effects were not observed in studies that used small amounts of the active drug as a control.

Expectation effects are likely to play a role here, the authors write, which could also mean that studies using waitlists as a control group could overestimate the treatment effects of psychedelics. “If a participant has optimistic anticipations regarding the suggested experimental intervention, yet subsequently perceives themselves as being allocated to a waitlist-control group, their outcomes might deteriorate due to disappointment or the conviction that improvement is unlikely without being assigned to the active treatment,” they write. Future studies should consider the effect of study design on outcomes, they conclude, and suggest that using an active drug as placebo may be the best of the five options they investigated in reducing potential bias in psychedelic study design.

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Is New Jersey next?

Last week, New Jersey psychedelics bill 2283 came back to life in the State Senate with a second reading in the state’s Senate Health, Human Services and Senior Citizens Committee. The bill, introduced in January, initially proposed that the state establish a board to develop and implement a psilocybin services program within 18 months of the bill’s passing. It was significantly amended in committee over the summer, and it now proposes establishing a state-regulated psilocybin services program similar to that in Oregon and Colorado. Generally, states’ psychedelics bills get more tempered in committee; this is a rare case in which the needle has moved in the opposite direction to propose a more ambitious approach to psychedelics.

Psilocybin as an “anti-distressant”

Psilocybin is being investigated as a treatment for depression or anxiety, as well as a wide range of other issues, like obsessive-compulsive disorder, chronic pain, Lyme disease, and irritable bowel syndrome. Rather than thinking about the drug as an antidepressant, then, perhaps it could be conceptualized as an “anti-distressant,” a broader term that is less specific about its mechanism of action. 

In a new piece published in Nature Mental Health, University of Toronto researchers Danica Johnson and Joshua Rosenblat write that this reframing of psilocybin’s effects could be useful in evaluating the drug’s effects on general wellness and spirituality, and could also lead to changes in how researchers approach psychedelic studies. While current trials investigate the drug’s effects for one indication — say, treatment-resistant depression or PTSD — thinking of psilocybin as an “anti-distressant” could help the field move away from looking at just one specific disorder. 

Using AI to study psychedelics

“AI and psychedelics medicines are among the most high-profile evolving disruptive innovations within mental healthcare in recent years,” write a group of Melbourne-based researchers in a new paper published in the Annals of the New York Academy of Sciences. Thus, the authors set out to understand how AI is being used in the psychedelics field by reviewing nine papers published in the last five years. 

Six themes arose from those papers, including using AI to identify potential novel drug candidates, to crunch large amounts of data to find correlations between biomarker data and drug treatment outcomes, and even to help with post-session integration and support. While most studies focus on the ability of AI to improve our understanding of psychedelic use in humans, one 2020 paper posited a new direction: exploring whether “DMT-like hallucinations” could be replicated in computers’ neural networks as a way of modeling how psychedelics could work in human brains. 

The authors also note that there are a range of ethical and security issues to consider in continuing work using AI to understand psychedelics, especially if AI technology is used directly in research studies. “Excessive interaction with AI may lessen or diminish human contact, and this may have follow-on effects regarding the quality of therapy with a poorer therapeutic alliance,” they write. Or, even worse, AI interaction could result in “a harmful psychotherapy experience.” Stolen data could also be an issue if participants are divulging personal information to AI chatbots, or providing health records to researchers. “While it may be tantalizing (and somewhat frightening) to consider future exploration of cybernetics blending human and AI machine cognitive function and consciousness, there are obvious ethical existential red flags regarding what it means and is to be human,” the authors write. 

• Nautilus explores the emerging science and research around using MDMA in couples therapy. 

• Soul Centro, a psychedelic retreat center in Costa Rica, is under investigation after a woman died during an ibogaine session there, reports Mattha Busby for VICE. The woman’s partner, family, and other attendees at the session say that Soul Centro was not transparent about her death.

• For Wired, the ever-prolific Mattha Busby writes about the increasing potency of various types of psilocybin mushrooms, which could lead to some accidentally big trips. 

You’re all caught up! We’ll be back in your inbox on Monday with a 5 Questions interview.

*This post has been updated to correct details about the “active placebo” condition in Li et al. (2024).

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