MindShift

The Big Story

New Clues for a Potential Alzheimer’s Treatment. Psychedelics are known to act through the brain’s 5-HT2A receptor, a target many MindShift readers should be familiar with by now. But researchers at the University of Michigan have demonstrated that even neurons completely lacking this receptor showed increased plasticity after exposure to a mescaline-like compound. These neurons are located in a brain region that is among the first to deteriorate in Alzheimer’s disease. Published in Molecular Psychiatry, the findings suggest that psychedelics might one day help restore neural connections and ease symptoms in patients.

Over the past few years, a growing body of research has hinted that psychedelics, even at microdosing levels, could slow or reverse disease progression. Some evidence also indicates that their effects on serotonin and dopamine receptors may help combat Alzheimer’s-related depression. 

Science & Innovation

Two roads, same trip. European researchers found that psilocybin evolved at least twice in mushrooms, independently. In Angewandte Chemie, they show that the common magic mushroom species (Psilocybe) use one biochemical pathway, while fiber cap mushrooms (Inocybe) follow a different route to the same compound. This is a classic case of convergent evolution, when separate species invent the same solution independently. Why did mushrooms evolve the ability to produce psilocybin, not once, but at least twice? What evolutionary advantage does this compound offer them?
→ Forbes

Psilocybin relieves depression for five years. The study involved only 24 participants and lacked a placebo group, but the findings remain promising. Two-thirds of the patients stayed depression-free five years after receiving just two doses of psilocybin combined with 13 hours of psychotherapy. Published in the Journal of Psychedelic Studies, the authors suggested that such long-lasting effects might stem from “positive behavioral feedback loops.”
→ The Conversation

The National Institutes of Health will fund atai’s development of a treatment for opioid use disorder. Non-hallucinogenic psychedelic compounds and their lower risk profile are attracting increasing interest from both investors and public health. The NIH has pledged up to $11.4 million to support atai Life Sciences’ development of compounds that target the brain’s 5-HT2A receptor (like LSD, psilocin, and mescaline) without triggering a trip.
→ atai Life Sciences

Psychedelics may not be the right answer for postpartum depression. At least, that is what a recent UC Davis study in mice suggests. Published in Nature Communications, the research found that psilocybin worsened anxiety and depressive-like behaviors in rodents with perinatal mood disorders. Furthermore, the offspring of treated mice also displayed anxiety and depression-like symptoms into adulthood. The researchers propose that these effects may have been transmitted by lactation.
→ UC Davis

Society & Policy

Is ayahuasca tourism commodifying indigenous tradition? In a recent documentary, Kichwa indigenous rights activist Nina Gualinga discusses how outsiders have exploited her community. For decades, oil companies have extracted resources from Kichwa lands, and now, their spiritual practices are being marketed through ayahuasca retreats, often with little regard for their cultural significance.
→ Aeon

The philosopher who wants his peers to try psychedelics. As a discipline concerned with the nature of reality and the self, philosophy’s embrace of psychedelics is long overdue, says Justin Smith-Ruiu. “I find that my experiments have significantly widened the range of accounts of the nature of reality that I am disposed to take seriously,” he told Wired, before publishing his recent book, “On Drugs: Psychedelics, Philosophy, and the Nature of Reality”, where he suggests exploring “all the modes of consciousness available to us”.
→ The New York Times
→ The Guardian

The latest updates on the regulation front. The past three weeks have seen most policy shifts happening in the United States.

• New York - lawmakers consider allowing psilocybin for medicinal purposes and held a first hearing this week on its potential benefits and risks. → Times Union

• Michigan - a court allows the psychedelic mushroom festival Entheofest to take place at the University of Michigan. → CBS News

• Massachusetts – lawmakers are pushing a dozen new bills, from therapeutic pilots to full legalization, with unexpected support from law enforcement. → Lucid News

Business

Beckley and Atai to discuss a Phase III clinical trial with the FDA. This follows a Phase II study, which showed that a mebufotenin benzoate nasal spray improved patients’ scores by 12.9 points on the Montgomery-Åsberg Depression Rating Scale (MADRS). Called BPL-003, the psychedelic demonstrated even greater efficacy at higher doses, with a 19.0-point improvement after eight days, sustained at 13.7 points after 12 weeks. The companies have announced plans to discuss their Phase III trial design with the US FDA, aiming to begin enrollment in the first quarter of 2026.
→ Clinical Trial Arena 

AI to design a safer psychedelic compound. Backed by Y Combinator and a roster of prominent tech founders, including OpenAI, Mindstate Design Labs used an AI model to develop its first drug candidate, MSD-001. A derivative of 5-MeO-MiPT, or “moxy,” the compound has demonstrated safety in a Phase I clinical trial. It seeks to reduce the risks of traditional psychedelics by minimizing hallucinogenic effects while preserving therapeutic benefits. “We created the least psychedelic psychedelic that’s still psychoactive,” says CEO Dillan DiNardo.
→ Wired

In brief

The best tripping resorts. When a wellness magazine ranks the best luxury psychedelic retreats, you know the trend is moving toward mainstream. → Ethos

A debated recollection. In her best-selling memoir, venture capitalist Amy Griffin says that under the influence of MDMA, she recovered memories of being raped. → The New York Times

Losing my religion. Psychedelic experiences have the potential to shatter people’s faith at their core. → American Psychological Association

Inedible truth. These “Magic mushroom” gummies sold at smoke shops are likely to contain no psilocybin at all, says a new study. → Oregon State University

Scientific dispute. Two experts from Harvard and Johns Hopkins discuss their disagreement on whether we have enough evidence to approve psychedelics as medicine. → Undark

Facing mortality. A large placebo-controlled trial will test whether psilocybin can ease existential distress in patients with advanced cancer. → UCHealth

Gut feelings. A Tufts MD discusses her work with psilocybin to treat irritable bowel syndrome (IBS) and other gut-brain disorders. → DocWire News

Hanging in the balance. In Nova Scotia, a court hearing for a man accused of leading psychedelic ceremonies turned into a tribute to the benefits of ayahuasca. → CBC

Deflaming trips. Scientists are exploring how psychedelic drugs could modulate the immune system to combat inflammation in conditions such as asthma. → British Pharmacological Society

High hopes, low evidence? The evidence isn’t strong enough yet to offer psychedelics to patients, argue a group of British psychiatrists. → Euronews

Lasting relief. Results from 88 patients strengthen the evidence for the lasting mental health effects of psilocybin therapy.  → The Bulletin

If you have a little more time

"How could a single dose of something have such a remarkable impact?" recalls Yale psychiatrist Benjamin Kelmendi. The question arose after two of his patients with severe OCD unexpectedly stopped attending their appointments. Later, he discovered they had turned to magic mushrooms. "They had participated in some sort of ceremonial therapeutic setting to take psilocybin mushrooms. It was striking how much better they seemed," Kelmendi explains in a long interview.
→ Yale University