From the Editor

“Trump signs order to accelerate access to psychedelic drug treatments”

– Reuters, 18 April 2026

Last week, the U.S. president signed an executive order easing the way for more research on psychedelics for mental illness. It’s another example of the enthusiasm that many – policymakers, politicians, patients, families, members of the public – have for these drugs. Past work has indicated some effectiveness in treating depression. But how much of it can be explained by placebo? Psychedelics are, after all, challenging to study, in part because of difficulties with blinding (people can figure out whether they receive a psychedelic or placebo).

Dr. Zachary J. Williams (of the University of California, Los Angeles) and his co-authors attempt to shed light on this issue with a new, smart study published in JAMA Psychiatry. In it, they did a meta-analysis, comparing the effectiveness of psychedelic-assisted therapy (PAT) and open-label traditional antidepressants (TADs) for the treatment of major depression, drawing on 24 studies. “These findings suggest that PAT is no more effective than TADs under equal-unblinding conditions for the treatment of depression and highlight the potential role of blinding integrity.” We consider the paper and its implications.

And, on the topic of psychedelics, Dr. Kevin H. Yang (of the University of California, San Diego) and his co-authors look to quantify the number of people using psilocybin in the United States. In a priority data letter for The American Journal of Psychiatry, they used data from the National Survey on Drug Use and Health, a survey with more than 59 000 respondents. “With approximately 8 million individuals estimated as having used in the past year, naturalistic psilocybin use is sufficiently prevalent that psychiatrists are likely to encounter patients who use it outside of clinical settings.”

And in the third selection, an essay from The Globe and Mail, Brandon Hahn writes personally about his experiences with mental illness, noting public intolerance and tolerance – and meaningful gestures. “Sometimes support looks like red tape and a pile of forms. Sometimes it looks like a chair that faces the window while holding a hand.”

DG

Selection 1: “Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions: A Systematic Review and Meta-Analysis”

Zachary J. Williams, Hannah Barnett, Balázs Szigeti

JAMA Psychiatry, 18 March 2026  Online First

Current treatments for depression include selective serotonin (SSRIs) and norepinephrine reuptake inhibitors (SNRIs) and a few other medications, such as mirtazapine. These are collectively referred to as traditional antidepressants (TADs). A comprehensive meta-analysis found a significant TAD vs placebo difference (also known as specific-treatment or between-arm effect), but the magnitude of the difference was approximately 2.4 units on the 17-item Hamilton Depression Rating Scale (HAM-D). This small difference raised questions around whether TADs provide a clinically meaningful benefit over placebos. Psychedelic-assisted therapy (PAT), which is the combined treatment of psychotherapy and psychedelics, has emerged as a novel depression treatment, attracting much attention. Unlike TAD studies, PAT studies have reported larger PAT vs placebo differences, with a mean effect of approximately 7.3 HAM-D units.

In open-label trials, patients are aware of their treatment; in contrast, blinded trials conceal treatment allocation. Even when trials are formally blinded, patients can sometimes deduce their treatment due to adverse effects and/or other factors. This phenomenon is called functional unblinding and may inflate the drug-placebo difference. Functional unblinding is exceedingly common in psychedelic trials due to the drugs’ intense subjective effects. In a blinded trial, approximately 50% of patients can correctly guess their treatment allocation (assuming 2 arms and 1:1 allocation); in PAT trials, the correct guess rate is 90% to 95%, even when an active placebo is used…

Here’s what they did:

  • They conducted a systematic review and meta-analysis of the comparative effectiveness of PAT vs. open-label TADs.
  • They searched PubMed “for trials of PAT and open-label TADs for the treatment of major depression without comorbidity in adults without psychosis in the outpatient setting.”
  • “Extraction was supplemented with data from a review and meta-analysis of antidepressant drugs to assess the open-label vs blinded TAD difference. Data Extraction and Synthesis Depression scores were extracted by 2 independent reviewers; estimates were pooled with both bayesian and frequentist mixed-effects models. Reporting follows the PRISMA guideline.”
  • Primary outcome: “the mean within-arm effect from baseline to primary end point (ie, patient improvement between PAT and open-label TAD trials on the 17-item Hamilton Depression Rating Scale) was compared.”

Here’s what they found:

  • They retrieved 619 records from PubMed; 24 met the inclusion criteria. 
  • Studies. There were 16 open-label TAD (7921 patients) and eight PAT trials (249 patients). Among the PAT trials, six were formally blinded (213 patients) and two were open label (36 patients).
  • Effectiveness. PAT was no more effective than open-label TAD treatment, with an estimated difference of 0.3 favoring open-label TADs.
  • Outcomes. Open-label TADs were associated with better outcomes than blinded treatment, with an estimated difference of 1.3. That said, the same difference was not observed for PAT.

A few thoughts:

1. This is a clever, timely, and important study, published in a major journal.

2. The main findings in three sentences: “In trials of depression, PAT was not more effective than open-label TADs. Blinding made a difference for TADs, but not for PAT, confirming that PAT trials are effectively always open label. These results argue against highly optimistic narratives surrounding PAT and highlight the importance of blinding integrity.” 

3. “Against highly optimistic narratives” – ouch.

4. For a deeper dive into this study, Dr. John Torous (of Harvard University) did an excellent podcast interview with the corresponding author. You can find it here: 

https://jamanetwork.com/journals/jamapsychiatry/pages/jama-psychiatry-author-interviews

(It’s the second podcast.) 

5. There are different interpretations of this study, but it doesn’t seem too controversial to suggest that – at least for now – the enthusiasm for psychedelics is greater than the evidence.

6. Like all studies, there are limitations. The authors note several, including that some of the psychedelic trials exclusively recruited patients with treatment-resistant depression but no antidepressant trial focused on that condition.

The full JAMA Psychiatry paper can be found here:

https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2846479


Selection 2: “Prevalence and Correlates of Past-Year Psilocybin Use in the United States”

Kevin H. Yang, Avery Eun, Joseph J. Palamar

The American Journal of Psychiatry, 21 April 2026  Online First

Psilocybin use has increased in the United States amid decriminalization efforts and growing public interest. Numerous jurisdictions have decriminalized possession of psilocybin, and Oregon became the first state to establish a regulated psilocybin services program in 2023, followed by Colorado in 2025. These policy changes parallel increasing clinical interest, including the breakthrough therapy designation by the U.S. Food and Drug Administration (FDA) of psilocybin for treatment-resistant depression in 2018 and major depressive disorder in 2019. While clinical trials have begun to demonstrate the safety and efficacy of psilocybin in medically supervised settings for mental health conditions such as depression, far less is known about the benefits and risks of psilocybin when used outside of controlled settings. This distinction is important, as the therapeutic effects observed in clinical trials depend on careful screening, controlled dosing, product purity, and psychological support, which may not be present during naturalistic use. Reports of adverse effects from unsupervised use, including anxiety, paranoia, and prolonged psychological distress, have been documented, and poison center reports involving psilocybin have increased sharply.

Despite increasing use and related public health concerns, nationally representative data on psilocybin have been limited because national surveys have historically asked only about lifetime use or grouped psilocybin with other hallucinogens.

So begins a letter by Yang et al.

Here’s what they did:

  • They used survey data from the 2024 NSDUH, “an annual cross-sectional survey representative of the noninstitutionalized U.S. population.” 
  • “Weighted prevalence estimates were calculated for past-year psilocybin use overall and stratified according to age, sex, race/ethnicity, annual household income, education, past-year use of other substances… and past-year major depressive episode (MDE).” 
  • They did different statistical analyses, including multivariable logistic regression adjusting for covariates.

Here’s what they found:

  • There were almost 59 0000 respondents with an overall response rate of 11.3%.
  • Use. “In 2024, an estimated 2.8%… of individuals age 12 and older used psilocybin in the past year, corresponding to approximately 8.0 million individuals.”
  • Age. Compared with those in the 35- to 49-year range, individuals ages 18–25 had higher odds of past-year psilocybin use (adjusted odds ratio=1.41), while those age 50 and older had lower odds (0.35). 
  • Sex and race. Females had lower odds of use compared to males (0.60), as did those identifying as Black (0.40) or Hispanic (0.69), compared to White individuals. 
  • Other use. Past-year use of most substances examined was associated with psilocybin use, including cannabis (13.62), LSD (7.87), ketamine (6.03), cocaine (1.90), alcohol use disorder (1.32).
  • Depression. Past-year MDE was also associated with increased odds of psilocybin use (1.37).

A few thoughts:

1. This letter provides numbers, quantifying the use of psilocybin.

2. The main finding in three words: eight million individuals.

3. Perspective: the number of people using isn’t incredible. But with increased efforts at legalizing across North America, more and more people are likely to use in the coming years.

4. That’s part of a larger substance picture, of course. Consider: there are almost as many cannabis dispensaries as there are Starbucks in the United States. The irony: at a time when governments have become less tolerant of tobacco, they are more permissive of cannabis, psilocybin, and other substances.

5. Like all studies, there are limitations. The authors note several, including “reliance on self-report may introduce social desirability and recall bias.”

The full American Journal of Psychiatry letter can be found here:

https://psychiatryonline.org/doi/10.1176/appi.ajp.20251343



Selection 3: “I’ve lived with mental illness long enough to know most of the work happens quietly”

Brandon W. Hahn

The Globe and Mail, 16 April 2026

The waiting room is quiet in that way only waiting rooms manage. Not silent. Just muted. A television hums with a morning show no one is watching. A receptionist types with the confidence of someone who knows exactly where the printer jam is going to happen next.

I am early. I am always early. When you’ve spent most of your life managing appointments tied to your brain, punctuality stops being a personality trait and becomes a coping strategy. Early means prepared. Early means control. Early means you might get home before your thoughts decide to take the scenic route.

The chairs are arranged in a semicircle that suggests conversation but discourages it. Everyone is together, but no one is connected.

So begins an essay by Hahn.

He continues: “Mental illness has a strange relationship with public space. It’s private, until it isn’t. Invisible, until it leaks. I’ve lived with serious mental illness long enough to know that most of the work happens quietly, between appointments, between conversations, between moments that never make it into policy discussions or funding announcements. This is the part that doesn’t photograph well.”

He talks about public spaces – and lingering stigma. “Public transit is a masterclass in how society handles discomfort. There are rules, unspoken but firm. Don’t make eye contact. Don’t take up too much space. Don’t be strange unless you’re entertaining enough to justify it. Mental health exists here too, wedged between backpacks and coffee cups, but it has to behave itself.”

Stigma exists, yes, but there is also tolerance. “I’ve watched people decide, in a split second, whether someone’s distress is acceptable. Whether it’s medical. Whether it’s inconvenient. Whether it’s someone else’s problem. These decisions are rarely malicious. They’re practical. Reflexive. A city learning to keep moving… Once, a driver waited an extra minute while someone gathered themselves. Once, a stranger offered a seat without making a production of it. Once, someone looked at me like I was a person and not a potential delay. These moments don’t trend. They don’t scale. But they stay with you.”

He adds: “I’ve spent years advocating for clearer, more humane conversations around serious mental illness. But the moments that have changed me most were never on any type of soapbox. They were in places where no one is trying to be inspirational. Places where the work is simply to get through the day without disappearing. Places like a warming centre, which has its own rhythm. Coffee first. Then quiet. Then stories that circle the room without ever landing. People are careful with their pasts here. They offer them the way you’d offer change. In small amounts. Just enough to get by.”

He speaks about the importance of gestures. “What I wish we talked about more are the small choices. The receptionist who uses your name. The driver who waits. The stranger who doesn’t stare. These are not solutions. They are gestures. But gestures accumulate.”

“Mental health is often framed as a crisis and sometimes it is. But most days, it’s quieter than that. It’s procedural. It’s logistical. It’s deciding whether today is a day for eye contact or headphones. It’s learning which doors open easily and which ones require explanation.”

A few thoughts:

1. This is a well-written essay.

2. Stigma has faded, yes. This piece reminds us, however, that it continues.

3. Hearing from people with lived experience is important; it grounds us as clinicians. He speaks about his experience in a thoughtful way. He also offers perspective. “There is a version of mental health discourse that treats lived experience like a credential you flash to gain entry into a conversation. I understand the instinct. Proof matters. But I’ve come to believe that lived experience is less about authority and more about attention. You notice different things. You listen differently. You understand how fragile dignity can be and how resilient.” Thoughtful.

The full Globe essay can be found here:

https://www.theglobeandmail.com/life/first-person/article-mental-heath-support-public

Reading of the Week. Every week I pick articles and papers from the world of Psychiatry.