Journal of Psychopharmacology
August 29, 2026
Marlene L. Tai, B. Szigeti, Amanda E. Downey et al.
BACKGROUND Psilocybin, a serotonergic psychedelic found in hallucinogenic mushrooms, is metabolized to psilocin, the compound responsible for its psychoactive effects. Psilocybin has demonstrated therapeutic potential for neuropsychiatric conditions. While recent trials have primarily used orally administered synthetic psilocybin, alternative formulations and delivery methods may offer...
The lancet. Psychiatry
May 1, 2026
Joseph J Taylor, Balázs Szigeti, Noah D Silverberg et al.
Placebo effects are among the greatest paradoxes in medical research. Although more data on placebos are available from placebo-controlled trials than on any treatment in medicine, there has been comparatively little deep interrogation of issues related to their measurement, appraisal, and interpretation. Most of the work that has been done, including that in psychiatry, is narrowly focused on...
JAMA Psychiatry
March 18, 2026
Zachary J. Williams, Hannah Barnett, Balázs Szigeti
10 citations
Importance: Psychedelic-assisted therapy (PAT) trials have high levels of functional unblinding, which biases results when comparing PAT with blinded interventions. Because PAT is effectively always open label, treatment results should be compared with those of open-label traditional antidepressants (TADs), so potential benefits associated with patients knowing their treatment is equal between...
July 7, 2025
Balázs Szigeti
preprint
Background: Individuals with bipolar II disorder (BD-II) and depression face limited treatment options and are often excluded from psilocybin therapy trials due to theoretical concerns of precipitating mania or psychosis. Although psilocybin has demonstrated antidepressant effects when combined with psychotherapy, adverse event reporting is inconsistent, and restrictive eligibility criteria...
Nature Medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
Psychedelic substances exhibit complex interactions with the 'set and setting' of use, that is, the mental state of the user and the environment in which a psychedelic experience takes place. Despite these contextual variables' known importance, psychedelic research has lacked methodological rigor in reporting extra-pharmacological factors. This study aimed to generate consensus-based...
Alcohol and alcoholism (Oxford, Oxfordshire)
May 14, 2025
Hannah Thurgur, Ben Sessa, Laurie Higbed et al.
3 citations
Safety and tolerability data from the first open-label feasibility study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for alcohol use disorder was recently published. This paper presents a Bayesian analysis of the impact of MDMA-assisted psychotherapy on treatment success, defined as 2-level reduction in the World Health Organization (WHO) drinking risk at the 3 months...
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 9, 2025
Ellen Bradley, Kimberly Sakai, Gisele Fernandes-Osterhold et al.
23 citations
Mood dysfunction is highly prevalent in Parkinson's disease (PD), a main predictor of functional decline, and difficult to treat-novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease from previous trials. In this open-label pilot...
Psychological Medicine
June 1, 2024
Balázs Szigeti, Brandon Weiss, Fernando E. Rosas et al.
74 citations
To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075). We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram...
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2024
Balázs Szigeti, Boris D. Heifets
62 citations
Clinical trials of psychedelic compounds like psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltrptamine (DMT) have forced a reconsideration of how nondrug factors, such as participant expectations, are measured and controlled in mental health research. As doses of these profoundly psychoactive substances increase, so does the difficulty in concealing the treatment condition in the...
Sci Rep
July 26, 2023
Balázs Szigeti, David Nutt, Robin Carhart-Harris et al.
33 citations
In medical trials, 'blinding' ensures the equal distribution of expectancy effects between treatment arms in theory; however, blinding often fails in practice. We use computational modelling to show how weak blinding, combined with positive treatment expectancy, can lead to an uneven distribution of expectancy effects. We call this 'activated expectancy bias' (AEB) and show that AEB can inflate...
British Journal of Clinical Pharmacology
July 17, 2023
Balázs Szigeti, Lawrence D. Phillips, David Nutt
13 citations
The two pillars of modern medical research are where in most randomized controlled trials (RCTs), the active treatment is compared with placebo. A recent expert consensus survey endorsed the statement that 'Results from placebo-controlled trials are more reliable than results from any other study design',1 reflecting that placebo controlled RCTs are considered to be the gold standard. However,...
October 19, 2022
Stefan Baumann, Robin Carhart-Harris, David Nutt et al.
2 citations
preprint
Microdosing is the practice of regularly using very low doses of psychedelic drugs. Anecdotal reports suggest that it may enhance well-being, creativity and cognition. Here, we use data from a self-blinding microdose trial, a large (n=240) placebo-controlled citizen science trial of microdosing to investigate whether tolerance develops during microdosing. We conceptualized tolerance as the...
Elife
March 2, 2021
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
192 citations
Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a 'self-blinding' citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their...
December 11, 2020
Balázs Szigeti, Laura Kärtner, Allan Blemings et al.
1 citation
Article Figures and data Abstract eLife digest Introduction Materials and methods Results Discussion Appendix 1 Data availability References Decision letter Author response Article and author information Metrics Abstract Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such...
Journal of Psychopharmacology
May 7, 2018
Balázs Szigeti, Adam Winstock, David Erritzøe et al.
17 citations
BACKGROUND: Neuroimaging studies imply that the regular use of ±3,4-methylenedioxymethamphetamine (MDMA), the major constituent of ecstasy pills, alters the brain's serotonergic system in a dose-dependent manner. However, the relevance of these findings remains unclear due to limited knowledge about the ecstasy/MDMA use pattern of real-life users. AIMS: We examined the representativeness of...
Balázs Szigeti
1 citation
preprint
On August 9th the US Food and Drug Administration’s (FDA) rejected 3,4-methylenedioxymethamphetamine assisted therapy (MDMA-AT) as a treatment for post-traumatic stress disorder (PTSD) despite seemingly positive trial results. A major reason cited was functional unmasking, which combined with enthusiasm about MDMA, raised concerns about the objectivity of these trials. Here, we define what is...
Balázs Szigeti, Ellen Bradley, Joshua Woolley
preprint
On August 9th the US Food and Drug Administration’s (FDA) rejected 3,4-methylenedioxymethamphetamine assisted therapy (MDMA-AT) as a treatment for post-traumatic stress disorder (PTSD), despite seemingly positive trial results. A major reason cited was functional unmasking, which combined with enthusiasm about MDMA, raised concerns about the objectivity of these trials. Here, we define what is...