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Qualitative content analysis of expectations in participants with depression about to begin LSD microdosing treatment: Identifying the need for psychedelic expectancy measures.

Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani, Rachael Sumner, Anna Forsyth, William Evans, Todd Smith, Nicholas Hoeh, Frederick Sundram, David Menkes, Suresh Muthukumaraswamy, Lisa Reynolds

Neuropharmacology December 1, 2025 Peer reviewed DOI: 10.1016/j.neuropharm.2025.110670 via PubMed

Summary

Participants with major depressive disorder (MDD) shared their expectations before starting a microdosing regimen of LSD in an open-label trial. Sixteen out of twenty-three participants cited previous treatment failures as motivation, while others were influenced by media and personal connections. Expectations varied, with some anticipating changes in consciousness or neural rewiring. The study highlights media's role in shaping these expectations and suggests that hope can motivate participants and buffer disappointment.

Study at a glance

Design open-label trial
Sample size 23
Population individuals with major depressive disorder (MDD)
Key finding Hope acted as a motivator and a disappointment buffer for participants expecting healing through psychedelics.

Abstract

Expectations can impact antidepressant treatment and psychedelic therapy, often enhancing placebo effects and influencing outcomes. However, research in this context is lacking. Our study explored the expectations of participants with major depressive disorder (MDD) before microdosing lysergic acid diethylamide (LSD) in an open-label trial. Twenty-three individuals with MDD completed a semi-structured interview about their expectations before commencing an LSD microdosing regimen. Interviews were transcribed and analysed using qualitative content analysis and compared with Credibility/Expectancy Questionnaire scores. Response categories were motivation, influence, expected effects, expected mechanisms, and hope. Over half of the participants (16/23 participants) cited previous treatment failure as a motivation for participating, with additional motivations including long-term depression (7/23), interest in psychedelics (9/23), desire for microdosing to be available to others (4/23) and recommendation by a professional (2/23). Media (12/23) and friends/family (5/23) were major influences on microdosing opinions, as was the desire to avoid influence (10/23). Participants expected various effects, including changes to consciousness (5/23), subtle effects (10/23) or had no expectations (12/23). Some participants were unsure about mechanisms (7/23), but others believed microdosing might cause neural rewiring (11/23) or changes to thought patterns (7/23). Participants were optimistic (8/23), cautious (11/23), and/or excited about the research (7/23). Our study highlights the role of media in shaping expectations and the extent to which participants expect healing through psychedelics. Hope acted as a motivator and a disappointment buffer. Future research should develop a psychedelic-specific expectancy measure covering additional factors not covered by current measures.

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