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 DOI: 10.1016/j.neuropharm.2025.110670 via PubMed
Summary
AI-generated from the abstractBefore starting a low-dose LSD regimen, people with major depression held varied expectations shaped largely by media and personal experience. Over half had tried other treatments that failed. Many expected subtle effects or had no specific expectations, while some anticipated changes in consciousness or neural rewiring. Hope served both as a motivator and a buffer against disappointment. The findings underscore how media influences expectations and suggest that current expectancy measures miss important factors specific to psychedelic therapy.
Study at a glance
| Characteristics | Qualitative study Open-label Peer reviewed |
|---|---|
| Sample size | 23 |
| Population | Individuals with major depressive disorder (MDD) |
| Intervention | LSD microdosing |
| Topics | Depression LSD Microdosing |
| Keywords | Expectancy Hope |
| Citations | 4 |
| Key finding | Participants' expectations before microdosing LSD were shaped by media and prior treatment failure, with hope acting as both a motivator and a disappointment buffer. |
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.