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.
