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 B Menkes, Suresh Muthukumaraswamy, Lisa Reynolds
Neuropharmacology December 1, 2025 DOI: 10.1016/j.neuropharm.2025.110670 (opens in new tab)
Study at a glance
AI-extracted from the abstract| 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 Motivation Psychedelics Qualitative research |
| Citations | 4 |
| Key findings | 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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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Participants' expectations before microdosing LSD were shaped by media and prior treatment failure, with hope acting as both a motivator and a disappointment buffer.
Synthesized
Comparable studies
Other qualitative studies on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic microdosing benefits and challenges: an empirical codebook Active microdosing community | 2019 | Mixed-methods study | |
| Experiences of microdosing psychedelics in an attempt to support wellbeing and mental health. People who microdose psychedelic drugs | 2023 | Qualitative study | n = 13 |
Citations in the library
Cited by 2
- Expectations and Motivations for Participation in Clinical Trials Utilizing Psychedelics for Treatment-Resistant Depression: A Qualitative Study. Brain and Behavior June 1, 2026
- LSD microdosing for major depressive disorder: Mood and pharmacokinetic outcomes from a Phase 2a trial Progress in Neuro-Psychopharmacology and Biological Psychiatry February 18, 2026
Cites 43
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
- Psychedelics and the essential importance of context. Journal of Psychopharmacology February 15, 2018
- The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects. ACS Pharmacology & Translational Science December 10, 2020
- Set and setting, psychedelics and the placebo response: An extra-pharmacological perspective on psychopharmacology Journal of Psychopharmacology November 16, 2016
and 38 more in the library