What is it like to microdose LSD for depression? a thematic analysis of participant interviews from an open-label trial

Interest in psychedelic microdosing — the repeated use of very small doses of classic serotonergic psychedelics such as LSD, DMT and psilocybin — has grown alongside renewed attention to psychedelic therapeutics. Community reports and retrospective surveys suggest microdosing is used to target mood, cognition and energy, and many self-directed microdosers report improvements in depression and anxiety. However, rigorous clinical research in psychiatric populations is limited, and clinical studies in healthy volunteers have produced mixed or null findings. The authors emphasise that major depressive disorder (MDD) is a plausible indication for microdosing research given its high prevalence and the shortcomings of current antidepressant treatments, and that qualitative inquiry can add critical depth to quantitative trials by capturing lived experience and unexpected effects. This study aimed to explore the lived experience of people with MDD who completed an open‑label LSD microdosing pilot. Using post‑treatment semi‑structured interviews, the researchers sought to identify common experiential themes related to microdosing, how participants perceived changes (or lack of change) over the trial, and how these experiences might inform future clinical research and dosing protocols.

The report is a secondary qualitative analysis of an open‑label pilot trial of LSD microdosing in people with MDD. Data were collected between July 2023 and April 2024. Seventeen participants completed an 8‑week microdosing regimen (two doses per week, 16 doses total), with 15 doses taken at home and one administered in clinic. Dosing began at 8 µg and was titrated between 4 and 20 µg according to subjective effects; participants were instructed to increase dose if they felt little or no effect and to reduce dose if daily functioning was disrupted. On dosing days participants were encouraged to engage in a self‑selected psychologically beneficial activity about one hour after dosing. The extracted text does not clearly report detailed inclusion/exclusion criteria beyond the presence of MDD. After completing the regimen participants attended a final trial visit and took part in semi‑structured interviews (20–60 minutes) conducted by members of the research team. Interviews were recorded, transcribed with automated transcription plus human oversight, anonymised and provided with participant consent. The researchers reported that the study conforms to the Standards for Reporting Qualitative Research (SRQR). The analytic approach was inductive reflexive thematic analysis. The first analyst read transcripts twice, generated 84 initial codes in NVivo and, after consultation with colleagues, reduced these to 16 codes which were then organised into themes and subthemes. The analysis was conducted within a critical realist stance and reviewed by a multidisciplinary team; the authors note the possibility that this health‑focused expertise may introduce bias toward health‑related interpretations.

Seventeen participants completed interviews; the sample comprised four females and 13 males aged 24–60 years, with a majority identifying as New Zealand European (N = 13). From the interview data the researchers identified five primary themes: (1) enhanced self‑determination, (2) increased connectedness, (3) improved cognitive processing, (4) better emotional well‑being, and (5) negative effects. Enhanced self‑determination encompassed increased motivation to act, mental/ cognitive motivation and a sense that doing activities made a meaningful difference. Many participants described renewed drive to engage in tasks, exercise or creative pursuits they had previously abandoned; examples included restored interest in socialising and hobbies. Participants emphasised that activity engagement often produced positive downstream effects on mood and functioning. Increased connectedness was reported at three levels: connection to the self (greater self‑awareness and monitoring of mood), connection to others (easier social engagement, reduced social anxiety and more presence in relationships), and connection to something larger (nature, spirituality, a sense of belonging). Several participants described renewed appreciation for the world and improved interpersonal contact that they linked to better wellbeing. Improved cognitive processing included reports of enhanced emotional processing (ability to ‘‘zoom out’’ from ruminative detail, greater resilience in the face of stress), increased mindfulness and present‑moment awareness, and improved focus or concentration. Participants gave examples of coping differently with adverse events and being better able to attend to work or tasks. One participant said they felt they could ‘‘stop focusing on little details … and zoom out,’’ and another observed a reduction in rumination around difficult events. Participants commonly reported improvements in emotional well‑being, including better mood and a reduction in depressive symptoms. Several described feeling ‘‘less sad’’ or that a negative cloud over their mood had been reduced, while others said microdosing made their emotional burden more bearable rather than producing euphoria. However, responses were heterogeneous. The negative‑effects theme captured two patterns: some participants perceived no change, and some experienced unwanted physical or psychological effects. Reported side effects included feeling spaced out, light‑headedness or dizziness, and occasional next‑day ‘‘hangover’’‑like sluggishness. The researchers also note that some participants reported no appreciable impact from LSD microdosing. From the thematic data the authors proposed a cyclical mechanism: enhanced self‑determination, increased connectedness and improved cognitive processing interact bidirectionally to produce better emotional well‑being. They propose a ‘‘therapeutic zone’’ of dose intensity reached via titration, with doses too low producing no effect and doses too high risking adverse experiences. The extracted text references a figure illustrating this model but the figure itself is not included in the provided text.

C. and colleagues interpret the findings as indicative that LSD microdosing has potential therapeutic relevance for people with MDD, insofar as participants reported increased motivation, social and existential connectedness, and improved cognitive and emotional processing that together were associated with better mood. The authors situate these qualitative themes alongside earlier anecdotal and some experimental literature reporting similar effects (for example, increases in motivation, mindfulness and connectedness), while acknowledging that controlled clinical trials have often found small or transient effects in healthy samples. The authors draw theoretical links between their findings and self‑determination theory, suggesting that enhanced autonomy, competence and relatedness could underpin the observed increases in activity engagement and subsequent mood benefits. They also argue that connectedness — to self, others and nature — may be a protective factor against depression and could interact with self‑determination and cognitive processing to improve depressive symptoms. Regarding cognitive effects, the authors note that improvements might be more detectable in a clinical sample than in healthy volunteers because of ceiling effects in the latter group. The authors acknowledge important limitations. Foremost is the open‑label design without a placebo control, which prevents causal attribution and leaves results vulnerable to expectancy effects and other non‑specific influences such as trial participation or the encouraged activity schedule. They note that the trial included an app prompting mood‑enhancing behaviours about an hour after dosing, and it is unclear whether changes in self‑determination derived from the drug, from those encouraged behaviours, or from their combination. The sample also predominantly had moderate to low depression severity, limiting generalisability to more severe cases. The authors recommend future placebo‑controlled trials with active placebo conditions, quantitative symptom trajectories, and a wider range of depression severities. Finally, C. and colleagues highlight practical implications they see in the data: the potential value of a titration protocol to find an individualised ‘‘therapeutic zone,’’ and the possibility that incorporating structured activity engagement into microdosing protocols could support beneficial cycles of motivation, connection and cognitive processing. They caution that microdosing is unlikely to be universally effective and that expectations should be managed.

The study provides qualitative insight into how participants with MDD experienced an open‑label LSD microdosing regimen. Participants reported that microdosing was associated with greater self‑determination, reconnection with self and others, and improved cognitive and emotional processing, which the authors propose interact to enhance emotional well‑being. Some participants experienced side effects or no change, emphasising heterogeneity of response. Because the trial was open‑label, the authors stress that reported benefits may reflect expectancy or natural symptom variation rather than a direct pharmacological effect, and they conclude that placebo‑controlled trials are required to determine efficacy and optimal dosing strategies.