“A sense of the bigger picture:” A qualitative analysis of follow-up interviews with people with bipolar disorder who self-reported psilocybin use

Bipolar disorder (BD) affects roughly 2.4% of the global population and is notable for far more days spent depressed than manic or hypomanic, with depressive episodes accounting for the bulk of long‑term morbidity, functional impairment and suicide risk. Existing pharmacological treatments for bipolar depression have limited efficacy and carry risks (including possible precipitated affective switching), and people with BD have been systematically excluded from modern psilocybin clinical trials because of safety concerns, particularly the theoretical risk that serotonergic psychedelics could trigger Treatment Emergent Affective Switching (TEAS; a switch from depression to hypomania or mania). Case reports of psychedelic‑associated manic reactions exist but are few and heterogenous, leaving important gaps in knowledge about how people with BD experience psilocybin in naturalistic contexts and what contextual factors may contribute to adverse events. A. and colleagues designed a mixed‑methods study to centre people with BD who have used psilocybin mushrooms and to explore subjective impacts, contextual factors associated with adverse reactions, and implications for future clinical trials. Following an international Phase I survey, this Phase II component used semi‑structured follow‑up interviews to gain in‑depth qualitative data about patterns of benefit and harm after full‑dose psilocybin experiences and to elucidate factors (for example, dose, concurrent substance use, sleep and social setting) that participants perceived as shaping outcomes.

The researchers used an explanatory sequential mixed‑methods design. Phase I was an international web‑based survey (reported elsewhere) from which a purposive subsample of respondents was invited for Phase II qualitative interviews. Phase II recruitment required participants to be aged 18+, have a self‑reported prior full‑dose psilocybin mushroom experience, reside in North America, be willing to be contacted, and to meet DSM‑5 criteria for a bipolar spectrum diagnosis as confirmed via the Structured Clinical Interview for DSM‑5 (SCID). Individuals who only practised microdosing were excluded. No restriction was placed on current symptom severity. Fifteen interviewees were selected to maximise diversity in demographics and in reported outcomes (including both very positive and very negative experiences). Clinical assessors administered the SCID via secure Zoom, and semi‑structured interviews (1–1.5 hours) were conducted by a single trained clinician–researcher over Zoom and audio‑video recorded. Interviews followed an interview guide developed collaboratively with clinicians, researchers and people with lived BD experience, addressing reasons for use, contexts, what occurred during use, and intentions regarding future use. Transcripts were professionally transcribed and managed in NVivo. For analysis, the team applied reflexive thematic analysis. Multiple researchers developed a preliminary coding framework, independently coded transcript samples, iteratively refined codes through regular meetings, and conducted theme development via recursive review and reflexive discussion. The study was conducted within a Community‑Based Participatory Research model with lived‑experience contributors involved in design, coding, interpretation and manuscript development.

Fifteen participants aged 27–50 completed Phase II interviews (9 women, 5 men, 1 genderqueer). After SCID confirmation, 13 were diagnosed with BD‑I and 2 with BD‑II. Thematic analysis produced three primary themes: (1) mental health improvements, (2) undesired mental health impacts, and (3) contextual factors that influenced outcomes. Under mental health improvements, participants reported (a) decreased severity and impact of depressive symptoms occurring shortly after and sometimes persisting for days to months, including reports of greater functional capacity; (b) enhanced emotion processing characterised by increased openness to feelings, cathartic release and therapeutic insight; (c) development of new perspectives that helped participants feel a 'bigger picture' and reduced reactivity to daily stressors; and (d) greater relaxation and, in some cases, improved sleep following the experience. Several participants described these processes as contributing to sustained mood improvement even when low mood recurred. Undesired mental health impacts included (a) changes in sleep (insomnia, fragmented or agitated sleep) that for some preceded or accompanied symptom worsening; (b) increased mania or hypomania severity after some psilocybin experiences, with one participant describing repeated psychedelic‑linked hypomanic episodes and others describing an inconsistent relationship between dosing and mania; (c) psychiatric hospitalisation attributed by some participants to manic or psychotic symptoms following psilocybin use; and (d) distressing sensory experiences (e.g. terrifying dissociative states, persistent hallucinations or heightened tinnitus) that in severe cases required clinical care. Participants variably reported use of pharmaceutical or over‑the‑counter sleep aids to manage post‑experience insomnia. Contextual factors that participants consistently identified as influential included polysubstance use and uncertain or excessive dose (often associated with worse outcomes), the social setting (solo versus social/festival environments—with overstimulating public settings sometimes linked to adverse outcomes and some solitary or supported settings linked to beneficial introspective experiences), and pre‑use sleep deprivation (described by some as creating a "perfect storm" for adverse effects). The researchers also note variability: identical or similar doses produced different outcomes across occasions for some individuals, and some who experienced challenging or clinically significant adverse reactions later reported that those experiences contributed to new life perspectives.

The authors interpret their findings as evidence that adults with BD who have used psilocybin mushrooms in naturalistic contexts report a wide range of outcomes, spanning meaningful reductions in depressive symptoms and improved emotion processing to episodes of worsened sleep, emergent hypomania/mania and, in some instances, hospitalisation or prolonged distress. They position this as the first qualitative study focused on people with BD and psilocybin use and suggest that qualitative methods are valuable for hypothesis generation in this nascent area. A key interpretive point is that increased emotion processing and the formation of new perspectives may be important change processes linked to reductions in bipolar depressive symptoms. The authors relate these processes to constructs from psychotherapy literature (for example, reduced experiential avoidance and increased psychological flexibility) and note parallels with findings from unipolar depression studies. They emphasise the complex and bidirectional role of sleep: psilocybin experiences were associated with both improved sleep/relaxation for some participants and disturbed sleep for others, with sleep disturbance sometimes preceding or accompanying adverse manic outcomes. The authors highlight contextual factors—particularly poly‑substance use, dosing uncertainties, stimulating social environments and pre‑use sleep deprivation—as recurring contributors to negative outcomes, while also acknowledging high variability across individuals and occasions. They discuss paradoxical cases in which very challenging experiences later yielded perspective shifts reminiscent of post‑traumatic growth, and therefore argue for finer distinctions between dangerous dosing (e.g. polysubstance use, unsupervised mixing with medications) and challenging but potentially integrative experiences. Limitations acknowledged by the authors include a largely white sample, restriction to North American participants, self‑selection bias, potential social desirability and recall biases, the uncontrolled naturalistic context that precludes causal inference, and a small purposive sample. The authors recommend cautious interpretation and advocate for small, controlled feasibility trials with specific safety precautions (for example, sleep optimisation, minimising environmental stimulation, therapeutic support and monitoring for hypo/mania, excluding individuals actively manic or in mixed states, and limiting cannabis and other recreational substances) to evaluate safety and preliminary efficacy of psilocybin‑assisted approaches in BD.

The authors conclude that while clear risks exist for people with BD using psilocybin—ranging from sleep disruption and emergent hypo/mania to rare hospitalisation—some individuals also report meaningful mental health improvements after use. Given the historical exclusion of people with BD from psychedelic research, the limited evidence base for those exclusions, and the substantial unmet need for effective treatments for bipolar depression, the authors call for more research. They indicate that their findings will inform an upcoming UCSF feasibility trial of psilocybin‑assisted psychotherapy for BD‑II depression in adults aged 30–65 using an open‑label dose escalation design intended to assess initial safety and efficacy while minimising risk.