Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychotic Symptoms

The paper situates itself in the history of psychedelic research, noting that since the First Wave in the 1950s people with personal or familial histories of psychotic symptoms have routinely been excluded from clinical studies and treatment programmes. The authors describe multiple reasons for this exclusion: clinician and regulatory caution, early misperceptions that psychedelics are psychotomimetic (i.e. mimic psychosis), and politicised reactions that followed early research. They also highlight countervailing evidence and perspectives: destabilisation linked to psychedelics appears mostly in uncontrolled, recreational contexts rather than in supported clinical settings, and longstanding Indigenous practices show individuals with hallucinations participating in—and sometimes leading—psychedelic rituals without clear worsening of psychosis. The introduction further notes that ethnoracially diverse participants and people with broader psychiatric presentations have been underrepresented in contemporary psychedelic trials, with direct consequences for BIPOC communities given higher rates of psychosis diagnoses in some groups. This study therefore set out to investigate expert opinion about the rationale for excluding people with psychotic symptoms from psychedelic-assisted psychotherapy (PAP). The specific aims were to understand when such exclusions might be justified, what the implications of blanket exclusions are, and whether an expert consensus exists about the potential for PAP to be safe or beneficial for some people with psychotic symptoms. The authors framed the question in light of recent advances combining psychotherapy with pharmacology and the increasing interest in trauma-informed models that might align with certain psychedelic-assisted approaches.

La and colleagues used an expert consultation, qualitative design based on in-depth semi-structured interviews. The sample comprised 12 deliberately selected experts from the United States and Canada whose expertise spanned clinical psychology, psychiatry, medicine, and psychedelic research; affiliations included institutions such as Johns Hopkins, Yale, and the University of Toronto. Selection was purposive rather than random, targeting individuals with substantial experience or interest in working with psychedelics and/or psychotic symptoms. Two participants reported lived experience of psychosis. The mean professional experience reported was 23 years and 92% of participants had direct clinical experience with the therapeutic effects of psychedelics. Interviews followed a semi-structured template covering past clinical experience, theoretical questions (e.g. compatibility of psychedelics with psychotic symptoms), and practical recommendations for trial design and safety. Recordings were transcribed automatically and checked for accuracy by two team members. The analytic approach was Interpretative Phenomenological Analysis (IPA), a qualitative method that emphasises participants’ lived experience and the investigators’ interpretative synthesis; major themes were identified and coded across transcripts and some statements were allowed to fall under multiple themes. Ethical procedures included written informed consent, audio recording with participant permission, and institutional Research Ethics Board approval. The extracted text does not provide verbatim details of software used for coding beyond the IPA approach nor specific inter-rater reliability metrics.

Twelve expert interviews generated six broad themes: (1) the necessity of structured guidance and support when delivering psychedelic treatments; (2) the potential causal or maintaining role of physical and emotional trauma in psychotic symptoms; (3) the historical pathologisation and problematic terminology in psychiatry; (4) considerations for inclusion and exclusion criteria in PAP; (5) the entropic brain theory as it relates to psychedelic effects on people with psychotic symptoms; and (6) distinctions and overlaps between psychotic episodes and spiritual emergence. A clear consensus emerged that blanket exclusion of all people with psychotic symptoms from PAP is not universally justified. Instead, experts argued candidacy should be assessed case-by-case, taking into account symptom type, severity, duration, functional impairment, and the quality of the therapeutic alliance. Many participants emphasised the heterogeneity of "psychosis"—for example, auditory hallucinations, paranoid delusions, brief/transient versus chronic presentations—and noted that not all psychotic experiences are distressing or disabling. Several experts suggested that individuals with mild or non-debilitating symptoms, or those whose psychotic phenomena are secondary to trauma or mood disorders, might be appropriate candidates under highly supportive conditions. On pharmacological candidates, MDMA was frequently mentioned as a potentially favourable "starter" molecule because of its capacity to foster safety, openness, and self-compassion in trauma processing; some experts proposed psilocybin as a higher-risk, higher-reward option, and ketamine as comparatively safe for patients with psychotic features because of its clinical profile. Ayahuasca was raised as more likely to cause problems in people with a history of psychotic symptoms. Clinical safety recommendations for an initial pilot included excluding acutely psychotic individuals, prioritising people who are stable and have good support networks, building strong therapeutic rapport through thorough preparation, providing extensive post-session integration, and in some cases offering inpatient or day-programme level monitoring. Several experts advised readiness to manage medication interactions and to prescribe antipsychotics if necessary; monitoring sleep and physical health (cardiac history, metabolic and renal/hepatic function, drug use) was also recommended. Demographically, the expert sample was majority male (9/12, 66%) and majority White (10/12, 84%), with 4 participants (33.3%) identifying as sexual minorities; the authors note this imbalance as a limitation. Experts also recommended that any future trials stratify participants by putative aetiology (e.g. trauma-related versus primarily genetic/neurodevelopmental) and symptom profile to reduce heterogeneity and enhance safety.

La and colleagues interpret the expert opinions as supporting a more nuanced stance than current blanket exclusions: while many existing trial and outpatient contexts lack the intensive psychosocial supports needed to safely include people with psychotic symptoms, the experts believe PAP is not inherently contraindicated for all such individuals. The discussion emphasises a trauma-informed framework, noting that trauma can produce sustained biological and epigenetic changes and that behavioural interventions (such as CBT) can produce lasting neurobiological effects analogous to pharmacotherapy. In this light, combining evidence-based psychotherapies with psychedelics might offer therapeutic access to underlying drivers of psychotic symptoms rather than only treating surface-level manifestations. Key limitations acknowledged by the authors include the non-random, purposive sampling of experts, the heterogeneity and imprecision of the term "psychosis" across participants, and the limited ethnic and racial diversity of the expert panel. The authors therefore recommend cautious next steps: pilot trials that loosen exclusion criteria in a controlled, highly supported context; stratification by likely cause of psychotic symptoms (genetic vs environmental/trauma-related); and careful selection of compounds and candidate profiles (for example, prioritising people with trauma-associated, mild or transient psychotic features). The paper frames these steps as necessary both for scientific understanding and for addressing equity concerns whereby marginalised groups have been disproportionately excluded from access to promising treatments.

The experts concluded that further empirical study is required to determine how people with psychotic symptoms might benefit from psychedelic-assisted psychotherapy. They emphasised that not all individuals with psychotic symptoms are the same: candidates more likely to be appropriate include those whose symptoms are secondary to trauma or mood disorders, are less severe or chronic, are open to psychedelic therapy, meet medical requirements, and can form a reliable therapeutic relationship. The consensus was that psychotic symptoms alone should not be an absolute contraindication; rather, careful screening, comprehensive psychosocial supports, appropriate monitoring (including readiness to prescribe antipsychotics), and possibly inpatient-level care are necessary to offer PAP safely and effectively to this population. The extracted text does not include a completed final sentence from the original conclusion.