Expert Opinion on Psychedelic-Assisted Psychotherapy for People with Psychopathological Psychotic Experiences and Psychotic Disorders

La and colleagues set the scene by tracing how people with psychotic symptoms were systematically excluded from psychedelic research after mid-20th century abuses and the spread of the idea that psychedelics are ‘‘psychotomimetic’’ (i.e. mimic psychosis). The introduction notes that most modern trials preserve exclusionary criteria despite limited controlled evidence that psychedelics precipitate or worsen psychosis in supported clinical settings, and that exclusion has equity consequences because psychotic-spectrum presentations are overrepresented among some racialised groups. The study therefore aims to explore expert views on why personal or familial histories of psychotic symptoms are commonly used as exclusion criteria for psychedelic clinical research and treatment programmes, and to identify when such exclusions might be justifiable versus when psychedelic-assisted psychotherapy (PAP) could be safe or beneficial. The investigators framed the work as an expert consultation to elicit practical recommendations for candidate selection, safeguards, and future research directions.

An expert consultation design was used. The researchers purposively recruited 12 experts from the United States and Canada with experience in psychiatry, clinical psychology, medicine, and/or psychedelic research and practice; affiliations included institutions such as Johns Hopkins, Yale, and University of Toronto. Two participants reported lived experience of psychotic symptoms. Selection was non-random and targeted to individuals able to address nuanced clinical questions. Data were collected via semi-structured, in-depth interviews guided by a template of questions covering past clinical experience, theoretical perspectives, candidate selection, safety concerns, and trial design (Box 1). Written informed consent was obtained, interviews were audio-recorded, transcribed with automated software and checked by two team members, and the study received Research Ethics Board approval from the University of Ottawa. The analytic approach was Interpretative Phenomenological Analysis (IPA). Transcripts were coded to identify major themes; statements were grouped by theme and synthesised into narratives representing the range of expert opinions. The authors reported participant demographic and experiential characteristics and used the thematic synthesis to produce clinical recommendations and research priorities. The extracted text does not clearly report the exact interview length or the timing of interviews.

Twelve experts participated; the extracted text reports a mean of 23 years' professional experience, and that 92% had direct experience with therapeutic effects of psychedelics. Demographics in the sample were predominantly male (9/12, 66%) and White (10/12, 84%); 4/12 (33.3%) identified as sexual minorities. Two participants had lived experience of psychosis. Six broad themes emerged from the IPA: (1) the need for structured support during psychedelic treatment, (2) trauma's potential role in the development and maintenance of psychotic symptoms, (3) historical pathologisation and problematic psychiatric terminology, (4) inclusion and exclusion criteria for psychedelic treatment, (5) debates about the entropic brain theory and its implications, and (6) distinctions and overlaps between psychotic episodes and spiritual emergence. Experts emphasised the heterogeneity of ‘‘psychosis’’ and argued that the label alone does not predict response or risk. Many described psychosis as a continuum; several distinguished spiritual emergences from clinically impairing psychotic disorders. A recurring practical point was that candidate assessment should focus on symptom severity, distress, and functional impairment rather than the mere presence of psychotic experiences. Regarding PAP for people with psychotic symptoms, there was broad agreement that it is not categorically contraindicated. Several experts suggested PAP might be beneficial for some individuals under tightly controlled conditions, particularly when psychotic symptoms are mild or non-debilitating, are secondary to trauma or mood disorders, or when strong therapeutic rapport and support systems exist. However, participants were cautious about treating acutely psychotic or destabilised individuals in outpatient settings. Views on specific compounds varied. Multiple experts nominated MDMA as a ‘‘starter’’ or promising compound for trauma-related psychotic presentations because of its empathogenic qualities and capacity to reduce fear responses; several emphasised the importance of accompanying psychotherapy. Psilocybin and other classical psychedelics were seen as potentially higher risk in some presentations (reactivation of trauma or destabilisation), though some experts still considered them useful in selected cases. Ketamine was described as having a distinct, possibly safer clinical profile for certain patients and as an agent with rapid antidepressant and anti-suicidal effects; ayahuasca was identified by at least one participant as more likely to precipitate problems in people with psychotic histories. Concerns about amphetamine-like effects of MDMA and the abuse potential of some agents were also raised. Experts proposed practical safeguards and candidate criteria for an initial pilot trial: exclude people in the midst of an acute episode, target people with mild-to-moderate or trauma-related psychotic symptoms, ensure thorough medical and psychosocial screening (including cardiac and substance-use history), build strong therapeutic rapport, provide extensive preparatory and integration psychotherapy, consider inpatient or closely supervised settings for higher-risk participants, monitor sleep and symptoms post-dosing, and have plans to manage emergent psychosis including temporary antipsychotic use if needed. Age, medical comorbidity, family history, and social supports were noted as important selection variables. Finally, experts regarded broad, blanket exclusion of all individuals with psychotic symptoms from PAP trials as likely unjustified when protocols include sufficient supports; nevertheless, they agreed exclusions are defensible for studies that cannot provide intensive, personalised care.

The authors situate the expert findings within a broader argument that psychosocial and trauma-informed approaches deserve a central role in treating psychotic symptoms. They note cognitive behavioural therapy (CBT) is effective for psychosis and can induce biological changes analogous to pharmacotherapy, suggesting that combining evidence-based psychotherapy with PAP could potentiate therapeutic effects. Trauma was repeatedly characterised as a plausible causal or maintaining factor for many psychotic experiences, which the experts saw as a rationale for investigating MDMA or other trauma-focused PAP modalities. La and colleagues interpret the consensus as indicating that exclusion of all people with psychotic symptoms from PAP is likely overbroad. Instead, they propose stratified research pathways that differentiate causes (for example, genetic versus environmentally mediated presentations), symptom clusters, and levels of severity. The authors recommend that initial empirical work adopt cautious pilot designs that implement the clinical safeguards suggested by experts and consider inpatient or highly supervised formats for higher-risk participants. Limitations the authors acknowledge include non-random, purposive sampling of experts and limited ethnic and racial diversity among interviewees, which may bias perspectives. They also note conceptual ambiguity because ‘‘psychosis’’ covers a heterogeneous spectrum, making it difficult to know whether experts were always referring to comparable clinical presentations. Finally, the authors highlight that expert opinion cannot substitute for controlled empirical data and call for clinical trials designed to test safety and efficacy in stratified subgroups. Implications discussed by the authors include recommending pilot trials with loosened exclusion criteria for appropriately selected subgroups (for example, trauma-related psychotic symptoms, psychotic features secondary to mood disorder, or mild/transient symptoms), and systematic monitoring of safety and functional outcomes. They frame these next steps as necessary to address ethical and equity concerns arising from current blanket exclusions and to generate data to inform future practice and policy.

The experts concluded that further empirical studies are needed to determine how people with psychotic symptoms might benefit from psychedelic-assisted psychotherapy. Not everyone with psychotic experiences would be a candidate; those more likely to benefit, according to the panel, include individuals whose psychotic symptoms are trauma-related or secondary to mood disorders, who have less severe or less chronic symptoms, who meet medical requirements, and who can form a therapeutic alliance and are not currently paranoid or destabilised. The consensus was that psychotic symptoms alone should not be an automatic exclusion, but that provision of extensive supports, precautions, and specific clinical conditions is essential to safely and effectively offer PAP to this population.