Psilocybin use has increased in the US alongside promising therapeutic potential for depression, raising concerns that individuals may forgo conventional mental health treatment for unsupervised psilocybin use. However, no nationally representative studies have examined whether psilocybin use is associated with differential treatment utilization or perceived unmet need for mental health care among individuals with depression.

We analyzed data from 6,793 individuals aged ≥ 12 years with a past-year major depressive episode (MDE) from the 2024 National Survey on Drug Use and Health, a nationally representative survey of the noninstitutionalized US population. Sociodemographic and substance use characteristics were first compared by past-year psilocybin use. We then examined associations between past-year psilocybin use and eight past-year mental health treatment outcomes using Poisson regression, adjusting for sociodemographic characteristics, other past-year substance use, psychotherapeutic prescription misuse, and alcohol use disorder.

Among individuals with past-year MDE, an estimated 7.3% (95% CI: 6.4–8.3) used psilocybin in the past year. In multivariable models, psilocybin use was not associated with any mental health treatment utilization, including outpatient, inpatient, or telehealth treatment; prescription medication use for mental health; seeing a doctor for depressive feelings; or prescription medication use for depressive feelings. However, psilocybin use was associated with greater perceived unmet treatment need (52.0% vs. 33.9%; aPR = 1.44; 95% CI: 1.04–2.01).

Findings suggest that psilocybin use among individuals with depression co-occurs with perceived unmet need for conventional mental health care but is not associated with lower utilization of any conventional mental health treatments.

Anorexia nervosa is a debilitating eating disorder with high mortality and chronicity rates owing to the paucity of effective existing treatments. Several clinical trials using psilocybin therapy have demonstrated therapeutic efficacy and safety in psychiatric conditions, including anorexia nervosa.

This study aimed to further assess the safety, feasibility and potential efficacy of psilocybin therapy in anorexia nervosa.

This single-blind, within-individual pilot study recruited 21 females with anorexia nervosa, who underwent three dosing sessions with oral psilocybin (COMP360) over 6 weeks in a fixed order (1 mg, 25 mg, 25 mg), alongside talk therapy and adjunctive to treatment as usual. Adverse events were monitored throughout the study. Primary clinical outcome measures were global Eating Disorder Examination Interview (EDE) and Readiness and Motivation Questionnaire (RMQ) precontemplation scores. Primary time points for the EDE were the 6-week final visit, 3-month follow-up and 6-month follow-up; and for the RMQ, they were the 6-week final visit and comparison between dosing days. Global EDE Questionnaire scores were a key secondary outcome. Key time points were the 6-week final visit and comparison between dosing days. There was a 12-month remote follow-up.

Psilocybin was well tolerated by all participants. The most common adverse events were headache, nausea and dizziness. Two serious adverse events (suicide attempts) were reported for one participant within the 6–12-month period. Relative to baseline, participants displayed significant improvements in their eating disorder symptoms (EDE scores: p < 0.0001, d = 0.98, 6 months) and motivation to change (RMQ scores: p = 0.0017, d = 0.65, 12 months). However, there was a large variation in improvement and maintenance during the follow-up.

This study further provides preliminary support for the feasibility, safety and potential efficacy of this intervention to treat adult females with anorexia nervosa, and warrants further investigation in larger and more rigorously designed studies.

Psychedelics such as psilocybin are known for their hallucinogenic properties and have also been reported to produce long-lasting therapeutic effects in depression and possibly also other psychiatric disorders. Several lines of evidence suggest that psilocybin exerts its effects through activation of 5-HT2A receptors located postsynaptically to serotonergic neurons, for example, in the frontal cortex, parts of the limbic system, including the amygdala and hippocampus, and striatum. The present study was conducted to shed further light on psilocybin-induced changes in gene expression.

Samples from the medial prefrontal cortex, cingulate cortex, hippocampus, amygdala, and striatum were collected from 24 male Wistar rats 90 min after they had been injected with either saline or psilocybin (2 mg/kg) and subjected to multi-region transcriptional profiling using 3prime-RNASeq technology.

Nfkbia and Sgk1 were upregulated in all the studied regions, Ddit4 was upregulated in four regions, and Gpd1, Apold1, Sox9, Tsc22d3, and Slc2a1 were differentially expressed in two regions. Other cases of differentially expressed genes were region-specific.

Whereas psilocybin was not found to alter the expression of genes encoding enzymes, transporters, or receptors implicated in the serotonergic signalling, or those specifically involved in the regulation of the synaptic activity of other neurotransmitters, a common denominator for many of the genes impacted by psilocybin is that they have previously been found to be activated by glucocorticoids.

Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of psilocybin have shown promise in treating mood disorders, sparking interest in other dosing practices. According to anecdotal reports and observational studies, microdosing psilocybin yields benefits to mental health; however, rigorously controlled trials have failed to produce compelling evidence for this.

To conduct a phase II, double-blind, placebo-controlled, randomised partial crossover trial to compare microdosing psilocybin to placebo for MDD, evaluating its safety, tolerability and preliminary antidepressant effects.

Forty adults with MDD will be randomised to four doses of psilocybin (2 mg) or placebo (maltodextrin) once weekly over 4 weeks, then four doses of psilocybin (2 mg) once weekly for an additional 4 weeks. The primary efficacy end-point will be change in depression symptoms, as measured at baseline (0 weeks), after the experimental phase (4 weeks), and after the open-label phase (8 weeks). A battery of mood, well-being, attention, creativity, mindfulness and pro-sociality measures will be administered at each time point. Follow-ups will occur every 6 months for up to 2 years after the trial start date, as part of a long-term extension study.

The results of the primary outcome of this trial will be published as a manuscript in a peer-reviewed science or medical journal regardless of the magnitude or direction of effect.

Findings will inform future research on microdosing psilocybin for MDD, regarding dose regimens, effect sizes and expectancy bias. Findings will also facilitate discussions on the comparable benefits of sub- versus threshold doses of psilocybin and the therapeutic value of radically altered perception.

ClinicalTrials.gov identifier: NCT05259943.

Interest in psilocybin as a treatment for depression has risen over the past decade, fuelled by promising clinical trials and a rapidly evolving regulatory landscape. Media coverage plays a critical role in shaping public perceptions, yet little is known about how psilocybin is portrayed in global anglophone online news for the treatment of depression.

This study examines the comprehensiveness and sentiment of English-language online news articles (n = 125) discussing psilocybin as a treatment for depression from January 2000 to May 2024. Articles were sourced from the top 30 global anglophone news outlets, assessed using a 13-item instrument for comprehensiveness, and analysed for sentiment across five thematic categories. A separate sub-analysis was completed for Irish media.

Findings indicate a significant increase in coverage over time, with 43.2% of articles published between 2022 and 2024, predominantly from the USA (68%). While 90.4% of articles cited researchers, fewer addressed risks (47.2%), long-term evidence (46.4%), or patient perspectives (25%). Sentiment analysis revealed a very positive sentiment across articles which was 2.27 on a scale from −5 (most negative) to + 5 (most positive) (SD 1.33), with no significant changes over the time period. Reporting on psilocybin’s onset and duration of effects increased significantly, reflecting growing clinical evidence. However, coverage remains concentrated in prominent outlets, with limited attention to patient experiences and long-term safety.

These findings highlight the media’s role in shaping discourse on emerging treatments and suggest a need for more balanced reporting to align public understanding with scientific evidence. This study provides a foundation for future research on media portrayals of psilocybin and implications for public perception and policy.

Motor functional neurological disorder (FND) is a common illness associated with significant functional impairment. There are no effective pharmacotherapies, and despite the early promise of physiotherapy studies, many suffer disabling symptoms in the long term. There is a theoretical rationale for combining psychedelics with physiotherapy; however, the potential benefit of this approach and optimal treatment model remains unexplored. Here, we present the protocol for the first study investigating the tolerability, feasibility, and potential efficacy of two distinct treatment regimens of psilocybin-assisted physiotherapy for refractory motor FND: a moderate dose that incorporates movement tasks during the acute drug effects versus a standard dose alone.

Twenty-four participants with refractory motor FND will be randomised in a 1:1 ratio to either (1) psilocybin 15 mg, with movement tasks conducted during the acute drug effects, or (2) psilocybin 25 mg alone. All participants will receive two sessions of FND-specific physiotherapy pre-dosing, six sessions of physiotherapy post-dosing, and undergo follow-up visits one week and four weeks following their final physiotherapy session. A battery of outcome measures will be completed as scheduled, assessing tolerability, feasibility, motor FND symptom severity, psychiatric and physical symptoms, quality of life, treatment expectations, intensity of the acute drug effects, personality, motor function, force-matching performance, resting-state and task-based brain imaging, and subjective experiences of the study treatment.

These findings will assist the design of an adequately powered randomised controlled trial in this cohort. The findings may also inform the feasibility of psychedelic treatment in related functional and neuropsychiatric disorders.

Psychospiritual distress affects many patients with cancer, contributing to diminished quality of life, decreased survival and a desire for hastened death. The current standard of care, which primarily consists of antidepressants and psychotherapy, has demonstrated only modest benefits. Psilocybin-assisted therapy (PAT) has shown evidence of rapid, durable, and significant effects on measures of both depression and anxiety in this patient population.

A 51-year-old man diagnosed with metastatic lung cancer, referred to palliative care (PC) with a prognosis of less than 6 months, experienced depression and anxiety in the context of demoralization and existential distress. His suffering persisted despite psychotherapy and treatment with 100 mg of sertraline. He was granted access to PAT through Health Canada’s Special Access Program (SAP) and was treated with 25 mg of oral psilocybin in a homecare setting, with preparative and integrative therapy prior to and following the PAT session.

PAT was well tolerated, with significant decreases in both anxiety and depression. The patient subjectively reported a sustained reduction in suffering and improved well-being at 2 months post-intervention.

PAT, when utilized within an appropriate therapeutic framework, may be safely delivered at home and may serve as an effective and long-lasting treatment for symptoms of anxiety and depression associated with psychospiritual symptoms of existential distress in PC. Future studies should examine differences in outcomes between clinical and homecare settings for PAT, and could include creating practice guidelines and protocols for home-based PAT.

Major depressive disorder (MDD) is a significant public health concern, and current treatments often have limitations in effectiveness and adherence. Psilocybin, a psychedelic compound found in certain mushrooms, is being explored as a potential treatment for depression. It primarily acts through the serotonin 5-HT2A receptor but interacts with 5-HT1A and 5-HT2C receptors. Its precise mechanisms remain under investigation.

(1) To consolidate evidence on psilocybin’s efficacy and safety for depression and the role of 5HT2a, (2) to identify limitations in the literature, and (3) to highlight areas needing further research.

This systematic review follows PRISMA guidelines and analyses 22 studies, including randomised controlled trials (RCTs) and open-label studies. The studies cover various populations, including individuals with treatment-resistant depression, different dosing regimens, and adjunctive therapies.

Psilocybin therapy shows substantial and rapid antidepressant effects, often after one or two sessions with psychological support. Improvements are sustained for weeks or months in many cases. Psilocybin is generally well-tolerated, with mild adverse effects such as anxiety during administration and transient headaches, which are manageable in controlled settings.

Psilocybin demonstrates promise as a novel treatment for depression, especially for individuals unresponsive to conventional antidepressants. Further research is needed to refine dosing, explore long-term effects, and understand its mechanisms of action.

Since physician-assisted dying (PAD) has become a part of the clinical dialogue in the United States (US) and other Western countries, it has spawned controversy in the moral, ethical, and legal realm, with significant cross-country variation. The phenomenon of PAD includes 2 practices: Euthanasia and medical aid in dying (MAiD). Although euthanasia has been allowed in different parts of the world, in the US it is illegal. MAiD has been enacted into law in some jurisdictions. As the practice involves people at the end of life (EOL), often with cancer, and sometimes struggling with psychiatric symptoms; they gain added salience in the field of Consultation-Liaison (CL) Psychiatry in general and Psycho-Oncology in particular.

The current paper reviews a case where a patient did request for MAiD and successfully carried it through, this case became more salient, as the CL Psychiatry department was intimately linked at various stages of care for the patient.

In describing the case several other aspects of EOL care issues were touched upon, and the various debates as well as treatment modalities, for an individual requesting for medical aid in dying were described.

MAiD will possibly remain a sensitive and controversial topic of discussion across the spectrum of healthcare, and as responsible and compassionate advocates for the patients, clinicians need to engage more with the debate surrounding it and facilitate informed decision making. We believe that the present case will throw light on to this enigmatic practice and help in furthering the dialogue surrounding MAiD.

Recent years show an exponential increased interest (“renaissance”) in the use of psychedelics for the treatment of mental disorders and broader. Some of these treatments, such as psilocybin for depression, are in the process of formal regulation by regulatory bodies in the US (FDA) and Europe (EMA), and as such on the brink of real-world implementation. In the slipstream of these developments increasing commercial initiatives are taking shape. The European Psychiatric Association (EPA) acknowledges both the therapeutic potential of psychedelic substances and the challenges for both research and clinical implementation. Steps need to be taken toward a well-balanced policy based upon sound scientific evidence and research, aiming at safe, ethical responsible integration of psychedelic therapy available for all patients who can potentially benefit.

In this EPA policy paper, we highlight the potential benefits, and also the challenges of psychedelic treatments, which can be relevant for the future real-world implementation of these treatments.

In addition to an overview of the current evidence and hypotheses of working mechanisms of psychedelic treatment, this policy paper specifically highlights the importance of the psychosocial components of the treatment as well as the ethical and professional aspects playing a role in real-world implementation.

Four recommendations are formulated for further research and clinical implementation.

Psilocybin is being investigated as a treatment for a myriad of disorders, including treatment-resistant depression. The main focus has been on positive effects, with little attention paid to negative outcomes, especially in clinical settings. Quantitative methodology limits further exploration of such events and can also miss improvements not captured on rating scales.

To highlight potential adverse events of psilocybin and underline limits of quantitative methodology, calling for process evaluations alongside clinical trials.

This is a case of a participant in a phase 2b clinical trial of psilocybin for treatment-resistant depression who presented with increased suicidal ideation and a prolonged period of severely restricted eating following administration, leading to a period of destabilisation and a need for support. Despite the difficulties encountered and the participant's limited improvement on rating scales, she found the experience to have been helpful and led her to make changes to her life which she found beneficial. She described her experience in a written account to the authors.

The case was summarised and the written account was thematically analysed and synthesised into a logic model.

Psilocybin could lead to temporary worsening of suicidal ideation and instigate prolonged adverse events that outlast its acute effects. Paradoxically, it could simultaneously lead to an improvement in functional outcomes which is not clear on depression rating scales. This calls for a qualitative exploration of serious adverse events and participant accounts to deepen our understanding of the psilocybin experience and its different outcomes.

Understanding variations in knowledge and attitudes of psychiatrists to psilocybin therapy is important for the collective discourse about the potential impact on clinical practice and public health in Ireland.

A 28-item questionnaire was designed based on previous studies and distributed to psychiatrists in Ireland via online mailing lists and at in-person academic events.

151 psychiatrists completed the questionnaire (73.3% were under 40 years of age, 76.0% were trainees, and 49.0% were female). In the total sample, 81.5% agreed that psilocybin therapy shows promise in the treatment of psychiatric disorders and 86.8% supported funding research, 86.8% would be willing to refer a patient if it was licensed and indicated, and 78.1% would consider the treatment for themselves, if indicated. Conversely, 6.6% agreed that psilocybin therapy was unsafe even under medical supervision, and 21.9% thought it was potentially addictive. 15.9% of the total sample reported at least one concern including, lack of robust evidence, long-term effectiveness, superiority to current interventions, potential harmful effects, cost and accessibility, and impartiality. Less than half of respondents felt knowledgeable (40.0%) and 9.9% felt adequately prepared to participate in psilocybin therapy. Consultant psychiatrists trended towards less optimism for a potential role in bipolar depression and emotionally unstable personality disorder compared to trainee psychiatrists.

Overall psychiatrists in Ireland held positive attitudes towards psilocybin therapy. However, there was a lack of knowledge evident. Addressing the knowledge gap and aligning with the best available evidence will be key if psychedelic therapy is to prevail in a clinical setting.

To investigate the association between pre-trial expectancy, suggestibility, and response to treatment in a trial of escitalopram and investigational drug, COMP360, psilocybin, in the treatment of major depressive disorder (ClinicalTrials.gov registration: NCT03429075).

We used data (n = 55) from our recent double-blind, parallel-group, randomized head-to-head comparison trial of escitalopram and investigational drug, COMP360, psilocybin. Mixed linear models were used to investigate the association between pre-treatment efficacy-related expectations, as well as baseline trait suggestibility and absorption, and therapeutic response to both escitalopram and COMP360 psilocybin.

Patients had significantly higher expectancy for psilocybin relative to escitalopram; however, expectancy for escitalopram was associated with improved therapeutic outcomes to escitalopram, expectancy for psilocybin was not predictive of response to psilocybin. Separately, we found that pre-treatment trait suggestibility was associated with therapeutic response in the psilocybin arm, but not in the escitalopram arm.

Overall, our results suggest that psychedelic therapy may be less vulnerable to expectancy biases than previously suspected. The relationship between baseline trait suggestibility and response to psilocybin therapy implies that highly suggestible individuals may be primed for response to this treatment.

Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation.

Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice.

The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = −0.29, p = 0.037).

Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.