Acceptability of psilocybin-assisted group therapy in patients with cancer and major depressive disorder: Qualitative analysis.

BACKGROUND: The present study explored the acceptability of psilocybin-assisted group therapy from the perspective of patients with cancer and depression who participated in a clinical trial assessing the safety and efficacy of this novel intervention. METHODS: Guided by the conceptual framework of acceptability, the authors conducted semi-structured interviews with participants of the psilocybin trial. Data were analyzed using template and thematic analyses. RESULTS: Participants' (n = 28) perspectives on the acceptability of the group and simultaneous sessions was generally positive, both in terms of safety and efficacy: first, the groups contributed to increase participants' sense of safety and preparedness as they were engaging in the therapy; and second, the groups fostered a sense of connection and of belonging, which served to enrich and deepen the meaning of participants' experience, ultimately opening a dimension of self-transcendence and compassion. Other subthemes related to factors influencing the acceptability of the group approach included: 1) the importance of the therapeutic framework, 2) the complementary value of individual sessions, 3) disruptive factors related to the group and/or simultaneous setting, and 4) opportunities and challenges related to group size and how to structure interactions. CONCLUSIONS: This study enhances understanding of what promotes acceptability of the psilocybin-assisted therapy group model for the treatment of MDD in cancer patients. PLAIN LANGUAGE SUMMARY: We conducted exit interviews with participants of a phase 2 trial of psilocybin-assisted therapy (PAT) conducted in a community cancer center, to assess the acceptability of a novel psilocybin delivery model combining simultaneous individual therapy and group sessions. Our findings support the acceptability of this intervention and suggest that in addition to being feasible, it might also enhance participants' perceived safety and efficacy compared to uniquely individual or group delivery models of PAT. Our analysis highlights critical factors conditioning acceptability and suggests new ways PAT may be scaled and integrated into cancer care.

Psychedelic-assisted therapy for treating anxiety, depression, and existential distress in people with life-threatening diseases.

BACKGROUND: Psychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks. OBJECTIVES: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM 3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size). AUTHORS' CONCLUSIONS: Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.

[Psychedelic-assisted psychotherapy in palliative medicine]. / Thérapie assistée par psychédéliques en médecine palliative.

Depression, anxiety and existential distress associated with terminal illness have a major impact on quality of life among palliative care patients. Psychedelics are emerging as catalysts for reflective, introspective and sometimes spiritual exploration as part of psychotherapy, with potentially rapid and long-lasting multiple beneficial effects. Psychedelic-assisted psychotherapy (PAP) combines preparation, substance intake, and integration of experiences to facilitate profound psychospiritual change. Despite methodological and administrative hurdles, interest in this innovative approach continues to grow because of its potential to offer remission where conventional approaches have shown little benefits.

La dépression, l'anxiété et la détresse existentielle liées aux maladies terminales ont un impact majeur sur la qualité de vie despatients. Les psychédéliques apparaissent comme des catalyseurs pour l'exploration réflexive, introspective et parfois spirituelle dans le cadre d'une psychothérapie, avec des effets bénéfiques multiples potentiellement rapides et durables. La thérapie assistée par psychédéliques (TAP) combine la préparation, la prise de substances et l'intégration des expériences pour faciliter l'avènement de changements psychospirituels profonds. Malgré les obstacles méthodologiques et administratifs, l'intérêt pour cette approche novatrice continue de croître en raison de son potentiel à offrir des rémissions là où les approches conventionnelles s'avèrent peu efficaces.

Improvement in OCD symptoms associated with serotoninergic psychedelics: a retrospective online survey.

A renewed interest in the use of psychedelics for treating obsessive compulsive disorder (OCD) has emerged in the last 20 years. But pre-clinical and clinical evidence remain scarce, and little is known about the factor determining the magnitude and persistence of the therapeutic effect. We therefore designed a retrospective online survey to explore, in the general population using psychoactive drugs, their impact on OCD symptoms. We also assessed the attitude of the participants towards the substance in term of frequency of intakes. In a sample of 174 participants, classic psychedelics were reported as the only substances effective at reducing OCD symptoms. In classic psychedelics users, symptoms reduction was associated with the intensity of acute effects, itself correlated to the dose. Reports on the persistence of the therapeutic effect varied from weeks to months, but we could not find any predicting factor. Finally, the occurrence and frequency of subsequent intakes, which seemed to be limited in our sample, were predicted by the magnitude and persistence of the therapeutic effect, respectively. Our observations support the hypothesis of classic psychedelics efficacy in reducing OCD symptoms but a careful evaluation of the persistence of this effect is still needed.

Patient-Related Barriers to the Prescription of Cannabinoid-Based Medicines in Palliative Care: A Qualitative Approach.

Background: A minority of palliative care patients benefit from prescribed cannabinoid-based medicines (CBMs). Objective: The objective of this study was to explore the perceptions, expectations, and experiences of CBM usage among palliative care patients and to evaluate whether and how they may constitute an obstacle to prescription. Design: This is a qualitative study involving semistructured in-depth interviews with 10 patients hospitalized in a palliative care unit in Geneva, Switzerland. The data were analyzed using the interpretative phenomenological analysis method. Results: Semistructured interviews were conducted on 10 patients (average age of 73.3 years), mainly with advanced cancer. Most patients favored CBM use in palliative care and distinguished it from recreational use. Seven themes were identified from patients' perceptions, experiences, and expectations during the interviews: right time to begin CBMs, off-label use, information about side effects, lack of a safe medical framework, costs, relatives, and social acceptance of CBMs. Conclusion: The obstacles described by the patients seem to be surmountable with specific measures at the clinical level. We suggest training health professionals in a palliative care setting, especially in explaining the effects and side effects. CBMs will undoubtedly play a more significant role in palliative care medicine in the years to come.

"I Am Not the Same Man ": A Case Report of Management of Post-COVID Refractory Dyspnea.

The SARS-CoV-2 pandemic brings with it a significant number of post-COVID symptoms, including persistent dyspnea and neuropsychological sequelae. The palliative approach in the treatment of these refractory symptoms is effective and widely applicable in different settings. We report the case of a patient with refractory dyspnea admitted to a specialized palliative care unit with a very poor prognosis. The application of different tools of the palliative approach proved to be effective: a detailed advanced care planning and open communication, the respect for the patient's wishes and optimal use of his resources-the salutogenesis- an adaptation of the rhythm of care to that of the patient. The patient was then discharged for rehabilitation, and finally returned home.

A century of research on psychedelics: A scientometric analysis on trends and knowledge maps of hallucinogens, entactogens, entheogens and dissociative drugs.

A scientometric analysis was realized to outline clinical research on psychedelics over the last century. Web of Science Core Collection was searched up to March 18, 2022, for publications on psychedelics. Network analyses and bibliometrics were combined, to identify research themes and trends with Bibliometrix and CiteSpace. The primary aim was to measure research trends evolution over time, and the secondary aims were to identify bibliometric performance and influence networks of publications, authors, institutions, and countries. Sensitivity analyses were conducted for 2016-2022, and 2021 time periods. We included 31,687 documents (591,329 references), which aggregated into a well-structured network with credible clustering. Research productivity was split into an early less productive period mainly focusing on safety issues, and a "psychedelic renaissance" after the 1990s. Major trends were identified for hallucinogens/entheogens, entactogens, novel psychoactive substances (NPS), and on dissociative substances. There was a translational evolution from the bench to the bedside, with phase 2 and 3 trials and/or evidence synthesis in particular. The most recent trends concerned NPS, ketamine-associated brain changes, and ayahuasca-assisted psychotherapy. The USA and Canada were the most productive settings for the research overall, and more recently this geographical distribution became more prominent, reflecting legislative context/policy making. A translational evolution of psychedelics has been occurring, that has brought approval of esketamine for depression and will likely lead to approval of additional psychedelics across mental and physical conditions. Toxicology screening tools for NPS are urgently needed, which in turn might follow the same translational evolution of psychedelics in the future.

Top Ten Tips Palliative Care Clinicians Should Know About Psychedelic-Assisted Therapy in the Context of Serious Illness.

Psychedelic-assisted therapy (PAT) is a burgeoning treatment with growing interest across a variety of settings and disciplines. Empirical evidence supports PAT as a novel therapeutic approach that provides safe and effective treatment for people suffering from a variety of diagnoses, including treatment-resistant depression, substance use disorder, and post-traumatic stress disorder. Within the palliative care (PC) field, one-time PAT dosing may lead to sustained reductions in anxiety, depression, and demoralization-symptoms that diminish the quality of life in both seriously ill patients and those at end of life. Despite a well-noted psychedelic renaissance in scholarship and a renewed public interest in the utilization of these medicines, serious illness-specific content to guide PAT applications in hospice and PC clinical settings has been limited. This article offers 10 evidence-informed tips for PC clinicians synthesized through consultation with interdisciplinary and international leading experts in the field with aims to: (1) familiarize PC clinicians and teams with PAT; (2) identify the unique challenges pertaining to this intervention given the current legalities and logistical barriers; (3) discuss therapeutic competencies and considerations for current and future PAT use in PC; and (4) highlight critical approaches to optimize the safety and potential benefits of PAT among patients with serious illness and their caregivers.