Older adults in psychedelic-assisted therapy trials: A systematic review.

BACKGROUND: Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder. AIMS: The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. METHODS: A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE. RESULTS: 4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. CONCLUSIONS: While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

Psychedelics in Addiction Treatment-Navigating a Sociopolitical Rift.

This Viewpoint discusses the use of psychedelics in treatment for substance use disorders.

Psychedelic therapies reconsidered: compounds, clinical indications, and cautious optimism.

The clinical investigation of psychedelic medicines has blossomed over the last 5 years. Data from a Phase 3 industry trial and a multicenter Phase 2 industry trial, in addition to multiple early phase investigator-initiated and industry trials, have now been published in peer-reviewed journals. This narrative review summarizes both the recent data and the current clinical trials that are being conducted with various classes of "psyche-manifesting" substances, which may prove beneficial in the treatment of a broad range of conditions. Methodological considerations, unique challenges, and next steps for research are discussed in keeping with the uniquely "experiential" nature of these therapies.

Psychedelic Research and Therapeutic Practices: Embracing Communities, Groups, and Traditional Knowledge.

The global prevalence of substance abuse and mental disorders continues to challenge healthcare systems, with one in eight individuals affected. The therapeutic potential of psychedelics is recognized not only for treating mental disorders but also for enhancing well-being and promoting pro-social behaviors. Conventional biomedical research models fall short in addressing the broader health needs of populations and poorly suited for overcoming barriers to service delivery. This special issue includes six articles that explore alternative approaches to psychedelic research and practice, emphasizing collaboration with diverse actors, including indigenous communities, and incorporating traditional knowledge systems into contemporary psychedelic research. They underscore the need for innovative research methods that engage multidisciplinary approaches while promoting culturally relevant outcome measures. They emphasize the importance of shifting from punitive drug policies to those grounded in public health and human rights, allowing for multi-country studies and the development of evidence-based care models for community mental health. Incorporating traditional knowledge and community-based methodologies into psychedelic science is vital for its evolution beyond biomedical research for widespread dissemination, offering new avenues for improved health outcomes and promotion of human flourishing.

Psychedelic Science, Contemplative Practices, and Indigenous and Other Traditional Knowledge Systems: Towards Integrative Community-Based Approaches in Global Health.

As individuals and communities around the world confront mounting physical, psychological, and social threats, three complimentary mind-body-spirit pathways toward health, wellbeing, and human flourishing remain underappreciated within conventional practice among the biomedical, public health, and policy communities. This paper reviews literature on psychedelic science, contemplative practices, and Indigenous and other traditional knowledge systems to make the case that combining them in integrative models of care delivered through community-based approaches backed by strong and accountable health systems could prove transformative for global health. Both contemplative practices and certain psychedelic substances reliably induce self-transcendent experiences that can generate positive effects on health, well-being, and prosocial behavior, and combining them appears to have synergistic effects. Traditional knowledge systems can be rich sources of ethnobotanical expertise and repertoires of time-tested practices. A decolonized agenda for psychedelic research and practice involves engaging with the stewards of such traditional knowledges in collaborative ways to codevelop evidence-based models of integrative care accessible to the members of these very same communities. Going forward, health systems could consider Indigenous and other traditional healers or spiritual guides as stakeholders in the design, implementation, and evaluation of community-based approaches for safely scaling up access to effective psychedelic treatments.

Commentary: Evidence-Informed Recommendation to Achieve Approximate Parity in the Allowed Number of Doses for Common Psychedelics.

In recent years, policymakers have proposed and implemented regulatory changes promoting the deprioritization, decriminalization, or state-level legalization of one or more psychedelic substances, usually referencing data from clinical trials as reasons to support liberalizing drug control policies. As psychedelic policies continue to be drafted, personal possession limits may be considered for inclusion in those regulations. If "allowable amount" limits are to be written into law to set personal possession limits, then such amounts should be more consistently related to psychedelic doses found to be safe and efficacious in clinical trials, existing data on moderate-high doses commonly used in various naturalistic settings, and the few studies that estimate psychedelic dose equivalence based on the intensity of subjective effects. In this commentary, we provide an evidence-informed table of typical moderate-high doses for seven commonly used psychedelic substances. These estimates of comparable moderate-high doses can be used to inform "allowable amount" values for psychedelic substances. When such limits are written into legislation, the adoption of evidence-informed comparable limits akin to those presented here would be an important first step toward ensuring greater parity and consistency in drug policy, relative to limits that have little or no scientific basis.

Policy considerations that support equitable access to responsible, accountable, safe, and ethical uses of psychedelic medicines.

There is mounting evidence suggesting psychedelic and entactogen medicines (namely psilocybin and 3,4-methylenedioxymethamphetamine [MDMA]), in conjunction with proper psychosocial support, hold the potential to provide safe, rapid acting, and robust clinical improvements with durable effects. In the US, both psilocybin and MDMA have been granted Breakthrough Therapy designations by the US Food and Drug Administration and may potentially receive full FDA approval with similar regulatory considerations occurring in multiple countries. At the same time, regulatory changes are poised to increase access to legal or decriminalized psychedelic use in various non-medical settings. This review provides a brief discussion on the historical use of psychedelic medicines, the status of the empirical evidence, and numerous significant policy considerations that must be thoughtfully addressed regarding standards-of-practice, consumer protection, engagement of communities, safeguarding access for all, and developing data standards, which supports the responsible, accountable, safe, and ethical uses of these medicines in clinical, faith-based, and other contexts. We provide suggestions for how public health and harm reduction can be supported through a public-private partnership that engages a community of stakeholders from various disciplines in the co-creation and dissemination of best practices and public policies.

If the Doors of Perception Were Cleansed, Would Chronic Pain be Relieved? Evaluating the Benefits and Risks of Psychedelics.

Psychedelic substances have played important roles in diverse cultures, and ingesting various plant preparations to evoke altered states of consciousness has been described throughout recorded history. Accounts of the subjective effects of psychedelics typically focus on spiritual and mystical-type experiences, including feelings of unity, sacredness, and transcendence. Over the past 2 decades, there has been increasing interest in psychedelics as treatments for various medical disorders, including chronic pain. Although concerns about adverse medical and psychological effects contributed to their controlled status, contemporary knowledge of psychedelics suggests that risks are relatively rare when patients are carefully screened, prepared, and supervised. Clinical trial results have provided support for the effectiveness of psychedelics in different psychiatric conditions. However, there are only a small number of generally uncontrolled studies of psychedelics in patients with chronic pain (eg, cancer pain, phantom limb pain, migraine, and cluster headache). Challenges in evaluating psychedelics as treatments for chronic pain include identifying neurobiologic and psychosocial mechanisms of action and determining which pain conditions to investigate. Truly informative proof-of-concept and confirmatory randomized clinical trials will require careful selection of control groups, efforts to minimize bias from unblinding, and attention to the roles of patient mental set and treatment setting. PERSPECTIVE: There is considerable promise for the use of psychedelic therapy for pain, but evidence-based recommendations for the design of future studies are needed to ensure that the results of this research are truly informative.

Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations.

Psilocybin-facilitated psychotherapy shows potential transdiagnostic efficacy for a range of mental health conditions. Though vulnerable populations bear disproportionate mental health burden, they have been largely neglected in the clinical psilocybin literature. However, if the field is to best respond to the diverse needs of individuals from vulnerable populations, care must be taken to ensure these individuals are represented in the empirical research. This report calls attention to this concern by detailing the challenges and opportunities associated with evaluating psilocybin-facilitated psychotherapy in vulnerable populations. First, we show how working with vulnerable populations must be considered in the context of an often-problematic past and differential exposure to and experience with classic psychedelics. We then provide actionable recommendations for future research testing psilocybin-facilitated psychotherapy in vulnerable populations, including an emphasis on recruitment strategies, the appropriate communication and assessment of subjective effects, building therapeutic alliance, multicultural competence, and flexible study designs. On these premises we call for future work in this area, underscoring that there is vast room for improvement and expansion in this rapidly advancing field of study.

The Potential of Psychedelics for End of Life and Palliative Care.

End of life and palliative care has improved in recent decades but the psychopharmacological options available to clinicians and patients in these contexts remain limited. In particular, psychological factors such as depression, existential distress, and well-being remain challenging to address with current medications. Here, we review recent research on the use of psychedelics in clinical settings with a particular focus on patients with life-threatening diagnoses. We propose that psychedelics may provide clinicians with an additional psychopharmacological treatment in the context of end of life and palliative care.

Psilocybin-Assisted Group Therapy and Attachment: Observed Reduction in Attachment Anxiety and Influences of Attachment Insecurity on the Psilocybin Experience.

Attachment insecurity is determined early in life, is a risk factor for psychopathology, and can be measured on two separate continuous dimensions: attachment anxiety and attachment avoidance. Therapeutic changes toward more secure attachment correlate with reduction in psychiatric symptoms. Psilocybin-assisted psychotherapy has demonstrated promise in the treatment of psychopathology, such as treatment-resistant depression and substance use disorders. We hypothesized that psilocybin-assisted psychotherapy would reduce attachment anxiety and attachment avoidance, thus increasing attachment security. We also hypothesized that baseline measures of attachment insecurity, which can reflect a diminished capacity for trust and exploration, would inform the quality of the psilocybin session. Participants were male long-term AIDS survivors with moderate-severe demoralization (n = 18). Using the Experiences in Close Relationships scale, we measured attachment insecurity at baseline as well as immediately, and 3 months, after completion of a brief group therapy course, which included a single midtreatment open-label psilocybin session conducted individually. Clinically important aspects of the psilocybin session were assessed using the revised Mystical Experience Questionnaire and the Challenging Experience Questionnaire the day following psilocybin administration. Self-reported ratings of attachment anxiety decreased significantly from baseline to 3-months post-intervention, t(16) = -2.2; p = 0.045; d rm = 0.45; 95% CI 0.01, 0.87. Attachment avoidance did not change significantly. Baseline attachment anxiety was strongly correlated with psilocybin-occasioned mystical-type experiences, r(15) = 0.53, p = 0.029, and baseline attachment avoidance was strongly correlated with psilocybin-related challenging experiences, r(16) = 0.62, p = 0.006. These findings have important implications for the general treatment of psychopathology as well as optimizing psilocybin-assisted psychotherapy as a broadly applicable treatment modality.

Psilocybin-assisted group therapy for demoralized older long-term AIDS survivor men: An open-label safety and feasibility pilot study.

BACKGROUND: Psilocybin therapy has shown promise as a rapid-acting treatment for depression, anxiety, and demoralization in patients with serious medical illness (e.g., cancer) when paired with individual psychotherapy. This study assessed the safety and feasibility of psilocybin-assisted group therapy for demoralization in older long-term AIDS survivor (OLTAS) men, a population with a high degree of demoralization and traumatic loss. METHODS: Self-identified gay men OLTAS with moderate-to-severe demoralization (Demoralization Scale-II ≥8) were recruited from the community of a major US city for a single-site open-label study of psilocybin-assisted group therapy comprising 8-10 group therapy visits and one psilocybin administration visit (0·3-0·36 mg/kg po). Primary outcomes were rate and severity of adverse events, and participant recruitment and retention. The primary clinical outcome was change in mean demoralization from baseline to end-of-treatment and to 3-month follow-up assessed with a two-way repeated measures ANOVA. Trial registration: Clinicaltrials.gov (NCT02950467). FINDINGS: From 17 July 2017 to 16 January 2019, 18 participants (mean age 59·2 years (SD 4·4)) were enrolled, administered group therapy and psilocybin, and included in intent-to-treat analyses. We detected zero serious adverse reactions and two unexpected adverse reactions to psilocybin; seven participants experienced self-limited, severe expected adverse reactions. We detected a clinically meaningful change in demoralization from baseline to 3-month follow-up (mean difference -5·78 [SD 6·01], ηp 2 = 0·47, 90% CI 0·21-0·60). INTERPRETATION: We demonstrated the feasibility, relative safety, and potential efficacy of psilocybin-assisted group therapy for demoralization in OLTAS. Groups may be an effective and efficient means of delivering psychotherapy pre- and post-psilocybin to patients with complex medical and psychiatric needs. FUNDING: Carey Turnbull, Heffter Research Institute, NIMH R25 MH060482, NIH UL1 TR001872, River Styx Foundation, Saisei Foundation, Sarlo Foundation, Stupski Foundation, Usona Institute, US Department of Veterans Affairs (Advanced Neurosciences Fellowship and IK2CX001495).

Psychedelic-Assisted Group Therapy: A Systematic Review.

Contemporary research with classic psychedelic drugs (e.g., lysergic acid diethylamide (LSD) and psilocybin) is indebted to the twentieth-century researchers and clinicians who generated valuable clinical knowledge of these substances through experimentation. Several recent reviews that highlight the contributions of this early literature have focused on psychedelic-assisted individual psychotherapy modalities. None have attempted to systematically identify and compile experimental studies of psychedelic-assisted group therapy. In therapeutic settings, psychedelics were often used to enhance group therapy for a variety of populations and clinical indications. We report on the results of a systematic review of the published literature in English and Spanish on psychedelic-assisted group therapies. Publications are characterized by their clinical approach, experimental method, and clinical outcomes. Given the renewed interest in the clinical use of psychedelic medicines, this review aims to stimulate hypotheses to be tested in future research on psychedelic-assisted psychotherapy, group process, and interpersonal functioning.

'Spirituality' and 'cultural adaptation' in a Latino mutual aid group for substance misuse and mental health.

A previously unknown Spanish-language mutual aid resource for substance use and mental health concerns is available in Latino communities across the USA and much of Latin America. This kind of '4th and 5th step' group is a 'culturally adapted' version of the 12-step programme and provides empirical grounds on which to re-theorise the importance of spirituality and culture in mutual aid recovery groups. This article presents ethnographic data on this organisation.

Enhanced sensitivity of the MRL/MpJ mouse to the neuroplastic and behavioral effects of chronic antidepressant treatments.

Chronic administration of antidepressant drugs produce changes in neuroplasticity and behavior in rodents, effects that may be associated with the slow emergence of clinical therapeutic effects. Owing to the uncertainty over the effects of chronic antidepressant treatments in mice, these experiments compared the regulation of neurogenesis, neurotrophin levels, and behavior produced by chronic antidepressant treatments between two inbred mouse strains, MRL/MpJ and C57BL/6J. The MRL/MpJ strain is associated with enhanced wound healing and tissue regeneration, whereas C57BL/6J mice are used commonly for behavioral studies. Proliferation and survival of hippocampal progenitor cells were measured using flow cytometry, a new platform that rapidly quantifies the incorporation of 5-bromo-2-deoxyuridine (BrdU). Hippocampal cell proliferation was increased significantly after chronic administration of fluoxetine (FLX: 5, 10 mg/kg, intraperitoneal (i.p.), b.i.d.) or desipramine (DMI: 5, 10 mg/kg, i.p., b.i.d.) for 21 days in MRL/MpJ mice, but not in C57BL/6J mice. Hippocampal progenitor cells born prior to chronic antidepressant treatments were not affected in either mouse strain. Protein levels of brain-derived neurotrophic factor (BDNF) in MRL/MpJ mice were elevated significantly in the frontal cortex, hippocampus, and amygdala after chronic FLX treatment, but increased only in the frontal cortex by chronic DMI. In contrast, BDNF levels in C57BL/6J mice were decreased in the hippocampus and increased in the amygdala after chronic FLX, and were decreased in the brain stem after chronic DMI. Novelty-induced hypophagia (NIH) was used to examine a behavioral effect produced by chronic antidepressant treatment. MRL/MpJ mice, chronically administered FLX or DMI, had significantly shorter latencies to consume food when exposed to a novel environment than untreated mice, whereas there were no effects on the behavior of C57BL/6J mice. In conclusion, robust effects of chronic antidepressant treatments on hippocampal cell proliferation and BDNF levels paralleled the ability of these drugs to produce changes in NIH behavior in MRL/MpJ, while none of these effects were produced in C57BL/6J mice. The greater responsiveness of MRL/MpJ mice may be important for drug discovery, for genetic studies, and for understanding the neural mechanisms underlying the physiological and behavioral effects of chronic antidepressant treatments.