Psychedelic Medicine

Psilocybin shows encouraging outcomes for patients with cancer and major depressive disorder (MDD). However, there is insufficient evidence on the use of evidence-based psychotherapeutic interventions to consistently guide and standardize psilocybin preparation, dosing, and integration. Meaning-centered psychotherapy (MCP) is a manualized, brief psychotherapeutic intervention that enhances meaning and purpose among recipients. This article substantiates the rationale for using MCP as a psychotherapeutic intervention to accompany psychedelic-assisted therapy (PAT) with psilocybin for patients with cancer and MDD.

We sampled seven patients with cancer and MDD who previously received PAT with psilocybin followed by group MCP in a phase 2 open-label trial, as well as six therapists who delivered the interventions. First, electronic open-ended response surveys were distributed to explore participant experiences during the phase 2 trial and elicit recommendations to adapt MCP for psilocybin. Second, the research team developed a 5-session model of MCP and psilocybin therapy (MCP-PSIL) based on survey responses. Finally, four focus groups were conducted (two with patients and two with therapists) to expand on patient experiences during the phase 2 trial and gather feedback on MCP-PSIL.

Seven patients (ages 53–80 years) and six therapists (mental health professional experience ranging 9–44 years) participated in both surveys and focus groups. Focus groups underscored the value of experiences related to psilocybin, the group, and MCP, as distinct elements and in conjunction. Participants shared key recommendations to enhance combined psilocybin and MCP experiences and the 5-session MCP-PSIL model. The importance of the group format was also emphasized while noting that individual MCP may be indicated in certain circumstances.

Findings suggest that MCP is a natural therapeutic partner to guide patients throughout the PAT continuum. As MCP-PSIL is tested in the future, we anticipate MCP will leverage the PAT experience by building therapist capacity to optimize care while reducing avoidable distress for patients and maximizing their meaning-making opportunities.

Little is known about the correlates of repeated non-medical lysergic acid diethylamide (LSD) use. Therefore, we aimed to determine the prevalence and correlates of past-year LSD use among people aged 18 years and older in the United States who first used LSD at least 5 years ago.

Using data from the 2015–2019 National Survey on Drug Use and Health, we examined the estimated weighted prevalence of past-year LSD use and explored potential demographic, psychosocial, and drug use correlates using univariable and multivariable modeling.

Among US adults who had initiated LSD use at least 5 years ago, 4.2% were estimated to have used LSD in the past year. Estimated past-year LSD use prevalence decreased with time since first use, dropping from 14.4% among those who first used LSD 5 years ago to 0.1% among those who first used LSD 46–50 years ago. On multivariable analysis, past-year LSD use was positively associated with being male, never having been married, living in poverty, having a higher level of education, lifetime stimulant use, being approached by a drug seller in the past 30 days, having ever sold illegal drugs, perceiving LSD as lower risk, perceiving LSD as more available, and having attempted suicide in the past year. Past-year LSD use was negatively associated with having children in the home, living in a small metropolitan area, and years since LSD use initiation.

Past-year LSD use is infrequent among lifetime LSD users and appears to decline with time since the initiation of LSD use. Perceived risk (lower) and perceived availability (higher) of LSD were the factors associated with the largest adjusted odds ratios for past-year LSD use. Further research is needed to understand the infrequency of LSD use among lifetime LSD users and its public health implications.

Cancer poses an existential threat for patients and caregivers. Psilocybin-assisted therapy (PAT) has emerged as a potential tool to meet these existential needs, yet little is known about how patients describe this element of their cancer journey, and how it might be affected by PAT, especially in the group therapy context.

To explore how patients with cancer and depression describe their existential journey through the experience of cancer and group PAT.

Grounded in the Conceptual Model of Existential Experience in Adults with Advanced Cancer, this study is a qualitative analysis of existing data from semi-structured exit interviews with participants (n = 28) of the psilocybin trial, “The Safety and Efficacy of Psilocybin in Cancer Patients with Major Depressive Disorder” (NCT04593563). This study uses a qualitative descriptive approach paired with template analysis to analyze interview transcripts.

Our analysis revealed three overarching themes: (1) Participants described cancer prompting a deepened lived understanding of their mortality, as well as a re-prioritization of their attention, relationships, and efforts; (2) Therapeutic intentions for participating in the PAT trial went beyond relief of depression and extended to gaining a new perspective toward existential worries and building spiritual resources; (3) Participants described the lasting effects of PAT as a healing, unfolding transformation, noting an enhanced sense of meaning, agency, aliveness, and connectedness.

Our findings provide important insights into the existential experiences of people with cancer and depression, as well as the potential role of PAT, in a novel group therapy context, in addressing existential suffering and fostering personal growth.

The neuropsychological effects of psychedelic compounds are well-documented; however, their respiratory activity is less clear. Since respiration is a physiologically significant process and psychedelics have increasingly attracted attention in therapies, assessing the potential effects on respiration is relevant.

The present narrative literature review compiled evidence on serotonergic modulation, anti-inflammatory, and proposed bronchodilatory effects of psychedelics, as outlined in preclinical, clinical, and mechanistic studies. Targeted searches in PubMed, Scopus, and Google Scholar were used to identify sources, focusing on those that measured respiratory parameters directly or indirectly.

Preclinical evidence suggests that the respiratory effects of classical psychedelics might occur through serotonergic pathways of the central nervous system, regulation of airway smooth muscle tone, and anti-inflammatory mechanisms. In their studies, Nau et al. (2015) and Flanagan et al. (2020) observed rodent models of asthma with respiratory modulation based on objective measures, including flexiVent or whole-body plethysmography. Nevertheless, human studies have not confirmed bronchodilatory effects: Methodological limitations, historical legal prohibition, and the methodological focus on the neuropsychiatric outcome limit respiratory-centered studies.

Interpretation is limited by animal models, heterogeneous compounds/doses, non-standardized respiratory endpoints, and possible confounding by set/setting and acute anxiety. Human experimentation is also restricted by safety and ethics. Future research must standardize respiratory outcomes (spirometry, body plethysmography, airway resistance), prospectively define time of measurement relative to dosing, and compare routes of administration (inhaled vs. oral, intranasal, IV). This could be accomplished by combining neurophysiology (e.g., EEG/fMRI) with simultaneously recorded respiratory measures, possibly helping to elucidate central-peripheral connections.

Although evidence in animals hints at the possible beneficial effects of classical psychedelics on respiratory health, such as anti-inflammatory effects and bronchodilation, it is unclear whether these findings can be applied to the clinical setting. Future studies should utilize strong, ethically acceptable designs that integrate objective respiratory outcomes in animal and human models and address treatment potential and safety levels.