Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

Reports of self-compassion and affect regulation in psilocybin-assisted therapy for alcohol use disorder: An interpretive phenomenological analysis.

OBJECTIVE: The primary aim of this qualitative study was to delineate psychological mechanisms of change in the first randomized controlled trial of psilocybin-assisted psychotherapy to treat alcohol use disorder (AUD). Theories regarding psychological processes involved in psychedelic therapy remain underdeveloped. METHOD: Participants (N = 13) mostly identified as non-Hispanic and White, with approximately equal proportions of cisgender men and women. Participants engaged in semistructured interviews about their subjective experiences in the study. Questions probed the nature of participants' drinking before and after the study as well as coping patterns in response to strong emotions, stress, and cravings for alcohol. Verbatim transcripts were coded using Dedoose software, and content was analyzed with interpretive phenomenological analysis. RESULTS: Participants reported that the psilocybin treatment helped them process emotions related to painful past events and helped promote states of self-compassion, self-awareness, and feelings of interconnectedness. The acute states during the psilocybin sessions were described as laying the foundation for developing more self-compassionate regulation of negative affect. Participants also described newfound feelings of belonging and an improved quality of relationships following the treatment. CONCLUSION: Our results support the assertion that psilocybin increases the malleability of self-related processing, and diminishes shame-based and self-critical thought patterns while improving affect regulation and reducing alcohol cravings. These findings suggest that psychosocial treatments that integrate self-compassion training with psychedelic therapy may serve as a useful tool for enhancing psychological outcomes in the treatment of AUD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Therapeutic Effects of Ceremonial Ayahuasca Use for Methamphetamine Use Disorders and Other Mental Health Challenges: Case Studies in an Indigenous Community in Sonora, Mexico.

This paper describes three case studies from an outpatient intercultural therapeutic program founded and run by Yaqui health professionals and traditional healers to serve members of the Yaqui tribe residing in Sonora, Mexico. This pilot therapeutic program has been designed specifically for Indigenous individuals, incorporating the ceremonial use of naturally derived psychedelics in addressing substance use disorders and other mental health issues. The program employs a community-based approach, integrating various traditional Indigenous healing practices like the sweatlodge (temazcal), medicinal plant preparations, and the ritualistic use of selected psychedelics from natural sources (such as ayahuasca, peyote, and secretions from Incilius alvarius). These approaches are complemented by culturally attuned group and individual psychotherapy sessions, as well as group sports, community meals, collaborative construction efforts for a permanent clinical infrastructure, and cultural engagements such as art, crafts, and collective music. To evaluate the program's efficacy, safety, and cultural implications, an ongoing observational study is being conducted by an international team of researchers. The preliminary results demonstrate therapeutic progress and improved psychometric outcomes observed in the three case studies presented, indicating promise for this intercultural therapeutic intervention.

Assessing the Acceptability of Yoga Among Patients with and without Chronic Pain Enrolled in a Licensed Opioid Treatment Program.

There is a pressing need to identify non-opioid, evidence-based treatments to address the high prevalence of chronic pain in licensed opioid treatment programs (OTP). Yoga is an effective pain coping strategy but is not widely used by OTP patients. Few studies have examined underlying factors related to poor yoga utilization in this population. Seventy-one participants with and without chronic pain enrolled in a hospital-based OTP completed an acceptability survey assessing pain, current pain coping strategies, prior yoga experience, willingness to try yoga, and beliefs about yoga. Participants with and without chronic pain were compared, as were participants with and without prior yoga experience. The relationships between primary study variables in the chronic pain group were also explored. Participants reported using over-the-counter medications, meditation, stretching, and exercise to manage chronic pain, but yoga was not commonly used. Participants with prior yoga experience reported higher willingness to try yoga and more favorable beliefs about yoga than participants without prior yoga experience. There were no significant differences in willingness to try yoga between participants with and without chronic pain. Among participants with chronic pain, there was a positive association between total number of pain coping strategies used and willingness to try yoga. This study adds to the existing literature on the implementation of yoga programs into OTPs by demonstrating the acceptability of yoga in patients with opioid use disorder, including those experiencing chronic pain, and encourages additional research exploring implementation.

Prospective examination of the therapeutic role of psychological flexibility and cognitive reappraisal in the ceremonial use of ayahuasca.

BACKGROUND: Evidence suggests that psychedelic-assisted therapy carries transdiagnostic efficacy in the treatment of mental health conditions characterized by low mood and the use of avoidance coping strategies. AIMS: While preliminary evidence suggests that psychological flexibility and emotion regulation processes play an important role within psychedelic therapy, this prospective study addressed methodological gaps in the literature and examined the ability of ayahuasca to stimulate acute states of cognitive reappraisal and long-term changes in psychological flexibility and mood. The study also explored whether moderating factors predisposed participants to experience therapeutic changes. METHODS: Participants (N = 261) were recruited from three Shipibo ayahuasca retreat centers in Central and South America and completed assessments on mood, psychological flexibility, and acute ceremonial factors. Expectancy, demand characteristics, and invalid responding were controlled for with several validity scales. RESULTS/OUTCOMES: Participants reported significant reductions in negative mood after three months, as well as increases in positive mood and psychological flexibility. Acute experiences of reappraisal during the ayahuasca ceremony exerted the strongest moderating effects on increases in positive mood and psychological flexibility. Increases in psychological flexibility statistically mediated the effects of acute psychological factors, including reappraisal, on changes in positive mood. CONCLUSIONS/INTERPRETATION: These results highlight the role of acute psychological processes, such as reappraisal, and post-acute increases in psychological flexibility as putative mechanisms underlying positive outcomes associated with psychedelics. These results also provide support for the integration of third-wave and mindfulness-based therapy approaches with psychedelic-assisted interventions.

Attitudes and Beliefs about the Therapeutic Use of Psychedelic Drugs among Psychologists in the United States.

Psychologists are a vital component of mental health treatment and their perceptions of psychedelic-assisted therapy are critical for future implementation. This cross-sectional quasi-experimental electronic survey study explored the attitudes about psychedelics used in treatment among 366 clinical psychologists in the United States. Participants expressed cautiously favorable attitudes toward therapeutic psychedelic experiences but indicated concern about possible psychiatric and neurocognitive risks. Most participants indicated that they lack an understanding of the full range of effects of psychedelics, would need to seek out additional consultation, and endorsed positive beliefs in the potential of psychedelic treatment and the need for further research. Overall, this research identified the need to increase education and training about psychedelics for psychologists in order to help increase knowledge and reduce stigma about psychedelic therapies.

Psilocybin for the Treatment of Depression: A Promising New Pharmacotherapy Approach.

Depression is highly prevalent and represents the leading cause of global disability and primary contributor to overall global burden of disease. Several lines of evidence from early-phase experimental trials suggest that serotonergic psychedelics, particularly psilocybin, with therapeutic support show great promise in the treatment of depression with large effect sizes. Neuroimaging data have also revealed the dynamic effects of psilocybin on functional activity within and between neural regions. This chapter reviews the methods and findings from three small human laboratory clinical trials examining the effects of psilocybin therapy for patients with major depressive disorder and treatment-resistant depression. Insights from functional magnetic resonance imaging and qualitative analyses are also presented, as well as a discussion of study limitations and future directions for the research.

Race, Ethnic, and Sex Differences in Prevalence of and Trends in Hallucinogen Consumption Among Lifetime Users in the United States Between 2015 and 2019.

Background: The current study is one of the first to examine race, ethnic, and sex differences in the prevalence of and trends in hallucinogen use among lifetime users in the United States. Methods: Data came from the 2015-2019 National Survey on Drug Use and Health and included respondent's reporting ever-using hallucinogens (n = 41,060; female = 40.4%). Descriptive and multinomial logistic regression analyses were conducted in Stata. Results: Highest prevalence of past year hallucinogen use was among Asian females (35.06%), which was two-or-more times larger than prevalence of past year use among White males/females and Native American males. More than half of White males/females, Multiracial males, and Hispanic males reported had ever-used psilocybin or LSD, whereas less than one-quarter of Black males/females reported lifetime psilocybin use, and less than a third of Black females reported lifetime LSD use. Native American males had the lowest prevalence of lifetime MDMA use (17.62-33.30%) but had the highest lifetime prevalence of peyote use (40.37-53.24%). Pacific Islander males had the highest prevalence of lifetime mescaline use (28.27%), and lifetime DMT use was highest among Pacific Islander males/females (15.68-38.58%). Black, Asian, and Multiracial people had greater odds of past-year (ORs = 1.20-2.02; ps < 0.05) and past-month (ORs = 1.39-2.06; ps < 0.05) hallucinogen use compared to White people. Females had lower odds of past-year (OR = 0.79; ps < 0.05), past-month (OR = 0.78; ps < 0.05) hallucinogen use compared to males, except for lifetime use of MDMA (OR = 1.29; ps < 0.05). Conclusions: These findings should inform public health initiatives regarding potential benefits and risks of hallucinogen use among racial/ethnic groups and women.

Methadone maintenance patients lack analgesic response to a cumulative intravenous dose of 32 mg of hydromorphone.

OBJECTIVES: Acute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST). METHODS: Individuals (N = 8) without chronic pain were maintained on 80-100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection. RESULTS: No significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity. CONCLUSIONS: The findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.

Naturalistic Use of Mescaline Is Associated with Self-Reported Psychiatric Improvements and Enduring Positive Life Changes.

Mescaline is a naturally occurring psychoactive alkaloid that has been used as a sacrament by Indigenous populations in spiritual ritual and healing ceremonies for millennia. Despite promising early preliminary research and favorable anecdotal reports, there is limited research investigating mescaline's psychotherapeutic potential. We administered an anonymous online questionnaire to adults (N = 452) reporting use of mescaline in naturalistic settings about mental health benefits attributed to mescaline. We assessed respondents' self-reported improvements in depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol and drug use disorders (AUD and DUD). Of the respondents reporting histories of these clinical conditions, most (68-86%) reported subjective improvement following their most memorable mescaline experience. Respondents who reported an improvement in their psychiatric conditions reported significantly higher ratings of acute psychological factors including mystical-type, psychological insight, and ego dissolution effects compared to those who did not report improvements (Cohen's d range 0.7 - 1.5). Many respondents (35-50%) rated the mescaline experience as the single or top five most spiritually significant or meaningful experience(s) of their lives. Acute experiences of psychological insight during their mescaline experience were associated with increased odds of reporting improvement in depression, anxiety, AUD and DUD. Additional research is needed to corroborate these preliminary findings and to rigorously examine the efficacy of mescaline for psychiatric treatment in controlled, longitudinal clinical trials.

Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer.

People with advanced cancer are at heightened risk of desire for hastened death (DHD), suicidal ideation (SI), and completed suicide. Loss of Meaning (LoM), a component of demoralization, can be elevated by a cancer diagnosis and predicts DHD and SI in this population. We completed a randomized controlled trial in which psilocybin-assisted psychotherapy (PAP) produced rapid and sustained improvements in depression, demoralization, and hopelessness in people with cancer. Converging epidemiologic and clinical trial findings suggests a potential antisuicidal effect of this treatment. To probe our hypothesis that PAP relieves SI through its beneficial impacts on depression and demoralization (LoM in particular), we performed secondary analyses assessing within- and between-group differences with regard to LoM and an SI composite score. Among participants with elevated SI at baseline, PAP was associated with within-group reductions in SI that were apparent as early as 8 h and persisted for 6.5 months postdosing. PAP also produced large reductions in LoM from baseline that were apparent 2 weeks after treatment and remained significant and robust at the 6.5 month and 3.2 and 4.5 year follow-ups. Exploratory analyses support our hypothesis and suggest that PAP may be an effective antisuicidal intervention following a cancer diagnosis due to its positive impact on hopelessness and demoralization and its effects on meaning-making in particular. These preliminary results implicate psilocybin treatment as a potentially effective alternative to existing antidepressant medications in patients with cancer that are also suicidal, and warrant further investigation in participants with elevated levels of depression and suicidality.

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).

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

BACKGROUND: A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses. METHODS: The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration. RESULTS: Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives. CONCLUSION: These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.

Individual Experiences in Four Cancer Patients Following Psilocybin-Assisted Psychotherapy.

A growing body of evidence shows that existential and spiritual well-being in cancer patients is associated with better medical outcomes, improved quality of life, and serves as a buffer against depression, hopelessness, and desire for hastened death. Historical and recent research suggests a role for psilocybin-assisted psychotherapy in treating cancer-related anxiety and depression. A double-blind controlled trial was performed, where 29 patients with cancer-related anxiety and depression were randomly assigned to treatment with single-dose psilocybin (0.3 mg/kg) or niacin in conjunction with psychotherapy. Previously published results of this trial demonstrated that, in conjunction with psychotherapy, moderate-dose psilocybin produced rapid, robust, and enduring anxiolytic, and anti-depressant effects. Here, we illustrate unique clinical courses described by four participants using quantitative measures of acute and persisting effects of psilocybin, anxiety, depression, quality of life, and spiritual well-being, as well as qualitative interviews, written narratives, and clinician notes. Although the content of each psilocybin-assisted experience was unique to each participant, several thematic similarities and differences across the various sessions stood out. These four participants' personal narratives extended beyond the cancer diagnosis itself, frequently revolving around themes of self-compassion and love, acceptance of death, and memories of past trauma, though the specific details or narrative content differ substantially. The results presented here demonstrate the personalized nature of the subjective experiences elicited through treatment with psilocybin, particularly with respect to the spiritual and/or psychological needs of each patient.

Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial.

BACKGROUND: Clinically significant anxiety and depression are common in patients with cancer, and are associated with poor psychiatric and medical outcomes. Historical and recent research suggests a role for psilocybin to treat cancer-related anxiety and depression. METHODS: In this double-blind, placebo-controlled, crossover trial, 29 patients with cancer-related anxiety and depression were randomly assigned and received treatment with single-dose psilocybin (0.3 mg/kg) or niacin, both in conjunction with psychotherapy. The primary outcomes were anxiety and depression assessed between groups prior to the crossover at 7 weeks. RESULTS: Prior to the crossover, psilocybin produced immediate, substantial, and sustained improvements in anxiety and depression and led to decreases in cancer-related demoralization and hopelessness, improved spiritual wellbeing, and increased quality of life. At the 6.5-month follow-up, psilocybin was associated with enduring anxiolytic and anti-depressant effects (approximately 60-80% of participants continued with clinically significant reductions in depression or anxiety), sustained benefits in existential distress and quality of life, as well as improved attitudes towards death. The psilocybin-induced mystical experience mediated the therapeutic effect of psilocybin on anxiety and depression. CONCLUSIONS: In conjunction with psychotherapy, single moderate-dose psilocybin produced rapid, robust and enduring anxiolytic and anti-depressant effects in patients with cancer-related psychological distress. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00957359.