Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Personality change in a trial of psilocybin therapy v. escitalopram treatment for depression.

BACKGROUND: Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action. METHODS: In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up. RESULTS: PT was associated with decreases in neuroticism (B = -0.63), introversion (B = -0.38), disagreeableness (B = -0.47), impulsivity (B = -0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = -0.47) and disagreeableness (B = -0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = -0.38), disagreeableness (B = -0.26), impulsivity (B = -0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = -0.46) remaining decreased at month 6. No significant between-condition differences were observed. CONCLUSIONS: Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.

The Conditional Effects of Savoring on the Relationship between Minority Stress and Alcohol Misuse in an LGBTQIA + Sample.

Background: Alcohol-related difficulties are a significant public health concern in lesbian, gay, bisexual, transgender, questioning, intersex, asexual, and people with other sexual orientations and forms of gender identity (LGBTQIA+) communities. Considering these concerns, there is a strong push to develop affirming and strength-based prevention efforts. Unfortunately, such efforts are undermined by the lack of protective LGBTQIA + models for alcohol misuse. To this end, the purpose of the current study was to evaluate whether savoring, the ability to create, maintain, and prolong positive emotions, meets basic criteria for a protective factor for alcohol misuse in a sample of LGBTQIA + adults. Methods: The sample was comprised of 226 LGBTQIA + adults who completed an online survey. Results: Results indicated that savoring was inversely related to alcohol misuse. In addition, the relationship between minority stress and alcohol misuse varied as a function of savoring; at high levels of savoring (a score of 136.63 on the Savoring Beliefs Inventory), the relationship between minority stress and alcohol misuse was non-significant. Conclusions: In combination, these findings offer preliminary support for savoring as a protective factor for alcohol misuse among different LGBTQIA + communities. However, longitudinal and experimental research is needed to solidify the role of savoring in minimizing alcohol-related problems in this population.

A Randomized Controlled Trial of Brief Skills Training in Affective and Interpersonal Regulation (STAIR) for Veterans in Primary Care.

This randomized controlled trial assessed the efficacy of a five-session version of Skills Training in Affective and Interpersonal Regulation (STAIR) among veterans obtaining treatment in primary care. Veterans who screened positive for either posttraumatic stress disorder (PTSD) or depression (N = 26) were enrolled and randomized into either five-session STAIR or treatment as usual (TAU). Assessments of PTSD symptoms (PTSD Checklist for DSM-5; PCL-5), depression (Beck Depression Inventory-II; BDI-II), emotion regulation (Difficulties in Emotion Regulation Scale; DERS), and social engagement difficulties (World Health Organization Disability Assessment 2.0; WHODAS-2) were assessed at pretreatment, posttreatment, and 3-month follow-up assessments. Participants assigned to the five-session STAIR condition reported significant improvements on all measures, whereas those assigned to TAU showed no change. Group × Treatment interactions were significant for all outcomes, and effect sizes for the interactions ranged from moderate to large, Hedge's gs = 0.81 for the PCL-5, 1.15 for the BDI-II, 0.75 for the DERS, and 0.81 for the WHODAS-2. The results indicate that five-session STAIR, a brief, skills-focused treatment, may be effective in reducing a range of symptoms and in improving social functioning among veterans treated in primary care settings.

Clinician Perceptions Related to the Use of the CBT-I Coach Mobile App.

Objective: Clinicians' perceptions of CBT-I Coach, a patient-facing mobile app for cognitive-behavioral therapy for insomnia (CBT-I), are critical to its adoption and integration into practice. Diffusion of innovations theory emphasizes the influence of perceptions, including the relative advantage to current practice, the compatibility to clinicians' needs, the complexity, the innovation's trialability, and observability. This study intended to evaluate the use and perceptions of CBT-I Coach among Veterans Affairs (VA)-trained CBT-I clinicians. Participants and Methods: Clinicians (N = 108) were surveyed about their use, feedback, and perceptions of CBT-I Coach a year after the app became available. Results: Overall perceptions of CBT-I Coach were favorable. Fifty percent of clinicians reported using CBT-I Coach, with 98% intending to continue use. The app was perceived to increase sleep diary completion and homework compliance. Clinicians viewed the app as providing accessibility to helpful tools and improving patient engagement. Of those not using the app, 83% endorsed intention to use it. Reasons for nonuse were lack of patient access to smart phones, not being aware of the app, not having time to learn it, and inability to directly access app data. Those who reported using CBT-I Coach had more favorable perceptions across all constructs (p < .01 - p < .001), except relative advantage, compared to nonusers. Users perceived it as less complex and more compatible with their practice than nonusers. Conclusions: Continued efforts are needed to increase adoption and enhance use of CBT-I Coach, as well as study if reported benefits can be evidenced more directly.

Telemental Health Delivery of Skills Training in Affective and Interpersonal Regulation (STAIR) for Rural Women Veterans Who Have Experienced Military Sexual Trauma.

This pilot study assessed the feasibility, acceptability, and initial efficacy of a skills-focused treatment delivered via video teleconferencing (VTC) to women veterans living in rural areas who had experienced military sexual trauma (MST). The Skills Training in Affective and Interpersonal Regulation (STAIR) program focuses on teaching emotion management and interpersonal skills in 8 to 10 sessions. The STAIR program may be a good fit for individuals in rural areas for whom social isolation and low social support are particularly problematic. Clinic-to-clinic VTC was used to connect a STAIR therapist with veterans for weekly individual therapy sessions. The participants (n = 10) reported high satisfaction with the intervention and would recommend the program to others. There were significant pretreatment to posttreatment improvements in social functioning, Hedge's g = 1.41, as well as in posttraumatic stress disorder symptoms, Hedge's g = 2.35; depression, Hedge's g = 1.81; and emotion regulation, Hedge's g = 2.32. This is the first report of the successful application of a skills-focused treatment via VTC for women veterans.

PTSD and Trauma-Related Difficulties in Sexual Minority Women: The Impact of Perceived Social Support.

This study examined posttraumatic stress disorder (PTSD) and related symptoms among sexual minority (SM) and heterosexual women and the influence of social support on the relationship between SM status and symptoms. We hypothesized that SM women would endorse higher symptoms of PTSD and related difficulties and that social support would moderate the relationship between SM status and symptoms. The sample, women seeking treatment for PTSD related to interpersonal violence (n = 477; mean age = 36.07 years; 22.9% SM) completed clinician-administered measures of PTSD and self-report measures of trauma-related difficulties and social support. The rate of PTSD diagnosis was higher for SM women. Social support and SM status were significantly associated with suicidality, self-perceptions, depression, somatic complaints, and functional impairment. The interaction between social support and SM status was significant for both functional impairment (ß = -.26) and somatic complaints (ß = -.39). High social support had an equal, positive effect among SM and nonminority women, whereas low social support had a greater negative impact among SM women. Results suggested the particular salience of social support on functioning and symptom severity among SM women and the potential importance of including interventions addressing social support into PTSD treatments for SM women.

Psychiatric risks for worsened mental health after psychedelic use.

BACKGROUND: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. METHODS: A "bottom margin analysis" approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies (N = 807). We define "negative response" by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. RESULTS: We find that 16% of the cohort falls into the "negative responder" subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample (b = 1.425, p < 0.05). CONCLUSION: We infer that the presence of a personality disorder may represent an elevated risk for psychedelic use and hypothesize that the importance of psychological support and good therapeutic alliance may be increased in this population.

Preliminary evidence for the importance of therapeutic alliance in MDMA-assisted psychotherapy for posttraumatic stress disorder.

Background: MDMA-assisted psychotherapy (MDMA-AP) is a combined psychotherapeutic and pharmacologic intervention that shows promise in the treatment of posttraumatic stress disorder (PTSD). Although therapeutic alliance has been established as a key predictor across psychotherapies and is emphasised within MDMA-AP treatment manuals, research has not yet examined the relationship between therapeutic alliance and MDMA-AP treatment outcomes.Objective: Examine whether therapeutic alliance predicts changes in PTSD symptoms following MDMA-AP.Method: Twenty-three individuals with chronic PTSD participated in a MDMA-AP clinical trial that included a randomised (MDMA vs. placebo) and open-label phase. The present analyses focused on participants who were administered MDMA over the course of the randomised and open-label phases (n = 22). Therapeutic alliance was assessed using the Working Alliance Inventory at sessions baseline (pre-session 3) and sessions 4 and 9. PTSD symptoms were assessed using the Clinician Administered PTSD Scale and the Impact of Events Scale-Revised.Results: Controlling for baseline clinician-assessed PTSD severity, therapeutic alliance at sessions 4 and 9 (but not baseline) significantly predicted post-MDMA-AP clinician-assessed PTSD severity. Controlling for baseline self-reported PTSD severity, therapeutic alliance at baseline (although this did not survive correction for multiple comparisons) and sessions 4 and 9 predicted post-MDMA-AP self-reported PTSD severity.Conclusions: The present results provide the first preliminary evidence for the relationship between the therapeutic alliance and treatment outcomes within MDMA-AP for PTSD. These findings highlight the important role of psychotherapy, and common psychotherapeutic factors, within MDMA-AP. Replication in studies with larger and more diverse clinical samples remain necessary.Trial registration: ClinicalTrials.gov identifier: NCT00090064.

Among individuals with chronic posttraumatic stress disorder, therapeutic alliance predicted changes in posttraumatic stress disorder severity following MDMA-assisted psychotherapy.Therapeutic alliance may play a key role in facilitating therapeutic improvement within MDMA-assisted psychotherapy.Further research remains necessary to confirm these preliminary findings and the role of therapeutic alliance in MDMA-assisted psychotherapy.

Who are you after psychedelics? A systematic review and a meta-analysis of the magnitude of long-term effects of serotonergic psychedelics on cognition/creativity, emotional processing and personality.

This systematic review and a meta-analysis synthesised the results from contemporary, randomized and non-randomized controlled studies to assess lasting (one week minimum) changes on cognition/creativity, emotional processing and personality from serotonergic psychedelics. PubMed, Embase and PsycInfo were searched in July 2022. Risk of bias was assessed using Rob 2.0 and ROBINS-I. Ten studies met the eligibility criteria which involved 304 participants. No statistically significant effects were found for the majority outcome measures across the three constructs. A meta-analysis of emotional recognition outcomes found an overall significant effect for faster reaction times in the active treatment groups for disgust (SMD=-0.63, 95% CI=[-1.01 to -0.25], I2 = 65%) and sadness (SMD=-0.45, 95% CI=[-0.85 to -0.06], I2 = 60%). Future research should include larger samples, better control conditions, standardized doses and longer follow-up periods to confirm these preliminary findings.

Prevalence and therapeutic impact of adverse life event reexperiencing under ceremonial ayahuasca.

The present study examined the safety and efficacy of the ceremonial use of ayahuasca in relation to reports of heightened life event reexperiencing under psychedelics. The study examined (1) the prevalence of specific types of adverse life event reexperiencing, (2) characteristics predictive of reexperiencing, (3) the psychological character of reexperiencing, and (4) the impact of reexperiencing on mental health. Participants were recruited from three ayahuasca healing and spiritual centers in South and Central America (N = 33 military veterans, 306 non-veterans) using self-report data at three timepoints (Pre-retreat, Post-retreat, 3-months post-retreat). Reexperiencing adverse life events under ayahuasca was common, with women showing particularly high probability of reexperiencing sexual assault, veterans reexperiencing combat-related trauma, and individuals with a self-reported lifetime diagnosis of post-traumatic stress disorder exhibiting a substantively higher prevalence of reexperiencing. Reexperiencing was associated with states of cognitive reappraisal, psychological flexibility, and discomfort during ceremonies, and participants who reexperienced adverse life events exhibited greater reductions in trait neuroticism following their ceremonies. Clinical implications of these results for the application of psychedelics to mood and stress disorders are discussed.

Examining the Therapeutic Effect of Ceremonial Ayahuasca on Narcissistic Personality and Antagonistic Externalizing in Adults.

Changes in narcissistic traits (e.g., entitlement) following the ceremonial use of ayahuasca were examined across three timepoints (baseline, postretreat, 3-month follow-up) in a sample of 314 adults using self- and informant-report (N = 110) measures. Following ceremonial use of ayahuasca, self-reported changes in narcissism were observed (i.e., decreases in Narcissistic Personality Inventory [NPI] Entitlement-Exploitativeness, increases in NPI Leadership Authority, decreases in a proxy measure of narcissistic personality disorder [NPD]). However, effect size changes were small, results were somewhat mixed across convergent measures, and no significant changes were observed by informants. The present study provides modest and qualified support for adaptive change in narcissistic antagonism up to 3 months following ceremony experiences, suggesting some potential for treatment efficacy. However, meaningful changes in narcissism were not observed. More research would be needed to adequately evaluate the relevance of psychedelic-assisted therapy for narcissistic traits, particularly studies examining individuals with higher antagonism and involving antagonism-focused therapeutic approaches.

A critical evaluation of QIDS-SR-16 using data from a trial of psilocybin therapy versus escitalopram treatment for depression.

BACKGROUND: In a recent clinical trial examining the comparative efficacy of psilocybin therapy (PT) versus escitalopram treatment (ET) for major depressive disorder, 14 of 16 major efficacy outcome measures yielded results that favored PT, but the Quick Inventory of Depressive Symptomatology, Self-Report, 16 items (QIDS-SR16) did not. AIMS: The present study aims to (1) rationally and psychometrically account for discrepant results between outcome measures and (2) to overcome psychometric problems particular to individual measures by re-examining between-condition differences in depressive response using all outcome measures at item-, facet-, and factor-levels of analysis. METHOD: Four depression measures were compared on the basis of their validity for examining differences in depressive response between PT and ET conditions. RESULTS/OUTCOMES: Possible reasons for discrepant findings on the QIDS-SR16 include its higher variance, imprecision due to compound items and whole-scale and unidimensional sum-scoring, vagueness in the phrasing of scoring options for items, and its lack of focus on a core depression factor. Reanalyzing the trial data at item-, facet-, and factor-levels yielded results suggestive of PT's superior efficacy in reducing depressed mood, anhedonia, and a core depression factor, along with specific symptoms such as sexual dysfunction. CONCLUSION/INTERPRETATION: Our results raise concerns about the adequacy of the QIDS-SR16 for measuring depression, as well as the practice of relying on individual scales that tend not to capture the multidimensional structure or core of depression. Using an alternative approach that captures depression more granularly and comprehensively yielded specific insight into areas where PT therapy may be particularly useful to patients and clinicians.

Increasing character strength knowledge, interest, and skill: preliminary evidence for a collaborative and multimethod assessment procedure.

Introduction: The study's objective was to evaluate whether a qualitative, collaborative, and multimethod assessment protocol increased reports of character strength interest, knowledge, and perceived skills. Methods: Thirty-two participants completed three phases of data collection. Participants were first screened for well-being, which was used as an auxiliary covariate to order participants into experimental conditions. Selected participants were randomly assigned to a control or collaborative and multimethod assessment (card sort × qualitative interview) condition. Participants completed pre- and post-measures of strength interest, knowledge, and perceived skill. In the final phase, second phase participants were invited to report on strength-related outcomes 24 h post-administration using an online survey. Results: A series of 2 (Assessment Condition) × 3 (Time) mixed ANOVAs were analyzed. Results revealed a significant assessment condition by time interaction for strength knowledge and perceived skill. Participants in the collaborative and multimethod assessment condition reported higher strength knowledge and perceived skills compared to control participants. These effects were maintained for 24 h. Conclusion: The findings offer preliminary yet sizable support for using collaborative and multimethod assessment procedures to increase strength knowledge and perceived skill. Because of the qualitative, collaborative, and individualized nature of our assessment protocol, the findings offer a low-cost and contextually bound pathway to increase strength-based outcomes.

Ayahuasca in the treatment of posttraumatic stress disorder: Mixed-methods case series evaluation in military combat veterans.

OBJECTIVE: Although ayahuasca-a plant-based psychedelic-is discussed as promising in the treatment of posttraumatic stress disorder (PTSD), evidence so far remains limited to retrospective case reports and qualitative surveys. No study to date has examined whether ayahuasca results in prospective and clinically meaningful changes in trauma symptoms across individuals with PTSD symptoms. METHOD: To address this gap, we conducted a convergent mixed-methods case series study on eight military veterans with PTSD who participated in a 3-day ayahuasca intervention in Central America. Clinically meaningful changes from pre- to posttreatment and at a 3-month follow-up were assessed in three ways using: (a) PTSD checklist-5 (PCL-5); (b) experience sampling measurement of momentary PTSD and mood symptoms; and (c) an open-ended survey on perceived benefits. RESULTS: The majority (87.5%; 7/8) of participants demonstrated reliable and/or clinically significant changes in PCL-5 symptoms by posttreatment, which were maintained by 70% (5/7) of veterans by the 3-month follow-up. On average, veterans also reported significant improvements in momentary PTSD symptoms, as well as negative and positive affect in daily life posttreatment, with 63% (5/8) reporting moderate-to-large improvements in these domains. Broad themes characterizing the perceived benefits of ayahuasca included deep positive emotions, decentering/acceptance, and purpose in life; adverse acute experiences were, however, reported. CONCLUSIONS: This study provides preliminary support for the clinically meaningful and lasting benefits of a brief ayahuasca intervention on PTSD/mood symptoms in military veterans. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effectiveness of biofeedback-assisted asynchronous telerehabilitation in musculoskeletal care: A systematic review.

Background: Musculoskeletal conditions are the leading cause of disability worldwide. Telerehabilitation may be a viable option in the management of these conditions, facilitating access and patient adherence. Nevertheless, the impact of biofeedback-assisted asynchronous telerehabilitation remains unknown. Objective: To systematically review and assess the effectiveness of exercise-based asynchronous biofeedback-assisted telerehabilitation on pain and function in individuals with musculoskeletal conditions. Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The search was conducted using three databases: PubMed, Scopus, and PEDro. Study criteria included articles written in English and published from January 2017 to August 2022, reporting interventional trials evaluating exercise-based asynchronous telerehabilitation using biofeedback in adults with musculoskeletal disorders. The risks of bias and certainty of evidence were appraised using the Cochrane tool and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE), respectively. The results are narratively summarized, and the effect sizes of the main outcomes were calculated. Results: Fourteen trials were included: 10 using motion tracker technology (N = 1284) and four with camera-based biofeedback (N = 467). Telerehabilitation with motion trackers yields at least similar improvements in pain and function in people with musculoskeletal conditions (effect sizes: 0.19-1.45; low certainty of evidence). Uncertain evidence exists for the effectiveness of camera-based telerehabilitation (effect sizes: 0.11-0.13; very low evidence). No study found superior results in a control group. Conclusions: Asynchronous telerehabilitation may be an option in the management of musculoskeletal conditions. Considering its potential for scalability and access democratization, additional high-quality research is needed to address long-term outcomes, comparativeness, and cost-effectiveness and identify treatment responders.

Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial.

Background: Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD). Aim: The aim of Part A of this study was to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the trial (Part B: not presented in this manuscript). Methods: In the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger's state-trait anxiety inventory. Results: SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores. These trends are likely to require confirmation in a larger sample size. Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience. Conclusion: Based on the data obtained from this part of the trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876.

Ayahuasca: A review of historical, pharmacological, and therapeutic aspects.

Ayahuasca is a psychedelic plant brew originating from the Amazon rainforest. It is formed from two basic components, the Banisteriopsis caapi vine and a plant containing the potent psychedelic dimethyltryptamine (DMT), usually Psychotria viridis. Here we review the history of ayahuasca and describe recent work on its pharmacology, phenomenological responses, and clinical applications. There has been a significant increase in interest in ayahuasca since the turn of the millennium. Anecdotal evidence varies significantly, ranging from evangelical accounts to horror stories involving physical and psychological harm. The effects of the brew on personality and mental health outcomes are discussed in this review. Furthermore, phenomenological analyses of the ayahuasca experience are explored. Ayahuasca is a promising psychedelic agent that warrants greater empirical attention regarding its basic neurochemical mechanisms of action and potential therapeutic application.

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.