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Journal articleJones G, Lowe MX, Nayak S, et al., 2025,
Examining differences in the effects and contexts of naturalistic psilocybin use for White participants vs. Participants of Color: A longitudinal online survey study.
, J Affect Disord, Vol: 370, Pages: 54-61BACKGROUND: Psilocybin (a psychoactive compound found in "magic mushrooms" or "shrooms") has been gaining increased attention in research and popular culture as a number of clinical and observational studies have demonstrated that it may have potential for improving mental wellbeing. Relatedly, there has been a substantial uptick in naturalistic (e.g., real-world, non-clinical) psilocybin use in the United States. While a number of longitudinal studies have demonstrated that naturalistic psilocybin use is linked to positive mental health outcomes on average, few studies have examined how the effects of psilocybin and contexts for psilocybin use may differ for White populations compared to Populations of Color. OBJECTIVE: To examine differences in health outcomes, subjective effects, and contexts of naturalistic psilocybin use in White participants compared to Participants of Color. METHODS: This study used data from a large, online longitudinal study of individuals who planned to engage in naturalistic psilocybin use (N = 2833). We used mixed-effects models to assess whether race/ethnicity (White vs. Participant of Color) moderated associations between time (Time 2 [initial assessment point for longitudinal measures], Time 5 [2-4 weeks post-psilocybin experience, and Time 6 [2-3 months post-experience]) and outcomes related to mental health (depression, anxiety, spiritual wellbeing, cognitive flexibility, emotion regulation [expressive suppression + cognitive reappraisal]). We also used exploratory chi-squared tests to examine differences in contexts for psilocybin use as well as differences in subjective effects related to the psilocybin experience. RESULTS: Race/ethnicity moderated the associations between time for predicting spiritual wellbeing (beta = -1.8; 95 % CI [-3.4, -0.17]; p < 0.05), cognitive flexibility (beta = -1.5 [-2.7, -0.26]; p < 0.05), and emotion regulation
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Journal articleKettner H, 2024,
Observational cohort study of a group-based VR program to improve mental health and well-being in people with life-threatening illnesses
, Frontiers in Virtual Reality, ISSN: 2673-4192Introduction. Being diagnosed with a life-threatening illness (LTI) is often accompanied by feelings of fear, uncertainty, and loneliness that can severely impact mental health. Relatively few interventions are available to address the existential concerns of individuals facing LTI, while treatment of the underlying physical ailment typically remains the priority of the healthcare system. Research has shown that psychedelic-assisted psychotherapy (PAT) holds promise for supporting mental health in people with LTIs. However, PAT’s potential in this population remains curtailed by several limitations, including regulatory and accessibility issues. Novel approaches that could provide some of the benefits of psychedelic experiences, while avoiding associated challenges, would therefore be highly desirable for supporting the mental well-being of people with LTIs. Among such interventions, VR-based experiences have been suggested as a promising candidate. We here evaluate a program that includes weakly representational, multi-user VR experiences based on a design aesthetic previously described as “numadelic”, which has been demonstrated to elicit self-transcendent experiences comparable to psychedelics.Methods. A prospective cohort study design was used to assess the effects of “Clear Light” (CL) a group-based, 6-session multimedia program that included VR experiences, video calls, and text chats spanning 3 weeks. Participants were individuals suffering from LTIs that self-selected to participate in the CL program. A total of N=15 participants were evaluated based on assessments one week before and after the program, using self-report measures of anxiety, depression, well-being, and secondary psychological outcomes.Results. The intervention was well-tolerated among participants. Significant improvements with moderate effect sizes were observed on self-reported measures of anxiety, depression, and well-being. Secondary measures assessing demor
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Journal articleBonnelle V, Feilding A, Rosas FE, et al., 2024,
Autonomic nervous system activity correlates with peak experiences induced by DMT and predicts increases in well-being.
, J Psychopharmacol, Vol: 38, Pages: 887-896BACKGROUND: Non-ordinary states of consciousness induced by psychedelics can be accompanied by so-called "peak experiences," characterized at the emotional level by their intensity and positive valence. These experiences are strong predictors of positive outcomes following psychedelic-assisted therapy, and it is therefore important to better understand their biology. Despite growing evidence that the autonomic nervous system (ANS) plays an important role in mediating emotional experiences, its involvement in the psychedelic experience is poorly understood. The aim of this study was to investigate to what extent changes in the relative influence of the sympathetic (SNS) and parasympathetic nervous systems (PNS) over cardiac activity may reflect the subjective experience induced by the short-acting psychedelic N,N-Dimethyltryptamine (DMT). METHODS: We derived measures of SNS and PNS activity from the electrocardiograms of 17 participants (11 males, mean age = 33.8 years, SD = 8.3) while they received either DMT or placebo. RESULTS: Results show that the joint influence of SNS and PNS ("sympathovagal coactivation") over cardiac activity was positively related to participants' ratings of "Spiritual Experience" and "Insightfulness" during the DMT experience, while also being related to improved well-being scores 2 weeks after the session. In addition, we found that the state of balance between the two ANS branches ("sympathovagal balance") before DMT injection predicted scores of "Insightfulness" during the DMT experience, as well as subsequent sympathovagal coactivation. CONCLUSION: These findings demonstrate the involvement of the ANS in psychedelic-induced peak experiences and may pave the way to the development of biofeedback-based tools to enhance psychedelic therapy.
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Journal articleAngyus M, Osborn S, Haijen E, et al., 2024,
Validation of the imperial psychedelic predictor scale.
, Psychol Med, Vol: 54, Pages: 1-9BACKGROUND: Access to psychedelic drugs is liberalizing, yet responses are highly unpredictable. It is therefore imperative that we improve our ability to predict the nature of the acute psychedelic experience to improve safety and optimize potential therapeutic outcomes. This study sought to validate the 'Imperial Psychedelic Predictor Scale' (IPPS), a short, widely applicable, prospective measure intended to be predictive of salient dimensions of the psychedelic experience. METHODS: Using four independent datasets in which the IPPS was completed prospectively - two online surveys of 'naturalistic' use (N = 741, N = 836) and two controlled administration datasets (N = 30, N = 28) - we conducted factor analysis, regression, and correlation analyses to assess the construct, predictive, and convergent validity of the IPPS. RESULTS: Our approach produced a 9-item scale with good internal consistency (Cronbach's α = 0.8) containing three factors: set, rapport, and intention. The IPPS was significantly predictive of 'mystical', 'challenging', and 'emotional breakthrough' experiences. In a controlled administration dataset (N = 28), multiple regression found set and rapport explaining 40% of variance in mystical experience, and simple regression found set explained 16% of variance in challenging experience. In another (N = 30), rapport was related to emotional breakthrough explaining 9% of variance. CONCLUSIONS: Together, these data suggest that the IPPS is predictive of relevant acute features of the psychedelic experience in a broad range of contexts. We hope that this brief 9-item scale will be widely adopted for improved knowledge of psychedelic preparedness in controlled settings and beyond.
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Journal articleKettner H, Roseman L, Gazzaley A, et al., 2024,
Reply to Letter to the Editor: "Psychedelics in Older Adults: Difficulties of a Clear Therapeutic Evidence".
, Am J Geriatr Psychiatry -
Journal articleErritzoe D, Barba T, Greenway KT, et al., 2024,
Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial
, EClinicalMedicine, Vol: 76, ISSN: 2589-5370Background Psilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination. Methods This is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD. Participants were recruited from a hospital in the UK. Inclusion criteria: major depressive disorder (DSM-IV), moderate to severe depression (HAM-D ≥ 17), no MRI or SSRI contraindications, confirmed diagnosis by a GP or mental healthcare professional, aged 18-80, both genders, and competent in English. Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET). The primary outcome measure was change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, which has been reported previously. Herein, we present results at the 6-month follow-up time point. Measures of social functioning, connectedness, and meaning in life constituted the study’s secondary outcomes during follow-up. Safety in the follow-up period was not assessed. This trial is registered at ClinicalTrials.gov, NCT03429075.Findings Between January 15th, 2019 and March 20th , 2020, 59 patients were enrolled and 30 (11 females (37%) and 19 males (63%)) were assigned to the psilocybin group and 29 (9 females (31%) and 20 males (69%)) to the escitalopram group. 25 participants
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Journal articleMurphy RJ, Sumner RL, Godfrey K, et al., 2024,
Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide.
, Psychopharmacology (Berl)INTRODUCTION: Enhanced creativity is often cited as an effect of microdosing (taking repeated low doses of a psychedelic drug). There have been recent efforts to validate the reported effects of microdosing, however creativity remains a difficult construct to quantify. OBJECTIVES: The current study aimed to assess microdosing's effects on creativity using a multimodal battery of tests as part of a randomised controlled trial of microdosing lysergic acid diethylamide (LSD). METHODS: Eighty healthy adult males were given 10 µg doses of LSD or placebo every third day for six weeks (14 total doses). Creativity tasks were administered at a drug-free baseline session, at a first dosing session during the acute phase of the drug's effects, and in a drug-free final session following the six-week microdosing regimen. Creativity tasks were the Alternate Uses Test (AUT), Remote Associates Task (RAT), Consensual Assessment Technique (CAT), and an Everyday Problem-Solving Questionnaire (EPSQ). RESULTS: No effect of drug by time was found on the AUT, RAT, CAT, or EPSQ. Baseline vocabulary skill had a significant effect on AUT and RAT scores. CONCLUSIONS: Despite participants reporting feeling more creative on dose days, objective measurement found no acute or durable effects of the microdosing protocol on creativity. Possible explanations of these null findings are that laboratory testing conditions may negatively affect ability to detect naturalistic differences in creative performance, the tests available do not capture the facets of creativity that are anecdotally affected by microdosing, or that reported enhancements of creativity are placebo effects.
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Journal articleKettner H, Roseman L, Gazzaley A, et al., 2024,
Effects of Psychedelics in Older Adults: A Prospective Cohort Study.
, Am J Geriatr Psychiatry, Vol: 32, Pages: 1047-1059OBJECTIVE: Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psychological mechanisms of guided psychedelic group experiences in OA and a matched sample of younger adults (YA). METHODS: Using a prospective observational cohort design, we identified 62 OA (age ≥60 years) and 62 matched YA who completed surveys two weeks before, a day, two weeks, four weeks, and six months after a psychedelic group session. Mixed linear regression analyses were used to investigate longitudinal well-being changes, as well as baseline, acute, and post-acute predictors of change. RESULTS: OA showed post-psychedelic well-being improvements similar to matched YA. Among baseline predictors, presence of a lifetime psychiatric diagnosis was associated with greater well-being increases in OA (B = 6.72, p = .016 at the four-week key-endpoint). Compared to YA, acute subjective psychedelic effects were less intense in OA and did not significantly predict prospective well-being changes. However, relational experiences before and after psychedelic sessions emerged as predictors in OA (r(36) = .37,p = 0.025). CONCLUSIONS: Guided psychedelic group sessions enhance well-being in OA in line with prior naturalistic and controlled studies in YA. Interestingly, acute psychedelic effects in OA are attenuated and less predictive of well-being improvements, with relational experiences related to the group setting playing a more prominent role. Our present findings call for further research on the effects of psychedelics in OA.
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Journal articleSiegel JS, Subramanian S, Perry D, et al., 2024,
Psilocybin desynchronizes the human brain.
, Nature, Vol: 632, Pages: 131-138A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials1-4. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus5-8. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.
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Journal articleBrouwer A, Carhart-Harris RL, Raison CL, 2024,
Psychotomimetic compensation versus sensitization.
, Pharmacol Res Perspect, Vol: 12It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.
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