Psilocybin-assisted Therapy Research Articles

Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial

Psilocybin has been suggested as a novel, rapid-acting treatment for depression. Two consecutive doses have been shown to markedly decrease symptom severity in an open-label setting or when compared to a waiting list group. To date, to our knowledge, no other trial compared a single, moderate dose of psilocybin to a placebo condition. In this double-blind, randomised clinical trial, 52 participants diagnosed with major depressive disorder and no unstable somatic conditions were allocated to receive either a single, moderate dose (0.215mg/kg body weight) of psilocybin or placebo in conjunction with psychological support. MADRS and BDI scores were assessed to estimate depression severity, while changes from baseline to 14 days after the intervention were defined as primary endpoints. The trial took place between April 11th, 2019 and October 12th, 2021at the psychiatric university hospital in Zürich, Switzerland and was registered with clinicaltrials.gov (NCT03715127). The psilocybin condition showed an absolute decrease in symptom severity of-13.0 points compared to baseline and were significantly larger than those in the placebo condition (95% CI-15.0 to-1.3; Cohens' d=0.97; P=0.0011; MADRS) and-13.2 points (95% CI;-13.4 to-1.3; Cohens' d=0.67; P=0.019; BDI) 14 days after the intervention. 14/26 (54%) participants met the MADRS remission criteria in the psilocybin condition. These results suggest that a single, moderate dose of psilocybin significantly reduces depressive symptoms compared to a placebo condition for at least two weeks. No serious adverse events were recorded. Larger, multi-centric trials with longer follow-up periods are needed to inform further optimisation of this novel treatment paradigm. The study was funded by the Swiss National Science Foundation, Crowdfunding, the Swiss Neuromatrix Foundation, and the Heffter Research Institute.

Beliefs and Perceived Barriers Regarding Psychedelic-assisted Therapy in a Pilot Study of Service Members and Veterans With a History of Traumatic Brain Injury.

Posttraumatic stress disorder (PTSD) and depression are common in service members and veterans, and the response to currently available treatments is often modest at best. Recent studies suggest potential benefit with psychedelic-assisted therapies (PATs), particularly 3,4-methylenedioxymethamphetamine-assisted therapy for PTSD and psilocybin-assisted therapy for depression. This study examined beliefs and perceived barriers regarding PAT among service members and veterans to inform the delivery of these treatments if they are approved by the FDA. Twenty-one service members and veterans (67% male, 81% White, and 43% active duty) with a history of traumatic brain injury and co-occurring cognitive and psychological symptoms completed a measure assessing baseline knowledge and views of PAT, read a brief psychoeducation regarding PAT, and then responded to questions related to their beliefs and perceived barriers to PAT. Before psychoeducation, participants reported a neutral view of psychedelic drugs (M = 2.76; range: 1-5), PAT (M = 3.33), and interest in PAT (M = 3.10). After psychoeducation, participants reported a significantly more positive view of psychedelic drugs (M = 3.24, P = .014) and interest in PAT (M = 3.67, P = .016). Overall, participants indicated that they would support PAT availability in medical settings if proven beneficial (M = 4.52; 5 = "agree strongly") and they would support a loved one engaging in PAT (M = 4.29). The most frequently reported health concerns were concern of long-term effects (43%), fear of losing their mind (33%), fear of personality changes (33%), and fear of traumatic brain injury complications (24%). The most frequently endorsed barriers were time commitment, transportation, financial concerns, work, and childcare (33%-19%), with 48% reporting no barriers. This is the first study to explore beliefs and perceived barriers regarding PAT among service members and veterans. These results indicate that military populations may be interested in PAT, particularly if psychoeducation and outreach regarding these treatments occurred. If FDA approved, it will be important to facilitate command support and address logistical barriers to ensure appropriate access within military contexts.

Psychotherapists' openness to engage their patients in Psilocybin-Assisted Therapy for mental health treatment

Despite psychedelic research initially ceasing in the 1970–80s, the findings documented encouraged researchers to re-examine the safety and efficacy of treating mental health with psychedelics. Of particular focus, psilocybin has shown to have therapeutic potential for a variety of mental health problems and was granted breakthrough therapy status by the FDA. Should psilocybin eventually become legally licensed, the success of Psilocybin-Assisted Therapy (PAT) may largely rely on clinicians' openness to engage their eligible patients with PAT. We therefore assessed 119 psychologists' openness to recommend PAT, perceived barriers/facilitators to informing patients about PAT, and factors affecting their openness to involve patients with PAT if FDA approved. While 77.4 % of psychologists agreed they would inform eligible patients about PAT, 91.6 % stated they would still recommend psychotherapies that do not involve psilocybin first. 76.5 % endorsed that knowledge on psilocybin would increase their likelihood to inform patients about PAT. More positive attitudes and beliefs about psilocybin, greater self-reported knowledge of psilocybin, personal history of psychedelic usage, and more positive attitudes towards medical cannabis (MC) was associated with greater openness to engage patients with PAT. Our regression analysis revealed that attitudes towards MC and beliefs about psilocybin were the only significant predictors of psychotherapists' openness towards PAT. These findings provide relevant information to institutions planning educational programs for mental health professionals about psilocybin and Psychedelic-Assisted Therapies.

Psilocybin-assisted therapy improves psycho-social-spiritual well-being in cancer patients

BackgroundWhile psychedelics have been shown to improve psycho-spiritual well-being, the underlying elements of this change are not well-characterized. The NIH-HEALS posits that psycho-social-spiritual change occurs through the factors of Connection, Reflection & Introspection, and Trust & Acceptance. This study aimed to evaluate the changes in NIH-HEALS scores in a cancer population with major depressive disorder undergoing psilocybin-assisted therapy. MethodsIn this Phase II, single-center, open label trial, 30 cancer patients with major depressive disorder received a fixed dose of 25 mg of psilocybin. Participants underwent group preparation sessions, simultaneous psilocybin treatment administered in adjacent rooms, and group integration sessions, along with individual care. The NIH-HEALS, a self-administered, 35-item measure of psycho-social spiritual healing was completed at baseline and post-treatment at day 1, week 1, week 3, and week 8 following psilocybin therapy. ResultsNIH-HEALS scores, representing psycho-social-spiritual wellbeing, improved in response to psilocybin treatment (p < 0.001). All three factors of the NIH-HEALS (Connection, Reflection & Introspection, and Trust & Acceptance) demonstrated positive change by 12.7 %, 7.7 %, and 22.4 %, respectively. These effects were apparent at all study time points and were sustained up to the last study interval at 8 weeks (p < 0.001). LimitationsThe study lacks a control group, relies on a self-report measure, and uses a relatively small sample size with limited diversity that restricts generalizability. ConclusionsFindings suggest that psilocybin-assisted therapy facilitates psycho-social-spiritual growth as measured by the NIH-HEALS and its three factors. This supports the factors of Connection, Reflection & Introspection, and Trust & Acceptance as underlying elements for psycho-social-spiritual healing in cancer patients, and validates the use of the NIH-HEALS within psychedelic research.

Educational Materials and Image Induction Increase Treatment Credibility

ABSTRACT Patient-perceived treatment credibility is linked to important outcome measures including symptom reduction, therapeutic alliance, patient satisfaction, and attrition rates. However, few studies have tested strategies to enhance treatment credibility. The present study investigates the effect of brief, written educational materials and the use of an image induction prime on perceptions of credibility for cognitive behavioral therapy and psilocybin-assisted therapy for depression. Participants (N = 493) rated the perceived credibility of depression treatments before and after reading brief educational materials. Half of the participants were asked an image induction question containing the construct of open-mindedness. Results indicate that brief educational materials of about 300 words significantly increased perceived treatment credibility for both therapies, with a large effect size (Cohen’s d = .91). The use of an image induction prime further increased perceived credibility for psilocybin-assisted therapy for depression (Cohen’s d = .38). These strategies offer an efficient and cost-effective way to enhance treatment credibility. Future studies testing variations of the image induction prime might prove fruitful for optimizing the technique.

Music programming for psilocybin-assisted therapy: Guided Imagery and Music-informed perspectives.

The psychedelic drug psilocybin has been successfully explored as a novel treatment for a range of psychiatric disorders. Administration of psilocybin requires careful attention to psychological support and the setting in which the drug is administered. The use of music to support the acute psychoactive effects of psilocybin is recommended in current guidelines, but descriptions of how to compile music programs for the 4-6 h long sessions are still scarce. This article describes the procedural steps and considerations behind the curation of a new music program, the Copenhagen Music Program, tailored to the intensity profile of a medium/high dose psilocybin. The method of Guided Imagery and Music is presented as a music therapeutic framework for choosing and sequencing music in music programming and the Taxonomi of Therapeutic Music is presented as a rating tool to evaluate the music-psychological intensity of music pieces. Practical examples of how to organize the process of music programming are provided along with a full description of the Copenhagen Music Program and its structure. The aim of the article is to inspire others in their endeavours to create music programs for psychedelic interventions, while proposing that an informed music choice may support the therapeutic dynamics during acute effects of psilocybin.

The psychedelic renaissance: can psilocybin possibly combat depression?

The psychedelic renaissance: can psilocybin possibly combat depression?

Group Format Psilocybin-Assisted Therapy: Commentary on the HOPE trial (HOPE: a pilot study of psilocybin-enhanced group psychotherapy in patients with cancer)

Group Format Psilocybin-Assisted Therapy: Commentary on the HOPE trial (HOPE: a pilot study of psilocybin-enhanced group psychotherapy in patients with cancer)

19.3 Psilocybin-Assisted Therapy for MDD: Current Evidence and Clinical Considerations

19.3 Psilocybin-Assisted Therapy for MDD: Current Evidence and Clinical Considerations

Psilocybin-assisted therapy for reducing alcohol intake in patients with alcohol use disorder: protocol for a randomised, double-blinded, placebo-controlled 12-week clinical trial (The QUANTUM Trip Trial)

IntroductionAlcohol use disorder is a difficult-to-treat psychiatric disorder and a major burden on public health. Existing treatment efficacy is moderate, and relapse rates are high. Preliminary findings suggest that psilocybin,...

The Watts Connectedness Scale: a new scale for measuring a sense of connectedness to self, others, and world

RationaleA general feeling of disconnection has been associated with mental and emotional suffering. Improvements to a sense of connectedness to self, others and the wider world have been reported by participants in clinical trials of psychedelic therapy. Such accounts have led us to a definition of the psychological construct of ‘connectedness’ as ‘a state of feeling connected to self, others and the wider world’. Existing tools for measuring connectedness have focused on particular aspects of connectedness, such as ‘social connectedness’ or ‘nature connectedness’, which we hypothesise to be different expressions of a common factor of connectedness. Here, we sought to develop a new scale to measure connectedness as a construct with these multiple domains. We hypothesised that (1) our scale would measure three separable subscale factors pertaining to a felt connection to ‘self’, ‘others’ and ‘world’ and (2) improvements in total and subscale WCS scores would correlate with improved mental health outcomes post psychedelic use.ObjectivesTo validate and test the ‘Watts Connectedness Scale’ (WCS).MethodsPsychometric validation of the WCS was carried out using data from three independent studies. Firstly, we pooled data from two prospective observational online survey studies. The WCS was completed before and after a planned psychedelic experience. The total sample of completers from the online surveys was N = 1226. Exploratory and confirmatory factor analysis were performed, and construct and criterion validity were tested. A third dataset was derived from a double-blind randomised controlled trial (RCT) comparing psilocybin-assisted therapy (n = 27) with 6 weeks of daily escitalopram (n = 25) for major depressive disorder (MDD), where the WCS was completed at baseline and at a 6-week primary endpoint.ResultsAs hypothesised, factor analysis of all WCS items revealed three main factors with good internal consistency. WCS showed good construct validity. Significant post-psychedelic increases were observed for total connectedness scores (η2 = 0.339, p < 0.0001), as well as on each of its subscales (p < 0.0001). Acute measures of ‘mystical experience’, ‘emotional breakthrough’, and ‘communitas’ correlated positively with post-psychedelic changes in connectedness (r = 0.42, r = 0.38, r = 0.42, respectively, p < 0.0001). In the RCT, psilocybin therapy was associated with greater increases in WCS scores compared with the escitalopram arm (ηp2 = 0.133, p = 0.009).ConclusionsThe WCS is a new 3-dimensional index of felt connectedness that may sensitively measure therapeutically relevant psychological changes post-psychedelic use. We believe that the operational definition of connectedness captured by the WCS may have broad relevance in mental health research.

Psilocybin-Assisted Therapy Found to Improve Depression, Offer Other Benefits

Psilocybin-Assisted Therapy Found to Improve Depression, Offer Other Benefits

Demystifying Psychedelic Treatments in Psychiatry: Is Ego Dissolution the Solution?

Demystifying Psychedelic Treatments in Psychiatry: Is Ego Dissolution the Solution?

How Important Is a Guide Who Has Taken Psilocybin in Psilocybin-Assisted Therapy for Depression?

ABSTRACT Promising outcomes of Psilocybin-Assisted Therapy (PAT) for depression have generated concerted efforts to replicate, extend, and refine protocols to maximize efficacy. Psychotherapy research reveals that clients benefit most when important components of treatment align with their personal preferences. One open question related to PAT concerns the importance of the psilocybin experience of the guides (trained professionals present during acute effects). We sought to assess the importance of a guide who had used psilocybin to potential clients with depressive symptoms. Over 800 MTurk respondents with depressive symptoms rated the import of a guide who had used psilocybin relative to alternative characteristics in guides and cognitive behavioral (CBT) therapists. Importance ratings for guides who had used psilocybin significantly exceeded the “somewhat important” level (50 on a 0–100 scale), other guide-related qualities, and comparable ratings for a cognitive behavioral therapist who shared demographics, had experience with depression and received cognitive therapy personally. People of color (those who are not Caucasian) and those who had previous therapy gave significantly higher importance ratings for guides who had used psilocybin. Participants who chose to list other qualities important for guides listed very similar ones for CBT therapists, often emphasizing proper training and an empathic demeanor. Guides who have used psilocybin, who inform clients of the fact, might have advantages for facilitating PAT’s antidepressant effects, as least in a subset of clients.

Analysis of Psilocybin-Assisted Therapy in Medicine: A Narrative Review.

Psilocybin-containing mushrooms have been consumed by various cultures in many different parts of the world for thousands of years. Psilocybin, a classic psychedelic, contains unique psychoactive properties and has been incorporated into religious ceremonies and investigated for its medicinal value. In the mid-20th century, psilocybin, along with most other classic psychedelics (5HT-2A agonists), was classified as a Schedule I substance, bringing a halt to research on its medicinal utility. The resurgence of clinical trials involving psilocybin in the 21st century has produced promising results concerning the treatment of addiction, depression, and end-of-life mood disorders. Results from these trials have shown significant reductions in depression and anxiety when compared with a placebo, and one trial found no significant difference when compared to a routinely prescribed selective serotonin reuptake inhibitor (SSRI). Studies conducted with patients with advanced-stage cancer have demonstrated that psilocybin may also be beneficial at reducing depression and anxiety associated with psychological crises due to a terminal diagnosis. Psilocybin therapy in the treatment of addiction, which is notoriously difficult to treat, has shown encouraging results. Due to its low toxicity and low risk of overuse, psilocybin has the potential to have a significant influence in the field of addiction medicine. Psilocybin addiction research has been primarily focused on nicotine and alcohol and, in a few small, open-label trials, has shown superiority over traditional therapies. Psilocybin has a relatively unique and incompletely understood mechanism of action, which allows it to be given at several isolated periods. This infrequent dosing regimen has been shown to produce durable effects with minimal toxicity. This review analyzes the potential of psilocybin in the treatment of addiction, depression, and end-of-life mood disorders. In addition, it will discuss the difficulties involved with conducting scientific research on psychedelic compounds, adverse effects, and the therapeutic measures that are necessary to accompany the safe and effective administration of these psychoactive chemicals.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

The Neglected Role of Psychotherapy for Treatment-Resistant Depression.

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up.

Background:Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.Aims:This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin.Methods:This randomized, waiting-list controlled study enrolled 27 patients aged 21–75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose.Results:All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression.Conclusions:These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.

Exploring the Credibility of Psilocybin-assisted Therapy and Cognitive-behavioral Therapy for Depression

ABSTRACT Depression treatments succeed with many but leave others unimproved, and they can generate concerns about side effects, time, and cost. Psilocybin has generated media attention and empirical support for antidepressant effects, but lay impressions of its effectiveness are unclear. Although perceptions of treatment credibility contribute to outcome, beliefs about the credibility of psilocybin-assisted therapy (PAT) among potential patients remain uninvestigated, especially relative to cognitive-behavioral therapy (CBT), a common, empirically-validated approach. The present study examined credibility ratings for CBT and PAT among individuals reporting depressive symptoms. Participants (N = 803) from Amazon’s MTurk platform reported demographics, depressive symptoms, and psychotherapy experience, then read data-based vignettes describing each therapy and rated their credibility. Individuals rated CBT as more credible than PAT. Those with therapy experience rated CBT as more credible than those without. Men and lifetime hallucinogen users rated PAT more credible than women and non-users, but few other predictors accounted for much variance in credibility. Results suggest that potential clients appear cautious about PAT. As continued work examines the effectiveness of psychedelic-assisted interventions, researchers and clinicians must consider patients’ beliefs about treatments as potential predictors of outcomes. Additionally, the paradigm used here might have potential for examining credibility of many interventions.

Investigating cue-reactivity as biomarker for treatment success in psilocybin-assisted therapy for alcohol use disorder

Investigating cue-reactivity as biomarker for treatment success in psilocybin-assisted therapy for alcohol use disorder

Study Protocol for "Psilocybin as a Treatment for Anorexia Nervosa: A Pilot Study".

Background: Anorexia nervosa (AN) is a serious and life-threatening psychiatric condition. With a paucity of approved treatments, there is a desperate need for novel treatment avenues to be explored. Here, we present (1) an overview of the ways through which Public Patient Involvement (PPI) has informed a trial of psilocybin-assisted therapy for AN and (2) a protocol for a pilot study of psilocybin-assisted therapy in AN currently underway at Imperial College London. The study aims to assess the feasibility, brain mechanisms and preliminary outcomes of treating anorexia nervosa with psilocybin.Methods: (1) PPI: Across two online focus groups, eleven individuals with lived experience of AN were presented with an overview of the protocol. Their feedback not only identified solutions to possible barriers for future participants, but also helped the research team to better understand the concept of “recovery” from the perspective of those with lived experience. (2) Protocol: Twenty female participants [21–65 years old, body mass index (BMI) 15 kg/m2 or above] will receive three oral doses of psilocybin (up to 25 mg) over a 6-week period delivered in a therapeutic environment and enveloped by psychological preparation and integration. We will work with participant support networks (care teams and an identified support person) throughout and there will be an extended remote follow-up period of 12 months. Our two-fold primary outcomes are (1) psychopathology (Eating Disorder Examination) across the 6-month follow-up and (2) readiness and motivation to engage in recovery (Readiness and Motivation Questionnaire) across the 6-week trial period. Neurophysiological outcome measures will be: (1) functional magnetic resonance imaging (fMRI) brain changes from baseline to 6-week endpoint and (2) post-acute changes in electroencephalography (EEG) activity, including an electrophysiological marker of neuronal plasticity.Discussion: The results of this pilot study will not only shed light on the acceptability, brain mechanisms, and impression of the potential efficacy of psilocybin as an adjunct treatment for AN but will be essential in shaping a subsequent Randomised Control Trial (RCT) that would test this treatment against a suitable control condition.Clinical Trial Registration: identifier: NCT04505189.