Psilocybin-assisted Therapy Research Articles

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.

Is MDD the right target for early-stage psychedelic-assisted therapy trials?

AbstractThe recently published Imperial College study of a Phase II, double-blind, randomized, controlled trial comparing psilocybin-assisted therapy to a six-week titration of escitalopram for Major Depressive Disorder (MDD) should raise concerns for this illness category as a target of early psychedelic research given a goal of FDA approval. There are three reasons why MDD is the wrong target at this stage of research development. Firstly, the psychiatric category of MDD is heterogeneous, vaguely-defined, and overdiagnosed in a way that will problematize finding a reliable signal with psychedelic interventions (or any intervention), particularly within non-severe cases. Secondly, current rating scales for MDD (QIDS used in the Imperial College trial, but also HAM-D) are limited in approximating the kinds of things we ultimately care most about with depressive states, namely functional status, quality of life, and well-being: measures that seem more salient for psychedelic interventions and which are not adequately captured by these rating scales used in a majority of clinical trials. And thirdly, there are inherent conflicts between psychiatric conceptualizations of MDD (and its symptom amelioration) and the kinds of perspectives on one’s suffering often occasioned by psychedelic experiences themselves: while these kinds of psychedelic-catalyzed openings may lead to a form of acceptance or equanimity with regards to one’s life circumstances this could be in many ways orthogonal to reductions in HAM-D scores. We argue that for these reasons MDD is a non-ideal target at this stage of the science and propose alternative directions.

Psilocybin for End-of-Life Anxiety Symptoms: A Systematic Review and Meta-Analysis.

ObjectiveTo systematically examine the effectiveness and tolerability of psilocybin for treating end-of-life anxiety symptoms. MethodsThe Medline, Embase, CENTRAL, and PsycINFO databases were searched up to November 25, 2020. We enrolled clinical trials investigating psilocybin for treating end-of-life anxiety symptoms. Meta-analysis was conducted using random-effects model. ResultsOverall, five studies were included, revealing that psilocybin was superior to the placebo in treating state anxiety at 1 day (Hedges’ g, -0.70; 95% confidence interval, -1.01 to -0.39) and 2 weeks (-1.03; -1.47 to -0.60) after treatment. Psilocybin was more effective than placebo in treating trait anxiety at 1 day (-0.71; -1.15 to -0.26), 2 weeks (-1.08; -1.80 to -0.36), and 6 months (-0.84; -1.37 to -0.30) after treatment. Psilocybin was associated with transient elevation in systolic (19.00; 13.58–24.41 mm Hg) and diastolic (8.66; 5.18–12.15 mm Hg) blood pressure compared with placebo. The differences between psilocybin and placebo groups with regard to allcause discontinuation, serious adverse events, and heart rates were nonsignificant. ConclusionPsilocybin-assisted therapy could ameliorate end-of-life anxiety symptoms without serious adverse events. Because of the small sample sizes of the included studies and high heterogeneity on long-term outcomes, future randomized controlled trials with large sample sizes are needed.

New Frontiers or a Bursting Bubble? Psychedelic Therapy Beyond the Dichotomy.

The publication in April 2021 of the Imperial College London Phase II study investigating the efficacy of psilocybin-assisted therapy vs. escitalopram for depression reported differences in the primary outcome measure (the QIDS-SR16) between experimental and control arms as statistically insignificant (1). However, secondary measures of depression, and other relevant measures (see Appendix), favored psilocybin to escitalopram. Soon thereafter, a range of expert commentaries offered interpretations, including that the researchers were unfortunate in their choice of pre-registered primary outcome, the trial was underpowered perhaps revealing an overconfidence in designing the study, and the limitations of depression rating measures to capture the return of positive mood and well-being. Partially in response to these publications, discussions in research and online communities have grown around the over-hyping of psychedelic treatments, bringing into focus concerns over psychedelic therapy trial methodology [for a peer-reviewed critique, see (2)]. This opinion piece explores these concerns to propose a response to this special issue’s question, “Can Psychedelic Therapies Open a New Frontier in Mental Healthcare (Or Will the Bubble Burst)?” Drawing on our experiences of working within psychedelic clinical trials and NHS psychiatry, we offer here a deflationary answer to this question, suggesting both will occur and outlining some of the facets, stakes and opportunities entailed.

Psychedelic-Assisted Psychotherapy Practices and Human Caring Science: Toward a Care-Informed Model of Treatment

Psychedelic therapies intentionally combine a caring/healing environment, psychotherapy, and psychedelic medicine as a powerful means of treating intractable conditions of depression and posttraumatic stress disorder. This article utilizes the nursing theory of human caring science, as articulated by Jean Watson, to describe the essential and fundamental human caring qualities in psychedelic therapy. By mapping these qualities onto the traits of a psychedelic therapist, articulated by Janis Phelps and illustrating them with qualitative, exemplar data from a psilocybin assisted therapy study, we have created a nursing-informed philosophical theoretical framework with which to begin to examine questions related to trust enhancement between patient and therapist, therapeutic communication of openness to patient experiences, mutual learning between therapist and patient, the influence spiritual or psychedelic practices of the therapist on outcomes, optimizing therapeutic healing environments, and care of the physical body during psychedelic therapy sessions. This article is intended to identify themes and generate hypotheses for future nursing-informed psychedelic psychotherapy research.

Effects of psilocybin-assisted therapy on treatment-resistant depression

Introduction Major depressive disorder is a highly prevalent clinical condition, affecting more than 300 million individuals worldwide. About 1/3 of patients with MDD fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression (TRD). Novel antidepressants with rapid and sustained effects on mood and cognition could represent a breakthrough in the TRD and may potentially improve or save lives. Psilocybin, a classic hallucinogen, more commonly found in the Psilocybe mushrooms has a combined serotonergic and glutamatergic action. The preliminary evidence of antidepressant effects of psilocybin-assisted therapy indicates the potential of psilocybin-assisted therapy as a novel antidepressant intervention.ObjectivesThe authors elaborate a narrative literature review about the effects of Psilocybin-based therapy on patients diagnosed with treatment-resistant depression.MethodsPubMed database searched using the terms “Treatment-Resistant Depression AND Psilocybin” and targeting clinical trials. References of selected articles and review articles were also assessed.Results2 articles evaluate psilocybin effects in 32 patients with TRD and showed that two doses of psilocybin alongside psychological support significantly reduces depressive symptoms. All patients presented some reduction in symptoms from baseline to one week after the second dose and reproduced immediate and substantial improvements in depression that ultimately could sustain up to 6 months.ConclusionsPsilocybin-assisted therapy is a very appealing new possibility in the treatment of depression. However, due to the small populations of the existing trials, future studies are needed to prove this positive association and to fully understand Psilocybin’s mechanisms of actions and effects.DisclosureNo significant relationships.

Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder

Major depressive disorder (MDD) is a substantial public health burden, but current treatments have limited effectiveness and adherence. Recent evidence suggests that 1 or 2 administrations of psilocybin with psychological support produces antidepressant effects in patients with cancer and in those with treatment-resistant depression. To investigate the effect of psilocybin therapy in patients with MDD. This randomized, waiting list-controlled clinical trial was conducted at the Center for Psychedelic and Consciousness Research at Johns Hopkins Bayview Medical Center in Baltimore, Maryland. Adults aged 21 to 75 years with an MDD diagnosis, not currently using antidepressant medications, and without histories of psychotic disorder, serious suicide attempt, or hospitalization were eligible to participate. Enrollment occurred between August 2017 and April 2019, and the 4-week primary outcome assessments were completed in July 2019. A total of 27 participants were randomized to an immediate treatment condition group (n = 15) or delayed treatment condition group (waiting list control condition; n = 12). Data analysis was conducted from July 1, 2019, to July 31, 2020, and included participants who completed the intervention (evaluable population). Two psilocybin sessions (session 1: 20 mg/70 kg; session 2: 30 mg/70 kg) were given (administered in opaque gelatin capsules with approximately 100 mL of water) in the context of supportive psychotherapy (approximately 11 hours). Participants were randomized to begin treatment immediately or after an 8-week delay. The primary outcome, depression severity was assessed with the GRID-Hamilton Depression Rating Scale (GRID-HAMD) scores at baseline (score of ≥17 required for enrollment) and weeks 5 and 8 after enrollment for the delayed treatment group, which corresponded to weeks 1 and 4 after the intervention for the immediate treatment group. Secondary outcomes included the Quick Inventory of Depressive Symptomatology-Self Rated (QIDS-SR). Of the randomized participants, 24 of 27 (89%) completed the intervention and the week 1 and week 4 postsession assessments. This population had a mean (SD) age of 39.8 (12.2) years, was composed of 16 women (67%), and had a mean (SD) baseline GRID-HAMD score of 22.8 (3.9). The mean (SD) GRID-HAMD scores at weeks 1 and 4 (8.0 [7.1] and 8.5 [5.7]) in the immediate treatment group were statistically significantly lower than the scores at the comparable time points of weeks 5 and 8 (23.8 [5.4] and 23.5 [6.0]) in the delayed treatment group. The effect sizes were large at week 5 (Cohen d = 2.5; 95% CI, 1.4-3.5; P < .001) and week 8 (Cohen d = 2.6; 95% CI, 1.5-3.7; P < .001). The QIDS-SR documented a rapid decrease in mean (SD) depression score from baseline to day 1 after session 1 (16.7 [3.5] vs 6.3 [4.4]; Cohen d = 2.6; 95% CI, 1.8-3.5; P < .001), which remained statistically significantly reduced through the week 4 follow-up (6.0 [5.7]; Cohen d = 2.3; 95% CI, 1.5-3.0; P < .001). In the overall sample, 17 participants (71%) at week 1 and 17 (71%) at week 4 had a clinically significant response to the intervention (≥50% reduction in GRID-HAMD score), and 14 participants (58%) at week 1 and 13 participants (54%) at week 4 were in remission (≤7 GRID-HAMD score). Findings suggest that psilocybin with therapy is efficacious in treating MDD, thus extending the results of previous studies of this intervention in patients with cancer and depression and of a nonrandomized study in patients with treatment-resistant depression. ClinicalTrials.gov Identifier: NCT03181529.

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

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. 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. 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. 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.

Psilocybin-assisted therapy for depression: How do we advance the field?

In the quest for new treatment options for depression, attention is being paid to the potential role of psychedelic drugs. Psilocybin is of particular interest given its mechanism of action, its benefits in early trials and its relatively low side effects burden. This viewpoint outlines a number of key issues that remain to be elucidated about its potential use in the clinical environment, including clarification of the profile of people most likely to benefit and those who might experience adverse effects, longer-term outcomes and the role of psychotherapeutic input alongside the drug itself. There are also opportunities to understand better, the neurobiology underpinning its effects.

Psilocybin-assisted therapy of major depressive disorder using Acceptance and Commitment Therapy as a therapeutic frame

Psychedelic-assisted therapy is based on the premise that psychedelic substances can act as catalysts or adjuncts to psychotherapeutic processes. Recent clinical trials involving psychedelic-assisted therapy have generally employed a similar three-part structure consisting of preparation, support during the dosing sessions, and subsequent “integration.” However, the content of these sessions and the frame through which the therapists approach participants and understand the clinical process has thus far been inconsistent among studies. In designing a manualized therapy protocol for a small clinical trial of psilocybin-assisted therapy for major depressive disorder, our group sought to delineate an explicit and replicable, evidence-based model that intentionally builds upon both the neurobiological actions of the medication and the phenomenology of the drug experience. Having identified considerable concordance in proposed mechanisms of change between Acceptance and Commitment Therapy (ACT) and psilocybin therapy, we employed ACT as an overarching psychotherapeutic framework. We hypothesize that the psilocybin experience can provide direct experiential contact with ACT processes that increase psychological flexibility, and that these deeply felt experiences may in turn be reinforced during ACT-informed follow-up therapy sessions. In this paper, we describe the rationale for selecting ACT, areas of potential synergism between ACT and psilocybin-therapy, the basic structure of our treatment model, and limitations to this approach.

Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia.

Psilocybin-assisted therapy for anxiety and depression: implications for euthanasia.

The Definition of Healing Depends on How One Defines Health

While 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.In 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.NIH-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).The study lacks a control group, relies on a self-report measure, and uses a relatively small sample size with limited diversity that restricts generalizability.Findings 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.

The cyclic psychedelics.

Back to table of contents Previous article Next article ArticleNo AccessThe Cyclic PsychedelicsSIDNEY COHENSIDNEY COHENSearch for more papers by this authorPublished Online:1 Apr 2006https://doi.org/10.1176/ajp.125.3.393AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail "The Cyclic Psychedelics." American Journal of Psychiatry, 125(3), pp. 393–394 Access content To read the fulltext, please use one of the options below to sign in or purchase access. Personal login Institutional Login Sign in via OpenAthens Register for access Purchase Save for later Item saved, go to cart PPV Articles - American Journal of Psychiatry $35.00 Add to cart PPV Articles - American Journal of Psychiatry Checkout Please login/register if you wish to pair your device and check access availability. Not a subscriber? Subscribe Now / Learn More PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development. Need more help? PsychiatryOnline Customer Service may be reached by emailing [email protected] or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.). FiguresReferencesCited byDetailsCited byPsychotherapists' openness to engage their patients in Psilocybin-Assisted Therapy for mental health treatmentJournal of Affective Disorders, Vol. 323Higher Wisdom: Eminent Elders Explore the Continuing Impact of PsychedelicsJournal of Nervous & Mental Disease, Vol. 194, No. 7Endeavour, Vol. 22, No. 1What is Drug Abuse?1 January 1978 | Journal of Drug Issues, Vol. 8, No. 1 Volume 125Issue 3 September 1968Pages 393-394 Metrics PDF download History Published online 1 April 2006 Published in print 1 September 1968