Psilocybin-assisted Psychotherapy Research Articles

Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy

Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these ‘real-world’ patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, Mage = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report

Psilocybin has reemerged as a promising treatment for difficult-to-treat depression (DTD). Although there is limited evidence regarding interactions between psilocybin and other psychotropic drugs, clinical trials require that patients discontinue their antidepressants before study entry to isolate the benefits of psilocybin and to minimize the risk of adverse events. We present the first case of an adult patient with DTD who received psilocybin-assisted psychotherapy (PAP) in combination with two serotoninergic antidepressants (duloxetine and vortioxetine). Since he displayed a partial response after the first PAP session, he agreed to discontinue duloxetine (but refused to stop vortioxetine) before the second PAP session to see if it could improve the therapeutic efficacy of psilocybin. However, his anxiety and depressive symptoms worsened. Psilocybin was well-tolerated in both PAP sessions; mild headaches were the main adverse effects experienced by the patient, and there were no cardiovascular safety concerns. This case report suggests that serotoninergic antidepressants combination with psilocybin appears to be safe and that antidepressant discontinuation prior to PAP may not be necessary. Since the continuation of antidepressants during PAP has the potential to improve treatment acceptability and accessibility, future research should assess whether psilocybin can be administered concurrently with antidepressants.

Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin

Psilocybin-assisted psychotherapy (PAP) has been associated with antidepressant effects. Trials to date have typically excluded participants with complex presentations. Our aim was to determine the feasibility of PAP in a complex population, including high levels of treatment resistance in major depressive and bipolar disorder and patients with baseline suicidality and significant comorbidity. We also evaluated flexible repeated doses over a 6-month period. Adults with treatment-resistant depression as part of major depressive or bipolar II disorder without psychosis or a substance use disorder were eligible to participate. Subjects were randomized to immediate treatment or waitlist control, with all eventually receiving PAP. Participants had one, two, or three psilocybin sessions with a fixed doseof 25mg. Each dose was accompanied by preparation and integration psychotherapy sessions. Acceptability, safety, tolerability, and efficacy were evaluated (this study was registered at ClinicalTrials.gov: NCT05029466). Participants were randomized to immediate treatment (n=16) or delayed treatment (n= 14). 29/30 were retained to the week-2 primary endpoint. Adverse events were transient, with no serious adverse events. Greater reductions in depression severity as measured by the Montgomery-Åsberg Depression Rating Scale (MADRS) were observed in the immediate treatment arm compared to the waitlist period arm with a large hedge's g effect size of 1.07 (p<0.01). Repeated doses were associated with further reductions in MADRS scores compared to baseline. PAP was feasible in complex patients with preliminary antidepressant efficacy and adequate safety and tolerability. Repeated doses were associated with greater reductions in depression severity. This work was funded by Brain and Cognition Discovery Foundation(BCDF), Usona, and Braxia Scientific.

A Systematic Review of Interventions forDemoralization in Patients with Chronic Diseases.

Demoralization, a significant mental health concern in patients with chronic diseases, can have a large impact on physical symptom burden and quality of life. The present review aimed to evaluate the effectiveness of interventions for demoralization among patients with chronic diseases. PubMed, Scopus, Embase, and Web of Science were systematically searched. Research on providing interventions to patients with chronic diseases that included quantitative data on demoralization was then systematically reviewed. Fourteen studies were included, most of which considered demoralization as a secondary outcome. Interventions included evidence-based meaning-centered psychotherapy, dignity therapy, psilocybin-assisted psychotherapy, and others. Ten studies used randomized controlled designs. Six of these investigated evidence-based meaning-centered therapy, and four investigated dignity therapy, showing the best empirical support for these intervention types. Most studies showed significant impacts on demoralization in patients with chronic diseases. This systematic review provides insights into potential psychological interventions for reducing demoralization in patients with chronic diseases. Randomized controlled designs and adequately powered samples, with demoralization as the primary outcome, are needed to more clearly evaluate its effectiveness.

A Neuroanatomic and Pathophysiologic Framework for Novel Pharmacological Approaches to the Treatment of Post-traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating disorder inflicting high degrees of symptomatic and socioeconomic burdens. The development of PTSD results from a cascade of events with contributions from multiple processes and the underlying pathophysiology is complex, involving neurotransmitters, neurocircuitry, and neuroanatomical pathways. Presently, only two medications are US FDA-approved for the treatment of PTSD, both selective serotonin reuptake inhibitors (SSRIs). However, the complex underlying pathophysiology suggests a number of alternative pathways and mechanisms that may be targets for potential drug development. Indeed, investigations and drug development are proceeding in a number of these alternative, non-serotonergic pathways in an effort to improve the management of PTSD. In this manuscript, the authors introduce novel and emerging treatments for PTSD, including drugs in various stages of development and clinical testing (BI 1358894, BNC-210, PRAX-114, JZP-150, LU AG06466, NYV-783, PH-94B, SRX246, TNX-102), established agents and known compounds being investigated for their utility in PTSD (brexpiprazole, cannabidiol, doxasoin, ganaxolone, intranasal neuropeptide Y, intranasal oxytocin, tianeptine oxalate, verucerfont), and emerging psychedelic interventions (ketamine, MDMA-assisted psychotherapy, psilocybin-assisted psychotherapy), with an aim to examine and integrate these agents into the underlying pathophysiological frameworks of trauma-related disorders.

Psilocybin-assisted psychotherapy for cancer patients

Despite significant advances in symptom management for patients affected by serious illness, physicians lack effective legal treatments for individuals suffering from demoralization, death anxiety, and existential distress. Psilocybin-assisted psychotherapy employs psilocybin-containing mushrooms or synthetic psilocybin grounded in indigenous traditions and within the context of a therapeutic mindset and environment ("set and setting") to achieve altered states of consciousness that promote healing and psychospiritual growth while reducing suffering. Current research evidence suggests that this form of therapy could serve as a safe and effective therapeutic tool for such patients.&#x0D; This presentation will describe a case series of patients with advanced cancer who received physician-supervised home-based psilocybin-assisted psychotherapy in Montreal, Canada. Our experience postulates the safety and efficacy of this laborious treatment process. By executing this clinical practice in the public healthcare system of Quebec for the first time, we have made an attempt to provide equitable access to these clinical therapies. Having performed these treatments outside the context of clinical trials, we have been able to tailor the therapeutic frame and treatment approach to a more patient-centric and culturally-informed manner. That being said, given the existing ​societal discrimination and stigma against this form of therapy, including by healthcare professionals, there remain further barriers to overcome in the equitable provision of care, especially to certain segments of the population. ​The authors will discuss these and potential solutions to addressing them.

Palliative care patients' attitudes and openness towards psilocybin-assisted psychotherapy for existential distress.

Patients with incurable illnesses often experience existential distress, profoundly impacting their well-being. Current medical approaches have limitations in addressing these burdens. Psilocybin, a promising psychedelic compound, may offer therapeutic benefits. This pilot survey study aimed to investigate the attitudes and openness toward psilocybin-assisted psychotherapy (PAT) among patients with incurable illnesses. The objective is to assess patients' attitudes toward PAT and identify potential barriers and concerns, including exploring the association between beliefs in psilocybin's therapeutic benefits and interest in receiving this treatment. The survey study was conducted at the Tampa General Hospital Palliative Care Outpatient office in the United States. Participants were 32 English-fluent patients, aged 18 or older, with incurable illnesses. The survey included demographic questions, a validated tool to measure existential distress, and questions about knowledge and concerns regarding psilocybin. Attitudes toward PAT and interest in its future use were assessed using Likert scale responses. Among the 31 analyzed participants, 51.6% expressed interest in future psilocybin treatment, while 32.3% did not indicate interest. Belief in the psilocybin's therapeutic benefits for stress and anxiety significantly correlated with interest in use. Concerns included risk of psychosis, lack of trained providers, and potential for exploitation. No demographic factors were associated with interest or levels of distress. This pilot study provides insights into the attitudes and concerns toward PAT among patients with incurable illnesses. Over half of participants expressed interest. However, concerns regarding its use were identified, with patients' concern for the risk of exploitation associated with PAT as an especially novel concern documented in this patient population. This highlighted the need for further education of risks and benefits or PAT by trained clinicians and rigorous training of clinicians with the establishment of safeguards against exploitation. Further research is necessary to explore the potential benefits of PAT and related non-psilocybin psychedelic compounds in addressing existential distress among patients with incurable illnesses.

Psilocybin-assisted psychotherapy for the treatment of PTSD in UK armed forces veterans: A feasibility study protocol

Veterans with posttraumatic stress disorder (PTSD) have poorer treatment responses than the general public, which suggests that alternative treatment approaches may be required to support veterans who do not benefit from standard evidence-based approaches. Psilocybin-assisted psychotherapy (PAP) involves administration of psilocybin in a supportive therapeutic setting. PAP has been evidenced to be safe and feasible in a range of recent studies supporting individuals with mental health difficulties including depression, obsessive compulsive disorder, and anxiety. This protocol paper outlines a study aiming to explore the safety and feasibility of PAP for veterans (n = 8) with PTSD. Participants will be offered two dosing sessions of 25 mg of psilocybin, followed by Cognitive Processing Therapy. Eligible participants are UK military veterans who meet criteria for current PTSD and who have completed thorough physical and psychological assessment. The study is subject to ethical approval by the Health Research Authority and Medicines and Healthcare products Regulatory Agency combined review.

HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients with Cancer.

Psilocybin-assisted psychotherapy shows promise in treating depression and existential distress in people with serious medical illness. However, its individual-based methodology poses challenges for scaling and resource availability. The HOPE trial (A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients with Cancer) is an IRB-approved open-label feasibility and safety pilot study examining psilocybin-assisted group therapy in cancer patients with a DSM-5 depressive disorder (including major depressive disorder as well as adjustment disorder with depressed mood). We report here the safety and clinical outcome measures including 6-month follow up data. Outcome measures were collected at baseline, 2-week and 26-weeks post intervention. The study involved three group preparatory sessions, one high-dose (25mg) group psilocybin session, and three group integration sessions with cohorts of four participants over a three week intervention. 12 participants completed the trial. No serious adverse events attributed to psilocybin occurred. The primary clinical outcome measures of change in symptoms of depression on the clinician administered 17-item-HAM-D showed clinically substantial decrease in HAM-D scores from baseline to the 2-week timepoint (21.5 to 10.09, p<0.001) and the 26-week timepoint (21.5 to 14.83, p=0.006). Six out of twelve participants met criteria for remission at 2 weeks, as defined by HAM-D < 7, three out twelve demonstrated a clinically significant change (4-6 points), and eight out of twelve demonstrated a clinically substantial change (7-12 points). This pilot study demonstrated the safety, feasibility, and possible efficacy of psilocybin-assisted group therapy for cancer patients dealing with depressive symptoms. Based on demonstrated efficacy and significant reductions in therapist time, future investigations with the group therapy model are warranted. This article describes a single-arm, open-label pilot study of psilocybin-assisted group therapy for patients dealing with symptoms of depression associated with a cancer diagnosis. Results indicate that this intervention was safe and feasible with a suggestion of efficacy. Group-format psilocybin-assisted therapy is a promising methodology that addresses challenges of scalability.

Psilocybin-assisted psychotherapy for treatment-resistant depression: Which psychotherapy?

This perspective paper explores the choice of psychotherapy for psilocybin-assisted psychotherapy for treatment-resistant depression. There is evidence to support the use of some psychotherapies in treating 'treatment-resistant' depression, and emerging evidence for the efficacy of psilocybin. The next step which is the focus of this paper is to identify psychotherapies that are both effective and congruent with the psilocybin experience. The evidence for the efficacy of the psychotherapies is drawn from a Cochrane review and the analysis of their congruence with the psilocybin experience is drawn from a qualitative meta-synthesis of the experience of psilocybin. The paper will examine whether three one-to-one psychotherapies identified as effective in the treatment of treatment-resistant depression are compatible with the psilocybin experience. Each psychotherapy will be examined in relation to its congruence with the qualitative evidence that suggests the choice of psychotherapy needs to give priority to the subjective experience, facilitate emotional processing, support connectedness with others, acceptance of the self as emotional and support change based on the person's insights into their relationships with others and the world in which they live. We conclude that interpersonal psychotherapy and intensive short-term dynamic psychotherapy align with that experience, although others are currently being trialled.

"But the reality is it's happening": A qualitative study of eating disorder providers about psilocybin-assisted psychotherapy.

This study invited providers who care for patients with eating disorders to inform engagement, communication, and collaboration with psilocybin-assisted psychotherapy interventions. Medical and mental health providers who treat patients with eating disorders were recruited via professional referral networks and participant driven sampling from across California to participate in one of five focus groups. Discussion topics included prior knowledge of psychedelic therapy, interest/concerns related to psilocybin therapy, and opportunities for collaboration. Study team members completed iterative rounds of coding with a grounded theory approach. A total of 32 participants reported a range of familiarity with psychedelics. Some raised concerns about the risks of administering psilocybin to malnourished patients and to those with psychological comorbidities. Despite these concerns, participants were hopeful to see psilocybin therapy as a treatment for patients with eating disorders. In anticipating challenges, providers had concerns about equity in access to care among publicly insured and non-English speaking patients. They requested opportunities for continuing education about psilocybin therapy. Our findings demonstrate provider interest in psilocybin therapy for the treatment of patients with eating disorders. As psilocybin therapy interventions are developed, providers caring for patients with eating disorders value collaboration to improve longitudinal patient outcomes. This study invited healthcare providers of patients with eating disorders to discuss their thoughts around the use of psilocybin-assisted psychotherapy in this population. Findings will help inform emerging psilocybin therapy clinical trials with the goal of successful translation and adoption in real world clinical settings.

Transient Elevation of Plasma Glucocorticoids Supports Psilocybin-Induced Anxiolysis in Mice.

While correlations between drug-induced cortisol elevation, self-reported anxiety, and treatment outcomes have been reported for human studies during psilocybin-assisted psychotherapy, the mechanistic relationship between psychedelic-associated alterations in plasma glucocorticoid responses and the time course of anxious responsiveness remains unclear. Using rodents, both time-bound manipulation of glucocorticoid concentrations and assessment of anxiety-like behaviors can be achieved. Here, 3 mg/kg IP psilocybin was found to have anxiolytic-like effects in C57BL/6 male mice at 4 h after treatment. These effects were not altered by pretreatment with a 5-HT2A antagonist but were blunted by pretreatment with a glucocorticoid receptor antagonist or suppression of psilocybin-induced corticosterone elevations. Anxiolytic-like effects were also observed at 4 h following treatment with the nonpsychedelic 5-HT2A agonist lisuride at a dose causing a similar increase in plasma glucocorticoids as that seen with psilocybin, as well as following stress-induced (via repeated injection) glucocorticoid release alone. Psilocybin's anxiolytic-like effects persisted at 7 days following administration. The long-term anxiolytic effects of psilocybin were lost when psilocybin was administered to animals with ongoing chronic elevations in plasma corticosterone concentrations. Overall, these experiments indicate that acute, resolvable psilocybin-induced glucocorticoid release drives the postacute anxiolytic-like effects of psilocybin in mice and that its long-term anxiolytic-like effects can be abolished in the presence of chronically elevated plasma glucocorticoid elevations.

Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model.

There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

ID: 212703 Augmenting rTMS With Psilocybin-Assisted Psychotherapy (PAP) for PTSD: A Proof-of-Concept Study Design

Post-traumatic stress disorder (PTSD) is a debilitating mental illness, often with a chronic course and major comorbidities such as treatment-resistant depression (TRD), drug abuse, and suicidality. Current treatments have a long time-to-remission and high nonresponse and recurrence rates; novel and efficacious treatments are necessary. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, FDA-approved, and efficacious treatment for TRD with few side effects. It is emerging as a treatment for PTSD; however, as a monotherapy its efficacy is neither high nor durable1. Recently, our group has combined rTMS with mindfulness therapy (TIMBER) for TRD and PTSD, with promising results2. Other emerging options are psychedelics, especially psilocybin, which has been efficacious for TRD3 and may hold promise for PTSD due to unique properties such as agonism of not only 5-HT2ARs (empathy, openness, creativity), but also 5HT1ARs (anxiolytic) and D1Rs (pro-cognitive) as well, unlike other psychedelics4. These additional properties make it uniquely suitable for psilocybin-assisted psychotherapy (PAP) in PTSD. Psilocybin and rTMS share one common mechanism of action: dampening the overactive default mode network in PTSD1,5. However, unlike MDMA, psilocybin has not yet been studied for PTSD4. We hypothesize that PAP combined with rTMS will have the most robust effects on PTSD, acting synergistically to ameliorate PTSD symptoms and extend the duration of response as well.

Neurobiological Correlates of Psilocybin Response in Depression.

Objective: To synthesize the neurobiological basis of brain-resetting effects of psilocybin and identify neuroimaging correlates of psilocybin response in depressed patients.Data Sources: MEDLINE(R), Embase, APA PsycINFO, Cochrane, and CINAHL were systematically searched on June 3, 2022, with no date restrictions using the following string: (psilocybin) AND (psychedelics) AND (MRI) OR (fMRI)) OR (PET)) OR (SPECT)) OR (imaging)) OR (neuroimaging)).Study Selection: After duplicates were removed from 946 studies, 391 studies remained, of which 8 qualified for full-text analysis, but only 5 fulfilled the eligibility criteria of randomized, double-blind, or open-label neuroimaging study with psilocybin treatment in depressed patients.Data Extraction: The Covidence platform was used for deduplication and bias assessment. The a priori data points included concomitant psychological intervention, modality of neuroimaging technique, changes in depression scores, brain functional changes, and association between functional and psilocybin response. Assessment bias was assessed with the standard risk of bias tool for randomized controlled trials and the tool for risk of bias in nonrandomized studies of interventions.Results: Four studies were open-label, and one was a combined open-label and randomized controlled trial using functional magnetic resonance imaging. Psilocybin-assisted psychotherapy was administered in 3 studies, 1 in refractory and 2 in nonrefractory patients. The remaining 2 studies were in refractory patients. The transient increase in psilocybin-induced global connectivity in major neural tracts and specific areas of brain activation was associated with antidepressant response.Conclusions: Transient functional brain changes with psilocybin therapy resemble the "brain reset" phenomenon and may serve as the putative predictors of psilocybin antidepressant response.

Psilocybin-Assisted Treatment of Depression, Anxiety and Substance use Disorders: Neurobiological Basis and Clinical Application

Successful therapy of mental disorders is very important in view of the high level of suffering of those affected. Since established pharmaceutical and psychotherapeutic approaches do not lead to the desired improvement in all cases, complementary or alternative treatment methods are intensively researched. Psilocybin-assisted psychotherapy seems particularly promising, and has been approved in the USA for larger clinical trials. Psilocybin belongs to the group of psychedelics and influences psychological experiences. In assisted therapy, psilocybin is administered in controlled doses under medical supervision to patients with different mental disorders. In the studies conducted so far, longer-term positive effects could be shown after just one or a few doses. In order to provide a better understanding of the potential therapeutic mechanisms, this article will first describe neurobiological and psychological effects of psilocybin. To better assess the potential of psilocybin-assisted psychotherapy for various disorders, clinical studies conducted so far with patients administered psilocybin are reviewed.

Exploring psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder.

Methamphetamine use disorder is a chronic relapsing condition associated with substantial mental, physical, and social harms and increasing rates of mortality. Contingency management and psychotherapy interventions are the mainstays of treatment but are modestly effective with high relapse rates, while pharmacological treatments have shown little to no efficacy. Psilocybin-assisted psychotherapy is emerging as a promising treatment for a range of difficult-to-treat conditions, including substance use disorders; however, no studies have yet been published looking at psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Here we review the rationale for psilocybin-assisted psychotherapy as a potential treatment for this indication, and describe practical considerations based on our early experience designing and implementing four separate clinical trials of psilocybin-assisted psychotherapy for methamphetamine use disorder.

The therapeutic potential of psychedelics: the European regulatory perspective

In the EU, mental health problems affect more than one in six people with considerable impacts for individuals and society and economic costs that exceed 4% of gross domestic product across the EU. 1 Organisation for Economic Co-operation and DevelopmentA new benchmark for mental health systems: tackling the social and economic costs of mental ill-health. OECD Health Policy Studies. OECD Publishing, Paris2021 Google Scholar , 2 Organisation for Economic Co-operation and DevelopmentEuropean UnionHealth at a glance: Europe 2018: state of health in the EU cycle. OECD Publishing, Paris2018 Google Scholar There is a need for effective, safe new treatments for mental disorders. In the past decade there has been a renewed interest worldwide in psychedelics as potential treatments for various mental health conditions, 3 Tullis P The rise of psychedelic psychiatry. Nature. 2021; 589: 506-509 Crossref PubMed Scopus (16) Google Scholar such as treatment-resistant depression, addictive disorders, post-traumatic stress disorder, and end-of-life psychological distress. 4 Goodwin GM Aaronson ST Alvarez O et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387: 1637-1648 Crossref PubMed Scopus (17) Google Scholar , 5 Johnson MW Garcia-Romeu A Griffiths RR Long-term follow-up of psilocybin-facilitated smoking cessation. Am J Drug Alcohol Abuse. 2017; 43: 55-60 Crossref PubMed Scopus (225) Google Scholar , 6 Agin-Liebes GI Malone T Yalch MM et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020; 34: 155-166 Crossref PubMed Scopus (107) Google Scholar , 7 Holze F Gasser P Müller F et al. Lysergic acid diethylamide–assisted therapy in patients with anxiety with and without a life-threatening illness: a randomized, double-blind, placebo-controlled phase II study. Biol Psychiatry. 2023; 93: 215-223 Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar These psychoactive compounds have overlapping effects via different mechanisms of actions which, in the context of therapeutic use, remain to be established. 8 Grieco SF Castrén E Knudsen GM et al. Psychedelics and neural plasticity: therapeutic implications. J Neurosci. 2022; 42: 8439-8449 Crossref PubMed Scopus (0) Google Scholar Psychedelic substances induce alterations of consciousness, including visual effects, transient feelings of oneness with the universe, transcendence of time and space, and ego dissolution, but can also induce anxiety and psychological distress, 9 Reiff CM Richman EE Nemeroff CB et al. Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of ResearchPsychedelics and psychedelic-assisted psychotherapy. Focus (Am Psychiatr Publ). 2021; 19: 95-115 PubMed Google Scholar which can be alleviated through interpersonal support during administration. 10 Barrett FS Bradstreet MP Leoutsakos JS Johnson MW Griffiths RR The Challenging Experience Questionnaire: characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol. 2016; 30: 1279-1295 Crossref PubMed Scopus (0) Google Scholar , 11 Johnson M Richards W Griffiths R Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008; 22: 603-620 Crossref PubMed Scopus (467) Google Scholar Classic psychedelics act via 5-HT2A receptor agonism and include mescaline, N,N-dimethyltryptamine, lysergic acid diethylamide, and psilocybin. Atypical psychedelics (eg, 3,4-methylenedioxymethamphetamine and ketamine), have different pharmacological mechanisms of action and also differ in terms of legal status (eg, ketamine and esketamine are approved as medicines in the EU). We do not, therefore, include atypical psychedelics in this discussion of the European regulatory context for potential therapeutic uses of psychedelics in mental disorders. The issues we raise here are informed by our work for the European Medicines Agency (EMA), the EMA's Central Nervous System Working Party, and the European College of Neuropsychopharmacology (ECNP).

The Therapeutic Potential of Psilocybin in Alcohol Use Disorder Recovery: A Literature Review

Introduction: Psilocybin (the active compound found in “magic mushrooms”) has been an area of recent focus in the academic and psychiatric community on account of its potential in treating a spectrum of substance use and concurrent disorders (SUCDs). This paper posits a literature review of the current research pertaining to psilocybin in treating alcohol use disorder (AUD) through a form of therapy known as psilocybin-assisted psychotherapy (PAP). Methods: To undertake this study, we performed a literature review of peer-reviewed studies examining the efficacy of psilocybin in treating AUD through PAP. Inclusion criteria for papers included papers published from 2010-present, peer-reviewed sources, and clinical studies and controlled experiments observing AUD in PAP settings. Exclusion criteria used in screening papers included those focusing on other psychedelic compounds and experiments examining psilocybin efficacy in non-PAP settings. Results: Our overview of the extant literature has determined that psilocybin has strong therapeutic potential for use in PAP settings to treat AUD. Furthermore, we have identified three principal pathways through which psilocybin can elicit promising effects: neurobiological alterations (e.g., neuroplastic effects), behavioral and psychological improvements (e.g., increased receptivity towards cognitive therapies), and spiritual development (e.g., spiritual encounters improving abstinence). Discussion: The use of psilocybin in the clinical context of AUD treatment is well supported in the field of psychedelic research. Behavioural therapies are of high importance when engaging in use of psilocybin for treating AUD patients. There are certain limitations to the applications of PAP, such as predisposition to certain mental illnesses, however, the future of psilocybin therapy is expansive, ranging from subsequent animal testing to microdosing experiments. Conclusion: While our literature review bears positive findings, we encourage further research and clinical trials to be conducted to establish a larger body of evidence towards supporting or rejecting the validity of PAP. Should future research validate the efficacy of PAP for AUD treatment, therapists and psychiatrists could have another tool in their treatment reserve to assist people with SUCDs.

Psilocybin-Assisted Psychotherapy as a Potential Treatment for Eating Disorders: a Narrative Review of Preliminary Evidence.

Eating disorders (ED) are a group of potentially severe mental disorders characterized by abnormal energy balance, cognitive dysfunction and emotional distress. Cognitive inflexibility is a major challenge to successful ED treatment and dysregulated serotonergic function has been implicated in this symptomatic dimension. Moreover, there are few effective treatment options and long-term remission of ED symptoms is difficult to achieve. There is emerging evidence for the use of psychedelic-assisted psychotherapy for a range of mental disorders. Psilocybin is a serotonergic psychedelic which has demonstrated therapeutic benefit to a variety of psychiatric illnesses characterized by rigid thought patterns and treatment resistance. The current paper presents a narrative review of the hypothesis that psilocybin may be an effective adjunctive treatment for individuals with EDs, based on biological plausibility, transdiagnostic evidence and preliminary results. Limitations of the psychedelic-assisted psychotherapy model and proposed future directions for the application to eating behavior are also discussed. Although the literature to date is not sufficient to propose the incorporation of psilocybin in the treatment of disordered eating behaviors, preliminary evidence supports the need for more rigorous clinical trials as an important avenue for future investigation.