Efficacy Of Psilocybin Research Articles

Masking Influences: A Systematic Review of Placebo Control and Masking in Psychedelic Studies.

Psychedelic-assisted therapy is becoming increasingly acknowledged as an effective therapeutic intervention for various psychiatric illnesses. However, the evaluation of masking success is rarely reported in trials. The objective of the present systematic review was to evaluate placebo-control and masking in studies exploring psychedelic-assisted therapy. Nine (k = 9) studies dating between January 2010 and March 2023 were retrieved using six databases, following strict inclusion and exclusion criteria. The results show that almost 78% of the studies had, at best, "poor" masking success. At the same time, 60% of active placebo and 75% of inactive placebo studies showed large effect sizes. In other words, masking influences, including benign unmasking, cannot be excluded. We therefore conclude that efficacy of psilocybin, Ayahuasca, or LSD is only one of the possible interpretations of large, positive changes in symptomatology for patients suffering from, for example, alcohol use disorder, anxiety with or without life-threatening disease, anxiety and/or depression with life-threatening cancer, treatment-resistant depression or major depressive disorder. We recommend care be taken to increase successful masking procedures and discuss alternative treatment designs to better control for potential masking influences.

Insights into the efficacy of psilocybin in treating depression and other disorders

This article discusses evidence that offers insights into the effects of psilocybin on the brain and its potential role in alleviating the symptoms of some neuropsychiatric conditions.

Psilocybin in the Management of Substance Use Disorders: A Summary of Current Evidence

Background: Following clinical trials on psilocybin for the treatment of pain, anxiety, and depression in patients with cancer, scientific interest emerged in its use for substance use disorders. Methods: In this review of the literature, we summarize available trials looking at the use of psilocybin in addiction Results: One double-blind, randomized clinical trial looked at the effect of psilocybin on heavy drinking in adults diagnosed with alcohol dependence. Several trials are currently ongoing to assess psilocybin’s efficacy in the management of different SUDs. Otherwise, the current evidence is insufficient to derive any conclusions on the possible efficacy of psilocybin in substance use disorders. Conclusions: More well-powered, blinded, randomized controlled trials are needed to investigate the possible therapeutic effects of psilocybin in addiction while identifying the appropriate conditions that promote its safe use.

Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects. We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc). Conducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes. Our findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats. Our study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.

Therapeutic potential of fungally derived psilocybin extract in morphine-dependent mice: A research protocol

Introduction: Psilocybin is a naturally occurring tryptamine derivative psychedelic compound potently produced by fungi members of the genus Psilocybe. Previous literature has highlighted psilocybin as a serotonin 2A receptor agonist with striking effects on neural plasticity and cognition. Recent studies explore the usage of psilocybin in addressing addictive behaviours and substance abuse. Small psilocybin doses have shown promising anti-addictive and withdrawal-minimizing properties in alcohol-dependent mice. This study will further investigate this emerging field through a novel lens. We propose a novel study to elucidate psylobicin’s effect on opioid addiction in mouse models. Methods: Morphine-dependent mice will be administered either saline vehicle or differing doses of psilocybin during a morphine-available period to monitor consumption. Though mechanistically ambiguous, psilocybin’s hypothesized entry into serotonin-dependent stress-conciliating pathways supports the hypothesis that mean morphine consumption will decrease in a dose-dependent manner to similar levels to popular opioid receptor agonist therapeutics, such as methadone. Furthermore, we will examine psilocybin's impact on withdrawal behaviour. After morphine deprival on dependent mice, sustained doses of psilocybin, methadone, and positive and negative controls will be administered. Results: By analyzing stress-indicative behaviours in mice, the efficacy of psilocybin as a withdrawal assistance agent can be elucidated. Results from the morphine-dependent mice are expected to consume less morphine than controls, and minimize withdrawal symptoms at a similar level to popular therapeutic options like methadone. Discussion: If successful, psilocybin’s anti-addictive potential will help provide a cheaper, more accessible therapeutic option in addressing the growing opioid crisis. Furthermore, controlled psilocybin dosages have been shown to have lesser dependence potential compared to modern opioid addiction therapeutics. Conclusion: This study’s novel approach will provide meaningful support in exploring the growing field of mycology and its potential to address other substance use disorders. Future research may explore outside the limitations of the mouse model, like the oral administration of the compounds rather than intraperitoneal injection.

Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis

ObjectiveTo determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs.DesignSystematic review and meta-analysis.Data sourcesFive electronic databases of published literature (Cochrane Central Register of Controlled Trials,...

Diagnosis & Treatment Options in Depression with comorbid Dementia

AbstractDepression and Dementia Professor Allan H Young, Head of Academic Psychiatry, Maudsley Hospital and King’s College London UK. allan.young@kcl.ac.uk Mood Disorders are common, encompass cognitive impairments and occur in later life including first onset after the age of 50 years of age. There is a considerable overlap between depression and dementia. The relationship between depression and dementia will be reviewed and the implications for diagnosis and treatment will be discussed. Novel agents targeting alternative neurotransmitter pathways and inflammatory processes are promising potential treatment options. Neurostimulation treatments play a role with ECT at present having the best utility for late onset depression. Key words: depression, dementia, antidepressants; pharmacotherapyDisclosure of Interest A. Young Grant / Research support from: Principal Investigator in the Restore-Life VNS registry study funded by LivaNova. Principal Investigator on ESKETINTRD3004: “An Open-label, Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression.” Principal Investigator on “The Effects of Psilocybin on Cognitive Function in Healthy Participants” Principal Investigator on “The Safety and Efficacy of Psilocybin in Participants with Treatment-Resistant Depression (P-TRD)” Principal Investigator on “A Double-Blind, Randomized, Parallel-Group Study with Quetiapine Extended Release as Comparator to Evaluate the Efficacy and Safety of Seltorexant 20 mg as Adjunctive Therapy to Antidepressants in Adult and Elderly Patients with Major Depressive Disorder with Insomnia Symptoms Who Have Responded Inadequately to Antidepressant Therapy.” (Janssen) Principal Investigator on “ An Open-label, Long-term, Safety and Efficacy Study of Aticaprant as Adjunctive Therapy in Adult and Elderly Participants with Major Depressive Disorder (MDD).” (Janssen) Principal Investigator on “A Randomized, Double-blind, Multicentre, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants with Major Depressive Disorder (MDD) with Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy.” Principal Investigator on “ A Study of Disease Characteristics and Real-life Standard of Care Effectiveness in Patients with Major Depressive Disorder (MDD) With Anhedonia and Inadequate Response to Current Antidepressant Therapy Including an SSRI or SNR.” (Janssen) UK Chief Investigator for Compass; COMP006 & COMP007 studies UK Chief Investigator for Novartis MDD study MIJ821A12201, Consultant of: Paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Flow Neuroscience, Novartis, Roche, Janssen, Takeda, Noema pharma, Compass, Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, Sage, Neurocentrx

Psychedelic Mushrooms: The Use of Psilocybin in the Treatment of Mental Disorders

Psychedelics are a class of hallucinogenic drugs. They have been explored particularly for treatment-resistant psychiatric illnesses. In recent years, advances in psychopharmacology have benefited thousands of patients with some type of mental disorder. Preliminary evidence has shown that psilocybin has shown promise in the treatment of psychiatric disorders, with the support of qualified doctors. Recent clinical studies have reported marked improvements in mental health in psilocybinassisted psychotherapy. In many studies, the safety and efficacy of psilocybin have been the primary objectives to show that it is a safe and valid therapeutic alternative to other forms of psychiatric medications. Currently, some studies prove that psilocybin is safe in a controlled environment. However, the use of psilocybin needs to be further studied to determine the efficacy and safety of potential applications in medicine.

Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes

Bipolar II disorder (BDII) is a debilitating condition frequently associated with difficult-to-treat depressive episodes. Psilocybin has evidence for rapid-acting antidepressant effects but has not been investigated in bipolar depression. To establish the safety and efficacy of psilocybin in patients with BDII in a current depressive episode. This was a 12-week, open-label nonrandomized open-label trial conducted at Sheppard Pratt Hospital. Participants aged 18 to 65 years with BDII, a current depressive episode longer than 3 months, and documented insufficient benefit with at least 2 pharmacologic treatments during the current episode were invited to participate. Of 70 approached, 19 met inclusion criteria and were enrolled. The trial was conducted between April 14, 2021, and January 5, 2023. A single dose of synthetic psilocybin, 25 mg, was administered. Psychotropic medications were discontinued at least 2 weeks prior to dosing. Therapists met with patients for 3 sessions during pretreatment, during the 8-hour dosing day, and for 3 integration sessions posttreatment. The primary outcome measure was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Secondary measures included MADRS scores 12 weeks posttreatment, the self-rated Quick Inventory of Depression Symptoms-Self Rating (QIDS-SR), and the self-rated Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF), each completed at baseline and all subsequent visits. Safety measures included the Columbia Suicide Severity Rating Scale (CSSRS) and the Young Mania Rating Scale (YMRS) completed at each visit. Of the 15 participants in this study (6 male and 9 female; mean [SD] age, 37.8 [11.6] years), all had lower scores at week 3, with a mean (SD) change of -24.00 (9.23) points on the MADRS, (Cohen d = 4.08; 95% CI, -29.11 to -18.89; P < .001). Repeat measures analysis of variance showed lower MADRS scores at all tested posttreatment time points, including the end point (Cohen d = 3.39; 95% CI, -33.19 to -16.95; adjusted P < .001). At week 3, 12 participants met the response criterion (50% decrease in MADRS), and 11 met remission criterion (MADRS score ≤10). At the study end point, 12 patients met both response and remission criteria. QIDS-SR scores and Q-LES-Q-SF scores demonstrated similar improvements. YMRS and CSSRS scores did not change significantly at posttreatment compared to baseline. The findings in this open-label nonrandomized open-label trial suggest efficacy and safety of psilocybin with psychotherapy in BDII depression and supports further study of psychedelics in this population.

Psychedelic Assisted Psychotherapy preparing your target using psychohistoriography: a Jamaican perspective.

The efficacy of psilocybin and other psychedelics as modes of treatment have been demonstrated through clinical trials and other studies in the management of a number of mental illnesses, including some treatment resistant cases. In Psychedelic Assisted Psychotherapy (PAP), psychedelics catalyze or enhance the experience fostered by psychotherapeutic methods. Psychohistoriographic Brief Psychotherapy, conceptualized by the late Professor Frederick Hickling in the 1970's in Kingston, Jamaica, offers a pathway for exploration in the Jamaican context. Applied to individuals, Psychohistoriographic Brief Therapy (PBT) has already shown success in patients with personality disorders in Jamaica through a process which includes documenting life experiences in a psychohistoriogram. In the De La Haye psilocybin Treatment Protocol (DPTP), micro-doses of crushed, dried psilocybin mushrooms are taken throughout an 8-week outpatient process of documenting the components of the psychohistoriogram, making use of the increased openness and empathy associated with the use of psychedelic agents. These sessions are followed by supervised in-office therapeutic/mystical doses of crushed, dried psilocybin mushrooms in the 9th week. Given the legal status and availability of psilocybin containing products in a few countries like Jamaica, there is a potential role for a regulated psychedelic industry contributing to the body of useful and rigorous clinical research which is needed in this area. Clients could benefit as we venture into this new frontier in psychiatry.

Psilocybin in Palliative Care: An Update.

This review article summarizes clinically and socially relevant developments over the past five years in the therapeutic use of the classical tryptamine psychedelic substance psilocybin, with respect to the common challenges faced by palliative care patients and their care teams. Psilocybin is available in whole fungal and isolated forms but is not yet approved for therapeutic use in the United States. Using targeted database and gray literature searches, and author recall, key sources were identified, reviewed, and synthesized as to the safety and efficacy of psilocybin in palliative care. Life-threatening or life-limiting illnesses and faced by palliative care patients are comorbid with emotional and spiritual distress. Research and field reports reviewed suggest that psilocybin has significant and in some cases, sustained anxiolytic, antidepressant, anti-inflammatory and entheogenic effects with a favorable safety profile. Limitations of the research include the risk for selection bias toward healthy, white, financially privileged individuals, and in general, follow-up timelines too short to appropriately evaluate durability of outcomes in psychospiritual benefits and quality of life. While more research is needed for palliative care populations specifically, reasonable inferences can be made regarding the potential for benefit to palliative care patients from psilocybin's demonstrated anxiolytic, antidepressant, anti-inflammatory and entheogenic effects. However, major legal, ethical and financial barriers to access exist for the general population; obstacles which are likely worsened for geriatric and palliative care patients. Empiric treatment and large-scale controlled trials of psilocybin should be conducted to further investigate the findings of the smaller studies reviewed here across a variety of populations, for a greater understanding of therapeutic benefit and clinically relevant safety criteria, and to support thoughtful legalization and medical access.

Knocking on the Doors of Perception: the role of psilocybin in substance use disorder treatment

IntroductionSubstance use disorders(SUDs) are a major health concern and current treatment interventions have proven only limited success. Despite increasing effectiveness, still about 50–60% relapse within 6–12 months after treatment [Cornelius et al., Addict Behav. 2003;28 381-386]. SUDs are defined as chronic disorders of brain reward system, motivation, and memory processes that have gone awry. Medication reducing craving and substance use is mainly available for alcohol dependence and to a lesser extent for other substances.Hallucinogens may represent a group of agents with potential anti-craving properties subsequently reducing substance use in SUD patients. For instance, lysergic acid diethylamide(LSD) and psilocybin have previously been shown to effectively alleviate symptoms of alcohol and nicotine dependence.ObjectivesNew treatments preferably focusing on reducing craving and subsequent substance use are therefore urgently needed. The hallucinogen psilocybin may provide a new treatment option for SUD patients, given the beneficial results observed in recent studiesMethodsSystematic revision of literature.ResultsIn the 1950s, a group of drugs with potential to alter consciousness were discovered (hallucinogens). Several studies suggested their anti-SUD potential, improving self-acceptance and interpersonal relationships, reducing craving and alcohol use. As a result of its recreational popularity during the 1960s, they were banned in 1967, greatly hampering scientific research in this field. Recently, psilocybin, an hallucinogenic substance in psilocybin-containing mushrooms has gained popularity in neuropsychological research, showing to increase trait openness, cognitive and behavioral flexibility, and ratings of positive attitude, mood, social effects, and behavior and even reported persistent positive changes in attitude and behavior. These findings might suggest a valuable compound for the treatment of psychiatric conditions with several additional studies providing supportive evidence for the therapeutic potential of psilocybin for SUD treatment and relapse prevention.ConclusionsWith the reported limited amount of side effects and potential beneficial effects of psilocybin in SUD, there are valid reasons to further investigate the therapeutic efficacy and safety of psilocybin as a potential SUD treatment. On the one hand, psilocybin may exert its anti-addictive properties by beneficial effects on negative emotional states and stress. On the other hand, psilocybin may improve cognitive inflexibility and compulsivity. Research on the efficacy of psilocybin on SUD is still limited to a handful of published studies to date. As a result, many important questions related to the use of psilocybin as a complement to current treatment of SUD and its working mechanisms remain unanswered. Before psilocybin can be implemented as a treatment option for SUD, more extensive research is needed.Disclosure of InterestNone Declared

A systematic review to assess the use of psilocybin in the treatment of headaches

IntroductionPsilocybin is a naturally occurring psychedelic compound whose effects have been seen in studies for treatment of depression, anxiety and pain management. Given its structural similarities to 5-hydroxytryptamine, a monoamine controlling brain modulation of pain input, preliminary studies sought to test serotonergic interactions of psilocybin with headaches.ObjectivesExplore efficacy of psilocybin as treatment for individuals with headaches, including migraines, essential headaches, cluster headaches and unclassified head pains.MethodsStudies were found from six major databases, with inclusion criteria consisting of participants with any type of headache using psilocybin as a treatment. Each study was independently screened by two reviewers at two stages, with inconsistencies reviewed by a third, senior reviewer.ResultsThe systematic review evaluated eight articles. Benefits of macrodosing were explored in one study which reported higher levels of pain relief in comparison to microdosing and conventional pain medications. Top benefits of microdosing as reported by participants included convenience, perceived safety and reduced side effects when compared to hallucinogenic doses of psilocybin. Participants across five studies reported improvements to their headaches as characterized by changes in frequency, intensity, duration and remission period. Reported improvements were clinically significant in the six studies and statistically significant in three papers. With psilocybin intervention, two studies reported a decrease in headache attack frequency, three studies reported a decrease in intensity, and one study indicated a decrease in duration. The greatest benefit reported was for psilocybin taken during a remission period, with the average length of that remission period between headaches extending for 91% of participants. One study focused on the dosages of psilocybin in relation to its efficacy, indicating that there was more headache pain relief amongst macrodosers, with a difference of 12.3% of participants experiencing pain reduction 3 days after dosage in comparison to microdosers. 18% of participants who experienced essential headaches also experienced hallucinations as a result of ingested psilocybin. Others showed a temporary increase in symptoms of anxiety and pain - 5.3% with microdosing and 14.1% macrodosing. One study observed an increase in average arterial pressure after ingestion.ConclusionsSix of eight screened papers showed that psilocybin was clinically significant in the treatment of headaches as captured through self-reports. While the first controlled study for psilocybin use for headaches was detailed in this study, psilocybin remains illegal in many countries, presenting a need for further regulated research.Disclosure of InterestNone Declared

The Efficacy of Psilocybin in the Treatment of Depression and Anxiety: A Meta-Analysis

Background: The use of psychedelic compounds to treat psychiatric disorders has become a very significant topic of research over the past several years. Psilocybin has risen to prominence as one of the most studied among these psychedelic compounds. Multiple trials have already shown that it can be a safe and efficacious treatment for various medical conditions. This study intends to perform a meta-analysis of data reported in clinical trials studying psilocybin’s effect on depression and anxiety. Methods: Articles were searched, screened, and ultimately selected using predetermined inclusion criteria. Data was collected from commonly used psychometric tests that measured mood and anxiety symptoms. Effect sizes were calculated by comparing scores in these tests at baseline and control to experimental groups. Sub-group analysis was performed to assess psilocybin’s effect on depression and anxiety during short, medium, and long-term time frames. Results: Statistical significance was achieved in reducing depression and anxiety symptoms compared to controls in multiple subgroups. Heterogeneity of the effect sizes was calculated using an I2 value which showed low to moderate values. Multiple tools were used to assess publication bias, and none could be found. Conclusion: Although research on psilocybin continues to show promise, the evidence is still at a preliminary phase, and more trials need to be conducted with larger patient populations over longer periods for psilocybin to potentially be approved in a community setting.

Psilocybin Efficacy and Mechanisms of Action in Major Depressive Disorder: a Review.

We aim to provide an overview of the current state of knowledge about the efficacy of psilocybin in the treatment of depression, as well as its mechanisms of action. Psilocybin has a large, rapid, and persistent clinical effect in the treatment of resistant or end-of-life depression. Tolerance is good, with mild side effects limited to a few hours after dosing. The studies conducted to date have had small sample sizes. One clinical trial has been conducted against a reference treatment (escitalopram) without showing a significant superiority of psilocybin in the main outcome. The neurobiological mechanisms, mostly unknown, differ from those of SSRI antidepressants. Psilocybin represents a promising alternative in the treatment of depression. Further research with larger sample sizes, particularly against reference treatments, is needed to better understand the neurobiological factors of its effects and to investigate its potential for use in everyday practice.

Compassionate use of psychedelics.

In the present paper, we discuss the ethics of compassionate psychedelic psychotherapy and argue that it can be morally permissible. When talking about psychedelics, we mean specifically two substances: psilocybin and MDMA. When administered under supportive conditions and in conjunction with psychotherapy, therapies assisted by these substances show promising results. However, given the publicly controversial nature of psychedelics, compassionate psychedelic psychotherapy calls for ethical justification. We thus review the safety and efficacy of psilocybin- and MDMA-assisted therapies and claim that it can be rational for some patients to try psychedelic therapy. We think it can be rational despite the uncertainty of outcomes associated with compassionate use as an unproven treatment regime, as the expected value of psychedelic psychotherapy can be assessed and can outweigh the expected value of routine care, palliative care, or no care at all. Furthermore, we respond to the objection that psychedelic psychotherapy is morally impermissible because it is epistemically harmful. We argue that given the current level of understanding of psychedelics, this objection is unsubstantiated for a number of reasons, but mainly because there is no experimental evidence to suggest that epistemic harm actually takes place.

Taking Psychedelics Seriously.

Background: Psychiatric research in the 1950s and 1960s showed potential for psychedelic medications to markedly alleviate depression and suffering associated with terminal illness. More recent published studies have demonstrated the safety and efficacy of psilocybin, MDMA, and ketamine when administered in a medically supervised and monitored approach. A single or brief series of sessions often results in substantial and sustained improvement among people with treatment-resistant depression and anxiety, including those with serious medical conditions.Need and Clinical Considerations: Palliative care clinicians occasionally encounter patients with emotional, existential, or spiritual suffering, which persists despite optimal existing treatments. Such suffering may rob people of a sense that life is worth living. Data from Oregon show that most terminally people who obtain prescriptions to intentionally end their lives are motivated by non-physical suffering. This paper overviews the history of this class of drugs and their therapeutic potential. Clinical cautions, adverse reactions, and important steps related to safe administration of psychedelics are presented, emphasizing careful patient screening, preparation, setting and supervision.Conclusion: Even with an expanding evidence base confirming safety and benefits, political, regulatory, and industry issues impose challenges to the legitimate use of psychedelics. The federal expanded access program and right-to-try laws in multiple states provide precendents for giving terminally ill patients access to medications that have not yet earned FDA approval. Given the prevalence of persistent suffering and growing acceptance of physician-hastened death as a medical response, it is time to revisit the legitimate therapeutic use of psychedelics.

Return of the psychedelics: Psilocybin for treatment resistant depression.

Psilocybin, the clinically most researched classic psychedelic has recently been tested for its safety and efficacy in a clinical population of treatment resistant depression. The efficacy of psilocybin in clinical depression previously demonstrated in the elecrophysiologic and neuroimaging findings as also in neuropsychological assessments is further validated by the findings of this rigorously conducted randomized trial. Mechanism of action of psilocybin and efficacy in treatment resistant depression are discussed in this paper. Ethical issues of conducting clinical trials with psychedelics are also discussed with particular emphasis on their relative safety and absence of addiction potential. Implications of these issues for conduct of larger trials for establishing risk benefit ratio in treatment resistant depression are further suggested.

The Heffter Research Institute: Past and Hopeful Future

This essay describes the founding of the Heffter Research Institute in 1993 and its development up to the present. The Institute is the only scientific research organization dedicated to scientific research into the medical value of psychedelics, and it has particularly focused on the use of psilocybin. The first clinical treatment study was of the value of psilocybin in obsessive-compulsive disorder. Next was a UCLA study of psilocybin to treat end-of-life distress in end-stage cancer patients. While that study was ongoing, a trial was started at Johns Hopkins University (JHU) to study the efficacy of psilocybin in treating anxiety and depression resulting from a cancer diagnosis. Following the successful completion of the UCLA project, a larger study was started at New York University, which is near completion. A pilot study of the value of psilocybin in treating alcoholism at the University of New Mexico also is nearing completion, with a larger two-site study being planned. Other studies underway involve the use of psilocybin in a smoking cessation program and a study of the effects of psilocybin in long-term meditators, both at JHU. The institute is now planning for a Phase 3 clinical trial of psilocybin to treat distress in end-stage cancer patients.

Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder

Safety, Tolerability, and Efficacy of Psilocybin in 9 Patients With Obsessive-Compulsive Disorder