Rediscovering Psilocybin as an Antidepressive Treatment Strategy

Zeiss, René; Gahr, Maximilian; Graf, Heiko

doi:10.3390/ph14100985

Cited by 10 publications

(6 citation statements)

References 94 publications

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“…Interestingly, a clear pattern emerged for past use of psychedelics—the higher the proportion of study participants who had used psychedelics in the past, the higher the post-psilocybin treatment effect observed. Past use of psychedelics has been proposed to create an expectancy bias among participants and amplify the positive effects of psilocybin 82 83 84 ; however, this important finding has not been examined in other meta-analyses and may highlight the role of expectancy in psilocybin research.…”

Section: Discussionmentioning

confidence: 99%

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

Metaxa,

Clarke

2024

BMJ

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Objective To determine the efficacy of psilocybin as an antidepressant compared with placebo or non-psychoactive drugs. Design Systematic review and meta-analysis. Data sources Five electronic databases of published literature (Cochrane Central Register of Controlled Trials, Medline, Embase, Science Citation Index and Conference Proceedings Citation Index, and PsycInfo) and four databases of unpublished and international literature (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, ProQuest Dissertations and Theses Global, and PsycEXTRA), and handsearching of reference lists, conference proceedings, and abstracts. Data synthesis and study quality Information on potential treatment effect moderators was extracted, including depression type (primary or secondary), previous use of psychedelics, psilocybin dosage, type of outcome measure (clinician rated or self-reported), and personal characteristics (eg, age, sex). Data were synthesised using a random effects meta-analysis model, and observed heterogeneity and the effect of covariates were investigated with subgroup analyses and metaregression. Hedges’ g was used as a measure of treatment effect size, to account for small sample effects and substantial differences between the included studies’ sample sizes. Study quality was appraised using Cochrane’s Risk of Bias 2 tool, and the quality of the aggregated evidence was evaluated using GRADE guidelines. Eligibility criteria Randomised trials in which psilocybin was administered as a standalone treatment for adults with clinically significant symptoms of depression and change in symptoms was measured using a validated clinician rated or self-report scale. Studies with directive psychotherapy were included if the psychotherapeutic component was present in both experimental and control conditions. Participants with depression regardless of comorbidities (eg, cancer) were eligible. Results Meta-analysis on 436 participants (228 female participants), average age 36-60 years, from seven of the nine included studies showed a significant benefit of psilocybin (Hedges’ g=1.64, 95% confidence interval (CI) 0.55 to 2.73, P<0.001) on change in depression scores compared with comparator treatment. Subgroup analyses and metaregressions indicated that having secondary depression (Hedges’ g=3.25, 95% CI 0.97 to 5.53), being assessed with self-report depression scales such as the Beck depression inventory (3.25, 0.97 to 5.53), and older age and previous use of psychedelics (metaregression coefficient 0.16, 95% CI 0.08 to 0.24 and 4.2, 1.5 to 6.9, respectively) were correlated with greater improvements in symptoms. All studies had a low risk of bias, but the change from baseline metric was associated with high heterogeneity and a statistically significant risk of small study bias, resulting in a low certainty of evidence rating. Conclusion Treatment effects of psilocybin were significantly larger among patients with secondary depression, when self-report scales were used to measure symptoms of depression, and when participants had previously used psychedelics. Further research is thus required to delineate the influence of expectancy effects, moderating factors, and treatment delivery on the efficacy of psilocybin as an antidepressant. Systematic review registration PROSPERO CRD42023388065.

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Section: Discussionmentioning

confidence: 99%

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

Metaxa,

Clarke

2024

BMJ

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“…Although the safety and efficacy of psilocybin as an antidepressant are the focus of most recent clinical trials (more than 100 clinical trials have been registered), there are still no definitive data that can establish whether psilocybin can offer substantial clinical improvement over existing antidepressant therapies [ 200 , 201 ]. It has recently been reported that the antidepressant response of psilocybin is not statistically stronger than the conventional antidepressant escitalopram [ 202 ].…”

Section: Psilocybe Cubensismentioning

confidence: 99%

The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology

Mastinu

Anyanwu

Carone

et al. 2023

IJMS

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The need to identify effective therapies for the treatment of psychiatric disorders is a particularly important issue in modern societies. In addition, difficulties in finding new drugs have led pharmacologists to review and re-evaluate some past molecules, including psychedelics. For several years there has been growing interest among psychotherapists in psilocybin or lysergic acid diethylamide for the treatment of obsessive-compulsive disorder, of depression, or of post-traumatic stress disorder, although results are not always clear and definitive. In fact, the mechanisms of action of psychedelics are not yet fully understood and some molecular aspects have yet to be well defined. Thus, this review aims to summarize the ethnobotanical uses of the best-known psychedelic plants and the pharmacological mechanisms of the main active ingredients they contain. Furthermore, an up-to-date overview of structural and computational studies performed to evaluate the affinity and binding modes to biologically relevant receptors of ibogaine, mescaline, N,N-dimethyltryptamine, psilocin, and lysergic acid diethylamide is presented. Finally, the most recent clinical studies evaluating the efficacy of psychedelic molecules in some psychiatric disorders are discussed and compared with drugs already used in therapy.

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“…On the other hand, psilocybin's effects at the 5HT receptors are responsible for decreased depression and suicidal behaviors, as well as increased memory and learning [11]. Further, it is believed that psilocin's activation of the 5HT-2A receptor is responsible for increased release of dopamine from the striatum, which is capable of regulating the defective reward pathway in patients who suffer from depression and with suicidal ideation [6].…”

Section: Review Mechanism Of Actionmentioning

confidence: 99%

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

Ziff¹,

Stern²,

Lewis³

et al. 2022

Cureus

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

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Rediscovering Psilocybin as an Antidepressive Treatment Strategy

Cited by 10 publications

References 94 publications

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

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

The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology

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

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