This commentary critically examines the interpretation and analytic choices in Goodwin and colleagues’ recent analysis of therapeutic alliance in psilocybin treatment for treatment-resistant depression. While the authors conclude that alliance did not meaningfully contribute to treatment efficacy, we argue that this interpretation is not supported by the reported results, which are, in...
First-line dictionary definitions of ‘plasticity’ describe it as the ability (of a thing) to be shaped or molded; we call this ‘plasticity proper’. In neuroscience, however, ‘neural plasticity’ or ‘neuroplasticity’ is defined as an induced change in brain function or structure. These two plasticities are not the same. Several (but not all) popular biomarkers of neuroplasticity index part of an...
Emerging evidence suggests psychedelic-assisted therapies ameliorate symptoms of psychopathology. However, less is known about how psychedelics influence positive psychological functioning (e.g., compassionate love, self-compassion, and life satisfaction). These constructs may be relevant in understanding how psychedelics exert their therapeutic effects, as they are central to both intra- and...
Background: Psilocybin-assisted therapy (PAT) has shown promise for alcohol use disorder (AUD) in randomized controlled trials (RCTs). However, the effects of open-label administration following blinded treatment are unclear. Here, we present safety and efficacy data from an open-label extension of a Phase II RCT (NCT02061293) examining PAT for AUD. Methods: Adults with AUD (N = 59) received a...
Abstract Background Psychedelic-assisted psychotherapy has shown potential for psychiatric disorders. However, the magnitude of symptom change in control groups remains poorly understood. We aim to evaluate within-group effects in control groups and compare them to treatment groups in psychedelic trials. Methods A systematic search was conducted up to 1 July 2025. The study protocol was...
Background: Posttraumatic stress disorder (PTSD) is a severe condition often complicated by co-occurring disorders, such as major depression, alcohol use disorder, and substance use disorders. A well-powered phase 3 randomized, placebo-controlled trial has shown that MDMA-assisted therapy (MDMA-AT) may be an effective treatment for severe PTSD. However, the psychological mechanisms driving the...
Abstract Background: Psychedelics can acutely induce mystical experiences and elevated positive mood, which may contribute to the potential benefits of psychedelic therapy. However, there remains limited understanding of the occurrence and importance of specific positive emotional experiences within psychedelic therapy. Therefore, we examined the effects of psychedelics on positive emotional...
Both psychotherapeutic interventions and pharmacological agents have demonstrated limited efficacy in the treatment of personality disorders (PDs). Emerging evidence suggests that psychedelic therapy, already showing promise in treating various psychiatric conditions commonly comorbid with PDs, may exert therapeutic effects by promoting adaptive changes in personality. Thus, psychedelic therapy...
A recent randomized, double-blind, placebo-controlled, parallel-group trial (NCT02061293) found that psilocybin-assisted therapy significantly improved drinking outcomes compared to an active placebo in adults with alcohol use disorder (AUD). In this secondary analysis, we assessed whether psilocybin-assisted therapy improved self-compassion and whether these changes predicted drinking...
Psilocybin, a serotonergic psychedelic, may have therapeutic benefits for Substance Use Disorders (SUDs), but its overall efficacy and safety remain uncertain. This systematic review assessed the safety and efficacy of psilocybin for SUDs through a systematic database search conducted via OVID on May 22, 2024, and summarized 26 ongoing clinical trials registered on clinicaltrials.gov. Among 16...
Background: Psilocybin has shown promise in therapeutic applications for mental disorders. Understanding the pharmacokinetics of psilocybin and its active metabolite psilocin is crucial for optimizing its clinical use and minimizing adverse effects. Methods: This systematic review involved a comprehensive search across MEDLINE, APA PsycINFO, and Embase databases, from inception to December...
Background/Objectives: Suicide accounts for 1.4% of global deaths, and the slow-acting nature of traditional treatments for suicide risk underscores the need for alternatives. Psychedelic therapies may rapidly reduce suicide risk. This systematic review evaluates impact of psychedelic therapies on suicide-related outcomes. Methods: A systematic search of MEDLINE, Embase, PsycINFO, and...
The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; which (b) facilitate positive...
Background Posttraumatic stress disorder (PTSD) affects 3.9% of the general population. While massed cognitive processing therapy (CPT) has demonstrated efficacy in treating chronic PTSD, a substantial proportion of patients still continue to meet PTSD criteria after treatment, highlighting the need for novel therapeutic approaches. Preliminary evidence supports the potential therapeutic action...
PAT elicited durable shifts in personality, suggesting normalization of abnormal personality trait expression in AUD. Further study is needed to clarify whether PAT exerts its beneficial effects by reducing impulsiveness or whether impulsive individuals inherently respond better to PAT.
Abstract Background: Personality disorders (PDs) are characterized by impairments in psychological functioning for which pharmacologic treatments have demonstrated limited efficacy. Psychedelics may offer a possible PD treatment, given preliminary evidence for their potential long-term positive effects on psychological functioning. However, little is known about safety or potential therapeutic...
Psilocybin-assisted psychotherapy (PAP) has shown promise in treating mood and anxiety disorders in patients with cancer. However, patients with cancer often suffer from more than just depression and anxiety, and so far, PAP's effect on other psychiatric symptoms remains largely unknown. To address this gap, we pooled previously unpublished data from two phase II, randomized, placebo-controlled...
Although psilocybin therapy is currently receiving attention as a novel intervention for a wide range of mental health concerns, limited research has examined the underlying psychological mechanisms (i.e., how) through which psilocybin therapy may bring about positive therapeutic changes. Qualitative research highlights the role of reductions in experiential avoidance (i.e., avoidance or...
Several phase II studies have demonstrated that psilocybin-assisted therapy shows therapeutic potential across a spectrum of neuropsychiatric conditions, including major depressive disorder (MDD). However, the mechanisms underlying its often persisting beneficial effects remain unclear. Observational research suggests that improvements in psychological flexibility may mediate therapeutic...
Introduction: Effective blinding is especially challenging in randomized controlled trials (RCTs) involving psychedelics due to the inherent alterations in consciousness that these compounds induce. In this systematic review and exploratory analysis, we aim at synthesizing the methodologies used in RCTs involving classic psychedelics and identify procedures that can help minimize unblinding and...
Background: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited...
Abstract Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin’s acute effects (4–6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting...
Background: MDMA-assisted psychotherapy (MDMA-AP) is a combined psychotherapeutic and pharmacologic intervention that shows promise in the treatment of posttraumatic stress disorder (PTSD). Although therapeutic alliance has been established as a key predictor across psychotherapies and is emphasised within MDMA-AP treatment manuals, research has not yet examined the relationship between...
Background: Amyotrophic lateral sclerosis (ALS) is an aggressive, terminal neurodegenerative disease that causes death of motor neurons and has an average survival time of 3-4 years. ALS is the most common motor neuron degenerative disease and is increasing in prevalence. There is a pressing need for more effective ALS treatments as available pharmacotherapies do not reverse disease progression...
Abstract Psilocybin and lysergic acid diethylamide (LSD) experiences can range from very positive to highly challenging (e.g., fear, grief, and paranoia). These challenging experiences contribute to hesitancy toward psychedelic-assisted psychotherapy among health care providers and patients. Co-use of 3,4-Methylenedioxy methamphetamine (MDMA) with psilocybin/LSD anecdotally reduces challenging...