Cluster B personality disorders (PDs) are highly comorbid with depression and are associated with attenuated antidepressant response. No clinical trials to date have reported on psilocybin-assisted psychotherapy (PAP) in comorbid treatment-resistant depression (TRD) and PDs. This is the first clinical trial to describe a subgroup of ten participants with a comorbid PD ( n = 9 cluster B; n = 1...
Psilocybin, a serotonergic psychedelic, has gained attention as a potential treatment for various psychiatric conditions. In this review, the authors summarize current clinical evidence related to psilocybin’s efficacy, safety, and mechanisms of action across psychiatric disorders. Findings from early-phase and small-scale clinical trials suggest rapid but variable reductions in depressive...
Anhedonia, a core symptom of depression, is often resistant to conventional treatments and significantly impacts quality of life. This secondary analysis aimed to evaluate the effects of psilocybin-assisted psychotherapy (PAP) on anhedonia severity in individuals with treatment-resistant depression (TRD). Participants (n = 30) with TRD and a primary diagnosis of Major Depressive Disorder or...
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...
PAP was associated with modest, short-term improvements in performance on measures of processing speed and executive function among individuals with TRD. While these changes appeared independent of mood, they did not consistently exceed expected practice effects. These findings highlight the need for adequately powered, controlled trials to clarify whether observed cognitive changes reflect...
Antidepressant effects with sub-anesthetic doses of intravenous ketamine have been previously demonstrated. However, previous studies have primarily evaluated the efficacy of acute treatment protocols, with limited research on maintenance treatment. Moreover, controlled maintenance studies have only included patients with treatment-resistant Major Depressive Disorder (TRD), with no maintenance...
Posttraumatic stress disorder (PTSD) is a severe, often difficult-to-treat condition, highlighting the need for innovative therapies. Interventional treatments, including neuromodulation, rapid-acting pharmacotherapies such as intravenous ketamine (IV-KET) and esketamine (ESK), and emerging psychedelic-assisted psychotherapies, offer promising solutions. This systematic review evaluates the...
Substance Use Disorders (SUDs) involve diminished control, risky use, impaired social interactions, and physical dependence. Despite their global prevalence and burden, treatment options remain limited. Ketamine (KET), an NMDA receptor antagonist, may aid SUD treatment by modulating glutamatergic neurotransmission. This systematic review evaluates KET's role in SUD treatment. This review...
Background: Psilocybin-assisted psychotherapy (PAP) is a promising treatment for various psychiatric disorders. However, the exact biological and psychological mechanisms of action of PAP remain to be determined. Examining predictors of PAP outcomes may help identify necessary processes for positive treatment outcomes. Mystical experiences are considered a key aspect of the subjective effects...
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...
Introduction: High-dose psilocybin has shown potential in treating various psychiatric disorders, but its perceptual and cognitive effects, along with the risk of adverse events, highlight the need for alternative treatment approaches. One such approach is the use of low-dose psilocybin, which does not significantly alter cognition or perception. While low-dose psilocybin has garnered growing...
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...
Objective: To compare changes in depression, anxiety, and suicidality symptoms after a single 25 mg oral dose of psilocybin between treatment-resistant depression participants not on antidepressants at screening to participants that discontinued antidepressant medications leading up to receiving psilocybin-assisted psychotherapy (PAP). Methods: Participants (n = 27) received at least one 25 mg...
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...
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...
Background: Bipolar II disorder (BD-II) is often associated with chronic and treatment resistant major depressive episodes. Psilocybin has shown promise for its rapid-acting antidepressant effects, though its impact on bipolar depression remains unexplored. In the present subgroup analysis of an already published trial on treatment-resistant depression (TRD), we aimed to preliminarily evaluate...
Psilocybin is a classic psychedelic with demonstrated preliminary clinical efficacy in a range of psychiatric disorders. Evaluating the impact of psilocybin on cognitive function is essential to unravel its potential benefits and risks. In this systematic review, we assessed psilocybin's effect on cognitive function through a comprehensive search of electronic databases from inception to...
Inadequate outcomes with monoamine-based treatments in depressive disorders are common and provide the impetus for mechanistically-novel treatments. Esketamine is a proven treatment recently approved for adults with Treatment-Resistant Depression (TRD) while psilocybin is an investigational treatment. Translation of the clinical meaningfulness for these foregoing agents in adults with TRD is...
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....
Background: Ketamine is an emerging treatment for treatment-resistant depression (TRD) associated with rapid and robust improvements in depressive symptoms and suicidality. However, the efficacy and safety of ketamine in transitional age youth (TAY; age 18–25) populations remains understudied. Methods: In this retrospective analysis, TAY patients (n = 52) receiving ketamine for TRD were matched...
Borderline personality disorder (BPD) has high rates of comorbidity with mood disorders, including treatment-resistant depression (TRD). Comorbidity of BPD with depression is associated with poorer response to antidepressants. Intravenous ketamine is a novel treatment for TRD that has not been specifically evaluated in patients with comorbid BPD. In this retrospective analysis of data collected...
Abstract Objectives: Ketamine is a glutamate N-methyl-D-aspartate receptor antagonist that can be used to treat major depressive disorder by single or repeated infusions. However, the accessibility and scalability of oral ketamine make it preferred over intravenous ketamine. In this systematic review, we aim to evaluate the efficacy, tolerability, and safety of oral ketamine, esketamine and...
Ketamine has demonstrated rapid and significant antidepressant effects in patients with treatment resistant depression (TRD). Herein, we conducted a systematic review to determine ketamine's efficacy as a function of the stage of treatment resistance (e.g., number of failed treatments) among individuals with TRD. A systematic search of PubMed and Scopus from inception to August 2021 was...
Over the past two decades, ketamine has emerged as a novel effective and safe rapid-acting antidepressant. While the vast majority of studies on ketamine have focused on its ability to reduce the severity of depression broadly, its effectiveness in specific domains such as cognition, anhedonia, suicidality, and workplace/social/scholastic functionality has been neglected. Similarly, current...
Few studies have evaluated the efficacy of ketamine-assisted psychotherapy (KAP) in the treatment of treatment-resistant depression (TRD) and substance use disorders (SUD). A systematic review of clinical trials reporting on the efficacy of KAP and discussing mechanisms of action, identified on PubMed and PsycInfo. Five randomized-controlled trials reported on the efficacy of KAP treatment and...