Major depressive disorder (MDD) and treatment-resistant depression (TRD) are prevalent and debilitating conditions. Over 50% of patients have inadequate response to first-line serotonergic antidepressants and are left with suboptimal treatment options. Rapid-acting and individually tailored treatments for MDD remain major unmet needs. This review discusses p...
Background: This systematic review and meta-analysis evaluates the efficacy and safety of psilocybin-assisted psychotherapy (PAP) for adults with major depressive disorder (MDD). Methods: A PROSPERO-registered search (CRD42024561979) of CENTRAL, Scopus, PsycINFO, and MEDLINE (2010-2024) identified clinical trials assessing PAP. Risk of bias was assessed usin...
Maintaining effective blinding is a major methodological challenge in psychedelic research. This study provides a comprehensive evaluation of blinding integrity in 120 healthy volunteers who received either psilocybin, MDMA, or methylphenidate (active placebo) in a double-blind, randomized controlled trial. Using a multi-level assessment incorporating forced...
The development of novel, rapid-acting treatments and the resurgence of interest in the therapeutic potential of psychedelic-like compounds has stimulated excitement and enthusiasm within the pharmaceutical industry, and provided new hope for millions of individuals suffering with mental illness such as major depressive disorder and post-traumatic stress dis...
About 30-50% of patients with advanced illness experience depression, anxiety, or decreased sense of purpose and autonomy. Together, these are called psychological distress. Treatment options such as medication and therapy are available; however, they do not always work and can be time-consuming and expensive. We need treatments that work well, quickly, and ...
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psychedelic science. Once relegated to the margins of psychopharmacology due to its association with counterculture and strict legal restrictions, psilocybin is now undergoing a scientific renaissance. This transform...
Introduction: The subjective effects of psilocybin on obsessive-compulsive disorder (OCD) are under-explored. Therefore, we conducted a qualitative study of participant experiences from the first randomized placebo-controlled trial of single-dose psilocybin combined with unstructured and non-directive support for individuals with treatment-refractory OCD. Ou...
Serotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. P...
The past two decades have seen the reemergence of research investigating the therapeutic potential of psychedelic drugs across neuropsychiatric illnesses. One condition, alcohol use disorder (AUD), is of relevance given the broad public health implications and both limited effectiveness and attrition associated with currently available treatments. While emer...
AimTo provide a balanced account of psilocybin treatment of depression for expectations to be appropriately set.MethodReview and discussion of key psilocybin efficacy studies. Reporting of side effects and risk of harm with psychedelic treatments. Comparisons and contrasts with ketamine studies of treatment-resistant depression (TRD).ResultEarly psilocybin s...
ImportancePsilocybin has demonstrated rapid and sustained antidepressant efficacy, with acute-phase effect sizes often more than double those for conventional antidepressants. However, concerns have been raised that high rates of functional unblinding in combination with trial participants with positive expectations of psychedelic use might bias treatment ou...
Ketamine and its enantiomers, esketamine and arketamine, have emerged as promising treatments for treatment-resistant depression (TRD). This cross-sectional study evaluates the regulatory alignment of 40 clinical trials listed on ClinicalTrials.gov, focusing on the methodological challenges. The study highlights methodological inconsistencies, particularly a...
Regulatory compliance is crucial in the clinical development of psychedelic substances, including psilocybin. This study aimed to examine the alignment of clinical trial protocols for psilocybin in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD) with established regulatory requirements.A cross-sectional investigation...
There is a growing body of clinical research on the therapeutic potential of psychedelics for the treatment of mental health disorders, notably depression. Accordingly, the new revision of the European Medicines Agency guideline on the clinical investigation of products for depression will incorporate a section covering specific regulatory recommendations fo...
Post-Traumatic Stress Disorder (PTSD) is a severe psychiatric condition that develops after exposure to trauma such as combat, natural disasters, or assault. It is characterized by re-experiencing trauma, avoidance, hyperarousal, and negative alterations in cognition and mood. Since its formal inclusion in the Diagnostic and Statistical Manual of Mental Diso...
BackgroundPsychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e...
Psychedelics are currently undergoing a scientific renaissance, with modern studies investigating therapeutic efficacy of psychedelic-assisted therapy in a range of psychiatric conditions. In particular, psilocybin-assisted therapy (PAT) has been suggested to have positive effects on patients suffering from depression and psychiatric distress associated with...
Introduction Since the last edition of the Black Book, several innovative agents have been approved or are poised to be approved in the coming year. These include novel antidepressants, the first muscarine agonist for the treatment of schizophrenia, the first psychedelic which may be approved for the treatment of PTSD (Post Traumatic Stress Disorder), and th...
Recent years have seen a resurgence in randomized, placebo controlled trials (RCTs) utilizing non-classical psychedelics (e.g. 3,4-methyl enedioxy methamphetamine [MDMA]), and classical psychedelics (e.g. psilocybin, lysergic acid diethylamide [LSD], and N,N-dimethyltryptamine [DMT/ayahuasca]) in conjunction with assisted therapy (AT) for psychiatric disorde...
Blinding of treatment allocation in clinical trials in psychiatry is regarded as an ideal. The potential impact of unblinding chimes with a general concern for psychological research: so-called demand characteristics can undermine confidence in findings from experimental and clinical studies. Scepticism can result in nihilism. The reliance on subjective repo...
