This article reviews the current clinical evidence for psilocybin and ayahuasca as therapeutic agents, examining data from over 134 registered clinical trials and key publications in the New England Journal of Medicine, JAMA, JAMA Psychiatry, and Nature Neuroscience. The review addresses four dimensions: (1) the state of clinical evidence for psilocybin and ayahuasca in major depression and...
Psilocybin extends lifespan in aged mice, and this has prompted extensive media speculation about possible human longevity benefits. We examined mortality among prominent psychedelic personalities, researchers, and advocates who claimed psychedelic use (n = 11) and compared them with cancer (n = 12) and aging researchers (n = 5). All groups exceeded population life expectancy, reflecting the...
Objectives/Goals: Mainstream interest in psilocybin (“shrooms”) has grown over the past several years as two US states have “legalized” psilocybin and clinical trials are underway for use in multiple mental health conditions. We evaluated self-reported use of psilocybin among community members in North Florida and trends in use from 2012 to the present. Methods/Study Population: Established in...
Objectives/Goals: We recently showed that a single dose of psilocybin, a serotonergic psychedelic, attenuated mechanical hypersensitivity for up to 28 days in a rat model of formalin-induced chronic centralized pain. The goal of this study is to determine whether psilocybin can alleviate chronic pain in a rat model of reserpine-induced chronic centralized pain. Methods/Study Population: Adult...
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...
Auditory steady-state responses (ASSRs), particularly at 40 Hz, are promising biomarkers for psychiatric disorders involving dysregulated neural synchronization. Although most ASSR studies have focused on the glutamatergic system, the serotonergic system, specifically 5-HT2A receptor signaling, has received limited attention. Psilocin, the active metabolite of psilocybin and a known 5-HT2A...
Intimate partner violence (IPV) poses a significant medical concern, predominantly affecting females. IPV-related brain injuries (IPV-BI), such as mild traumatic brain injury (mTBI) and non-fatal strangulation (NFS), sustained during physical attacks are common and often repetitive. Chronic neurobehavioral sequalae from IPV-BI are associated with neuroinflammation and impaired neuroplasticity,...
Major Depressive Disorder (MDD) and chronic pain are independently debilitating conditions that frequently co-occur. This comorbidity poses a significant clinical challenge, resulting in greater symptom severity, higher disability, and worse prognosis than either condition alone. Current therapies often address each disorder in isolation, leaving individuals with comorbid MDD and chronic pain...
Borderline personality disorder (BPD) is often comorbid with major depressive disorder (MDD), and there has been a suggestion in the literature that this comorbidity may interfere with MDD treatment response. Our objective was to conduct a pilot study of psilocybin in adults with BPD and MDD. Adults aged 18 to 65 years with a DSM-5 diagnosis of MDD and BPD were enrolled in an open-label pilot...
Ecology and EvolutionApril 1, 2026Kirsty J. Matthews Nicholass, Ilona Flis, Me Hanley et al.
ABSTRACT Research into psychedelic compounds is in resurgence because of the exciting potential for their use in the treatment of psychiatric and mental health disorders. Despite this revival, remarkably little is known about their evolution. One of the most intriguing psychedelic compounds is psilocybin, the compound found in ‘magic’ mushrooms and used in ritual ceremonies in North America for...
Psilocybin showed a rapid antidepressant response in several clinical trials, which offers new hope for treating depression. Astrocytes were associated with the etiology of depression and might contribute to the onset of psilocybin. In this study, we investigated the fast antidepressant effect of psilocybin and tested variations of GFAP (astrocytic markers) and C3 protein (markers of A1...
Human neurons derived from stem cells show increased structural complexity and stronger synaptic connections after exposure to psilocin, the active metabolite of the psychedelic psilocybin.
Understanding the toxicity of serotonergic tryptamines is becoming increasingly important from both clinical and forensic perspectives, yet experimental data for these compounds remain extremely limited. Despite their growing medical relevance and widespread non-medical use, there is still no systematic evaluation of their toxicological risks. This study presents the first comprehensive in...
Psilocybin-assisted therapy has emerged as a promising intervention for treatment-resistant depression (TRD), yet standardized and transparent therapeutic frameworks remain limited. This therapist manual was developed for the EPIsoDE trial, a phase IIb randomized clinical study investigating the efficacy and safety of psilocybin with adjunct psychotherapy in patients with TRD (NCT04670081). The...
Psychedelics are increasingly described as a new therapeutic approach in a variety of mental disorders including depression. Oral psychedelics such as psilocybin have an acute effect evolving over 6-8 h and are generally given in combination with psychological support. There is debate on the exact role of this support and how and by whom it should be delivered. This has significant implications...
Background: Self-stigma refers to the internalization of negative societal beliefs and has been associated with reduced self-efficacy, self-esteem and treatment avoidance among substance users. However, little research has explored antecedents of self-stigma such as substance use motives. This may be particularly salient for psilocybin which is used both as a therapeutic agent and a...
ElifeMarch 27, 2026Målin Schmidt, Anne Hoffrichter, Mahnaz Davoudi et al.3 citations
Psilocybin is studied as innovative medication in anxiety, substance abuse and treatment-resistant depression. Animal studies show that psychedelics promote neuronal plasticity by strengthening synaptic responses and protein synthesis. However, the exact molecular and cellular changes induced by psilocybin in the human brain are not known. Here, we treated human cortical neurons derived from...
Psilocybin can produce sustained benefits in affective and trauma-related disorders, yet if and how it reshapes sensory representations of learned valence associations remains largely unclear. To address this, we used longitudinal two-photon calcium imaging in awake C57BL/6 mice to examine how psilocybin modulates layer 2/3 auditory cortex activity at single-cell and population levels. Evoked...
CONTEXT: People living with serious illness frequently experience intense existential suffering related to awareness of finitude. Psychedelic-assisted therapies have been associated with reductions in death anxiety and existential distress, yet the experiential processes underlying transformations in the relationship with finitude remain insufficiently understood. OBJECTIVES: To synthesize...