Background: Psilocybin is a psychoactive compound found in hallucinogenic mushrooms and is rapidly dephosphorylated in vivo to psilocin, its pharmacologically active metabolite. Despite the growing clinical and scientific interest in these substances, information regarding their interaction with cytochrome P450 (CYP450) enzymes remains scarce, raising concerns about potential drug–drug...
Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive...
Abstract Lyme disease, caused by the bacterium Borrelia burgdorferi , is the most common vector-borne disease in the United States and Europe. Although antibiotics effectively treat most cases, an estimated 10–20% of patients develop post-treatment Lyme disease (PTLD), a chronic syndrome marked by fatigue, pain, cognitive difficulties, mood disturbance, and reduced quality of life. There are no...
S elective S erotonin R euptake I nhibitors (SSRIs) and two psychedelics, Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and MDMA (3,4-Methylenedioxymethamphetamine) act on serotonergic-related neural circuits and function as serotonin modulators. All three molecules are either currently used or proposed as novel therapeutic modalities to treat P ost- T raumatic S tress D isorder (PTSD)....
Abstract Repeated mild traumatic brain injury (RmTBI) can produce lasting cognitive, emotional, and social deficits (e.g., persistent post-concussion symptoms; PPCS). Despite the prevalence of RmTBI in sports, military, and domestic violence settings, effective treatments to alleviate the neurological consequences of RmTBI remain limited. Psilocybin, a serotonergic psychedelic, can enhance...
Abstract IMPORTANCE Microdosing psilocybin may be a novel treatment for major depressive disorder (MDD). OBJECTIVE Assessing the antidepressant effects and safety of repeated low doses of psilocybin in participants diagnosed with MDD. DESIGN This was a Phase II, randomized, double-blind, placebo-controlled clinical trial. SETTING The trial was conducted from July 2022 to December 2024 at two...
Detecting psilocybin use is challenging because it rapidly converts to its psychoactive metabolite psilocin, and both compounds are unstable in blood. Bufotenin, a structural isomer of psilocin, may exhibit comparable instability in blood. For reliable detection, we developed and validated an LC-MS/MS method to simultaneously quantify psilocin, bufotenin, and their metabolites, psilocin...
medRxivFebruary 19, 2026Amanda Gow, Emily Shih, Ryan Reid et al.
preprint
Abstract Background In 2020, Oregon became the first U.S. state to establish a regulated framework for adults to access psilocybin services using naturally-derived mushroom products. No studies have examined mental health outcomes among individuals receiving psilocybin in this context. Aims To evaluate changes in self-reported symptoms of depression, anxiety, and well-being 30-days...
psilocybin-assisted psychotherapy is a compelling therapeutic option warranting further investigation through rigorous, interdisciplinary research to promote an anthropologically/ethically grounded implementation in palliative settings, even beyond the oncology field.
Psilocybin is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. We hypothesized psilocybin given during adolescence, a time of heightened neuroplasticity, particularly in the forebrain, would affect emotional behavior and the associated underlying neuroanatomy, neurocircuitry, and epigenetics. Female and male mice...
The legal status of psilocybin mushrooms in Brazil remains ambiguous, despite increasing global scientific and public interest in their therapeutic and ceremonial use. This commentary examines the regulatory uncertainty surrounding psilocybin mushrooms in Brazil and situates the debate within broader legal, drug policy, public health, and Indigenous rights discussions. Building on academic...
In Canada, the use of both prescription medications and psychedelics has become increasingly prevalent. As of 2022, approximately 16.5% of Canadians—about 6.3 million individuals—were prescribed at least one antidepressant, with fluoxetine remaining one of the most commonly used options (IQVIA, 2023). Benzodiazepine use, including drugs like alprazolam, ranges between 5% to 10% nationwide, with...
People with cancer often experience anxiety and depression following a diagnosis and can face barriers to accessing treatment for their mental health. An increasing number of patients are considering alternative approaches to managing their mental health symptoms, such as the psychedelic, psilocybin. A growing number of clinical trials show significant and enduring improvements in mood and...
In our original case report we provide detailed accounts of two research participants who reported the emergence of spontaneously recovered, previously forgotten traumatic memories of sexual assaults during psilocybin treatment. In their commentary of this article, Kangaslampi et al. argue that we preemptively label the experiences as dissociated traumatic memories in the absence of...
BACKGROUND: Major depressive disorder (MDD) is the leading cause of disability worldwide, affecting roughly 322 million people. Recently, doses of psilocybin have shown promise in treating mood disorders, sparking interest in other dosing practices. According to anecdotal reports and observational studies, microdosing psilocybin yields benefits to mental health; however, rigorously controlled...
We carried out a systematic review of modern-era (1990-2025) placebo-controlled studies assessing the acute and post-acute effects of lysergic acid diethylamide, dimethyltryptamine and psilocybin on cognitive and psychological functions. From February 28 to March 19, 2025, PubMed and APA PsychINFO were systematically searched for placebo-controlled studies examining the influence of...
The serotonergic psychedelic psilocybin induces neural plasticity and profoundly alters consciousness. The benzodiazepine midazolam blunts neural plasticity and induces conscious sedation and amnesia at low doses. In our recent open label pilot study, we administered oral psilocybin (25 mg) along with intravenous midazolam at doses allowing a full psychedelic experience while blunting memory...
The therapeutic potential of psilocybin in treating psychiatric disorders has gained attention recently. While most research has focused on isolated psilocybin, evidence suggests that whole mushroom extracts exhibit greater efficacy, implicating a possible entourage effect of additional bioactive compounds. This study aimed to elucidate the holistic neuropharmacological effects of...
Psychedelics' characteristic acute subjective effects predict therapeutic benefits, such as decreases in depression and anxiety. Thus, optimizing treatment involves better understanding which factors shape subjective effects. Session facilitators, who support participants before, during, and after psychedelic administration sessions, form an important part of the setting of these experiences....
Fragile X Syndrome (FXS) is the most common inherited intellectual disability and a leading monogenic cause of autism spectrum disorder (ASD). As a synaptic disorder, FXS involves the loss of Fragile X messenger ribonucleoprotein 1 (FMRP), leading to abnormal dendrite development and immature dendritic spines. Serotonergic signaling, essential for neuronal development and circuit remodeling,...