Psilocybin Treatment as an Adjunct to Cognitive Behavioral Therapy for Eating Disorders: Therapeutic Rationale & Considerations for Protocol Development.

Eating disorders (EDs) remain challenging to treat, with high dropout and low remission rates in cognitive-behavioral therapy for EDs (CBT-ED). Psilocybin treatment (PT) demonstrates therapeutic potential to enhance CBT-ED by exerting several neurobiological, psychological, and experiential effects (e.g., antidepressant, neuroplasticity, emotional openness) ...

Efficacy and risks of psychedelics in treatment of posttraumatic stress disorder: A systematic review.

PurposeThe purpose of this review is to evaluate which psychedelics have the most efficacy data to support their use in the treatment of posttraumatic stress disorder (PTSD). This review also aims to assess safety data and concerns related to psychedelic therapies and identify demographic characteristics that may influence clinical outcomes.SummaryA systemat...

Serotonergic modulation of cortical gamma synchronization: right-lateralized psilocin effects on 40 Hz auditory steady-state responses in rats.

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 ...

Differential Effects of Acute and Chronic Fluoxetine on Psychedelic-Induced Behavior in Mice: Implications for Clinical Trials.

Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for mood and anxiety disorders, the same conditions under which psychedelic-assisted therapies are gaining renewed interest. However, it remains unclear how SSRI treatment may influence sensitivity to psychedelics, particularly through the shared engagement of serotonergic pathways. Here, ...

Synthesis and Characterization of Psilocybin Metabolites and Deuterated Analogs.

To support ongoing clinical trials, the major human metabolites of psilocybin were synthesized on a preparative scale, specifically psilocin-O-glucuronide and 4-hydroxyindole-3-acetic acid (4-HIAA), along with putative minor metabolites and several deuterium-labeled derivatives. Psilocybin, psilocin, psilocin-O-glucuronide, and 4-HIAA were assayed for engage...

Psilocybin or Nicotine Patch for Smoking Cessation: A Pilot Randomized Clinical Trial.

ImportanceAnnual tobacco-related death estimates are 480 000 in the US and 8 million worldwide, surpassing mortality for other abused substances. Most smoking cessation interventions result in modest long-term success.ObjectiveTo compare prolonged smoking abstinence rates in smokers receiving psilocybin plus cognitive behavioral therapy (CBT) with those rece...

Psilocybin shapes neural plasticity in selective brain networks.

Psilocybin and Ibogaine in Cocaine-Seeking: Extinction Enhancement Without Relapse Prevention.

Psychedelics have emerged as potential therapeutics for substance use disorders, yet preclinical data validating their efficacy remain limited. Here, we investigated the effects of a clinically inspired dose-escalation protocol of psilocybin and ibogaine on extinction and cue-induced reinstatement in Wistar male rats following intravenous cocaine self-admini...

[Perspectives opened up by the physiopathological understanding of psychiatric disorders].

Neuroimaging techniques have a rightful place in the field of psychiatry. They are essential for differential diagnosis, especially when the psychiatric presentation is atypical. Furthermore, they associate brain dysfunction with psychiatric disorders, but they cannot yet provide a definitive psychiatric diagnosis. However, from a therapeutic perspective, br...

Psychedelics and the Extracellular Matrix: Rewiring Neuroplasticity and Metaplasticity for Next-Generation Psychiatric Therapies.

Classic psychedelics, such as psilocybin, lysergic acid diethylamide (LSD), and N,N-dimethyltryptamine (DMT), have emerged as potent modulators of neuroplasticity and metaplasticity in the adult brain, offering novel therapeutic strategies for neuropsychiatric disorders. Recent findings reveal that beyond their transient psychotropic effects, these compounds...

Psilocybin-assisted therapy for demoralisation in hospice patients: feasibility, safety and preliminary efficacy.

ObjectivesTo assess the feasibility, safety and preliminary efficacy of psilocybin-assisted therapy (PAT) for demoralisation in terminally ill patients receiving home hospice care.MethodsIn this open-label pilot trial, 4607 home hospice patients at a large community hospice were screened over 22 months; 66 were approached, 15 enrolled and 10 received psilocy...

Psychedelic therapy and cultural humility.

ImportanceAs psychedelic-assisted therapies gain clinical legitimacy, their cultural portability remains underexamined. While promising results have emerged from trials on existential distress in life-limiting illness, most protocols reflect Euro-American values. The expansion of these therapies calls for a pivot toward cultural humility and renewed attentio...

Calcium activation mechanism of a noncanonical aromatic L-amino acid decarboxylase from psilocybin mushroom Psilocybe cubensis.

PcncAAAD is a noncanonical fungal aromatic L-amino acid decarboxylase (AAAD) featuring a unique appendage C-terminal domain (CTD) and two metal-binding sites. Unlike its mammalian and plant counterparts, PcncAAAD is activated by calcium, although the exact activation mechanism remains unclear. Here, we establish an in silico RMSD-based evaluation model throu...

Pharmacological regulation of adult brain neuroplasticity: Synergistic roles of neuropeptide signaling, psychedelics, and synaptic modulators.

Neuroplasticity refers to the ability of the brain to modify synaptic connections and reorganize neural circuits, underpinning cognitive function, emotional regulation, and recovery from injury. Recent advances have redefined adult neuroplasticity as more dynamic and therapeutically accessible than previously thought, spurring investigation into pharmacologi...

Psilocybin for psychiatric disorders: History, clinical trials, neuroimaging, and regulations.

Psilocybin, a classic psychedelic compound, has garnered renewed interest as a potential treatment for various psychiatric disorders. This review provides a comprehensive overview of psilocybin's history, recent clinical evidence, ongoing clinical trials, neuroimaging findings, and regulations. Historically used in spiritual and healing rituals, psilocybin w...

Pilot study of psilocybin in patients with post-treatment lyme disease.

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 qu...

Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine.

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 se...

SSRIs, Psilocybin, MDMA, and Disease Modeling: Strategies to Advance PTSD Treatment

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- ...

Efficacy and Safety of Psychoactive Tryptamines in Addiction: A Systematic Review.

BackgroundPsychedelics such as lysergic acid diethylamide (LSD) and psilocybin have shown a beneficial effect on substance use disorder (SUD) symptoms. In this systematic review, we aimed to assess the efficacy and safety of psychoactive tryptamines in patients with an SUD or non-substance-related disorder (i.e., gambling disorder) in order to provide a comp...

Delayed psilocybin treatment after repeated mild traumatic brain injury recovers chronic behavioural deficits, reduces microglial density, and enhances hippocampal neurogenesis in rats

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 serot...