There is currently a resurgence in exploring the utility of classical psychedelics to treat depression, addiction, anxiety disorders, cluster headaches, and many other neuropsychiatric disorders. A biological target of these compounds, and a hypothesized target for their therapeutic actions, is the 5-HT2A serotonin receptor. Here, we present 7 cryo-EM structures covering all major compound...
Illness anxiety (IA) is characterized by worry or fear in response to living with a chronic illness or a preoccupation with having or acquiring a serious disease in conjunction with absent to mild somatic symptomatology. Death anxiety (DA) may underpin IA and is more common in individuals with life-threatening illness. Treatments for DA and IA, such as psychotherapy and antidepressant drugs,...
Banisteriopsis caapi (Spruce ex Griseb.) Morton, a vine native to South America and belonging to the Malpighiaceae plant family, is well known for its role as a primary component in the renowned psychoactive beverage known as ‘ayahuasca’, which also includes the herb Psychotria viridis Ruiz & Pav. Ethnic groups have historically employed the concoction for ceremonial, therapeutic, and...
Psilocybin, MDMA, and LSD have recently emerged as popular psychedelic substances for use in psychopharmacology in managing various disorders including treatment-resistant depression, PTSD, and anxiety. These substances mainly affect the serotonergic receptors that involve the regulation of consciousness, perceptions, and cognition. These unique alterations in brain connectome show the...
The transition towards the brain state induced by psychedelic drugs is frequently neglected in favor of a static description of their acute effects. We use a time-dependent whole-brain model to reproduce large-scale brain dynamics measured with fMRI from 15 volunteers under 20 mg intravenous N,N-Dimethyltryptamine (DMT), a short-acting psychedelic. To capture its transient effects, we...
Abstract The recent renaissance in research on psychedelics such as psilocybin has highlighted their therapeutic potential including their lasting influences on brain function. Here we report that a single systemic administration of the serotonergic psychedelic psilocybin can durably promote social behaviour in the Cntnap2-knockout mouse model of autism. This effect can be blocked by...
Ketamine has been investigated as a treatment alternative for PTSD for the last 20 years, yet there have been virtually no reports of biological changes or biomarker characterisation related to treatment. To address this significant gap, this study analysed blood samples from 25 participants with PTSD who took part in an open-label 6-week trial of low dose oral ketamine treatment. Serum and...
Medications to treat substance use disorders (SUDs) remain suboptimal or, in the case of stimulants and cannabis, non-existent. Many factors have contributed to this paucity, including the biological complexity of addiction, regulatory challenges, and a historical lack of enthusiasm among pharmaceutical companies to commit resources to this disease space. Despite these headwinds, the recent...
Anecdotal reports and preliminary clinical trials suggest that the psychoactive alkaloid ibogaine and its active metabolite noribogaine have powerful anti-addictive properties, producing long-lasting therapeutic effects across a range of substance use disorders and co-occurring neuropsychiatric diseases such as depression and post-traumatic stress disorder. Here we report a gram-scale,...
Interpreting postmortem concentrations of 3,4-Methylenedioxymethamphetamine (MDMA) remains challenging due to the wide range of reported results and the potential idiosyncratic nature of MDMA toxicity. Consequently, forensic pathologists often rely on a body of evidence to establish conclusions regarding the cause and the manner of death in death involving MDMA. Given these issues, implementing...