Motivation: Acute effects of psychedelic drugs are under-reported in neuroimaging studies, warranting further investigation of their immediate pharmacology to explore the potential to monitor treatment response with imaging. Goal(s): Our goal was to assess acute impacts of serotonergic (psychedelic and non-psychedelic) agonists on hemodynamics in non-human primates (NHP). Approach:...
There has been a recent renewal of interest in the therapeutic potential of serotonergic psychedelics. Here, we uncover the essential role of ventral hippocampus (vHpc) GABAergic interneurons in the anxiolytic effect evoked by the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Integrating anatomical, pharmacological, and genetic approaches, we show that 5-HT2A receptors in the...
Abstract Psilocybin is a serotonergic psychedelic with therapeutic potential for treating mental illnesses 1–4 . At the cellular level, psychedelics induce structural neural plasticity 5,6 , exemplified by the drug-evoked growth and remodeling of dendritic spines in cortical pyramidal cells 7–9 . A key question is how these cellular modifications map onto cell type-specific circuits to produce...
Meditation-based interventions are novel and effective non-pharmacologic treatments for veterans with PTSD. We examined relationships between treatment response, early life trauma exposure, DNA polymorphisms, and methylation in the serotonin transporter (SLC6A4) and FK506-binding protein 5 (FKBP5) genes. DNA samples and clinical outcomes were examined in 72 veterans with PTSD who received...
MDMA is a promising adjunct to psychotherapy and has well-known abuse liability, although less than other amphetamine analogs. While the reinforcing dopamine (DA)-releasing properties of MDMA are on par with methamphetamine (METH), MDMA is a far more potent serotonin (5-HT) releaser, via the 5-HT transporter (SERT). MDMA-mediated 5-HT release in a major reward center, the nucleus accumbens...
Serotonergic psychedelics, known for their hallucinogenic effects, have attracted interest due to their ability to enhance neuronal plasticity and potential therapeutic benefits. Although psychedelic-enhanced neuroplasticity is believed to require activation of 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs), serotonin itself is less effective in promoting such plasticity. Also, the...
The distinct subjective effects that define psychedelics such as LSD, psilocybin or DOI as drug class are causally linked to activation of the serotonin 2A receptor (5-HT 2A R). However, some aspects of 5-HT 2A R pharmacology remain elusive, such as what molecular drivers differentiate psychedelic from non-psychedelic 5-HT 2A R agonists. We developed an ex vivo platform to obtain snapshots of...
There has been a recent renewed interest in the potential use of psychedelic drugs as therapeutics for certain neuropsychiatric disorders, including substance use disorders. The psychedelic drug 2,5-dimethoxy-4-iodoamphetamine (DOI) has demonstrated therapeutic efficacy in preclinical models of opioid use disorder (OUD). Alcohol is commonly co-used in individuals with OUD, but preclinical...
Serotonergic psychedelics and ketamine produce rapid and long-lasting symptomatic relief in multiple psychiatric disorders. Evidence suggests that despite having distinct molecular targets, both drugs may exert therapeutic benefit via their pro-neuroplastic effects. Following treatment with ketamine or serotonergic psychedelics, patients are reported to be more open to behavioral change, which...
Mounting evidence points towards a crucial role of the kynurenine pathway (KP) in the altered gut-brain axis (GBA) balance in severe mental illness (SMI, namely depression, bipolar disorder, and schizophrenia) and cardiometabolic comorbidities. Preliminary evidence shows that serotonergic psychedelics and their analogues may hold therapeutic potential in addressing the altered KP in the...