There has been substantial and growing interest in the therapeutic utility of drugs acting at serotonin 2A subtype (5-HT 2A ) receptors, increasing the need for characterization of potential beneficial and adverse effects of such compounds. Although numerous studies have evaluated the possible rewarding and reinforcing effects of 5-HT 2A receptor agonists, there have been relatively few studies...
The recent review of a new drug application for MDMA-assisted therapy for post-traumatic stress disorder by the United States’ Food and Drug Administration (FDA) highlighted epistemological and methodological challenges for evidence assessments. Similar challenges will also be faced in reviews of other compounds in early- and late-stage development, like psilocybin for depression. The...
Administration or consumption of classic psychedelics (CPs) leads to profound changes in experience which are often described as highly novel and meaningful. They have shown substantial promise in treating depressive symptoms and may be therapeutic in other situations. Although research suggests that the therapeutic response is correlated with the intensity of the experience, the neural circuit...
Results from clinical trials show that serotonergic psychedelics have efficacy in treating psychiatric disorders, where currently approved pharmacotherapies are inadequate. Developing psychedelic medicines, however, comes with unique challenges, such as tempering heightened anxiety associated with the psychedelic experience. We conceived a new strategy to potentially mitigate psychedelic...
Diviner's sage (Salvia divinorum; Lamiaceae) is the source of the powerful hallucinogen salvinorin A (SalA). This neoclerodane diterpenoid is an agonist of the human Κ-opioid receptor with potential medical applications in the treatment of chronic pain, addiction, and post-traumatic stress disorder. Only two steps of the approximately twelve step biosynthetic sequence leading to SalA have been...
Major depressive disorder is a multifactorial disorder that originates from a complex web of variables and overlaps with similar disorders (e.g., depression and anxiety). As such, animal models should account for the considerable symptom overlap between psychiatric disorders. We sought to extend the findings of behavioral assays that encompass both anxiety and stress/depression components. To...
Ketamine can induce persisting psychosis in a subset of individuals who use it chronically and heavily. Previously, we found that the psychopathology and cognitive impairments in patients with ketamine dependence (KD) exhibiting persistent psychosis (KPP) bear resemblances with schizophrenia, albeit with less severity in those with no persistent psychosis (KNP). Furthermore, we also showed that...
Standard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the GluN2B subunit of the NMDA receptor on...
Understanding the precise mechanisms of ketamine is crucial for replicating its rapid antidepressant effects without inducing psychomimetic changes. Here, we explore whether the antidepressant-like effects of ketamine enantiomers are underscored by protection against cytokine-induced reductions in hippocampal neurogenesis and activation of the neurotoxic kynurenine pathway in our...
CureusOctober 1, 2024Sana Rahman, Samiya Saher, Anurag Raje et al.
Ketamine-induced uropathy (KIU) is a serious consequence of chronic ketamine abuse, presenting with complex renal and urinary symptoms. This study describes a 34-year-old female with a history of chronic ketamine abuse, resulting in stage 3 chronic kidney disease (CKD) and severe urological complications. Despite discontinuing ketamine use five years ago, she remains dependent on ureteral...