Letheby’s "Philosophy of Psychedelics" relies on Predictive Processing to try and find unifying explanations relevant to understanding how serotonergic psychedelics work in psychiatric therapy, what subjective experiences are associated with their use and whether such experiences are epistemically defective. But if Predictive Processing lacks genuinely explanatory unifying power, Letheby’s...
Classic psychedelics are a loosely grouped class of drugs that activate serotonin 5HT2A receptors to induce complex behavioral, psychological, and physiological effects [1]; 5HT2A agonism induces the hallucinogenic experiences that distinguish psychedelics [2] while pre-medicating with a 5HT2A antagonist, such as ketanserin, prevents them [3,4]. In the 1950s and 1960s, after Albert Hoffman’s...
Introduction: The 5-HT1B receptor has a potential role in various psychiatric disorders such as depression, anxiety, and post-traumatic stress disorder. The objective of this study was to perform docking and molecular dynamics simulation to evaluate at atomic level the behavior of N,N-dimethyltryptamine (DMT) on 5-HT1B receptor.Methods: In this study, initially, a search for DMT was performed...
Abstract Rationale LSD is the prototypical psychedelic. Despite a clear central role of the 5HT 2a receptor in its mechanism of action, the contributions of additional receptors for which it shows affinity and agonist activity remain unclear. Objectives We employed receptor-enriched analysis of functional connectivity by targets (REACT) to explore differences in functional connectivity (FC)...
The approval of ketamine for treatment-resistant depression has created a model for a novel class of rapid-acting glutamatergic antidepressants. Recent research into other novel rapid-acting antidepressants – most notably serotonergic psychedelics (SPs) – has also proven promising. Presently, the mechanisms of action of these substances are under investigation to improve these novel treatments,...
Lysergic acid diethylamide (LSD) is a serotonergic psychedelic compound receiving increasing interest due to putative anxiolytic and antidepressant properties. However, the potential neurobiological mechanisms mediating these effects remain elusive. Employing in vivo electrophysiology, microionthophoresis, behavioral paradigms and morphology assays, we assessed the impact of acute and chronic...
Abstract Humans are inherently social beings. Being suggestible to each other's expectations enables pro‐social skills that are crucial for social learning and adaptation. Despite their high relevance for psychiatry, the neurobiological mechanisms underlying social adaptation are still not well understood. This review, therefore, provides a conceptual framework covering various distinct...
Treatment with ayahuasca during alcohol abstinence blocked the expression of alcohol self-administration in mice, and 5-HT2A receptor activation is critical for those effects to emerge. Our findings support a potential for ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.
Biophysical JournalMarch 1, 2022Matthew C Chan, Balaji Selvam, Heather J Young et al.
The serotonin transporter (SERT) initiates the reuptake of extracellular serotonin in the synapse to terminate neurotransmission. The cryogenic electron microscopy structures of SERT bound to ibogaine and the physiological substrate serotonin resolved in different states have provided a glimpse of the functional conformations at atomistic resolution. However, the conformational dynamics and...
Several Apocynaceae species, most notably Tabernanthe iboga, Voacanga africana and many Tabernaemontana species, produce ibogan-type alkaloids. Although a large amount of information exists about the Tabernaemontana genus, knowledge concerning chemistry and biological activity remains lacking for several species, especially related to their effects on the central nervous system (CNS). The aim...