The discovery of ketamine as a rapid-acting antidepressant spurred significant research to understand its underlying mechanisms of action and to identify other novel compounds that may act similarly. Serotonergic psychedelics (SPs) have shown initial promise in treating depression, though the challenge of conducting randomized controlled trials with SPs and the necessity of long-term clinical...
Explore2023J C Thambyrajah, H W Dilanthi, S M Handunnetti et al.
Melatonin and its precursor serotonin are neurochemicals that play an important role in the physiological regulation of mood, sleep, and behavior. Studies have suggested the possibility of changes in the levels of melatonin and serotonin following meditation. However, the outcome of Buddhist meditation on both these two neurochemicals collectively have not been studied yet. To assess the effect...
Michael Cunningham - Pharmacological Mechanism of the Non-hallucinogenic 5-HT2A Agonist Ariadne and Analogs (psychedelic molecules, 4th-5th September 2023, Prague, Czech Republic)
Welcome to the April edition of Going on Trial, a monthly newsletter covering clinical trials and drug development for autism and related conditions.In this issue, we're talking about a serotonin agonist's path to trial for autism, debate around a trial of psilocybin for fragile X syndrome and an analysis of placebo responses in a clinical trial of the vasopressin blocker balovaptan.Feel free...
Certain 4-substituted analogs of 1-(2,5-dimethoxyphenyl)isopropylamine (2,5-DMA) are psychoactive classical hallucinogens or serotonergic psychedelic agents that function as human 5-HT2A (h5-HT2A) serotonin receptor agonists. Activation of a related receptor population, h5-HT2B receptors, has been demonstrated to result in adverse effects including cardiac valvulopathy. We previously published...
Background: Classic serotonergic psychedelics have anecdotally been reported to show a characteristic pattern of subacute effects that persist after the acute effects of the substance have subsided. These transient effects, sometimes labeled as the ‘psychedelic afterglow’, have been suggested to be associated with enhanced effectiveness of psychotherapeutic interventions in the subacute period....
Psychedelic-assisted therapy (PAT) may treat various mental health conditions. Despite its promising therapeutic signal across mental health outcomes, less attention is paid on its potential to provide therapeutic benefits across complex medical situations within rehabilitation medicine. Persons with spinal cord injury (SCI) have a high prevalence of treatment-resistant mental health...
Rationale: The psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are often attributed to agonism at brain serotonin 5-HT2A receptors by N,N-dimethyltryptamine (DMT). To reduce first pass metabolism of oral DMT, ayahuasca preparations additionally contain reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as harmine....
There is now evidence from multiple Phase II clinical trials that psychedelic drugs can exert long-lasting anxiolytic, anti-depressant, and anti-drug abuse (nicotine and ethanol) effects in patients. Despite these benefits, the hallucinogenic actions of these drugs at the serotonin 2A receptor (5-HT2AR) limit their clinical use in diverse settings. Activation of the 5-HT2AR can stimulate both G...
The antidepressant-like activity of (+)-catharanthine and (-)-18-methoxycoronaridine [(-)-18-MC] was studied in male and female mice using forced swim (FST) and tail suspension tests (TST). The underlying molecular mechanism was assessed by electrophysiological, radioligand, and functional experiments. The FST results showed that acute administration (40 mg/kg) of (+)-catharanthine or (-)-18-MC...