Опубликована: Март 6, 2024
Subject Psychosocial Interventions and Psychotherapy Adult Clinical Psychology Psychiatry Psychopharmacology Collection: Oxford Scholarship Online
Язык: Английский
Nature Communications, Год журнала: 2023, Номер 14(1)
Опубликована: Дек. 15, 2023
Serotonergic psychedelics possess considerable therapeutic potential. Although 5-HT2A receptor activation mediates psychedelic effects, prototypical activate both 5-HT2A-Gq/11 and β-arrestin2 transducers, making their respective roles unclear. To elucidate this, we develop a series of 5-HT2A-selective ligands with varying Gq efficacies, including β-arrestin-biased ligands. We show that 5-HT2A-Gq but not 5-HT2A-β-arrestin2 recruitment efficacy predicts potential, assessed using head-twitch response (HTR) magnitude in male mice. further disrupting Gq-PLC signaling attenuates the HTR threshold level is required to induce psychedelic-like consistent fact certain partial agonists (e.g., lisuride) are non-psychedelic. Understanding role Gq-efficacy psychopharmacology permits rational development non-psychedelic agonists. also demonstrate block effects downregulation tachyphylaxis. Overall, Gq-signaling can be fine-tuned generate distinct from classical psychedelics.
Язык: Английский
Процитировано
44
Psychiatry Research, Год журнала: 2024, Номер 335, С. 115886 - 115886
Опубликована: Март 28, 2024
Язык: Английский
Процитировано
25
Ageing Research Reviews, Год журнала: 2024, Номер 96, С. 102211 - 102211
Опубликована: Фев. 1, 2024
Язык: Английский
Процитировано
13
Pharmacological Reports, Год журнала: 2023, Номер 75(6), С. 1362 - 1380
Опубликована: Окт. 24, 2023
Abstract Psychedelics are powerful psychoactive substances that alter perception and mood processes. Their effectiveness in the treatment of psychiatric diseases was known before their prohibition. An increasing number recent studies, due to indisputable resurgence serotonergic hallucinogens, have shown efficacy alleviating depression, anxiety, substance abuse therapies, existential distress patients facing life-threatening illness. generally considered be physiologically safe with low toxicity addictive potential. However, agonism at receptors should context possible serotonin-related cardiotoxicity (5-HT2A/2B 5-HT4 receptors), influence on platelet aggregation (5-HT2A receptor), proarrhythmic The use psychedelics has also been associated significant sympathomimetic effects both experimental clinical studies. Therefore, present review aims provide a critical discussion cardiovascular safety psilocybin, d-lysergic acid diethylamide (LSD), N,N-dimethyltryptamine, ayahuasca, mescaline, based results research trials humans. Experimental studies inconsistent information potential psychedelics. Data from point relative psychedelic-assisted therapies population “healthy” volunteers. there is insufficient evidence carried out microdoses psychedelics, still lack data disease. exact determination psychedelic (especially long-term therapies) requires further research.
Язык: Английский
Процитировано
20
Expert Review of Clinical Pharmacology, Год журнала: 2023, Номер 16(11), С. 1109 - 1123
Опубликована: Ноя. 2, 2023
Introduction The renewed interest in considering a range of stimulants, psychedelics and dissociatives as therapeutics emphasizes the need to draft an updated overview these drugs' clinical pharmacological issues.
Язык: Английский
Процитировано
13
Food Bioscience, Год журнала: 2023, Номер 55, С. 103044 - 103044
Опубликована: Авг. 12, 2023
Язык: Английский
Процитировано
12
The International Journal of Neuropsychopharmacology, Год журнала: 2025, Номер unknown
Опубликована: Янв. 2, 2025
Abstract Background Recent interest in the clinical use of psychedelics has highlighted plant-derived medicines like ayahuasca showing rapid-acting and sustainable therapeutic effects various psychiatric conditions. This traditional Amazonian plant decoction contains N,N-dimethyltryptamine (DMT) β-carboline alkaloids such as harmine. However, its is often accompanied by distressing nausea, vomiting, intense hallucinations, possibly due to complex pharmacokinetic/pharmacodynamic (PK-PD) interactions lack dose standardization. Methods study addresses these limitations testing a novel pharmaceutical formulation containing pure forms DMT harmine double-blind, randomized, placebo-controlled trial with 31 healthy male volunteers. We evaluated PK-PD monitoring drug metabolite plasma levels, subjective effects, adverse events, cardiovascular parameters. Each participant received three randomized treatments: 1) 100 mg buccal intranasal DMT, 2) placebo, 3) full placebo; using repeated-intermittent dosing scheme, that 10 (or placebo) was administered every 15 minutes. Results produced consistent PK profiles Cmax values 22.1 ng/ml acute resembling psychological duration 2–3 hours. Likewise, sustained-release 32.5 ng/ml, but lacked distinguishable compared placebo. All conditions were safe well tolerated, indicating formulation's suitability for applications. Conclusion underscores potential patient-oriented reduce risks improve outcomes treating mental health disorders.
Язык: Английский
Процитировано
0
Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2025, Номер unknown, С. 111259 - 111259
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Cellular and Molecular Life Sciences, Год журнала: 2025, Номер 82(1)
Опубликована: Янв. 21, 2025
The current opioid crisis has had an unprecedented public health impact. Approved medications for use disorder (OUD) exist, yet their limitations indicate a need innovative treatments. Limited preliminary clinical studies suggest specific psychedelics might aid OUD treatment, though most evidence remains observational, with few controlled trials. This review aims to bridge the gap between preclinical findings and potential applications, following PRISMA-ScR guidelines. Searches included MEDLINE, Embase, Scopus, Web of Science, focusing on in vivo involving opioids animals, excluding pain those lacking control groups. Forty met criteria, covering both classic non-classic psychedelics. Most showed that 18-methoxycoronaridine (18-MC), ibogaine, noribogaine, ketamine could reduce self-administration, alleviate withdrawal symptoms, change conditioned place preference. However, seven (two 2,5-dimethoxy-4-methylamphetamine (DOM), three one 18-MC, ketamine) no improvement over controls. A methodological quality assessment rated as having unclear quality. Interestingly, are limited iboga derivatives, which were effective, but these agents may have higher cardiovascular risk than other under-explored date. strengthens support translational testing targets OUD. It also suggests include broader range beyond derivatives can explore several ongoing questions field, such mechanism action behind therapeutic effect, safety profiles, doses, frequency administrations needed.
Язык: Английский
Процитировано
0
Expert Opinion on Emerging Drugs, Год журнала: 2025, Номер unknown
Опубликована: Апрель 3, 2025
Although long known for their psychoactive effects, psychedelic drugs have only recently been investigated medicinal use. Psilocybin has attracted the greatest interest with studies suggesting that it may be a useful agent in psychiatry and palliative care. Clinical trials included psilocybin were searched PubMed, Embase, ClinicalTrials.gov, demonstrating adult care are medical fields show treatment. is powerful drug needs to used caution but benefit some patients, including when other options failed. It best evidenced treatment resistant depression care, where patients usually treated specialist centers. novel mechanism of action, targeting 5HT2A receptor, can rapid onset action. There many questions regarding its use remain clarified, efficacy indications role as adjunctive psychotherapy. The psychoactive, or effects well documented, clinical importance disputed.
Язык: Английский
Процитировано
0