The selective 5-HT2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents DOI Creative Commons
Anders A. Jensen, Cláudia R. Cecchi, Meghan Hibicke

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 22, 2024

ABSTRACT Psychedelic-assisted psychotherapy has over the last decade emerged as a promising treatment strategy for mental health disease, and therapeutic potential in classical psychedelics such psilocybin, LSD 5-MeO-DMT is presently being pursued plethora of clinical trials. However, resurgent interest drugs therapeutics also prompted search novel agents with more specific pharmacological activities than rather promiscuous psychedelics. Here we present results an elaborate preclinical characterization one compound, LPH-5 [( S )-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine]. was found to be potent partial agonist at 5-HT 2A receptor (5-HT R) exhibit pronounced selectivity this related 2B 2C receptors range functional assays. (0.375 – 12.0 mg/kg, i.p. ) dose-dependently induced head-twitch responses (HTR) Sprague Dawley rats, substantial R engagement observed 0.5-1.0 mg/kg. Acute administration (1.5 i.p .) robust antidepressant-like effects Flinders Sensitive Line rats adrenocorticotropic hormone-treated (0.3 1.5 significant recently developed Wistar Kyoto rat model proposed reflect long-term produced by humans. In conclusion, selective activation, mediated here LPH- 5, seems hold antidepressant potential, suggesting that activity component key beneficial Hence, propose other R- agonists could psychiatric disease new generation psychedelic-derived antidepressant.

Язык: Английский

TAAR1 as an emerging target for the treatment of psychiatric disorders DOI Creative Commons
Jianfeng Liu, Ruyan Wu, Jun‐Xu Li

и другие.

Pharmacology & Therapeutics, Год журнала: 2023, Номер 253, С. 108580 - 108580

Опубликована: Дек. 22, 2023

Язык: Английский

Процитировано

13
Endocannabinoid Hydrolase Inhibitors: Potential Novel Anxiolytic Drugs DOI Creative Commons

Hong-Qing Zhao,

Yang Liu, Na Cai

и другие.

Drug Design Development and Therapy, Год журнала: 2024, Номер Volume 18, С. 2143 - 2167

Опубликована: Июнь 1, 2024

Abstract: Over the past decade, idea of targeting endocannabinoid system to treat anxiety disorders has received increasing attention. Previous studies focused more on developing cannabinoid receptor agonists or supplementing exogenous cannabinoids, which are prone various adverse effects due their strong pharmacological activity and poor selectivity, limiting application in clinical research. Endocannabinoid hydrolase inhibitors considered be most promising development strategies for treatment disorders. More recent efforts have emphasized that inhibition two major endogenous hydrolases, monoacylglycerol lipase (MAGL) fatty acid amide (FAAH), indirectly activates receptors by levels synaptic gap, circumventing desensitization resulting from direct enhancement signaling. In this review, we comprehensively summarize anxiolytic MAGL FAAH potential mechanisms, highlight reported novel natural products, provide an outlook future directions field. Keywords: inhibitors, system, disorders, anxiolytic, MAGL,

Язык: Английский

Процитировано

4
Serotonergic neuromodulation of synaptic plasticity DOI
Guilherme Shigueto Vilar Higa, Felipe José Costa Viana, José Fernando de Oliveira

и другие.

Neuropharmacology, Год журнала: 2024, Номер 257, С. 110036 - 110036

Опубликована: Июнь 12, 2024

Язык: Английский

Процитировано

4
Clinical Research on Lysergic Acid Diethylamide (LSD) in Psychiatry and Neuroscience DOI Creative Commons
Hossein Omidian,

Alborz Omidian

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 499 - 499

Опубликована: Март 29, 2025

Lysergic acid diethylamide (LSD) is gaining renewed interest as a potential treatment for anxiety, depression, and alcohol use disorder, with clinical trials reporting significant symptom reductions long-lasting effects. LSD modulates serotonin (5-HT2A) receptors, which, in turn, influence dysfunctional brain networks involved emotional processing cognition. It has also shown promise psychedelic-assisted psychotherapy, where mystical-type experiences are linked to improved psychological well-being. This review examines LSD’s pharmacokinetics, neurobiological mechanisms, safety considerations, including cardiovascular risks, vulnerability, the hallucinogen-persisting perception disorder (HPPD). Challenges such small sample sizes, variable dosing protocols, regulatory restrictions limit large-scale trials. Future research should focus on standardization, pharmacogenetic influences, personalized strategies ensure its safe effective integration into practice.

Язык: Английский

Процитировано

0
The Selective Serotonin 5-HT2A Receptor Agonist (S)-3-(2,5-Dimethoxy-4-(trifluoromethyl)phenyl)piperidine (LPH-5) Induces Persistent and Robust Antidepressant-Like Effects in Rodents DOI
Anders A. Jensen, Cláudia R. Cecchi, Meghan Hibicke

и другие.

ACS Pharmacology & Translational Science, Год журнала: 2025, Номер unknown

Опубликована: Май 29, 2025

Язык: Английский

Процитировано

0
Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective? DOI Creative Commons
Giuseppe Pasculli, Pierpaolo Busan, Eric S. Jackson

и другие.

Frontiers in Human Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Июнь 19, 2024

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has significant negative impact on quality of life, interventions for it have limited efficacy. Herein, we briefly review existing research the neurophysiological underpinnings -specifically, brain metabolic default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered investigated (e.g., in randomized clinical trials) treatment DS. The neural background likely to heterogeneous, some contribution from genetically determinants deficiencies basal ganglia cortical regions are thought play role appearance symptoms, which possibly results cascade events contributing impairments execution. In persistent DS, difficulties speech linked series associated aspects social anxiety avoidance. this context, SCN DMN (also influencing fronto-parietal, somato-motor, attentional networks) may worsening dysfluencies. Interestingly, metabolism SCN/DMN connectivity can modified psychedelics, been shown improve evidence psychiatric conditions depression, post-traumatic stress disorder, etc.) with psychological constructs rumination anxiety, also tend present To date, while there no controlled trials effects psychedelics anecdotal suggests these agents beneficial its characteristics. We suggest warrant investigation

Язык: Английский

Процитировано

2
Psychedelics as an intervention for psychological, existential distress in terminally ill patients: A systematic review and network meta-analysis DOI
Mattia Marchi,

Riccardo Farina,

Karim Rachedi

и другие.

Journal of Psychopharmacology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 10, 2024

Background: The interest in psychedelics as a therapeutic intervention for existential distress of people with terminal illness grounds on their mechanism action and effect the spiritual/existential aspects accompanying end-of-life experiences. Aims: This systematic review network meta-analysis aimed at examining efficacy safety psychedelic compounds terminally ill people. Methods: PubMed, CINAHL, PsycINFO, EMBASE, clinicaltrials.gov were searched randomized controlled trials (RCTs) administering illnesses. Meta-analysis estimated standardized mean difference (SMD) odds ratio (OR), corresponding 95% confidence intervals (95% CI), between treated control groups pairwise comparisons, using random-effects models. Post-treatment measures depression anxiety, proxies distress, tolerability primary outcomes. Results: Nine studies, involving 606 participants (362 psychedelics: psilocybin, ketamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide (LSD)) included. supported (SMD: −0.80 CI: −0.98, −0.63)) anxiety −0.84 −1.20, −0.48)). Network identified psilocybin most effective compound depression, LSD anxiety. However, head-to-head comparison did not reach statistical significance. rates treatment discontinuation adverse events controls comparable. Conclusions: Psychedelics, especially psilocybins LSD, showed promising effects Limitations include small number RCTs, methodological issues related to blinding, lack direct comparisons compounds. Larger studies comparative research are needed consolidate these findings.

Язык: Английский

Процитировано

1
Psychedelic use and bipolar disorder – An investigation of recreational use and its impact on mental health DOI
Thomas D. Meyer,

M.A. Ibrahim,

L. Vale

и другие.

Journal of Affective Disorders, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

0
The selective 5-HT2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents DOI Creative Commons
Anders A. Jensen, Cláudia R. Cecchi, Meghan Hibicke

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 22, 2024

ABSTRACT Psychedelic-assisted psychotherapy has over the last decade emerged as a promising treatment strategy for mental health disease, and therapeutic potential in classical psychedelics such psilocybin, LSD 5-MeO-DMT is presently being pursued plethora of clinical trials. However, resurgent interest drugs therapeutics also prompted search novel agents with more specific pharmacological activities than rather promiscuous psychedelics. Here we present results an elaborate preclinical characterization one compound, LPH-5 [( S )-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine]. was found to be potent partial agonist at 5-HT 2A receptor (5-HT R) exhibit pronounced selectivity this related 2B 2C receptors range functional assays. (0.375 – 12.0 mg/kg, i.p. ) dose-dependently induced head-twitch responses (HTR) Sprague Dawley rats, substantial R engagement observed 0.5-1.0 mg/kg. Acute administration (1.5 i.p .) robust antidepressant-like effects Flinders Sensitive Line rats adrenocorticotropic hormone-treated (0.3 1.5 significant recently developed Wistar Kyoto rat model proposed reflect long-term produced by humans. In conclusion, selective activation, mediated here LPH- 5, seems hold antidepressant potential, suggesting that activity component key beneficial Hence, propose other R- agonists could psychiatric disease new generation psychedelic-derived antidepressant.

Язык: Английский

Процитировано

0