Major depressive disorder is typically treated with selective serotonin reuptake inhibitors (SSRIs), however, SSRIs take approximately six weeks to produce therapeutic effects, if any. Not surprisingly, there has been great interest in findings that low doses of ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produce rapid and long-lasting antidepressant effects....
Serotonin 2A (5-HT2A) receptors are the primary site of action of hallucinogenic drugs and the target of atypical antipsychotics. 5-HT2A receptors are also implicated in executive function, including behavioral flexibility. Previous studies showed that 5-HT2A receptor blockade improved behavioral flexibility in rodent models related to autism spectrum disorder and schizophrenia. The current...
It has been brought to the authors' attention that Fig. 1 of "In vitro structure-activity relationship determination of 30 psychedelic new psychoactive substances by means of β-arrestin 2 recruitment to the serotonin 2A receptor" contained a mistake in the structures for 2C-B-FLY and Bromo-DragonFLY. This has now been corrected. The authors apologize for any inconvenience caused.
Psychedelic new psychoactive substances (NPS), compounds exerting their main pharmacological effects through the activation of the serotonin 2A receptor (5-HT2AR), continuously comprise a substantial portion of the reported NPS. However, these substances and their exact mechanism of action, differentiating them from non-psychedelic 5-HT2AR agonists, require further characterization. One...
Recent research has shown that classical serotonergic psychedelic (CSP) drugs may be used to ameliorate certain health issues and disorders. Here we hypothesised that CSP experiences, through their ability to induce awe and ego-dissolution, may result in a reduction of maladaptive narcissistic personality traits, such as a strong sense of entitlement and lack of empathy. Our objective was to...
A strategy to replace the ethylamine side chain of 2,5-dimethoxy-4- iodoamphetamine (DOI, 1a), and 2,5-dimethoxy-4-bromoamphetamine (DOB, 1b) with a cyclopropylamine moiety was successful in leading to compounds with high affinity at the 5-HT 2 family of receptors; and the more potent stereoisomer of the cyclopropane analogues had the expected (-)-(1R,2S)- configuration. Screening for affinity...
Despite several compounds entering clinical trials for the negative and cognitive symptoms of schizophrenia, few have progressed beyond phase III. This is partly attributed to a need for improved preclinical models, to understand disease and enable predictive evaluation of novel therapeutics. To this end, one recent approach incorporates "dual-hit" neurodevelopmental insults like neonatal...
BACKGROUND: Chronic exposure to the Δ9-tetrahydrocannabinol (THC), the main cannabis pharmacological component, during adolescence has been shown to be associated with an increased risk of depression and suicidality in humans. AIMS: Little is known about the impact of the long-term effects of chronic exposure to low doses of THC in adolescent compared to adult rodents. METHODS: THC (1mg/kg...
Abstract Adapting one’s attitudes and behaviors to group norms is essential for successful social interaction and, thus, participation in society. Yet, despite its importance for societal and individual functioning, the underlying neuropharmacology is poorly understood. We therefore investigated its neurochemical and neural correlates in a pharmacological functional magnetic resonance imaging...
Serotonergic psychedelics, substances exerting their effects primarily through the serotonin 2A receptor (5-HT2AR), continue to comprise a substantial portion of reported new psychoactive substances (NPS). The exact mechanisms of action of psychedelics still remain to be elucidated further, and certain pathways remain largely unexplored on a molecular level for this group of compounds. A...