Psilocybin has emerged as a promising therapeutic agent for psychiatric disorders characterised by cognitive rigidity and disrupted reward processing, including anorexia nervosa. While its pro-cognitive effects have been mechanistically probed almost exclusively through serotonin receptor subtype antagonism, the downstream contributions of dopaminergic syste...
Psilocybin, a serotonergic psychedelic, has gained attention as a potential treatment for various psychiatric conditions. In this review, the authors summarize current clinical evidence related to psilocybin’s efficacy, safety, and mechanisms of action across psychiatric disorders. Findings from early-phase and small-scale clinical trials suggest rapid but v...
Introduction: Cognitive flexibility is essential for behavioral adaptation in response to environmental changes and is impaired in various neuropsychiatric disorders. The serotonergic psychedelic psilocybin has shown potential in enhancing cognitive flexibility, although with mixed results. In this study, we investigated the effects of psilocybin on cognitiv...
BACKGROUND AND AIMS: Drug discrimination procedures have made important contributions to the pre-clinical investigation of psychedelic drugs, such as psilocybin, lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT) and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). One of the most important being to highlight the critical role of central 5-HT2A rece...
Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m−2; s.d. 3.7) who met Diagnostic a...
N,N-dipropyltryptamine (DPT) is a synthetic tryptamine hallucinogen which has been used psychotherapeutically in humans, but has been studied preclinically only rarely. In the present studies, DPT was tested in a drug-elicited head-twitch assay in mice, and in rats trained to discriminate lysergic acid diethylamide (LSD), N,N-dimethyl-4-phosphoryloxytryptami...
Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time...
A series of fluorinated analogues of the hallucinogenic tryptamines N,N-diethyltryptamine (DET), 4-hydroxy-N,N-dimethyltryptamine (4-OH-DMT, psilocin), and 5-methoxy-DMT was synthesized to investigate possible explanations for the inactivity of 6-fluoro-DET as a hallucinogen and to determine the effects of fluorination on the molecular recognition and activa...
The enantiomers of 3-(N-methylpyrrolidin-2-ylmethyl)-5-methoxyindole, 1, and 3-(N-methylpyrrolidin-2-ylmethyl)-4-hydoxyindole, 3, were prepared using an asymmetric synthesis that employed (+)- or (-)-proline. A new approach was developed that had certain advantages over the synthesis originally reported for the isomers of 1. (+/-)-3-(N-Methylpyrrolidin-3-yl)...
In order to further evaluate the extent to which particular 5-HT receptor subtypes (5-HT1, 5-HT2) might be involved in the behavioral effects of hallucinogenic drugs, rats were trained to discriminate mescaline (10 mg/kg i.p.) from saline and were given substitution (generalization) and combination (antagonism) tests with putatively selective serotonergic an...
The stimulus properties of 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and several related compounds were compared to those of (+)-lysergic acid diethylamide (LSD) and mescaline (3,4,5-trimethoxyphenylethylamine) in a two-lever, water-reinforced, drug discrimination task. In animals trained to discriminate LSD (0.08 mg/kg) f...
Fifteen rats were trained to discriminate between the tryptamine hallucinogen psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine; 1.0 mg/kg) and saline in a two-lever choice task. Dose-response and time-response curves were obtained. The psilocybin cue generalized to psilocin (the dephosphorylated congener of psilocybin) and to the prototypical indoleamine h...
Pigeons (N=4) were trained to discriminate between the effects induced by intramuscular (IM) injections of d-LSD and saline using a discrete-trial discrimination paradigm (choice between left and right hand key) in a conventional operant box. The solutions were administered IM15 min prior to the sessions. A FR15 schedule was in operation to produce food. Whi...
