Abstract Hallucinogens constitute a unique class of substances that cause changes in the user's thoughts, perceptions, and mood through various mechanisms of action. Although the serotonergic hallucinogens such as lysergic acid diethylamide, psilocybin, and N,N‐ dimethyltryptamine have been termed the classical hallucinogens , many hallucinogens elicit their actions through other mechanisms...
Pyrovalerone cathinones are potent psychoactive substances that possess a pyrrolidine moiety. Pyrovalerone-type novel psychoactive substances (NPS) are continuously detected but their pharmacology and toxicology are largely unknown. We assessed several pyrovalerone and related cathinone derivatives at the human norepinephrine (NET), dopamine (DAT), and serotonin (SERT) uptake transporters using...
Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to...
Summary Psilocybin is a serotonergic psychedelic with untapped therapeutic potential. There are hints that the use of psychedelics can produce neural adaptations, although the extent and time scale of the impact in a mammalian brain are unknown. In this study, we used chronic two-photon microscopy to image longitudinally the apical dendritic spines of layer 5 pyramidal neurons in the mouse...
Abstract Psychedelic drugs are gaining attention from the scientific community as potential new compounds for the treatment of psychiatric diseases such as mood and substance use disorders. The 5-HT 2A receptor has been identified as the main molecular target, and early studies pointed to an effect on the expression of neuroplasticity genes. Analysing RNA-seq data from the prefrontal cortex of...
New psychoactive stimulants and psychedelics continue to play an important role on the illicit new psychoactive substance (NPS) market. Designer stimulants and psychedelics both affect monoaminergic systems, although by different mechanisms. Stimulant NPS primarily interact with monoamine transporters, either as inhibitors or as substrates. Psychedelic NPS most potently interact with...
Abstract Rationale 4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe) is a potent serotonin 5-HT 2A/2C receptor agonist with hallucinogenic activity. There is no data on the 25I-NBOMe effect on brain neurotransmission and animal performance after chronic administration. Objectives We examined the effect of a 7-day treatment with 25I-NBOMe (0.3 mg/kg/day) on neurotransmitters’...
Abstract The status of serotonin 5HT 2A receptors (5HT 2A Rs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5HT 2A R density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study...
The anesthetic drug ketamine has been successfully repurposed as an antidepressant in human subjects. This represents a breakthrough for clinical psychopharmacology, because unlike monoaminergic antidepressants, ketamine has rapid onset, including in Major Depressive Disorder (MDD) that is resistant to conventional pharmacotherapy. This rapid therapeutic onset suggests a unique mechanism of...
BACKGROUND: Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not...