Psilocin (4-hydroxy-N, N-dimethyltryptamine) is a substituted tryptamine alkaloid and a nonselective serotonergic agonist acting predominantly at 5-HT2A/C receptors, with substantial binding to 5-HT1A and 5-HT2B receptors. Microdosing is the practice of taking a very small, sub-perceptual dose, typically 5% to 10% of a full recreational dose, to improve mood, creativity, and focus without...
Depression affects hundreds of millions globally, and in 2019, esketamine, an S-enantiomer of ketamine, was approved for treatment-resistant depression (TRD). While effective, esketamine carries risks, including abuse potential and adverse effects even at low doses. As a result, ketamine's metabolite, (2R,6R)-hydroxynorketamine ((2R,6R)-HNK), has garnered attention for its potential...
Deschloroketamine (DCK), a structural analogue of ketamine, has recently emerged on the illicit drug market as a recreational drug with a modestly long duration of action. Despite it being widely used by recreational users, no systematic research on its effects has been performed to date. Pharmacokinetics, acute effects, and addictive potential in a series of behavioural tests in Wistar rats...
Naphthylpyrovalerone (naphyrone) is a pyrovalerone cathinone that potently inhibits monoamine transporters and provides stimulatory-entactogenic effects. Little is known about the safety of naphyrone or its effects in vivo, and more research is needed to acquire knowledge about its fundamental effects on physiology and behaviour. Our objective was to investigate naphyrone's pharmacokinetics,...
Synthetic cannabinoid compounds are marketed as ‘legal’ marijuana substitutes, even though little is known about their behavioral effects in relation to their pharmacokinetic profiles. Therefore, in the present study we investigated the behavioral effects of systemic treatment with the two synthetic cannabinoids JWH-073 and JWH-210 and the phytocannabinoid Δ9-THC on locomotor activity and...
3,4-methylenedioxypyrovalerone (MDPV) is a potent pyrovalerone cathinone that is substituted for amphetamines by recreational users. We report a comprehensive and detailed description of the effects of subcutaneous MDPV (1-4 mg/kg) on pharmacokinetics, biodistribution and metabolism, acute effects on thermoregulation under isolated and aggregated conditions, locomotion (open field) and sensory...
Short-term moderate doses of serotonergic and dissociative hallucinogens can be useful in the treatment of anxiety. Recently, a trend has developed for long-term intermittent 'microdosing' (usually one-tenth of a 'full' active dose), with reports of long-lasting relief from anxiety and related disorders; however, there is no scientific evidence for the efficacy of therapeutic microdosing nor to...
Mephedrone (MEPH) is a synthetic cathinone derivative with effects that mimic MDMA and/or cocaine. Our study in male Wistar rats provides detailed investigations of MEPH's and its primary metabolite nor-mephedrone's (nor-MEPH) pharmacokinetics and bio-distribution to four different substrates (serum, brain, lungs, and liver), as well as comparative analysis of their effects on locomotion [open...
Metabolic and behavioural effects of, and interactions between Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are influenced by dose and administration route. Therefore we investigated, in Wistar rats, effects of pulmonary, oral and subcutaneous (sc.) THC, CBD and THC+CBD. Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h,...
-methylcathinone) is a synthetic cathinone analog of the recreational drug ecstasy. Although it is marketed to recreational users as relatively safe, fatalities due to hyperthermia, serotonin syndrome, and multi-organ system failure have been reported. Since psychopharmacological data remain scarce, we have focused our research on pharmacokinetics, and on a detailed evaluation of temporal...
Objectives: Aminoindanes (“bath salts”, a class of novel psychoactive substances, NPSs) increased rapidly in popularity on the recreational drug market, particularly after mephedrone and other synthetic cathinones were banned in the UK in 2010. Novel aminoindanes continue to emerge, but relatively little is known about their effects and risks. Their history, chemistry, pharmacology, behavioural...
Methoxetamine (MXE) is a novel psychoactive compound (NPS) that emerged in 2010 as a substitute for the dissociative anaesthetic ketamine. MXE has a reputation of carrying a lower risk of harm than ketamine, however a number of deaths have been reported. Currently very little is known about the psychopharmacological effects of this compound or its toxicity; therefore we tested, in Wistar rats,...