Role of the endogenous cannabinoid system in fear circuitry: Translational findings and clinical implications for post-traumatic stress disorder

Abstract

s / Drug and Alcohol Dependence 146 (2015) e34–e117 e61 Human pharmacology of mephedrone: A dose-finding pilot study Esther Papaseit1,3, Clara Perez-Mana1,3, Mitona Pujadas1, Francina Fonseca2, Marta Torrens2,3, Rafael De La Torre1,4, Magi Farre1,3 1 Human Pharmacology and Neurosciences, Hospital del Mar Medical Research Institute-IMIM, Barcelona, Spain 2 Drug Addiction Unit, Hospital del Mar-INAD, Barcelona, Spain 3 Universidad Autonoma de Barcelona-UAB, Barcelona, Spain 4 Universidad Pompeu Fabra-UPF, Barcelona, Spain Aims: Mephedrone is a synthetic cathinone included in the “Novel Psychoactive Substances” group. European epidemiological data showed a high prevalence of use. There are not experimental data in humans of the pharmacological effects of mephedrone. Objective was to obtain preliminary data on the effects of mephedrone and doses for future investigations. Methods: Nine healthy male, recreational users of psychostimulants, participated as outpatients in three different experimental sessions, inwhichoneof the substanceswasadministeredeachday. They receivedsingleoraldosesofmephedrone (n=3,50mg,100mg and placebo; n=3, 150mg, 200mg and placebo; n=3, 150mg, 200mg and MDMA 100mg). Drugs were administered doubleblind, and randomised (lower doses were allocated before higher doses for safety reasons in case of 150mg and 200mg). Study variables included: vital signs (blood pressure, heart rate, temperature, pupil diameter), subjective effects (visual analog scales-VAS, ARCI49 item short form, VESSPA questionnaire), and blood and urine samples for pharmacokinetics. Results: Mephedrone produced effects at 150 and 200mg, with dose-related increases of blood pressure, heart rate and pupil diameter (but not temperature).Mephedrone producedmore intense effects than MDMA. Mephedrone induced pleasurable effects (ARCI-MBG, VAS “good effects”, VAS “liking”), and mild changes in perceptions but not hallucinations. Conclusions:Mephedroneproducesdose-relatedeffects invital parameters and pleasurable subjective effects. Its pharmacologic profile is similar to MDMA and other psychostimulants. Financial support: Supported by grants from Instituto de Salud Carlos III (ISCIII, FIS-FEDER, FIS PI11/0196), ISCIII-Red de Trastornos Adictivos (RTA RD12/0028/0009). Clara Perez-Mana is a Rio Hortega fellowship (ISCIII, CM12/00085). Esther Papaseit is a Jordi Gras (PSMAR, 2013) and a Rio Hortega fellowship (ISCIII, CM12/00016, 2014). http://dx.doi.org/10.1016/j.drugalcdep.2014.09.534 Role of the endogenous cannabinoid system in fear circuitry: Translational findings and clinical implications for post-traumatic stress disorder Santiago Papini1,2, D.A. Hien1,2, Y. Neria2, F. Levin2 1 City College, New York, NY, United States 2 New York State Psychiatric Institute, New York, NY,