title: Pharmacology should be at the centre of all preclinical and clinical studies on new psychoactive substances (recreational drugs).
abstract: Despite the publication of a substantial body of preclinical and clinical information on recent recreational drugs such as 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and cathinone compounds such as mephedrone there remains a disturbing lack of consensus as to how dangerous these compounds are to the health of the individual and to society in general. This perspective proposes that use of good pharmacological practice should be mandatory in all preclinical and clinical studies. Its use will assist both translation and reverse translation of information produced in animals and clinical subjects. We propose several basic rules to be followed in all future studies. Preclinical studies should employ pharmacokinetic-pharmacodynamic integration thereby exposing animals to known or calculable drug concentrations. This will provide results relevant to pharmacology rather than toxicology and, crucially, data relevant to human drug use. Full experimental detail should be routinely provided, to allow comparison with other similar work. In clinical studies evidence should be provided that the drug under investigation has been ingested by the subjects being examined, and details given of all other drugs being ingested. Drug-drug interactions are an unavoidable confound but studies of a size that allows reliable statistical evaluation and preferably allows sub-group analysis, particularly by using meta-analysis, should help with this problem. This may require greater collaboration between investigative groups, as routinely occurs during pharmaceutical clinical trials. Other proposals include greater integration of preclinical and clinical scientists in both preclinical and clinical studies and changes in the law regarding Good Manufacturing Process (GMP) sourcing of drug for human studies.
authors.affiliation: School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK richard.green@nottingham.ac.uk.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Green
authors.affiliation: Division of Neurosciences and Mental Health, Imperial College London, London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004347:Drug Interactions; D006801:Humans; D013287:Illicit Drugs / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D013287:Illicit Drugs
keywords: 3,4-methylenedioxymethamphetamine; Ecstasy; integrative pharmacology; mephedrone; new psychoactive substances; pharmacokinetics; quantitative pharmacology; recreational drugs