There are many factors that influence the addictiveness of a drug. The route of administration is a major determinant of the speed of drug entry into the body and to receptors in the central nervous system. Clinical studies are in progress which determine the importance of different routes of administration and the relationship of blood concentrations of drug and active metabolites to concomitant drug effects. Studies of heroin, cocaine, methamphetamine, codeine and cannabis administration by the intravenous, smoked, intranasal and oral routes are underway or in the data analysis stage. Pharmacodynamic effects include subjective, cognitive and psychomotor performance, physiological measures and specific brain activity as assessed by fMRI. Plasma, urine, oral fluid, sweat, hair and skin are analyzed for drug and metabolites by solid phase extraction-gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. The intravenous and smoked routes produce a rapid onset of pharmacological effects together with an early appearance of drug and metabolites in blood. Evidence of delays in distribution to effector sites are observed following cannabis smoking, but drug effects following heroin and cocaine administration coincided more closely with concurrent blood concentrations. Onset of effects is delayed following intranasal and especially after oral administration. The emerging face of drug abuse is the plethora of new designer drugs. Two main classes of designer drugs are the synthetic cannabinoids and synthetic cathinones. The pharmacodynamics and pharmacokinetics of these new drugs are mostly unknown. We are endeavoring to conduct a controlled synthetic cannabinoid human administration study, but until this is possible, we are using human hepatocyte cultures and high resolution accurate mass spectrometry to characterize the metabolic profiles of these new designer drugs.

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