Objective: The aim was to summarize the clinical literature on interactions between common illicit drugs and prescription therapies. Methods: Medline, Iowa Drug Information Service, International Pharmaceutical Abstracts, EBSCO Academic Search Premier, and Google Scholar were searched from date of origin of database to March 2011. Search terms were cocaine, marijuana, cannabis, methamphetamine, amphetamine, ecstasy, N-methyl-3,4- methylenedioxymethamphetamine, methylenedioxymethamphetamine, heroin, gamma-hydroxybutyrate, sodium oxybate, and combined with interactions, drug interactions, and drugdrug interactions. This review focuses on established clinical evidence. All applicable full-text English language articles and abstracts found were evaluated and included in the review as appropriate. Results: The interactions of illicit drugs with prescription therapies have the ability to potentiate or attenuate the effects of both the illicit agent and/or the prescription therapeutic agent, which can lead to toxic effects or a reduction in the prescription agent's therapeutic activity. Most texts and databases focus on theoretical or probable interactions due to the kinetic properties of the drugs and do not fully explore the pharmacodynamic and clinical implications of these interactions. Clinical trials with coadministration of illicit drugs and prescription drugs are discussed along with case reports that demonstrate a potential interaction between agents. The illicit drugs discussed are cocaine, marijuana, amphetamines, methylenedioxymethamphetamine, heroin, and sodium oxybate. Conclusion: Although the use of illicit drugs is widespread, there are little experimental or clinical data regarding the effects of these agents on common prescription therapies. Scientific Significance: Potential drug interactions between illicit drugs and prescription drugs are described and evaluated on the Drug Interaction Probability Scale by Horn and Hansten.

L’objectif de cette thèse est de détailler les effets respiratoires induits par les associations de l’éthanol au THC et de l’éthanol au GHB. Les études ont été menées chez l’animal non anesthésié par pléthysmographie corps entier pendant les quatre heures suivant l’administration intrapéritonéale. Dans une première étape, les effets respiratoires de la prise isolée d’éthanol et de GHB ont été étudiés. Ces deux substances modifient le mode respiratoire : l’éthanol provoquant une tachypnée dès 3 g.kg-1, le GHB une respiration apneustique dès 600 mg.kg-1, sans insuffisance respiratoire (PaO2 normale). Les modifications des gaz du sang observées : acidémie pour l’éthanol et alcalose pour le GHB sont d’origine métabolique. A ces doses, ces deux substances perturbent aussi la conscience des animaux et la thermorégulation : l’éthanol induit une hypothermie et le GHB une évolution triphasique de la température : hypothermie/hyperthermie/ hypothermie. Les dosages sanguins et les études cinétiques menés lors de ces études confirment la vraisemblance de notre modèle et sa pertinence clinique et médicolégale. L’étude des associations à l’éthanol montre que les effets respiratoires du THC et du GHB sont conservés, seule leur association à la dose de 3 g.kg-1 d’éthanol a provoqué une baisse de la ventilation minute avec réduction du débit inspiratoire mais selon des mécanismes différents : baisse du volume courant pour l’association THC-éthanol et augmentation de la durée des apnées expiratoires pour celle du GHB à l’éthanol. Pour cette dernière, l’interaction cinétique observée après administration intrapéritonéale n’explique pas l’intensité du phénomène, une potentialisation est probable. / The objective of this thesis was to study the time-course of the respiratory effects of THC/ethanol and GHB/ethanol associations. Respiration was studied using whole body plethysmography in non-anesthetized rats during the four hours following intraperitoneal injection. In a first step, both GHB and ethanol affected the respiratory pattern. Ethanol caused bradypnea at doses greater than 3 g.kg-1 and GHB induced apneusis above 600 mg.kg-1. Arterial blood gases modifications were metabolic: acidemia with ethanol and alkalosis with GHB. At those doses, both substances altered consciousness and body temperature of animals. Ethanol induced hypothermia and GHB a temperature triphasic change: hypothermia/ hyperthermia/hypothermia. Blood determinations and kinetic studies reinforced the likelihood, and clinical and forensic relevancies of our animal model. Association studies showed that the respiratory effects of THC and GHB were unchanged in presence of ethanol. Association with 3 g.kg-1 ethanol dose only provoked a reduction in minute volume and in mean inspiratory flow, but mechanisms were different. Ethanol and THC induced a decrease in tidal volume; ethanol and GHB an increase in expiratory apnea duration. The observed kinetic interaction between ethanol and GHB did not explain phenomenon intensity; a potentialization could occur.