In conjunction with previous preclinical and human studies, the data suggest that adenosine modulating drugs may have value in the treatment of stimulant use disorders.Ĭhronic cocaine use results in measurable disruptions in the (DA) dopamine system. These preliminary data raise the possibility that adenosine antagonists may affect cocaine-dependent and non-dependent subjects differently. However, these differences also covaried with cigarette smoking status (not balanced between groups), and nicotine smoking is known to alter caffeine/paraxanthine metabolism via cytochrome P450 enzymes. The cocaine-dependent group expressed significantly higher paraxanthine levels than controls under 150 mg and 3–4 fold greater levels under 300 mg at 90 min and 150 min post caffeine dose. Large between-group differences in salivary paraxanthine (but not salivary caffeine) levels were obtained under both caffeine doses. Subjective effects results revealed dose × time and dose × group interactions on the ARCI A, ARCI LSD, and VAS ‘elated’ scales follow up tests did not show systematic differences between groups with regard to caffeine or d-amphetamine. Cardiovascular results revealed main effects of dose for diastolic blood pressure and heart rate follow up tests showed that controls were most sensitive to 300 mg caffeine and 20 mg amphetamine cocaine-dependent subjects were sensitive only to 300 mg caffeine. Levels of salivary caffeine and the primary caffeine metabolite paraxanthine were obtained on placebo and caffeine dosing days. Data were obtained on measures of cardiovascular effects, subjective drug effects (ARCI, VAS, DEQ), and a probabilistic reward-learning task sensitive to dopamine modulation. healthy control subjects, matched on moderate caffeine use. To compare and contrast the stimulant effects of adenosine antagonism to direct dopamine stimulation, we administered 150 mg and 300 mg caffeine, 20 mg amphetamine, and placebo to cocaine-dependent vs. Due to indirect modulation of dopamine transmission, adenosine receptor antagonists may be useful in either treating cocaine use or improving disrupted cognitive-behavioral functions associated with chronic cocaine use.
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