Possible Interaction: Cocaine and Dextroamphetamine

“Attack and threat behavior was effectively decreased by 0.25–1.0 mg/kg d-amphetamine and by 8 and 32 mg/kg cocaine.”

“Considering that the increase in dopamine levels in striatum and mesolimbic dopaminergic structures is believed to be of central importance to the rewarding properties of MDMA as well as of d- mphetamine an d coc aine, o ther factors could account for the discrepancy.”

“As in previous research, hooded rats treated with an acute high dose of d-amphetamine sulfate (5 mg/kg free base ) showed a dramatic defensive flight reaction to a novel stimulus (mechanical robot) that did not elicit flight from saline controls.”

“4 These observations suggest that the acceleration of striatal DM turnover rate elicited by (+)‐amphetamine and cocaine may be associated with an effect on motor activity.”

“Choice of the 20-mg dose of cocaine was significantly lower during d-amphetamine maintenance relative to when this cocaine dose was tested during placebo-d-amphetamine maintenance.”

“ D-amphetamine attenuated some of the subject-rated effects of cocaine.”

“During maintenance on the highest D-amphetamine dose , the heart rate increasing effects of cocaine were larger than observed during placebo maintenance.”

“We also predicted D-amphetamine would attenuate the behavioral effects of cocaine.”

“An adolescent who was simultaneously dependent on cocaine and treated for attention-deficit hyperactivity disorder (ADHD) with dexedrine developed symptoms of severe depression followed by suicidal behavior.”

“Preclinical studies using Long Access (LgA) cocaine self-administration procedures suggest D-amphetamine may act by preventing tolerance to cocaine ’s effects at the dopamine transporter (DAT).”

“Thus, treatment with D-amphetamine might reduce cocaine use by preventing sensitization-related changes in cocaine potency at the DAT, consistent with an incentive-sensitization view of addiction.”

“Given the extensive evidence that motivation for cocaine is dependent on drug dose [9], it follows that preventing enhanced cocaine potency with D-amphetamine effectively decreased responding for cocaine.”

“In support of this therapeutic approach, previous studies demonstrated that exposure to D-amphetamine , particularly at high doses [4], decreases cocaine use in humans as well as motivation to self-administer cocaine in nonhumans [5, 6].”

“One promising therapeutic avenue for treating cocaine abuse involves the use of D-amphetamine , as it is thought to interfere with the activity of cocaine at the DAT [3].”

“The observation that D-amphetamine prevented enhanced cocaine potency provides a persuasive explanation for why amphetamine-treated rats display decreased progressive ratio responding and cocaine-primed reinstatement.”

“These findings suggest that D-amphetamine leads to a lasting reduction of the incentive value of cocaine or cocaineassociated cues, which are posited to drive cocaine seeking and taking.”

“This reduced potency of cocaine is consistent with the current behavioral findings, in which D-amphetamine decreased motivation for cocaine and reinstatement of cocaine seeking.”

“Using a progressive ratio schedule of reinforcement following the intermittent access and D-amphetamine treatment period, Allain et al. demonstrated that D-amphetamine reduced motivation for cocaine.”

“While concurrent D-amphetamine treatment did not affect cocaine self-administration during intermittent cocaine access, it nevertheless produced lasting effects on motivation for cocaine that extended beyond cessation of treatment.”

“Although monoamine-releasing drugs such as d-amphetamine can decrease cocaine self-administration in human and animal laboratory studies, their potential for abuse limits clinical utility. “”