Repeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests that glutamate modulation may work to correct these adaptations and rapidly restore motivation for delayed non-drug rewards relative to immediate drug use. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, the investigators will test the effect of CI-581a on cocaine self-administration as compared to the active control.
52-min sub-anesthetic intravenous infusion of ketamine hydrochloride
administered as 0.11 mg/kg 2-min bolus followed by 0.60 mg/kg in saline over 50 min
52-min sub-anesthetic intravenous infusion of midazolam
administered as 2-min saline bolus followed by 0.025 mg/kg in saline infused over 50 min
52-min saline infusion during the first hospitalization to identify and exclude non-responders
used as a sham infusion in Inpatient Phase 1
This study (n=20) found that the mystical experience elicited by ketamine (but not dissociation or near-death-like experiences) may play an important role in ketamine's therapeutic potential for cocaine addiction.