Modafinil reduces smoked cocaine self-administration in humans: effects vary as a function of cocaine 'priming' and cost

Abstract

Background: The absence of an FDA-approved medication for the treatment of cocaine use disorder (CUD) may, in part, reflect the varying conditions present when the decision to use cocaine is made, with one medication unlikely to work under all conditions. The objective of this double-blind, placebo-controlled, human laboratory study was to test the effects of modafinil, a medication with mixed efficacy for the treatment of CUD, using a novel self-administration procedure designed to model distinct clinical scenarios.

Methods: During modafinil maintenance (0, 300 mg/day), participants chose to self-administer up to 7 doses of smoked cocaine (25 mg) under 9 conditions: immediately after exposure to: (a) cues associated with cocaine and a non-contingent cocaine administration, i.e. 'prime' (25 mg), (b) only cocaine cues, and (c) neither cues nor cocaine. Each condition was tested when self-administered cocaine cost $5, $10 and $15/dose.

Results: Nontreatment-seeking cocaine smokers (3 F,13 M), spending $388 ± 218/week on cocaine and with no history of alcohol use disorder, completed the study. Relative to placebo, modafinil robustly attenuated self-administration when cocaine was expensive ($10,$15/dose) and when there was no 'prime.' Modafinil had no effect on self-administration when cocaine was inexpensive ($5/dose) or when participants received a 'prime.'

Conclusions: Modafinil's effects on cocaine-taking varied substantially as a function of recent cocaine exposure and cost, which may help explain the mixed clinical findings. Modafinil may be most effective for preventing relapse in abstinent patients, particularly under conditions in which cocaine is costly, rather than initiating abstinence for those continuing to use cocaine.

Keywords: Cocaine use disorder; Medications development; Modafinil; Relapse prevention; Self-administration; Smoked cocaine.

Figure 1.

Mean number of cocaine choices (top) and amount of money spent on self-administration (bottom) as a function of modafinil dose, cost per cocaine administration, and cue/prime condition; each bar reflects data from all participants (n=16). Error bars represent + SEM. Asterisks denote a significant difference between active and placebo modafinil for each cue/prime and cost condition (*p < 0.01, ** p < 0.005). Note, chosen doses that were chosen and paid for were administered.

Figure 2.

Mean visual analog scale ratings as a function of modafinil dose and time within session (n=16 participants). Arrows indicate time at which cocaine (25 mg) was administered.