Cocaine use disorder is a persistent public health problem for which no widely effective medications exist. Self-administration procedures, which have shown good predictive validity in estimating the abuse potential of drugs, have been used in rodent, nonhuman primate, and human laboratory studies to screen putative medications. This review assessed the effectiveness of the medications development process regarding pharmacotherapies for cocaine use disorder. The primary objective was to determine whether data from animal and human laboratory self-administration studies predicted the results of clinical trials. In addition, the concordance between laboratory studies in animals and humans was assessed. More than 100 blinded, randomized, fully placebo-controlled studies of putative medications for cocaine use disorder were identified. Of the 64 drugs tested in these trials, only 10 had been examined in both human and well-controlled animal laboratory studies. Within all three stages, few studies had been conducted for each drug and when multiple studies had been conducted conclusions were sometimes contradictory. Overall, however, there was good concordance between animal and human laboratory results when the former assessed chronic drug treatment. Although only seven of the ten reviewed drugs showed fully concordant results across all three types of studies reviewed, the analysis revealed several subject-related, procedural, and environmental factors that differ between the laboratory and clinical trial settings that help explain the disagreement for other drugs. The review closes with several recommendations to enhance translation and communication across stages of the medications development process that will ultimately speed the progress toward effective pharmacotherapeutic strategies for cocaine use disorder.

Methylphenidate remains a first-line medication for treating ADHD in children and adults. However, its behavioral pharmacological similarities to methamphetamine and cocaine have historically creat...

Studies conducted with nonhuman laboratory animals have consistently shown that atypical antipsychotics that are mixed dopamine and serotonin antagonists attenuate the discriminative-stimulus effects of amphetamine. In the present experiment, eight healthy humans learned to discriminate 15 mg of oral d-amphetamine. After acquiring the discrimination (i.e., ≥80% correct responding on four consecutive days), the effects of a range of doses of d-amphetamine (0, 2.5, 5, 10, and 15 mg), alone and after pretreatment with risperidone (0 and 1 mg), a D₂ dopamine and 5-hydroxytryptamine (5-HT)₂ serotonin antagonist, were assessed. d-Amphetamine alone functioned as a discriminative stimulus and produced stimulant-like self-reported drug effects (e.g., increased ratings of “like drug”). These effects were generally a function of dose. Risperidone alone did not occasion d-amphetamine-appropriate responding, but impaired performance. Risperidone pretreatment significantly attenuated the discriminative-stimulus effects of d-amphetamine, and some of the self-reported drug effects. The results of the present experiment suggest that combining drug-discrimination and self-reported drug-effect questionnaires may be an effective strategy for assessing the behavioral effects of agonist-antagonist interactions. Future studies should compare the behavioral effects of d-amphetamine after pretreatment with a selective D₂ dopamine (e.g., haloperidol) or 5-HT₂ serotonin (e.g., ritanserin) antagonist to determine the relative contribution of dopamine and serotonin systems in mediating the behavioral effects of stimulants in humans. The results of these studies might guide the development of a pharmacotherapy for the treatment of amphetamine abuse/dependence.