Current FDA regulatory guidance on the conduct of drug discrimination studies for NDA review: Does the scientific literature support recent recommendations?
Twelve male Sprague-Dawley rats were trained in a two-choice, food reinforced, drug discrimination task utilizing 10 mg/kg cocaine and saline as discriminative stimuli. Subjects were tested for stimulus generalization with a wide range of cocaine doses and several dose combinations of caffeine, ephedrine, and phenylpropanolamine (CEP). Caffeine produced only partial generalization. The triple CEP combinations resulted in complete generalization at high doses. All drugs produced response rate decrements at high doses. These data clearly indicate that certain look-alike stimulant products mimic the cocaine cue. The present data parallel human self-report data regarding the similarity in subjective profiles between illicit cocaine and the legal look-alike stimulants.