Discriminative stimulus effects of d-amphetamine, methylphenidate, and diazepam in humans.
Eight male community volunteers, who reported current psychomotor stimulant use, were trained to discriminate between the presence and absence of orally administered d-amphetamine 30 mg. During daily experimental sessions, in which a single drug dose or placebo was tested, physiological and subjective measures were assessed and subjects indicated their discrimination by responding on an operant color-tracking procedure. During four test of acquisition sessions, discriminative responding indicated that all subjects learned the discrimination, and d-amphetamine produced physiological and subjective effects typical of psychomotor stimulants. Generalization testing then followed in which dose-response curves were determined for the following drugs: d-amphetamine (3.75, 7.5, 15 and 30 mg), diazepam (5, 10, 20 and 40 mg), and methylphenidate (7.5, 15, 30 and 60 mg). d-Amphetamine and methylphenidate produced dose-related increases in d-amphetamine-appropriate responding, whereas no dose of diazepam substituted for d-amphetamine in any subject. d-Amphetamine and methylphenidate produced a similar pattern of subjective changes, including increased ratings of euphoria and drug liking and decreased sedation. In contrast, diazepam increased subjective scales of sedation and dysphoria. These results are consistent with similar studies testing animals and humans and demonstrate the utility of human drug discrimination research as an integral component of drug abuse liability testing.
Heishman
S J
SJ
Clinical Pharmacology Branch, Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Henningfield
J E
JE
D000293:Adolescent; D000328:Adult; D001831:Body Temperature / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005793:Generalization, Psychological / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D011680:Pupil / Q000187:drug effects; D012119:Respiration / Q000187:drug effects
D008774:Methylphenidate; D003975:Diazepam; D003913:Dextroamphetamine