Acute hydrocortisone administration does not affect subjective responses to d-amphetamine in humans

Rationale: Stress and glucocorticoids facilitate and reinstate psychostimul ant self-administration in rodents. However, the effects of stress and gluc ocorticoids on the subjective and behavioral effects of psychostimulants ha ve not been well studied in humans. Objectives: To examine the effects of a cute hydrocortisone pretreatment on the subjective and behavioral effects o f d-amphetamine. Methods: Hydrocortisone (100 mg) and d-amphetamine (20 mg) were administered orally to 16 healthy male and female volunteers in a fou r-session, placebo-controlled. within-subject, crossover design. To prevent stomach irritation, subjects received rantidine hydrochloride before each experimental session. Dependent measures included self-reported mood and su bjective effects (Addiction Research Center inventory, the profile of mood states, and a series of visual analogue scales), vital signs, salivary cort isol, and psychomotor performance. Results: Hydrocortisone elevated salivar y cortisol levels, produced modest dysphoria, and reduced subjects' reports of wanting more drug. However, hydrocortisone pretreatment did not affect any of the physiological, behavioral, or subjective effects of d-amphetamin e. Conclusions: In contrast to the effects of glucocorticoids in rodent stu dies. these results indicate that an acute increase in cortisol does not en hance the psychostimulant effects of d-amphetamine in humans.