The purpose of this study was to investigate the cannabinoid and opioid mediated regulation on the effects of central Delta(9)-tetrahydrocannabinol (Delta(9)-THC) administration on hypothalamus-pituitary-adrenal (HPA) axis activity in the male rat. Intracerebroventricular (i.c.v.) administration of delta(9)-THC (25, 50, 100 microg/rat) markedly increased plasma adrenocorticotropin hormone (ACTH) and corticosterone concentrations. Time course effect studies revealed that both hormones secretion peaked at 60 min after Delta(9)-THC i.c.v. administration (50 microg/rat), decreased gradually and returned to baseline levels by 480 min. The i.c.v. administration of the specific cannabinoid receptor antagonist SR-141716A (3 microg/rat) significantly attenuated the increase of both hormones secretion induced by Delta(9)-THC (50 microg/rat). Nevertheless, higher doses (12.5 and 50 microg/rat) of this compound increased both ACTH and corticosterone plasma concentrations. Subcutaneous (s.c.) administration with the opiate receptor antagonist naloxone (0.3 mg/kg) was without effect but significantly diminished the increase of both hormones secretion induced by Delta(9)-THC (50 microg/rat). Taken together, these results indicate that opiate and cannabinoid receptors are involved in the activation of the HPA axis induced by Delta(9)-THC. Furthermore, the increase of ACTH and corticosterone secretion after the administration of higher doses of SR-141716A than those required to block such activation, suggests that endogenous cannabinoids are tonically inhibiting the release of both hormones or that this agonist-like activity may be part of an uncharacterized action of this compound not mediated by cannabinoid receptors.