EFFECTS OF VERAPAMIL ON MORPHINE-INDUCED EUPHORIA, ANALGESIA AND RESPIRATORY DEPRESSION IN HUMANS

Organic calcium (Ca++) channel antagonists enhance opiate-induced anal gesia and antagonize respiratory depression produced by morphine in ro dents. Our preliminary data indicated that verapamil reduces the subje ctive effects of morphine in humans. We therefore assessed morphine-ve rapamil interactions in 12 experienced, male polydrug users with histo ries of heroin abuse by using a double-blind, cross-over study design. Treatments consisted of two drug infusions. Either verapamil, 2.5 or 10 mg, or saline was infused, 30 ml i.v. over 2 min; half way through this infusion either 1 0 mg of morphine or saline was infused, 3 ml i. v. over 1 0 sec, via a second catheter. Autonomic parameters, responsi veness to pain and subjective self-reports of mood and feeling state w ere measured over 4 hr. Analgesia was measured using a finger pressure test and hand immersion in ice water. Respiration was measured by usi ng respiratory inductive plethysmography and transcutaneoUS CO2 levels . The Addiction Research Center Inventory (ARCI) was used to measure t he subjective effects. Morphine had a liminal effect on pain threshold , but verapamil potentiated this effect to elevate pain threshold sign ificantly. Verapamil did not affect the ability of morphine to increas e pain endurance or to produce respiratory depression. Morphine produc ed positive affective responses, as demonstrated by elevated scores on the Morphine-Benzedrine Group subscale of the ARCI. Verapamil alone p roduced no effects on any ARCI subscales; however, 10 mg of verapamil significantly reduced morphine-elevated MBG scores over a 3-hr period. The results suggest the euphorigenic and analgesic effects of opioids may be differentiated by using Ca++ channel blockers.