EVIDENCE THAT THE EFFECTS OF METHADONE AND MARIHUANA ON MALE REPRODUCTIVE-ORGANS ARE MEDIATED AT DIFFERENT SITES IN RATS

This study investigated the sites of action of methadone, Δ9-tetrahydrocannabinol (Δ9-THC) and cannabinol (CBN) in male reproductive organs using hypophysectomized (hypox), castrated (CD) and sham operated (SO) rats. Treatments were given as follows: the SO rats received either methadone, Δ9-THC, or CBN; the hypox received hCG plus the drugs; the CD rats received Δ9-THC or CBN plus testosterone (T) or dihydrotestosterone (DHT). Blood plasma T and DHT levels were quantitated in the SO and hypox rats and weights of ventral prostates (VP) and seminal vesicles (SV) were recorded in all groups. In addition, the effect of CBN on the 5-alpha reductase in the VP was determined. The results of the study show that methadone, Δ9-THC, or CBN treatment significantly decreased (P<0.01) T and DHT levels and the weights of VP and SV in the SO rats. In the hypox group treated with hCG plus Δ9-THC the stimulatory effect of hCG on VP and SV weights was significantly (P<0.01) blocked, but T and DHT levels were unaffected. Methadone treatment had no effect on either VP and SV weights or T and DHT levels in the hypox rats. The effect of CBN on the hypox rats was similar to that of Δ9-THC in all respects except that in CBN treatment plasma DHT levels were significantly decreased (P<0.01). In vitro and in vivo treatment demonstrated that CBN did not appear to have any effect on 5-alpha reductase in the VP. In the CD rats, Δ9-THC and CBN blocked the stimulatory effect of T and DHT on VP and SV weights. It is concluded that methadone affects the male accessory sex organs indirectly by influencing the hypothalamic hypophyseal axis whereas Δ9-THC and CBN effects appear to be both direct at the tissue levels and indirect at the hypothalamic-hypophyseal site.