Further studies on the dose-dependent stimulus properties of 5-methoxy-N,N-dimethyltryptamine.

In rats trained to distinguish the psychedelic compound 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline, the serotonin antagonist cyproheptadine completely blocked the drug's effects at a low dose, while cinanserin and methergoline partially blocked them, and methysergide had little effect. At a higher dose of 5-OMe DMT, methysergide and methergoline partially blocked the drug's effects, but cyproheptadine and cinanserin did not. The authors advise caution when drawing conclusions from studies using these drugs until their in vivo effects and mechanisms are better understood.

Study at a glance

Abstract

Twenty-two rats were trained to discriminate either 1.5 mg/kg of 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a standard two-lever operant procedure. Once responding was stable, various doses of several serotonin (5-HT) antagonists, i.e., cyproheptadine (CYP), methysergide (UML), cinanserin (CIN), and methergoline (MCE), were administered in combination with 5-OMe DMT, to assess the ability of each antagonist to attenuate each 5-OMe DMT-stimulus. The 5-OMe DMT-stimulus at 1.5 mg/kg was completely antagonized by CYP, and was partially attenuated by CIN and MCE. UML had negligible effects on 5-OMe DMT-appropriate responding. In the 3.0 mg/kg 5-OMe DMT-trained rats, UML and MCE partially blocked the 5-OMe DMT-stimulus; CYP and CIN had no significant effect on 5-OMe DMT-appropriate responding. The results suggest that until the in vivo effects and mechanism of action of 5-OMe DMT and certain 5-HT antagonists are better understood, caution is advised when conclusions are drawn from studies employing these agents.