A comparison of N,N-dimethyltryptamine, harmaline, and selected congeners in rats trained with LSD as a discriminative stimulus

In rats trained to distinguish LSD from saline, several N-substituted tryptamines produced intermediate levels of LSD-like responding: MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET elicited 41.3% LSD-appropriate responding at 6.0 mg/kg, but only 4 of 8 subjects completed the session, precluding statistical analysis. Bufotenine (25.8%) failed to substitute. None of the tryptamines substituted completely for LSD, though the pattern aligns with their known human hallucinogenic activity. Among beta-carbolines tested, only harmane showed intermediate substitution (49.5%); others, including harmaline and THBC, showed no significant generalization. The tryptamines overall showed greater similarity to the LSD stimulus than the beta-carbolines did.

Study at a glance

Abstract

1. A series of N-substituted tryptamines was compared with a series of beta-carbolines in rats trained to discriminate LSD (0.1 mg/kg) from saline. 2. Intermediate levels of substitution were elicited by MDMT (76.4%), DMT (77.9%), and DET (48.7%). 6-F-DET produced 41.3% LSD-appropriate responding at a dose of 6.0 mg/kg but only 4 of 8 subjects completed the test session thus precluding statistical analysis. Bufotenine (25.8%) also failed to substitute. Although none of the tryptamines substituted completely for LSD, the pattern of substitution is consonant with what is known of their activity in humans. MDMT, DMT, and DET are well established in the literature as hallucinogens but the same cannot be said for 6-F-DET and bufotenine. 3. Of the beta-carbolines tested, none substituted for LSD completely and only harmane elicited intermediate substitution (49.5%). No significant generalization of the LSD stimulus to 6-methoxyharmalan, harmaline, or THBC was observed. Thus, in contrast to the tryptamines, scant ability to substitute for LSD was observed in the beta-carbolines tested. 4. Taken together, the present data indicate that the representative tryptamines employed in the present study exhibit greater similarity to the LSD stimulus than do representative beta-carbolines. The receptor interactions responsible for these differences remain to be determined.