5-MeO-DIPT, a hallucinogenic drug similar to DMT, produced head-twitch responses in mice, an effect blocked by a serotonin 2A receptor antagonist. In rats trained to recognize LSD, 5-MeO-DIPT partially substituted for LSD (75% generalization) and suppressed response rates in a dose-dependent way; this effect was abolished by a 5-HT2A antagonist but not by a 5-HT1A antagonist. The drug showed micromolar affinity for 5-HT2A and 5-HT2C receptors and much higher affinity for 5-HT1A receptors in rat brain tissue. The results indicate that the 5-HT2A receptor is a key site of action for 5-MeO-DIPT, despite its in vitro selectivity for the 5-HT1A receptor.
Hallucinogenic compounds such as DMT, mescaline, and psilocybin can produce weak and transient self-administration in rhesus monkeys previously trained to self-administer MDMA. No compound generated reliable responding, and no subject self-administered DOI at rates above those for saline. In some sessions, 3 out of 4 subjects responded at rates between 0.75 and 3.0 responses per second when DMT, mescaline, or psilocybin were available, earning a majority of infusions and appearing intoxicated. This pattern suggests these hallucinogens may have weak reinforcing effects or mixed reinforcing and aversive properties.