Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys

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.

Study at a glance

Abstract

Relatively few studies have assessed the reinforcing effects of hallucinogenic compounds, and no such studies have attempted to engender contingent responding for these compounds in animals with behavioral histories that include experience with serotonergically mediated reinforcing effects. The objectives of the present study were to investigate the capacity of several hallucinogenic compounds to maintain self-administration behavior in rhesus monkeys with a previous history of 3,4-methylenedioxymethamphetamine (MDMA) self-administration, and to compare these effects across a range of doses of drugs from two structural classes (indolealkylamines and phenylisopropylamines). The results indicate that no compound generated reliable responding and that no subject ever self-administered 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI) at rates above those engendered by contingent saline. However, 3 out of 4 subjects did respond at rates between 0.75 and 3.0 responses/s in one or more sessions where N,N-dimethyltryptamine (DMT), mescaline or psilocybin were available. During some of these sessions in which self-administration was maintained, animals earned a majority of all available infusions and appeared intoxicated by the end of the session. This pattern of transient self-administration may indicate that these compounds have weak reinforcing effects, or mixed reinforcing and aversive effects.