Abstract
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the
pharmacological receptors essential for stimulus control. In the present investigation rats were trained
with psilocybin and tests were then conducted employing a series of other hallucinogens and
presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following
treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was
observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DA D2
antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence
of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and
MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907;
no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a
compound stimulus in which activity at the 5-HT2A receptor plays a prominent but incomplete role.
In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that
agonism at 5-HT1A receptors appears to play no role in psilocybin-induced stimulus control.
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the
pharmacological receptors essential for stimulus control. In the present investigation rats were trained
with psilocybin and tests were then conducted employing a series of other hallucinogens and
presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following
treatment with the 5-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was
observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DA D2
antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence
of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and
MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907;
no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a
compound stimulus in which activity at the 5-HT2A receptor plays a prominent but incomplete role.
In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that
agonism at 5-HT1A receptors appears to play no role in psilocybin-induced stimulus control.
