The International Journal of Neuropsychopharmacology
August 1, 2025
Valeria Bruno, Bruce Richardson, Martha López-canul et al.
In adult male rats, a high dose of psilocybin (10 mg/kg) did not produce rewarding effects in the conditioned place preference (CPP) paradigm, as there was no significant difference in time spent in the drug-paired compartment versus the vehicle-paired compartment. Psilocybin increased head-twitching, dog-shaking, and defecation while decreasing grooming, body licking, and rearing during conditioning sessions. These behavioral differences disappeared 48 hours after the last injection, indicating no long-term changes. The findings suggest psilocybin lacks rewarding properties and does not cause physical dependence, supporting its safety profile and therapeutic potential.
The International Journal of Neuropsychopharmacology
August 1, 2025
B. D. Richardson, Marco Pileggi, Thomas Prudhomme et al.
Psilocybin and lisuride both bind to 5-HT2A receptors, but only psilocybin produces hallucinogenic effects. In adult male mice, both drugs inhibited serotonin neuron activity in the dorsal raphe nucleus and dopamine neuron firing in the substantia nigra. A 5-HT2A antagonist blocked psilocybin's serotonin inhibition but not lisuride's, suggesting different mechanisms. Only lisuride showed an antidepressant-like effect at the highest doses. Psilocybin, but not lisuride, elicited head-twitch responses, and lisuride blocked those induced by psilocybin. Both drugs reduced locomotion. The findings indicate lisuride has antidepressant and sedative effects without hallucinogenic action, likely due to its distinct effects on serotonin and dopamine neurons.
The International Journal of Neuropsychopharmacology
February 1, 2025
Martha Lopez Canul, Vivienne Nguyen, Antonio Inserra et al.
Acute administration of psilocybin reduced mechanical allodynia in a rat model of neuropathic pain but had no effect on acute thermal pain in mice. In the neuropathic pain model, psilocybin at 3 mg/kg and 10 mg/kg significantly increased mechanical withdrawal thresholds at 0.5, 1, and 2 hours after administration compared to vehicle, with no difference between the two doses. In the hot plate test, psilocybin did not raise the thermal withdrawal threshold. These preliminary findings suggest psilocybin's pain-reducing action may specifically target neuropathic pain rather than generalized acute nociception, indicating potential for treating neuropathic pain.