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Updated: Jun 9, 2026

Administration of Δ9-Tetrahydrocannabinol (THC) in Adolescent and Adult Mice
Published on: August 1, 2025
The effect of Δ9-tetrahydrocannabinol on 5-HT3 receptors depends on the current density
K H S Yang1, D Isaev, M Morales
1Department of Biological Sciences, Schmid College of Science, Chapman University, One University Drive, Orange, CA 92866, USA.
Abstract:
The effects of Δ(9)-tetrahydrocannabinol (THC), the psychoactive component of cannabis, on the function of 5-HT type 3 (5-HT(3)) receptors were investigated using a two-electrode voltage clamp technique in Xenopus oocytes, and a whole-cell patch clamp technique in rat nodose ganglion neurons. In oocytes injected with 3 ng cRNA of 5-HT(3A) receptor, THC reversibly inhibited currents evoked with 5-HT (1 μM) in a concentration-dependent manner (IC(50)=1.2 μM). The extent of THC inhibition was inversely correlated with the amount of cRNA injected and the mean 5-HT(3A) receptor current densities. Pretreatment with actinomycin D, which inhibits transcription, decreased the mean 5-HT(3) receptor current density and increased the extent of THC inhibition on 5-HT(3) receptor-mediated currents. The IC(50) values for THC increased from 285 nM to 1.2 μM in oocytes injected with 1 and 3 ng of 5-HT(3A) cRNA, respectively. In radioligand binding studies on membrane preparations of oocytes expressing 5-HT(3A) receptors, THC did not alter the specific binding of a 5-HT(3A) receptor antagonist, [(3)H]GR65630. In the presence of 1 μM THC, the maximum 5-HT-induced response was also inhibited without a significant change in 5-HT potency, indicating that THC acts as a noncompetitive antagonist on 5-HT(3) receptors. In adult rat nodose ganglion neurons, application of 1 μM THC caused a significant inhibition of 5-HT(3) receptors, extent of which correlated with the density of 5-HT-induced currents, indicating that the observed THC effects occur in mammalian neurons. The inhibition of 5-HT(3) receptors by THC may contribute to its pharmacological actions in nociception and emesis.
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