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The cloned 5‐HT₃ receptor from NCB‐20 neuroblastoma cells was expressed in Xenopus oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5‐HT₃ receptors were voltage‐clamped at −70 mV. Anandamide, at the concentration range of 0.1–100 μM, reversibly inhibited 1 μM 5‐HT induced currents. The inhibition of 5‐HT induced currents by anandamide was concentration‐dependent with an EC₅₀ of 3.7 μM and slope value of 0.94. This inhibitory effect was not dependent on the membrane potential and anandamide did not have an effect on the reversal potential of 5‐HT‐induced currents. In the presence of 10 μM anandamide, the maximum 5‐HT‐induced response was also inhibited and the respective EC₅₀ values were 3.4 μM and 3.1 μM in the absence and presence of anandamide, indicating that …