Previous reports have shown that the Delta⁹-tetrahydrocannabinol (Delta⁹TCH), the major psychoactive cannabinoid components of marijuana, is able [corrected] to inhibit thyroid hormonal activity. The aim of this study was to characterize the CB1 functional expression in the rat thyroid by a multi-methods approach.

RT-PCR was used to detect the mRNA expression of the CB1 cannabinoid receptor (17.8+/-4.0% of the normalizing reference gene beta₂ microglobulin), as well as the expression of the endocannabinoid hydrolyzing enzyme, fatty acid amide hydrolase (46.9+/-4.3% of beta₂ microglobulin), in the rat thyroid gland.

The CB1-encoded protein was detected in its glycosylated form (63 kDa) by Western blot, employing a polyclonal antibody, while CB1 immunohistochemical localization showed an intracellular positive staining in both follicular and parafollicular cells. In addition, a 30% decrease in serum levels of both 3,5,3′ tri-iodothyronine (T₃) and thyroxine (T₄) was detected 4 h after the administration of the synthetic cannabinoid receptor agonist, WIN 55,212-2 (10 mg/kg i.p.). These effects were antagonized by pretreatment with the CB1 antagonist SR 141716A (3 mg/kg i.p.); thyrotrophin levels were unaffected by both treatments.

These data indicate that functional CB1 receptors which are able to modulate the release of T₃ and T₄ are expressed in the rat thyroid, and suggest a possible role of cannabinoids in the regulation of rat thyroid hormonal activity.