EFFECTS OF REPEATED ADMINISTRATION WITH CP-55,940, A CANNABINOID CB1 RECEPTOR AGONIST ON THE METABOLISM OF THE HEPATIC HEME

María García-Bravo1, Antonio Fontanellas1, Ana María Buzaleh2, Manuel Méndez1, José María Oliva1, Alcira Batlle2, Tomas Palomo1, Rafael Enríquez de Salamanca1

2Centro de Investigación sobre Porfirinas y Porfirias (CIPYP), CONICET, University of Buenos Aires, Argentina

Drugs metabolised by cythochrome P450s such as analgesics may induce acute attacks in patients with hepatic porphyrias. In recent years, preclinical and clinical studies suggest that cannabinoid pharmaceutical preparations may potentially be considered to treat pain. The purpose of the study was to examine the effects of CP-55,940, a cannabinoid CB1 receptor agonist, on the hepatic heme metabolism in mice.

To this aim, hepatic activities of aminolevulinic acid synthase (ALAS1) and heme oxygenase (HO), and cytochrome P-450s (CYPs) levels were determined in mice treated with CP-55,940 (0.5 mg/kg/day; i.p.; 5 or 24 days) .

The results revealed that treatment with CP-55,940 decreased (80%) CYPs concentrations and increased (158%) HO activity, however, ALAS1 activity decreased (37%) suggesting that regulatory free heme pool was not modified.

Our findings suggest that CP-55,940 and its metabolites do not behave as porphyrinogenic drugs and may potentially be safe to treat pain in patients with acute porphyrias.