Metabolic stimulation of mouse spleen lymphocytes by low doses of delta(9)-tetrahydrocannabinol

The present work was undertaken to study the metabolic response of mouse spleen lymphocytes to physiologically relevant doses of 9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC induced a 2-2.5-fold stimulation of both glucose oxidation to CO2 and phospholipid synthesis from glucose. This stimulation was (i) dose-dependent up to 1 mu M THC, (ii) mimicked by the synthetic cannabinoid HU-210, (iii) prevented by forskolin and pertussis toxin, and (iv) unaffected by the CB1 receptor antagonist SR141716A. THC was also able to antagonize the forskolin-induced elevation of intracellular cAMP concentration. In contrast, at non-physiological, cytotoxic doses (i.e. micromolar range) THC markedly depressed glucose metabolism in lymphocytes by a cannabinoid receptor-independent pathway. Results thus indicate that physiologically relevant doses of THC induce a metabolic stimulation of lymphocytes that seems to be mediated by a cannabinoid receptor-dependent pathway.