One of the characteristic pharmacological properties of CB1 receptor agonists is an ability to induce hypothermia (Pertwee 1985). The changes of body temperature caused by cannabinoids are dose dependent. According to Pertwee, higher doses of THC cause hypothermia by lowering the thermoregulatory "set point", while lower doses are hyperthermic. It has been postulated that differential Gs and Gi protein activation by CB1 receptors could explain these findings (Sulcova et al. 1998).
Cannabinoid-induced hypothermia is mediated by dopaminergic pathways (Pertwee 1992). It was proposed that AEA might not produce all of its effect on thermoregulation by a direct interaction on CB1 receptors present in hypothalamic thermoregulatory centres. SR 141716A did not block hypothermia caused by AEA (Adams et al. 1998), although this CB1 receptor antagonist reversed the hypothermia caused by WIN 55,212-2. The endocannabinoids N-arachidonoyl-dopamine and 2-arachidonoylglycerol (2-AG)-ether both caused hypothermia (Bisogno et al. 2000; Hanus et al. 2001), supporting the involvement of CB1 receptors in this process.
On the other hand, N-vanillyl-arachidonyl-amide (arvanil), a VR1 receptor agonist, was 100 times more potent than AEA in producing hypothermia (Di Marzo et al. 2000), which indicates that hypothermia caused by cannabimimetic compounds may not (only) be due to the activation of CB1 receptors.
It is possible that the endocannabinoid system is taking part in thermoregula-tion,too. However, itisstillquestionable whetherthiseffectoccursbythe activation of cannabinoid receptors and/or vanilloid receptor, or by other mechanisms.
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