The Contribution of cocoa additive to cigarette smoking addiction

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Page 180 of 207 RIVM report 650270002 Anandamide 750 µg/kg) into the hindlimb vasculature of anaesthetized rats was investigated. Anandamide caused a rapid dose-dependent reflex fall in blood pressure and an increase in ventilation when injected intra-arterially into the hindlimb. Vagotomy or carotid sinus sectioning had no significant effect on anandamide induced responses. Thus the endogenous cannabinoid, anandamide evoked CVR reflexes when injected intra-arterially into the rat hindlimb. These responses appear to be mediated as a reflex via VR1 located on sensory nerve endings within the hindlimb vasculature (17). In vitro studies (18, 19) with isolated guinea-pig bronchi, showed some effects of anandamide on the bronchus. Anandamide produced a modest contractile response in isolated guinea-pig bronchus compared with the vanilloid receptor agonist capsaicin. It seems that the anandamide induced contractile response in guinea-pig isolated bronchus is dependent upon the activation of vanilloid receptors on airway sensory nerves. The cannabinoid receptors do not appear to play a role in this regard (anandamide dose was not mentioned in the abstract) (18). In another study, it was shown that anandamide did not contract the guineapig bronchus significantly at concentrations up to 100 µM. The contractile effect to 100 µM anandamide was 40.53 ± 7.04% (19). Cardiovascular system blood pressure: see heart rate. heart rate: Anandamide induces marked cardiovascular effects in rats. It elicits a triphasic response: an immediate transient bradycardia and hypertension (phase I) is followed by a brief pressor response (phase II) and then a more prolonged decrease in blood pressure (phase III). The former (phase I) is mediated by VR1 receptor and the latter (phase III) is due to cannabinoid CB1 receptor activation. Mechanisms underlying the phase II effect are unknown (20). A study of the phase I cardiovascular effects of anandamide on rats showed that the systemic (i.v.) ED50 value (anandamide dose decreasing the heart rate and the blood pressure by 150 beats/min and 20 mmHg respectively) was 2.6 mg/kg body weight (bw) (21). The above described cardiovascular effects by anandamide were confirmed by another study. At doses between 3 and 30 mg/kg, timedependent cardiovascular changes were observed. An immediate bradycardia exceeding 50% was seen within 10-15 s of administration and lasted up to 11 minutes following the highest dose. In contrast the change in mean arterial pressure was biphasic: an immediate 20 % decrease in mean arterial pressure followed by a significant increase in blood pressure that lasted about 13 min after the highest dose (22). Renal system diuresis: no data available. saluresis: no data available. Nervous system central nervous system: The endocannabinoid anandamide is involved in modulating appetitive behaviour. Pre-satiated rats received an intrahypothalamic injection of anandamide (50 ng/0.5 µl) followed by measurement of food intake at 3 h post injection. Administration of anandamide induced significant hyperphagia. The intrahypothalamic anandamide initiates appetite by stimulation of CB1 receptors (23). In another study, pre-satiated male rats (n=18), received
RIVM report 650270002 Page 181 of 207 Anandamide subcutaneous injections of anandamide (0.5, 1.0, 5.0, 10.0 mg/kg) before 3-h, nocturnal food intake tests. All doses of anandamide induced significant overeating, with 1.0 mg/kg being most potent (24). The possible role of the endocannabinoid anandamide on modulating the behavioral and neurochemical consequences of semi-starvation was described in a study. The effect of very low dose anandamide (1 µg/kg) administration on food intake, cognitive function and catecholaminergic and serotonergic pathways in two murine brain areas concerned with appetite (hypothalamus) and learning (hippocampus), and the peripheral corticosterone response to the stress of 40% diet restriction was studied. Anandamide-treated mice consumed 44% more food (P
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