The Contribution of cocoa additive to cigarette smoking addiction

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