The Contribution of cocoa additive to cigarette smoking addiction

RIVM report 650270002 Page 187 of 207
Anandamide
Critical assessment
Chemical
No data available for assessment.
In vivo
The anandamide level is affected either by inhibition of the anandamide degrading
enzym or by inhibition of the anandamide transport through the cellmembrane.
Conclusion
Chemical
No data available for conclusion.
In vivo
The anandamide level is affected either by inhibition of the anandamide degrading
enzyme or by inhibition of the anandamide transport through the cellmembrane.
DEPENDENCY
Cannabinoids have a long history of consumption for recreational and medical
reasons. In humans, psychoactive cannabinoids produce euphoria, enhancement of
sensory perception, tachycardia, antinociception, difficulties in concentration and
impairment of memory. The cognitive deficiencies seem to persist after withdrawal.
The psychoactive cannabinoids increase the activity of dopaminergic neurons in the
ventral tegmental area-mesolimbic pathway. Since these dopaminergic circuits are
known to play a pivotal role in mediating the reinforcing (rewarding) effects of the
most drugs of abuse, the enhanced dopaminergic drive elicited by the cannabinoids is
thought to underlie the reinforcing and abuse properties of marijuana.Thus,
cannabinoids share a final common neuronal action with other major drugs of abuse
such as morphine, ethanol and nicotine in producing facilitation of the mesolimbic
dopamine system (13). There is evidence that cannabinoids cause tolerance and
physical dependence in humans and animals. The question is whether the endogenous
ligand for the cannabinoid receptor, anandamide, induces also behavioral tolerance
and physical dependence in rats. Rats were injected with anandamide (20 mg/kg i.v.)
daily for 2 weeks. To assess tolerance, on days 1, 8 and 15 of treatment, rats were
observed and behavior was tested. Two common methods were employed to assess
physical dependence: interruption of anandamide dosing and vehicle substitution or
administration of a cannabinoid CB1 receptor antagonist (3 mg/kg i.v.). Full or partial
tolerance developed to the classical behavioral effects elicited by the cannabinoids:
hypothermia, catalepsy, hypomotility, decrease in stereotypic activity (rearing and
grooming) and hindlimb splaying. No tolerance to anandamide was observed for
reduced defecation. An abstinence syndrome appeared after abrupt cessation of
cannabinoid intake and after withdrawal precipitated by CB1 receptor antagonist; the
withdrawal signs were scratching, licking and biting, eating of feces, ptosis, arched
back, wet dog shakes, head shakes, myoclonic spasms, writhing, forepaw fluttering,
teeth chattering and piloerection. These findings indicate that the endogenous
cannabinoid ligand, administered exogenously, induces both tolerance and physical
dependence in rats (44).
However, other studies (45, 46) indicate that anandamide has no addictive properties.
The recent discovery of anandamide, an endogenous ligand for cannabinoid
receptors, and the synthesis of SR141716A, a cannabinoid antagonist selective for