The Contribution of cocoa additive to cigarette smoking addiction
The Contribution of cocoa additive to cigarette smoking addiction The Contribution of cocoa additive to cigarette smoking addiction
Page 184 of 207 RIVM report 650270002 Anandamide No data available. Animal No data available. Repeated dose toxicity Subacute Subacute treatment of rats with anandamide (20 mg/kg i.p. for 15 days) resulted in behavioral tolerance without any change in cannabinoid receptor binding in the brain regions studied (striatum, cortex, hippocampus, and cerebellum), suggesting that receptor down-regulation was not involved in the development of anandamide behavioral tolerance (37). Semichronic No data available. Chronic No data available. Carcinogenicity Human No data available. Animal No data available. Reproduction toxicology Human The anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), had significantly lower activity (46 ± 17 versus 161 ± 74 pmol/min per mg protein) and protein content (0.10 ± 0.03 versus 0.23 ± 0.06 units) in lymphocytes of IVF-embryo transfer patients who failed to achieve an ongoing pregnancy than in those who became pregnant, and this was paralleled by a significant increase in blood anandamide (1.4 ± 0.8 ng/ml and 0.3 ± 0.3 ng/ml respectively). Taken together with the reported negative effects of anandamide on embryo implantation, it seems that low FAAH activity and subsequent increased anandamide levels in blood might be one of the causes of implantation failure or pregnancy loss (8). Animal The behavioural response to anandamide was examined in developing mice from day 13 into adulthood. It was observed that depression of ambulation in an open field and the analgetic response to anandamide were not fully developed until adulthood. In a separate set of experiments, five daily injections of anandamide (sc., 20 mg/kg) was administered during the last trimester of pregnancy. No effects on birth weight, litter size, sex ratio and eye opening were detected after maternal anandamide treatment. Further, no effects on open field performance of the offspring were observed until 4 weeks of age. However, from 40 days of age, a number of differences between the prenatal anandamide and control offspring were detected. Thus, the offspring from anandamide -treated dams showed impaired responsiveness to a challenge with anandamide expressed as a lack of immobility in the ring test for catalepsy,
RIVM report 650270002 Page 185 of 207 Anandamide hypothermia and analgesia. On the other hand, without challenge, they exhibited a spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic tendency. These data suggest that exposure to excessive amounts of anandamide during gestation alters the functioning of the anandamide-CB receptor system (38). Cannabinoids cause increase in the number of stillbirths and delay of delivery. The effect of anandamide on prostaglandin secretion in pregnant rats was investigated. Anandamide i.p. was injected with a daily dose of 0.02 mg/kg b.w. over the third week of gestation. Anandamide caused a delay of pregnancy and lowered serum prostaglandin (PG)F 1alpha and PGF 2alpha. There were increased number of stillbirths in anandamide treated dams. It was postulated that the delay of pregnancy and the augmentation of stillbirth is due to the low PG level (39). The anandamide was investigated on the postnatal development of the hypothalamopituitary axis (HPA) when administered during the third week of gestation. Rat pups were killed every fifth day from delivery to the 20th postnatal day; gonads, pituitary, and rest of body were weighed, and samples were collected for analysis of gonadotropin releasing hormone in the hypothalamus and luteinizing hormone, follicle stimulating hormone, prolactin, and growth hormone in the pituitaries and sera. Anandamide caused predominantly inhibitory effects on the measured parameters. The inhibition was most pronounced immediately following delivery, whereas at the end of the investigated period (20th postnatal day) no differences were observed (40) (no data on anandamide dose were mentioned in the abstract). Mutagenicity Human No data available. Animal No data available. Other Critical assessment The TDlo was 140 µg/kg i.p. for rats and 100 mg/kg s.c. for mice. The anandamide dose in cigarettes (12.5 ng/25 cigarettes) compared with the animal TDlo, seems to indicate that the anandamide level in cigarettes is insufficient to exert any systemic toxicological effects. Because no data are available on the inhalation toxicological effect of anandamide, the local pulmonary toxicological effect is unknown. Conclusion No data are available on inhalation toxicological effects of anandamide. The longterm effect of this compound via the respiratory system needs to be studied. INTERACTIONS Chemical No data available.
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RIVM report 650270002 Page 185 <strong>of</strong> 207<br />
Anandamide<br />
hypothermia and analgesia. On the other hand, without challenge, they exhibited a<br />
spontaneous decrease in open field activity, catalepsy, hypothermia and a hypoalgetic<br />
tendency. <strong>The</strong>se data suggest that exposure <strong>to</strong> excessive amounts <strong>of</strong> anandamide<br />
during gestation alters the functioning <strong>of</strong> the anandamide-CB recep<strong>to</strong>r system (38).<br />
Cannabinoids cause increase in the number <strong>of</strong> stillbirths and delay <strong>of</strong> delivery. <strong>The</strong><br />
effect <strong>of</strong> anandamide on prostaglandin secretion in pregnant rats was investigated.<br />
Anandamide i.p. was injected with a daily dose <strong>of</strong> 0.02 mg/kg b.w. over the third<br />
week <strong>of</strong> gestation. Anandamide caused a delay <strong>of</strong> pregnancy and lowered serum<br />
prostaglandin (PG)F 1alpha and PGF 2alpha. <strong>The</strong>re were increased number <strong>of</strong><br />
stillbirths in anandamide treated dams. It was postulated that the delay <strong>of</strong> pregnancy<br />
and the augmentation <strong>of</strong> stillbirth is due <strong>to</strong> the low PG level (39).<br />
<strong>The</strong> anandamide was investigated on the postnatal development <strong>of</strong> the hypothalamopituitary<br />
axis (HPA) when administered during the third week <strong>of</strong> gestation. Rat pups<br />
were killed every fifth day from delivery <strong>to</strong> the 20th postnatal day; gonads, pituitary,<br />
and rest <strong>of</strong> body were weighed, and samples were collected for analysis <strong>of</strong><br />
gonadotropin releasing hormone in the hypothalamus and luteinizing hormone,<br />
follicle stimulating hormone, prolactin, and growth hormone in the pituitaries and<br />
sera. Anandamide caused predominantly inhibi<strong>to</strong>ry effects on the measured<br />
parameters. <strong>The</strong> inhibition was most pronounced immediately following delivery,<br />
whereas at the end <strong>of</strong> the investigated period (20th postnatal day) no differences were<br />
observed (40) (no data on anandamide dose were mentioned in the abstract).<br />
Mutagenicity<br />
Human<br />
No data available.<br />
Animal<br />
No data available.<br />
Other<br />
Critical assessment<br />
<strong>The</strong> TDlo was 140 µg/kg i.p. for rats and 100 mg/kg s.c. for mice. <strong>The</strong> anandamide<br />
dose in <strong>cigarette</strong>s (12.5 ng/25 <strong>cigarette</strong>s) compared with the animal TDlo, seems <strong>to</strong><br />
indicate that the anandamide level in <strong>cigarette</strong>s is insufficient <strong>to</strong> exert any systemic<br />
<strong>to</strong>xicological effects. Because no data are available on the inhalation <strong>to</strong>xicological<br />
effect <strong>of</strong> anandamide, the local pulmonary <strong>to</strong>xicological effect is unknown.<br />
Conclusion<br />
No data are available on inhalation <strong>to</strong>xicological effects <strong>of</strong> anandamide. <strong>The</strong> longterm<br />
effect <strong>of</strong> this compound via the respira<strong>to</strong>ry system needs <strong>to</strong> be studied.<br />
INTERACTIONS<br />
Chemical<br />
No data available.
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