Abstract
We have examined the effects of the synthetic cannabinoids HU 210 and HU 211, the plant-derived cannabidiol and the endogenous cannabinoid anandamide on the viability and development of chick embryos. Fertilized White Leghorn chicken eggs were injected with the test compounds or carrier vehicle, via a drilled small hole in the egg, directly into the egg yolk. After nine days of exposure, the embryonal viability, length and wet weight of embryos, and wet weight of brains were measured, and the development stages were assessed according to the Hamburger and Hamilton (HH) scale. The potent synthetic cannabinoid receptor agonist HU 210 and the non-psychotropic cannabidiol were embryotoxic at the highest concentrations examined (10 µM and 50 µM, respectively), with no viable embryos after the HU 210 injection, and 20% viability after the cannabidiol injections. The effects of HU 210 on the chick embryo were attenuated by α-tocopherol and the cannabinoid receptor antagonist AM251, whereas only α-tocopherol gave a statistically significant protection against the embryotoxic effects of cannabidiol. This study shows that exposure to plant-derived or synthetic cannabinoids during early embryonal development decreases embryonal viability. Extrapolation of data across species is of course difficult, but the data would argue against the use of cannabinoids, be it recreationally or therapeutically, during pregnancy.
Highlights
Cannabis has a long history of medical and therapeutic use, and the discovery of the cannabinoid (CB) signalling system, comprising CB receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation, has led to an enormous expansion of the CB research field and in turn to the identification of new targets for therapeutic drugs[1,2,3]
We have investigated the effects of the synthetic cannabinoids HU 210 and HU 211, the plant-derived cannabidiol (CBD) and the endogenous cannabinoid anandamide (AEA) on the viability and development of chick embryos
At incubation day 10, 290 eggs were examined for weight and vascularization of the egg, embryonal mean crown-rump (C-R) length, mean wet embryonal weight, and mean wet brain weight (Table 1)
Summary
Cannabis has a long history of medical and therapeutic use, and the discovery of the cannabinoid (CB) signalling system, comprising CB receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation, has led to an enormous expansion of the CB research field and in turn to the identification of new targets for therapeutic drugs[1,2,3]. Compounds acting at CB receptors are highly lipophilic by nature and can cross barriers such as the placenta barrier, and if CBs are used during pregnancy, they enter the embryo or fetus and may increase the risk of neurobehavioral changes of the young infant[9]. In this respect, the CB receptor system actively regulates cell proliferation and differentiation both in vitro and in vivo[10], and it has been shown that feeding female rats with CB receptor ligands during pregnancy and/or lactation modify the maturation of various neurotransmitter systems during embryonic development[11,12]. We have investigated the effects of the synthetic cannabinoids HU 210 and HU 211, the plant-derived cannabidiol (CBD) and the endogenous cannabinoid anandamide (AEA) on the viability and development of chick embryos
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