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Effects of cannabinoids on the development of chick embryos in ovo
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology. (Jacobsson)
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Pharmacology.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

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 blunt end of the egg, directly into the egg yolk. After nine days of exposure, the embryonal viability and 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 (average HH stage 19 ± 3.5 compared to 34 ± 1.1 in the DMSO-treated control group) after the HU 210 injection, and 22% viability (average HH stage 11 ± 4.9) after cannabidiol injections. The effects of HU 210 on the chick embryo were attenuated by 100 µM of the antioxidant α-tocopherol and the cannabinoid receptor antagonist AM251 (1 µM), whereas only α-tocopherol gave a statistically significant protection against the embryotoxic effects of cannabidiol. HU 211, an enantiomer to HU 210 without cannabinoid receptor activity, and anandamide were without any significant effects on the viability and development of the chick embryo at the concentrations examined (up to 10 µM and 50 µM, respectively).

This study shows that exposure to both plant-derived and synthetic cannabinoids during early embryonal development decreased 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. 

Keyword [en]
cannabinoids, chick embryo, viability, Hamburger-Hamilton scale, α-tocopherol
National Category
Pharmacology and Toxicology
Research subject
URN: urn:nbn:se:umu:diva-51558OAI: diva2:484047
Available from: 2012-01-31 Created: 2012-01-26 Last updated: 2012-02-03Bibliographically approved
In thesis
1. Cannabinoids as modulators of cancer cell viability, neuronal differentiation, and embryonal development
Open this publication in new window or tab >>Cannabinoids as modulators of cancer cell viability, neuronal differentiation, and embryonal development
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Effekter av cannabinoider på cancerceller, neuronal differentiering och embryonal utveckling
Abstract [en]

Cannabinoids (CBs) are compounds that activate the CB1 and CB2 receptors. CB receptors mediate many different physiological functions, and cannabinoids have been reported to decrease tumor cell viability, proliferation, migration, as well as to modulate metastasis.

In this thesis, the effects of cannabinoids on human colorectal carcinoma Caco-2 cells (Paper I) and mouse P19 embryonal carcinoma (EC) cells (Paper III) were studied.  In both cell lines, the compounds examined produced a concentration- and time-dependent decrease in cell viability. In Caco-2-cells, HU 210 and the pyrimidine antagonist 5-fluorouracil produced synergistic effects upon cell viability. The mechanisms behind the cytocidal effects of cannabinoids appear to be mediated by other than solely the CB receptor, and a common mechanism in Caco-2 and P19 EC cells was oxidative stress. However, in P19 EC cells the CB receptors contribute to the cytocidal effects possibly via ceramide production.

In paper II, the association between CB1 receptor immunoreactivity (CB1IR) and different histopathological variables and disease-specific survival of colorectal cancer (CRC) was investigated. In microsatellite stable (MSS) cases there was a significant positive association of the tumor grade with the CB1IR intensity. A high CB1IR is indicative of a poorer prognosis in MSS with stage II CRC patients.

Paper IV focused on the cytotoxic effects of cannabinoids during neuronal differentiation. HU 210 affected the cell viability, neurite formation and produced a decreased intracellular AChE activity. The effects of cannabinoids on embryonic development and survival were examined in Paper V, by repeated injection of cannabinoids in fertilized chicken eggs. After 10 days of incubation, HU 210 and cannabidiol (without CB receptor affinity), decreased the viability of chick embryos, in a manner that could be blocked by α-tocopherol (antioxidant) and attenuated by AM251 (CB1 receptor antagonist).

In conclusion, based on these studies, the cannabinoid system may provide a new target for the development of drugs to treat cancer such as CRC. However, the CBs also produce seemingly unspecific cytotoxic effects, and may have negative effects on the neuronal differentiation process. This may be responsible for, at least some of, the embryotoxic effects found in ovo, but also for the cognitive and neurotoxic effects of cannabinoids in the developing and adult nervous system.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2012. 48 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1474
Cannabinoids, cell viability, neuronal differentiation, colorectal cancer, chick embryo
National Category
Pharmacology and Toxicology
Research subject
biokemisk farmakologi; Toxicology
urn:nbn:se:umu:diva-51560 (URN)978-91-7459-358-7 (ISBN)
Public defence
2012-02-24, Sal E04, by 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2012-02-03 Created: 2012-01-26 Last updated: 2012-02-27Bibliographically approved

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