The Grass isn’t Always Greener: The Effects of Cannabis on Embryological Development

Joseph Friedrich, Dara Khatib, Keon Parsa, Ariana Santopietro and G. Ian Gallicano

Abstract

With the increasing publicity of marijuana due to recent legislation, it is pertinent that the effects of foetal exposure to the drug are assessed. While in utero cannabis exposure has been associated with early pregnancy failure, birth defects and developmental delay, the mechanisms of such outcomes are largely unexplained. Furthermore, the use of cannabinoids in cancer treatment via growth inhibition and apoptosis may indicate how cannabis exposure likely harms a growing foetus.

Cannabinoid signalling is required for proper pre-implantation development, embryo transport to the uterus, and uterine receptivity during implantation. In post-implantation development, cannabinoid signalling functions in a multitude of pathways, including, but not limited to, folic acid, VEGF, PCNA, MAPK/ERK, and BDNF. Disrupting the normal activity of these pathways can significantly alter many vital in utero processes, including angiogenesis, cellular replication, tissue differentiation, and neural cognitive development. This paper aims to demonstrate the effects of cannabis exposure on a developing embryo in order to provide a molecular explanation for the adverse outcomes associated with cannabis use

Background

It has long been established that smoking tobacco during pregnancy causes increased risk of miscarriage, increased placental problems, reduction of birth weight, and a variety of birth defects [1]. In light of the recent legalization of marijuana in Colorado, Washington, Alaska and Washington, D.C., we felt it important to establish and publicize the causative relationship between cannabis usage and embryological outcomes. The main psychoactive cannabinoid in marijuana is delta-9-tetrahydrocannabinol (THC), which has a half-life of approximately 8 days in fat deposits and can be detected in blood for up to 30 days before becoming entirely eliminated from the blood [2]. These characteristics act as a direct risk factor to the developing embryo, as the maternal tissues act as reservoirs for THC and other cannabinoids.

Certain drugs cross the placenta to reach the embryo in the same manner as oxygen and other nutrients [3]. Drugs consumed during pregnancy can act directly on the embryo, or they can alter placental function, which is critical for normal growth and development. Ingestion of drugs can interfere with these functions, resulting in compromised fetal development and growth [3]. THC readily crosses the placenta, which, in conjunction with slow foetal clearance, results in prolonged foetal exposure to THC, even after consumption is discontinued [2].

The use of marijuana in early pregnancy is associated with many of the same risks as tobacco, including miscarriage, congenital malformations, and learning disabilities [4]. Adverse effects of marijuana use during pregnancy have been exacerbated over the years, as THC levels in marijuana have increased nearly 25-fold since 1970 [5]. This paper looks to examine recent studies on cannabinoids and embryonic development in

order to establish the mechanisms through which these cannabinoids act. A full overview of these mechanisms and downstream effects are provided in Fig. 1 and Table 1.

Conclusions

Under normal physiologic conditions, cannabinoid signalling exhibits a wide-range of downstream effects embryologically, as is illustrated by Fig. 1. This breadth of action ultimately manifests in the symptoms associated with cannabis use during pregnancy, including miscarriage, congenital malformations, and learning disabilities [1]. Cannabinoids have received renewed attention in the field of cancer treatment due to their pharmacologic activities in vivo as cell growth inhibitors, restrictors of cellular motility, and their ability to induce apoptosis across multiple cell lineages [40, 41]. However, by the same mechanisms that cannabinoids show promise in the field of cancer treatment, they prove equally dangerous to the viability and health of a developing embryo. A summary of these mechanisms is provided in Table 1.

The effects of cannabinoids on pre-implantation and embryologic development have the potential to elicit harmful outcomes post-natally. While the method of consumption can affect the severity of the embryologic effects, it is important to note that this paper is an overview of the effects solely of elevated cannabinoid signalling. A common means of cannabis consumption is smoking, which can add a number of toxins and thereby amplify harmful effects to the embryo. Given the trend of marijuana decriminalization and legalization across the United States, further epidemiological research should focus on the association between maternal cannabinoid use and observation post-natal outcome.

Open Access  This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

BMC Pharmacology and Toxicology BMC series – open, inclusive and trusted 201617:45  DOI: 10.1186/s40360-016-0085-6

©  The Author(s). 2016

Received: 28 July 2015,  Accepted: 24 August 2016, Published: 29 September 2016

Source:  http://bmcpharmacoltoxicol.biomedcentral.com/articles/10.1186/s40360-016-0085-6

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