Pregnancy is a very vulnerable period of time for both the mother and child. For this reason, pregnancy is often under extensive scrutiny and is a period of great interest for researchers attempting to understand the potential risks of a new therapeutic agent.
Cannabinoids, specifically cannabidiol (CBD), are no exception to this rule and healthcare providers must also take a hard look at the risk:benefit ratio for the use of these compounds during gestation.
This article will briefly review some of the current research regarding CBD and pregnancy with a focus on its potential health implications and its use during animal model as well as cell studies.
CBD and pregnancy: possible risks and adverse effects.
Lately, research has suggested that endocannabinoid system receptors have been found on various cells in the reproductive system. In fact, a study on Endocannabinoids in pregnancy states that CB1 and CB2 receptors, the main receptors of the endocannabinoid system, can be found on oocytes (female gametocyte) at all stages of their development.
Additionally, the author also mentions that AEA, NAPE-PLD and FAAH (hydrolytic enzymes in charge of cleaving the inactive forms of endocannabinoids from the cell membrane) have too been found in: secondary/ tertiary follicles, corpora lutea and albicantes.
What I mentioned before is important because cannabinoids also interact with these receptors and possibly affect vital processes such as oogenesis, spermatogenesis, implantation and early embryonic development. Although the mechanisms by which cannabinoids affect gestational development are not clearly elucidated, it is thought that they do so by interacting with the release and action of gonadotropins (sex hormones).
Studies on humans, rats, rabbits and rhesus monkeys reviewing the effect of THC on oocyte development demonstrated that THC may have a detrimental effect on development and ovulation by interrupting the hypothalamic-pituitary-ovarian axis. Subsequently, the interruption of this complex led to reductions in FSH (Follicle stimulating hormone) and LH (Luteinizing hormone) which are major regulatory hormones in ovulation and pregnancy. This in turn led to “poor” quality oocytes during in-vitro fertilization.
So what about CBD? A recent report on the effects of CBD on expression of P-gp and BCRP receptors in trophoblast cell lines showed some interesting results on the possible implications of acute and chronic CBD exposure in pregnant women.
Trophoblasts are a group of cells found on the outer layer of the blastocyst (a developmental stage in the embryo) which develop into a substantial portion of the placenta. P-gp and BCRP are important receptors found on trophoblasts and are highly involved in the process of drug interaction and transport.
According to the report, long-term exposure to CBD resulted in transcription inhibition and reduced expression of P-gp receptors in BeWo and Jar (trophoblast-like) cell lines. Because of P-gp’s important role in drug transport through the placenta during the first trimester, chronic exposure to CBD may have health implications for women that are being treated with drugs which need P-gp receptors to reach the fetus.
In the case of BCRP, there was an upregulation of transcription and expression of this receptor in the same trophoblast-like cell lines after chronic CBD exposure. This may be harmful as upregulated expression of BCRP is commonly seen in women with preterm labor and inflammation indicating that this type of CBD exposure could trigger an inflammatory response in trophoblasts during pregnancy.
Acute exposure to CBD also yielded similar results in the expression of P-gp and experiments also indicated a dose-response mechanism associated with CBD exposure (that is, higher concentrations of CBD lead to a more pronounced effect).
It is of great importance to note that many of the drugs that are safe to prescribe during pregnancy are substrates of both P-gp and BCRP receptors (such as Loratadine). Substrates are molecules that interact with specific receptors. Furthermore, disruption in the levels of these receptors can potentially lead to a dysfunctional placenta and a vulnerable/unprotected fetus.
CBD and pregnancy: potential benefits of CBD during gestation.
The effects of cannabinoids, in particular CBD, are not always detrimental in pregnancy as some research reports suggest otherwise. An article on Cannabis use in pregnancy and early life consequences points out that CBD may have antipsychotic, anxiolytic, and neuroprotective properties and can counteract the adverse effects of cannabis use (from THC) during pregnancy.
CBD’s antioxidant properties have also been linked to reduce cellular stress due to ROS (reactive-oxygen species). This property may inherently protect against damage to DNA or other important structures in the cell. Although it may be less clear as to how this may affect the fetus, it may confer certain benefits for the mother as antioxidants are important during gestation.
How CBD will be involved in pregnancy in the future
As always, many of the claims on CBD and the potential risks/benefits of its use for certain conditions need to be further studied. In the case of CBD and pregnancy, even though there seems to be more risks than benefits, this truly depends on many other factors such as dosage, frequency or the trimester at which it is given.
Particularly, because many cannabinoids work in a dose-response fashion, it is more important than ever for researchers to study at what dosage are these compounds conferring health benefits with limited side effects. All in all, the moral of the story suggests that research needs to continue on this matter and that no recommendations can yet be made for pregnant women that may be interested in using CBD based products.