Cannabis and Pregnancy 2.

2009.05.05

In most countries Cannabis is the most widely used illegal drug. Its use during pregnancy in developed nations is estimated to be approximately 10%. Recent evidence suggests that the endogenous cannabinoid system, now consisting of two receptors and multiple endocannabinoid ligands, may also play an important role in the maintenance and regulation of early pregnancy and fertility.

Human Studies

As with research on all drugs of abuse, studies into the influence of cannabis use during human pregnancy have been fraught with contradictions and controversies. Because ethical considerations prohibit controlled human experiments in this area, clinical research has been limited to epidemiologic and retrospective studies, case reports and small studies of volunteers. Clearly regulations prohibit the administration of drugs to women who may become pregnant, thus studies are confounded by issues in reporting and confirming drug use; concurrent use of other drugs; as well as non-standardized drug intake between users (different quantities of intake at different times during pregnancy). Estimates of cannabis use by pregnant women vary between 10–20%. Few studies have been conclusive regarding the effects of cannabis use during pregnancy. However, cannabis use has been correlated with low birth weight, pre maturity, and intrauterine growth retardation, presence of congenital abnormalities, perinata death and delayed time to commencement of respiration. Lifestyle and concomitant risk status is an important issue in interpreting prenatal marijuana outcomes. For example, in women with low-risk lifestyles, no evidence of increased meconium staining was noted among newborns of heavy marijuana users.

This observation contrasts with the first but not the second of two reports by Greenland and associates. One of the primary differences between the two Greenland studies was the generally higher standard of living and health among the sample in the later report.

Animal studies

A study utilizing pregnant rats’ bears directly upon the critical role that lifestyle may have in interacting with the teratogenic effects of cannabis. Briefly, different groups of pregnant rats were exposed to marijuana smoke while receiving diets varying in protein content. Pregnancies were markedly compromised when marijuana smoke was combined with a low protein diet; conversely, if marijuana smoke was coupled with a high-protein diet some risks associated with the cannabis exposure were attenuated.

Animal studies have suggested that exposure to THC in utero can result in long-term changes. Several early studies reported embryo toxicity, foetal toxicity, and specific teratological malformations in rats, guinea pigs, hamsters and rabbits associated with exposure to cannabis extracts during pregnancy. In general, the dosage of cannabinoids resulting in frank teratology was well beyond the range used by humans. Other studies with synthetic THC failed to produce specific congenital malformations even at high doses. However, some investigators have reported an increase in embryo toxicity and foetal toxicity at pharmacologically relevant concentrations. Studies have demonstrated that in Rhesus monkeys THC expo sure during early pregnancy produced miscarriage. These were associated with a rapid decrease in chronic gonadotropin and a subsequent fall in progesterone concentrations to non-detectable levels. When rhesus monkeys were exposed chronically to THC over a 5-year period, increased reproductive loss was observed; this loss consisted of more than just increased miscarriage, but also increased resorptions, abortions, foetal deaths, stillbirths and neonatal deaths. In mice THC increased the incidence of intrauterine deaths and reduced foetal weight. In addition exposed male mouse foetuses had significantly reduced testosterone concentrations and reduced testis weight. Exposure to THC shortly before or after birth may also result in impaired reproductive behavior in mice when they reach adulthood: one study showed that females were slower to show sexual receptivity and males were slower to mount under these conditions.