Prenatal Cannabis Exposure Negatively Impacts Boys Over Girls
Studies show that prenatal cannabis exposure causes brain changes in humans and rats, but that the tendency toward adult rat social problems was specific to male fetuses. Is the same true for humans?
With decriminalization/legalization changes in Canada, U.S. and worldwide, there is a desperate need for the scientific evidence on its impacts for public health. One of the most divisive issues is the safety of prenatal cannabis exposure.
Data collected from 2002-2014 in the U.S., indicated that 7.5% of pregnant women between 18 and 25 years old used cannabis, while the rate of use in all pregnant women was approximately 4%. One longitudinal study showed that 48% of women using cannabis prior to pregnancy continue using it throughout the pregnancy. The reported belief was that it would not be harmful to use it once or twice per week, and it does help with nausea
Studies of children exposed to cannabis in utero reveal normal intelligence scores compared to cohorts, but negatively altered cognition, attention and memory. As a group, these cannabis-exposed children also had increased incidence of depression and anxiety during adolescence.
Animal studies duplicated the findings in humans. Pregnant rats were exposed to various concentrations of cannabis. The offspring that were exposed exhibited problems with learning, memory and social interaction. It is important to note, however, that most experiments used male offspring as it is difficult to correct for the impact of hormonal variables on learning, memory, and social interactions in female rats. This led researchers to consider if cannabis exposure in utero had a gender impact difference. The answer is complex and definitely surprising.
THC (Δ9-Tetrahydrocannabinol), the major psychoactive substance of the cannabis, efficiently crosses the placenta and reaches the fetus. In the brain, the main target of the THC is the CB1R, the cannabinoid receptor type 1 and this affects the the development and maturing for neuronal cells.
The behavior studies in cannabis-exposed rats pointed to a problem in the prefrontal cortex, which is also the root of many psychiatric conditions. Specifically, it was determined that the social skills of the male rats were altered and that these changes lasted into adulthood. The same was not found in female counterparts.
Glutamatergic circuit, which is situated in the prefrontal cortex and nucleus accumbens in the brain, regulates reward-related behaviors. This circuit was changed following fetal cannabis exposure. The difference was not seen in the female rats, only in males. In addition, there was an increase in the excitability of the pyramidal neurons in males (only in this region), which confirmed the difference of the prenatal cannabis exposure on both sexes.
Scientists looked at the components that affect the endogenous cannabinoid system in order to minimize the effects of the THC. They observed a lower mRNA level of the brain receptor mGlu5 in males, and the same in females, with addition of mRNA for the TRPV1 and DAGLα.
Knowing this information, the group have tried to find a drug with specific properties that could restore the function of the mGlu5. They were successful, and with systemic administration of the compound, restored the social behavior of the PCE (prenatal cannabis exposure) males. The results for the females pointed out that TRPV1 is responsible for the long-term depression effects of the prenatal cannabis exposure, not the CB1R as it is the case for the males.
The results clearly indicate there is a difference in the prefrontal synaptic plasticity between two sexes, and prenatal cannabis exposure has different effects on males and females, which lasts into adulthood. This suggests also that therapy would have to be gender specific due to the different mechanism of action in both. Due to the difference in the physiology between rats and humans it remains to be seen if the difference is preserved in the human counterparts.