Prenatal cannabis exposure and the ‘double-hit’ hypothesis

A recent review article in the Neurotoxicology and Teratology journal warns of the possible effects of cannabis exposure on the developing fetus, and encourages expecting mothers to take a “pregnant pause” from their use of cannabis. Existing research has not shown that prenatal cannabis exposure...

A recent review article in the Neurotoxicology and Teratology journal warns of the possible effects of cannabis exposure on the developing fetus, and encourages expecting mothers to take a “pregnant pause” from their use of cannabis.

Existing research has not shown that prenatal cannabis exposure (PCE) causes lifelong cognitive, behavioural, or functional abnormalities; however, the researchers suggest that it may nevertheless have the subtler effect of rendering the fetus more vulnerable to future stressors, increasing the likelihood of developing cognitive abnormalities and altered emotionality later on in life.

Their argument hinges on the “double-hit hypothesis” and the critical role of the endogenous cannabinoid signaling system (ECSS) in the development of the fetus.

The “double-hit hypothesis” is the idea that an initial event (the “first hit”) may itself lack observable symptoms but nonetheless weakens or affects a system, leaving it more vulnerable to the effect of a future event (the “second hit”) which then results in unwanted consequences.  Without the first hit preceding it, the second hit on its own would have fallen below the threshold required to cause the unwanted consequences in question.

The ECSS is a network that exists in virtually every brain structure and organ system. It plays a critical role in the development of the brain throughout gestation, including supporting the formation of brain networks associated with mood, cognition, and reward. This system continues to play an important role in the adult brain.

When the mother consumes cannabis, THC readily crosses into the placenta and interacts with the receptors of the fetus’ ECSS. This interaction may disrupt the natural development of the receptors and networks of the ECSS, constituting the first hit to this system. Following this, a future stressor (i.e. maternal distress, in utero exposure to other drugs, a suboptimal caregiver relationship, etc.), which on its own would have been sub-threshold, may now result in the development of cognitive abnormalities and altered emotionality.

This theory may help to explain the disparity in existing PCE studies. If the presence of a second additional stressor is required for PCE to yield a cognitive or developmental abnormality, this would shed light on why some studies have reported such abnormalities resulting from PCE while others have not.

Presently, cannabis is the most extensively used illicit drug during pregnancy. Data from the 2011 and 2012 US National Survey on Drug Use and Health showed that 5.2% of pregnant women self-reported using cannabis in the past month. Actual rates of cannabis use during pregnancy may be considerably higher than self-reported figures. A report from the Canadian Centre on Substance Abuse states that several Canadian longitudinal studies have reported rates of use as high as “10-16% in middle-class samples to 23-30% in inner-city populations.”

Certainly, more research will be needed to better elucidate the effects of prenatal cannabis exposure and to test the theory proposed by this review. In the meantime, the authors suggest that women should take a pause from their cannabis use during pregnancy.

For interested readers, the journal article can be found here.

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