Prozac and Pregnancy Can Impact The Health of Three Generations - RxLeaf
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Prozac and Pregnancy Can Impact The Health of Three Generations

Dragana Komnenov PhD
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Three generations of unexposed descendents were neurologically impacted by their mother’s exposure to anti-depressive medication. Prozac and pregnancy may be a dangerous combination.

The prevalence of depression in pregnant women has physicians concerned. Currently available treatments include selective serotonin reuptake inhibitor (SSRI), such as fluoxetine (Prozac), which crosses the placenta. The effects on the developing fetus could potentially be very significant. Prozac and pregnancy is a combination that needs to be carefully considered.

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A recent study raised the alarm for anti-depressive medications and the  developing fetus. The findings were published in PNAS at the end of December, 2018, and used zebrafish as the animal model. This animal is routinely used in neurodevelopmental research. The zebra fish works because it is a vertebrate species with a high physiological and genetic similarity to humans. It is also easy to genetically manipulate.

When the zebra fish were exposed to Prozac at a critical stage of development, not only was the offspring negatively impacted, but this influence of low cortisol levels extended to three generations of unexposed descendants!

Pregnant Woman on a Bench

The key negative outcome was a reduction in cortisol levels and signaling, which are crucial for both neurodevelopment, and fetal development in general. The deficits were more pronounced in males than females. To further explore the possible mechanism of such effects, researchers found that the genes responsible for cortisol synthesis were significantly downregulated in three generations of fish following maternal exposure to Prozac.

SSRIs typically reduce cortisol levels that tend to be elevated due to chronic stress or trauma. High cortisol levels have been found to increase the gene coding for serotonin transporters, and thus increase the rate of serotonin uptake, thereby reducing brain levels of serotonin and causing depression.

Cortisol is called the “stress hormone.” It is, however, a very important hormone in the body for regulating immune functioning, metabolism, and give neurological benefits such as better memory retention.

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Do Cannabinoids For Depression Carry The Same Risk?

SSRIs (Selective Serotonin Reuptake Inhibtors) increase the levels of serotonin in the brain. Cannabinoids can do the same, but the mechanism is different. It is possible, then, that cannabis is a safer alternative during pregnancy.

SSRIs work by blocking serotonin receptors which normally transport serotonin into the nerve cell. As a result, serotonin concentration outside the nerve cells remains high.

Cannabinoid and serotonin receptors have also been found to interact, and it has been speculated that THC exerts its medicinal effect by impacting these receptors directly. But, cannabinoids also activate other receptors in the body, such as CB1 and CB2.

 

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The Citalopram-THC Study

One study demonstrated that activation of the CB1 receptor, by consuming cannabis, reduces the pharmacological effects of a Citalopram (an SSRI). CB1 was activated in the presence of THC. So, when THC was co-administered with Citalopram, there was no increase of serotonin in the brain. This would suggest that Citalopram and cannabis consumption are contraindicated.

The study tells us that it is the CB1 receptor activation that is stopping Citalopram from doing its job and preventing serotonin from being taken up by the nerve cells.  The most likely explanation is actually that CB1 activation inhibits the activity of serotonin receptors. This results in lowered circulating serotonin available for uptake inhibition by Citalopram.

In the context of the zebrafish study , it would be interesting to find out whether activation of CB1, along with exposure to Prozac, stopped the low levels of cortisol in the blood. For now, we can deduce possible outcomes specific to Prozac by combining the results of these studies.

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What Does This Mean for Prozac And Pregnancy, And Cannabis Consumption?

The available data suggests at least three implications.

FIRST: if indeed the lower cortisol levels found after exposure to the SSRI is a product of blocking of serotonin uptake, then therapeutic use of cannabis would help. THC would activate CB1 receptor, resulting in the inhibiting of serotonin receptors and increase in serotonin circulating.

SECOND: Prozac could also have off-target effects, unrelated to serotonin and cannabinoid receptors, in which case the side effects of the drug would outweigh its benefits (for use during pregnancy).

THIRD: the situation may be much more complex and coactivation of cannabinoid receptors, serotonin and even dopamine systems may produce or temper negative outcomes for offspring.

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For now, it remains to be determined whether the data from the zebrafish model can be recapitulated in humans, and if so whether CB1 activation could prevent this bad effects on human offspring as suggested by the animal studies.

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Dragana Komnenov
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