Long-term effects of prenatal exposure to cannabis examined

Summary: A study on the effects of prenatal exposure to synthetic cannabinoids in rats found that the drug leads to long-term health problems in their offspring. Male rats showed increased sensitivity to CO2, making them more prone to panic-like behavior, while females showed cardiovascular problems such as hypertension and tachycardia.

The study also noted poor sleep quality in men and a milder impact in women. These findings highlight the potential risks of cannabis use during pregnancy, with gender-specific effects observed in offspring.

Key Facts:

• Men exposed to cannabinoids in utero were more sensitive to CO2, which was associated with panic-like reactions.
• Women were more likely to have cardiovascular problems, including hypertension and tachycardia.
• Sleep quality deteriorated more in men than in women as a result of frequent wakefulness.

Source: FAPESP

Scientists who exposed pregnant rats to a synthetic cannabinoid that activates the same receptors in the brain as marijuana found effects of the drug on their offspring, such as cardiovascular problems in women and increased susceptibility to panic attacks in men, and showed that these adverse effects persisted . to adulthood.

An article about the research has been published in the American Journal of Physiology – Lung Cellular and Molecular Physiology.

The findings serve as a precaution when using cannabis medicinally or recreationally during pregnancy, the authors conclude.

The research was conducted with the support of FAPESP by researchers affiliated with São Paulo State University (UNESP) and University of São Paulo (USP) in Brazil. Previous research by the same group has shown the effects of intrauterine exposure to the cannabinoid on newborn and young rats.

“We observed long-term changes in behavior and especially in cardiorespiratory function in the animals exposed to the cannabinoid while still in the womb. The changes were different in men and women,” said Luis Gustavo Patrone, first author of the paper.

The study was part of his PhD research, which was supported by a grant from FAPESP, while he was a PhD candidate at the School of Agricultural and Veterinary Sciences (FCAV-UNESP) in Jaboticabal, São Paulo State, where he is now a postdoctoral researcher . .

In contrast to the neonates in the previous study, the adult individuals (80 days old) analyzed in this latter study showed no changes in baseline respiration, possibly due to an unknown compensatory mechanism during postnatal development.

One finding that did not differ from study to study was that intrauterine exposure to the cannabinoid increased adult men’s respiratory sensitivity to carbon dioxide (CO2).₂). The opposite result was observed in females.

“People have an increased sensitivity to CO₂ can cause panic attacks with shortness of breath and false choking alarms. In the animals in our experiment, this type of behavior consisted of attempts to escape from the room,” says Luciane Gargaglioni, last author of the paper and professor at FCAV-UNESP.

Cardiovascular function and sleep

The researchers also analyzed cardiovascular factors and sleep quality in the animals, concluding that exposure to the cannabinoid during fetal development led to a tendency to experience cardiovascular dysfunction in adulthood, with hypertension and tachycardia most commonly found in women.

Sleep quality deteriorated most in men, who suffered from sleep fragmentation due to frequent waking episodes. “They slept less, given the sum of sleep episodes,” Patrone said. Sleep quality also deteriorated in women, but less severely.

“Most scientific studies only assess parameters in men, assuming that the results are valid for both sexes, but in our laboratory we always make the distinction and the responses are often very different, as in this study,” says Gargaglioni.

A possible explanation for the difference between the results in men and women may be the action of sex hormones. In women, estrogen is known to be neuroprotective and can ward off the damaging effects of the cannabinoid on their brains.

In addition, the mammalian respiratory system is known to develop more slowly in males, which mainly occurs when testosterone levels peak during masculinization and sexual organ formation.

Later maturation of the lungs and of the brain areas responsible for controlling respiratory function likely made the men more vulnerable to the cannabinoid’s adverse effects.

The authors point out that observed maternal postpartum behavior showed no differences in maternal care for offspring due to exposure to the cannabinoid during pregnancy, compared to the control group, which was not given the substance.

About this neurodevelopmental research news

Author: Heloisa Reinert
Source: FAPESP
Contact: Heloisa Reinert – FAPESP
Image: The image is credited to Neuroscience News

Original research: Open access.
“Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid” by Luis Gustavo Patrone et al. American Journal of Physiology: Lung Cellular and Molecular Physiology

Abstract

Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid

The development of the respiratory system may be affected by the use of medications during pregnancy, as the prenatal phase is highly sensitive to pharmacological interventions, resulting in long-term consequences.

The harmful effects of external cannabinoids during pregnancy may be related to negative interference in the formation of the central nervous system, the function of the cardiorespiratory system and behavioral disorders.

Nevertheless, the impact of external cannabinoids on cardiorespiratory network development, chemosensitivity and its future consequences in adulthood is still unclear. We evaluated the effects of prenatal exposure to a synthetic cannabinoid (WIN 55.212-2, 0.5 mg kg⁻¹·day⁻¹) on the cardiorespiratory control and panic-like behavior of male and female rats in adulthood.

Exogenous exposure to cannabinoids during pregnancy resulted in a sex-dependent difference in respiratory control. In particular, men showed increased chemosensitivity to CO₂ and O₂while females showed reduced sensitivity.

There was altered cardiovascular control, with prenatally treated men and women being more susceptible to hypertension and tachycardia under adverse environmental conditions.

Furthermore, WIN-treated men showed higher fragmentation of sleep episodes, while women showed anxiolytic and panicolytic behavioral responses to CO.₂.

However, no changes were observed in the mechanical component of the respiratory system, and there were no neuroanatomical changes, such as changes in the expression of CB₁ receptors in the brain stem or in the quantification of catecholaminergic and serotonergic neurons.

These findings highlight that external interference in cannabinoid signaling during fetal development produces sex-specific, long-lasting effects on the cardiorespiratory system and behavioral responses in adulthood.