Prenatal exposure to synthetic cannabinoid alters breathing and cardiovascular health in rats

A series of experiments on rats found that prenatal exposure to a synthetic cannabinoid called WIN altered their breathing control. Male rats showed increased chemosensitivity to carbon dioxide and oxygen, while female rats exhibited decreased chemosensitivity. Males tended to have more fragmented sleep, and both male and female rats were more susceptible to hypertension and tachycardia under adverse environmental conditions. The findings were published in Translational Physiology.

Drug-related disorders are a significant public health concern. One of the most widely used drugs is cannabis, which is particularly prevalent among young individuals in their prime reproductive years. Alarmingly, there is an increasing number of people using cannabis during pregnancy. Despite this, there is a global trend toward legalizing cannabis, even though its effects on maternal health and children’s well-being remain inadequately studied.

Cannabis is derived from plants of the genus Cannabis, primarily the species Cannabis sativa and Cannabis indica. It contains chemical compounds called cannabinoids. The two most notable cannabinoids are THC (tetrahydrocannabinol), responsible for the drug’s psychoactive effects, and CBD (cannabidiol), which provides medicinal benefits without intoxication. Cannabis can be consumed in various forms, including smoking dried flowers (marijuana), ingesting edibles, or using oils and extracts. It is used recreationally for its mind-altering effects and medically to treat conditions such as chronic pain, epilepsy, and anxiety, though its use is still subject to legal and regulatory restrictions in many regions.

Study author Luis Gustavo A. Patrone and his colleagues hypothesized that maternal exposure to a synthetic cannabinoid called WIN (WIN 55,212-2) during pregnancy would affect the cardiorespiratory control and panic-like behaviors of their offspring in adulthood. They noted that epidemiological studies suggest a correlation between prenatal cannabis exposure and increased susceptibility to neuropsychiatric disorders. However, these studies are correlational and cannot definitively establish whether exposure to cannabinoids directly causes these effects.

To test their hypothesis, the researchers conducted a series of experiments on Wistar rats. Wistar rats are a commonly used laboratory strain known for their docile nature, rapid reproduction, and well-documented genetic and physiological traits. The rats were housed in cages, with up to six individuals per cage, and had free access to food and water.

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Pregnant female rats underwent surgery to implant osmotic pumps under the skin on their backs. These pumps were used to deliver the research drugs. The rats were divided into two groups. From the first day of pregnancy until the 21st day of gestation, one group received 0.5 micrograms per kilogram of body weight of the WIN synthetic cannabinoid daily. The other group received a control substance—dimethyl sulfoxide dissolved in water. The osmotic pumps were removed immediately after the rats gave birth.

When the offspring reached adulthood, the researchers conducted a series of experiments on them. The results showed that prenatal exposure to the synthetic cannabinoid influenced ventilatory control (breathing regulation) in a sex-specific manner. Adult male rats exhibited increased ventilatory responses to high concentrations of carbon dioxide and low oxygen during sleep. In contrast, adult female rats showed significantly reduced ventilatory responses to these conditions during both wakefulness and sleep. Neither sex showed changes in basal oxygen consumption or resting ventilation.

Male rats exposed to the cannabinoid also tended to experience more fragmented sleep, characterized by a higher number of shorter sleep episodes compared to unexposed males. Rats of both sexes exposed to the cannabinoid demonstrated increased susceptibility to hypertension (elevated blood pressure) and tachycardia (elevated heart rate) under adverse environmental conditions.

“We observed a long-term and sex-specific divergence in breathing control, where males and females exhibited opposite chemosensitive responses to adverse respiratory conditions. In addition, important cardiovascular changes were observed in adult rats prenatally exposed to cannabinoids. The indiscriminate use of cannabis has increased worldwide, including among pregnant women, driven by increasingly liberal government policies without established scientific knowledge about the medium- and long-term consequences. In this regard, our study serves as a precautionary note that must be taken into account when it comes to medicinal or recreational use of cannabis during pregnancy,” the study authors concluded.

The study sheds light on the effects of prenatal exposure to the WIN synthetic cannabinoid. However, it is important to note that the research was conducted on rats, not humans. While rats and humans share many physiological similarities, they are fundamentally different species, and the effects observed in rats may not necessarily translate to humans.

The paper, “Long-term effects on cardiorespiratory and behavioral responses in male and female rats prenatally exposed to cannabinoid,” was authored by Luis Gustavo A. Patrone, Alana T. Frias, Gabriel T. Fantinatti, Angelita M. Stabile, Wilfried Klein, Kênia C. Bícego, and Luciane H. Gargaglioni.