Prenatal exposure to cannabis impacts sociability of male offspring only

September 11, 2018

Science Daily/eLife

Taking cannabinoids during pregnancy can cause behavioural and neuronal deficits in adult male offspring, while females remain unaffected, says new research published in eLife.

The study in rats, from the Inserm and Aix-Marseille University Mediterranean Institute of Neurobiology, France, and Roma Tre University, Italy, in collaboration with Indiana University, US, suggests that prenatal cannabinoid use can lead to less sociability and increased neuronal excitability in males only. The findings also point towards a potential pharmacological strategy to help reverse these effects in humans.

Senior author Olivier Manzoni, Inserm Research Director at the Mediterranean Institute of Neurobiology, and Director of the CannaLab at the institute, says: "As cannabinoids can cross the placenta, they may interfere with fetal endocannabinoid signaling during neurodevelopment, which is involved in regulating a variety of processes such as pregnancy, appetite, pain sensation, and mediating the pharmacological effects of cannabis. This could in turn lead to some serious long-term deficits. But despite increasing reports of cannabis consumption during pregnancy, the long-term consequences of prenatal cannabinoid exposure remain incompletely understood."

To fill this knowledge gap, the international collaborators examined how prenatal cannabinoid exposure influences the synaptic and behavioral functions of the medial prefrontal cortex -- a brain region often implicated in neuropsychiatric disorders -- in adult male and female rats.

Their results revealed that males exposed to cannabinoids while in the uterus were less sociable than normal animals, and spent less time interacting with others. Their sniffing and playing behaviors were impaired, while the number of attacks among males remained unchanged. Additionally, the researchers saw that the exposed males had a heightened excitability of pyramidal neurons in the prefrontal cortex. None of these effects were seen in females.

"The deleterious effects of prenatal exposure to cannabinoids on social behavior were specific to male offspring only," explains co-first author Anissa Bara, who was a PhD candidate in Manzoni's lab at the time the study was carried out. "But while social interaction was specifically impaired in males, locomotion, anxiety and cognition remained unaffected in both sexes, suggesting discrete and sex-specific behavioral consequences of cannabinoid exposure during adulthood."

The results also revealed that the mGlu5 gene -- an effector of endocannabinoid signaling in the prefrontal cortex -- was reduced in the exposed males' prefrontal cortex. The team discovered that amplifying mGlu5 signaling could normalise the synaptic and behavioral deficits induced by prenatal exposure to cannabinoids partly by activating the cannabinoid type 1 receptor (CB1R). Similarly, later tests also revealed that enhancing levels of anandamide (a type of endocannabinoid) in exposed males helped to restore their social deficits via CB1R.

"Altogether, these results provide compelling evidence for sex-specific effects of prenatal cannabinoid exposure," concludes co-first author Antonia Manduca, Inserm Postdoctoral Researcher at the Mediterranean Institute of Neurobiology. "The fact that increasing mGlu5 signaling and enhancing anandamide levels helped to reverse the negative effects of early exposure in rats also hints at a new pharmacological strategy that could one day be trialled in humans."

https://www.sciencedaily.com/releases/2018/09/180911132101.htm

Prenatal cannabis use associated with low birth weights

The study, led by Colorado School of Public Health, shows a 50 percent increase in low birth weights among women who use cannabis during pregnancy

April 23, 2018

Science Daily/University of Colorado Anschutz Medical Campus

With marijuana use during pregnancy on the rise, a new study led by the Colorado School of Public Health shows that prenatal cannabis use was associated with a 50 percent increased likelihood of low birth weight, setting the stage for serious future health problems including infection and time spent in Neonatal Intensive Care Units.

"Our findings underscore the importance of screening for cannabis use during prenatal care and the need for provider counselling about the adverse health consequences of continued use during pregnancy," said the study's lead author Tessa Crume, PhD, MSPH, assistant professor of epidemiology at the Colorado School of Public Health at the University of Colorado Anschutz Medical Campus.

The study was published last month in The Journal of Pediatrics.

Crume and her colleagues utilized survey data from 3,207 women who participated in the Colorado Pregnancy Risk Assessment Monitoring System in 2014 and 15. They found the prevalence of marijuana use in the state of Colorado was 5.7 percent during pregnancy and 5 percent among women who were breastfeeding.

They also discovered that prenatal marijuana use was associated with a 50 percent increased chance of low birth weight regardless of tobacco use during pregnancy. Prenatal marijuana use was three to four times higher among women who were younger, less educated, received Medicaid or WIC, were white, unmarried and lived in poverty.

Crume said the numbers are surprising but also reflect changing attitudes toward marijuana, especially in a state like Colorado where it is legal.

"There is increased availability, increased potency and a vocal pro-cannabis advocacy movement that may be creating a perception that marijuana is safe to use during pregnancy," Crume said.

The National Survey on Drug Use and Health suggests that cannabis use among pregnant women has increased as much as 62 percent between 2002 and 2014. At the same time, the potency of the drug has increased six or seven fold since the 1970s along with the ways it is consumed -- eating, vaping, lotions etc.

"Growing evidence suggests prenatal cannabis exposure has a detrimental impact on offspring brain function starting in the toddler years, specifically issues related to attention deficit disorder," Crume said. "But much of the research on the effects of prenatal cannabis on neonatal outcomes was based on marijuana exposures in the 1980s and 1990s which may not reflect the potency of today's cannabis or the many ways it is used."

The study found that 88.6 percent of women who used cannabis during pregnancy also breastfed. The risk of cannabis to the infant through breastmilk remains unknown. Various studies have found that cannabinoids are passed to the baby in this way. One of the study's co-authors, Dr. Erica Wymore, MD, MPH, from Children's Hospital Colorado and the CU School of Medicine, is currently conducting a study to evaluate this issue.

The researchers recommend that health care providers ask pregnant women about their cannabis use and advise them to stop during pregnancy and lactation.

"Obstetric providers should refrain from prescribing or recommending cannabis for medical purposes during preconception, pregnancy and lactation," Crume said. "Guidance and messaging about this should be incorporated into prenatal care. And screening of pregnant women at risk for cannabis dependency should be linked to treatment options."

https://www.sciencedaily.com/releases/2018/04/180423125052.htm