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THC-disorder in New-born Rats Cured With “Wonder-drug” in Study

Oct 14, 2019

THC-disorder in New-born Rats Cured With “Wonder-drug” in Study

THC exposure in the womb could leave children vulnerable to psychotic experiences in early life, according to a new study published in Nature Neuroscience.

After dosing pregnant rats with the intoxicating cannabis compound, the study’s authors observed that the male offspring displayed a tell-tale neurological sign of psychotic disorders.

As more women are now using cannabis to relieve their morning sickness symptoms, the authors warn that these psychotic risks could easily be mirrored in humans.

But the researchers were able to reverse these neural changes by treating the adolescent rats with pregnenolone, an FDA-approved drug for the treatment of schizophrenia and other neurological conditions.


In the rat race

“The dose of THC was comparable to one joint – about 5 percent,” said Miriam Melis, an associate professor of pharmacology at the University of Cagliari, Italy, and lead author of the study. “And we exposed the mothers to what would be comparable in humans to the first six months [of pregnancy].”

Following that exposure, Melis and her team noted that the male offspring had over-active dopamine neurons in a brain region called the ventral tegmental area (VTA) – a well-recognized risk for vulnerability to psychotic disorders.

“We found that these neurons are hyperactive, and [this] is not only associated with sensation-seeking and risk-taking behavior, but with psychosis and drug addiction,” she told Analytical Cannabis. “The changes that we found in the VTA are similar to what happens to the pregnant rodents that have been exposed to alcohol or cocaine.”

As in humans, the symptoms of psychosis were more prevalent in the male rats than the females. “Schizophrenia – let's say it has a weakness for men,” Melis said, “a greater prevalence in males when compared to females.”

Melis and her team also observed that the male rat offspring were more sensitive to further THC exposure – a behavioral change that could have worrying implications if mirrored in humans.

“This high sensitivity was very important because there is a segment of the population that develop psychosis right after they use marijuana or synthetic cannabinoids,” Melis said.


A “wonder-drug” to reverse the effects of THC

Fortunately, the neural changes caused by THC seem to be reversed by pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.

“We treated the pups [with pregnenolone] for a few days to reprogram their brains [and] correct the deep changes in neural development that had been imposed by the exposure to THC,” Melis explained. “And we found that it was a wonder-drug because it was able to rescue both the functions of the dopamine neurons and their behaviour, so they were not sensitive anymore to THC.”

Pregnenalone is synthesized naturally from cholesterol in mammals and invertebrates, but also sold as a dietary supplement in certain retail stores. In clinical doses, it's been shown to improve stress-related disorders and ease the hypervigilance in the brain associated with social threats.

“This is an exciting finding that suggests a therapeutic approach for children born to mothers who used cannabis during pregnancy,” Joseph Cheer, a professor of anatomy and neurobiology at the University of Maryland School of Medicine who was involved with the research, said in a press statement.

“It also raises important questions that need to be addressed such as, how does pregnenolone exert its effects and how can we improve its efficacy? Do these detrimental effects persist into adulthood, and if so, could they also be treated in a similar way?”


Toking for two

But, while clinical doses of pregnenolone remains in trials, Melis and her team still caution mothers-to-be from using cannabis while pregnant.

“I hope that this study will increase the public awareness about the use of marijuana during pregnancy because there are too many children that suffer from your psychiatric disorders,” she said. “Forty percent of Americans would think that it's okay to smoke marijuana when you're pregnant, and our study clearly says that is not okay at all.”

A recent study in California found that marijuana use in the year prior to pregnancy had increased from 6.8 percent in 2009 to 12.5 percent in 2017, while cannabis use during pregnancy jumped from 1.95 to 3.38 percent in the same timeframe.

“Would you give a joint to a kid?” she asked. “I think you wouldn’t, so why would you need give it to a fetus?”

Another recent cannabis-pregnancy study found that prenatal cannabis and alcohol exposure in zebrafish increased offspring’s risk-taking behavior in later life.

“If cannabis is having the same effect as alcohol, then you would want to also recommend pregnant women avoid cannabis use during pregnancy,” Gregory Cole, a professor at North Carolina Central University and author of that study, told Analytical Cannabis in July. “They would have the same outcome for their baby, which could have a range of neurological and behavioral disorders that will continue into adulthood – they tend have more difficulties in school and can have trouble with the law because of the increased risk-taking behavior.”

 

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