Researchers at Western University have for the first time shown the molecular mechanisms at work that cause cannabidiol or CBD to block the psychiatric side effects of tetrahydrocannabinol (THC), the most important psychoactive chemical in cannabis.
It has been previously shown that cannabis strains with high levels of THC and low levels of CBD can cause increased psychiatric effects, including paranoia, anxiety and addictive behavior, but why what happened was not completely understood.
Steven Laviolette, PhD, and his research team used rats to investigate the role of a molecule in the brain's hippocampus called extracellular signal regulated kinase (ERK) that triggers the neuropsychiatric effects of THC.
"For many years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side effects," said Laviolette, a professor at Western's Schulich School of Medicine & Dentistry. . "Our findings identify for the first time the molecular mechanisms by which CBD can actually block these THC-related side effects."
The research, published in Journal of Neuroscience shows that rats given THC had higher levels of activated ERK, showed more anxiety behavior and were more sensitive to fear-based learning. Rats given CBD and THC acted as control rats: They had normal levels of activated ERK, less anxiety behavior, and were less sensitive to fear-based learning.
Based on these results, the research team suggests that CBD blocks THC's ability to overstimulate the ERK pathway in the hippocampus, thus preventing its adverse side effects.
“Our findings have important implications for prescribing cannabis and prolonged use of cannabis. For people who are more susceptible to cannabis-related side effects, for example, limiting their use to strains with high CBD and low THC content is crucial, says Laviolette. "More importantly, this discovery opens up a new molecular frontier for developing more effective and safer THC formulations."
PhD candidate and Vanier Scholar Roger Hudson, lead author of the study, says another interesting finding was that CBD alone had no effect on the ERK pathway. "CBD itself had no effect," he said. "However, by administering CBD and THC, we completely reversed the direction of change at the molecular level. CBD was also able to reverse the anxiety-like behavior and addictive-like behavior caused by THC."
Laviolette says they will follow up on these studies By continuing to identify the specific functions of this molecular mechanism, the research team will explore ways to formulate THC with fewer side effects and to improve the efficacy of CBD-derived therapies.
Reference: “Cannabidiol counteracts the psychotropic side effects of Δ-9- tetrahydrocannabinol in the Ventral Hippocampus Through Bi -Directional Control of ERK1-2 Phosphorylation ”by Roger Hudson, Justine Renard, Christopher Norris, Walter J. Rushlow and Steven R. Laviolette, September 30, 2019, Journal of Neuroscience .
DOI: 10.1523 / JNEUROSCI.0708-19.2019