Researchers at Western University in Ontario, Canada have demonstrated for the first time on a molecular level how cannabidiol (CBD) interferes with certain effects of tetrahydrocannabinol (THC).

Previous studies have demonstrated how strains of cannabis with higher concentrations of THC and lower levels of CBD can products effects such as paranoia and anxiety, but the reason why these occur has not been understood.

“For years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side-effects,” says Steven Laviolette, Ph.D. “Our findings identify for the first time the molecular mechanisms by which CBD may actually block these THC-related side-effects.”

Laviolette, who is a professor at Western University’s Schulich School of Medicine & Dentistry, and his team used rats to study how a molecule in the brain’s hippocampus called extracellular-signal-regulated kinase (ERK) triggers THC’s neuropsychiatric effects.

According to the team’s research published in the Journal of Neuroscience, there were higher levels of activated ERK, an increase anxious behaviors, and a greater sensitivity to fear-based learning in rats that were given THC.

In rats that received both THC and CBD, ERK levels were normal, anxious behaviors were reduced, and sensitivity to fear-based learning was diminished.

Based on the results, the research team has proposed that CBD is able to prevent negative effects produced by THC by blocking its ability to overstimulate the ERK pathway in the hippocampus.

Professor Laviolette says that the findings have important implications for cannabis prescriptions and long-term cannabis use, noting that it is critical to limit use to strains with high CBD and low THC content.

He says that the team’s discovery opens a new molecular frontier for developing safer more effective THC formulations.

According to lead author of the study and Ph.D. Candidate Roger Hudson, the ERK pathway was unaffected by CBD alone.

“CBD by itself had no effect,” said Hudson. “However, by co-administrating CBD and THC, we completely reversed the direction of the change on a molecular level. CBD was also able to reverse the anxiety-like behaviour caused by the THC.”

Laviolette says that the team will be following up on the study by continuing to identify specific features of the molecular mechanism, exploring ways to improve the efficacy of CBD-based therapies, and formulating THC with fewer side-effects.

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