The development of safer, more effective cannabis for patients and recreational users prone to its more severe side effects may be possible, thanks to a ground-breaking study by Western researchers.
Researchers at the Schulich School of Medicine & Dentistry have shown for the first time the molecular mechanisms at work that cause cannabidiol (CBD) to block the psychiatric side-effects caused by tetrahydrocannabinol (THC), the main psychoactive chemical in cannabis.
The study was published today in JNeurosci: The Journal of Neuroscience.
Previously, research showed that strains of cannabis with high levels of THC and low levels of CBD can cause increased psychiatric effects, including paranoia, anxiety and addictive-behaviours. But why that was occurring was not fully understood.
Schulich professor Steven Laviolette and his team used rats to investigate the role of a molecule in the brain’s hippocampus – extracellular-signal regulated kinase (ERK) – which triggers the neuropsychiatric effects of THC.
“For years we have known that strains of cannabis high in THC and low in CBD were more likely to cause psychiatric side-effects,” Laviolette explained. “Our findings identify for the first time the molecular mechanisms by which CBD may actually block these THC-related side-effects.”
In the study, rats given THC had higher levels of activated ERK, showed more anxiety and were more sensitive to fear-based learning. Rats given both CBD and THC had normal levels of activated ERK, less anxiety, and were less sensitive to fear-based learning.
Based on these results, the research team proposes that THC activates ERK while CBD inhibits it.
“Our findings have important implications for prescribing cannabis and long-term cannabis use. For example, for individuals more prone to cannabis-related side-effects, it is critical to limit use to strains with high CBD and low THC content,” Laviolette said. “More importantly, this discovery opens up a new molecular frontier for developing more effective and safer THC formulations.”
CBD alone had no effect on the ERK pathway, explained Schulich PhD candidate Roger Hudson, lead author on the study. However, by co-administrating CBD and THC, the team “completely reversed the direction of the change on a molecular level.”
CBD was also able to reverse the anxiety-like and addictive-like behaviours caused by the THC.
The team will follow up these studies by continuing to identify the specific features of this molecular mechanism. They will examine ways to formulate THC with fewer side effects and to improve the efficacy of CBD-derived therapies.