An impressive new study led by scientists at Canada’s Western University has for the first time revealed one of the molecular mechanisms by which cannabidiol (CBD) directly blocks the negative psychiatric side effects generated by tetrahydrocannabinol (THC).

The frequently identified correlation between marijuana use and the onset of mental illnesses such as schizophrenia is often thought to be associated with THC, the major psychoactive compound in the plant. Conversely, CBD has been found to possess impressive antipsychotic effects, so scientists have long hypothesized a balance between CBD and THC in marijuana is important.

A striking study from earlier this year suggested modern high-THC strains of marijuana can be linked to higher rates of psychosis. The study was observational, with no causal mechanism presented, but this new research may offer some of the first mechanistic evidence to suggest marijuana is safest when CBD and THC are more in balance.

The new study looked at a specific signaling pathway in the hippocampus regulated by a molecule called extracellular signal-regulated kinase (ERK). Dysregulation of this pathway has been previously implicated in anxiety behaviors related to schizophrenia. The new study first tested the effect of THC on this particular pathway in rats. Administered alone, THC was found to explicitly stimulate this ERK pathway, triggering anxiety-like behavior. However, when THC was administered with CBD an animal’s ERK levels remained normal, and the rats behaved in ways similar to the normal control group.

“CBD by itself had no effect,” says lead author Roger Hudson, explaining one of the more interesting elements of the research. “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 behavior and addictive-like behavior caused by the THC.”

Over the last couple of decades average THC concentrations in marijuana strains have been dramatically rising, while average CBD concentrations have been falling. In 2006 the average THC concentration of marijuana in the United States was around 5 percent, while now it is not uncommon to find strains with THC levels between 20 and 30 percent.

The new study offers some of the first clear causal evidence that a balance between CBD and THC in marijuana is essential to reducing possible deleterious side effects of long-term use, particularly in individuals more prone to mental illness.

“Our findings have important implications for prescribing cannabis and long-term cannabis use," says Steven Laviolette, corresponding author on the research. "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. More importantly, this discovery opens up a new molecular frontier for developing more effective and safer THC formulations.”

The next step for the researchers will be to further investigate this particular mechanism in the hopes of developing safer medicinal THC formulations.

The new study was published in the Journal of Neuroscience.

Source: Western University