Western University researchers explain the highs and lows of marijuana use

Researchers at Western University's Schulich School of Medicine & Dentistry have explained why marijuana in small doses can cause paranoia, and higher doses that mimic long-term exposure can result in apathetic and emotionally-blunted behaviour, or what some call the "stoner" phenomenon.

Steven Laviolette, PhD, a professor in the Departments of Anatomy and Cell Biology and Psychiatry, and his colleagues from Western's Addiction Research Group have shown that low doses versus high doses of marijuana-like drugs produce completely opposite effects on the neurons that regulate emotional response in the brain.

Laviolette and his colleagues, Brittany Draycott, Michael Loureiro, Tasha Ahmad, Huibing Tan and Jordan Zunder, reported their findings online in The Journal of Neuroscience.

Using animal models, Laviolette and his colleagues administered a low dose of a drug into the prefrontal cortex of the brain that mimics marijuana by directly activating cannabinoid receptors. Animals given a low dose of the drug showed increased associative fear memory, an emotional response comparable to paranoia in humans. When the research team examined much higher doses of the same drug, they found the exact opposite effect; those animals showed a lack of response to fear stimulus and demonstrated emotionally-blunted or depressive behaviour.

"What we found is that these effects on emotion were due to the ability of the drug to either ramp up or shut down the dopamine neurons in the brain depending on the dose," Laviolette says. "Through these findings we identify the brain's prefrontal cortex as a critical brain region for controlling marijuana-induced disturbances in emotional processing through a direct modulation of the brain's dopamine system."

The research team also found that pre-treatment with an antipsychotic medication was able to prevent the fear and paranoid behaviours induced by the low doses, and similarly, by blocking a specific receptor in the mid-brain, they were able to stop the ability of the higher doses to blunt emotional response.

"This has huge implications for identifying potential pharmacological means to prevent some of the undesired side-effects of marijuana," Laviolette says.