Identifying the cellular basis of altered brain function in long-term cannabis users

2020

Challenge

Cannabis, more colloquially known as marijuana, is quite literally a mind-altering drug — brain scanning studies show people who have used it for a long time have altered activity in specific areas of their brains. However, such non-invasive studies in human users cannot identify the specific cellular mechanisms responsible for these changes.

Advance

IRP researchers led by senior investigator Carl R. Lupica, Ph.D., conducted a study in rats that directly examined four neuronal pathways that converge on a brain region called the nucleus accumbens, which is involved in reward, habit learning, and addiction. The researchers found that long-term exposure to the main psychoactive chemical in cannabis, delta-9-tehrahydrocannabinol (THC), weakened signals sent to the nucleus accumbens from the prefrontal cortex, a brain region involved in decision making. In contrast, input to the nucleus accumbens from two brain structures involved in emotion and heightened sensitivity to drug cues, the amygdala and hippocampus, were strengthened by long-term exposure to THC.

Impact

This research provides insight into the cellular changes that underlie the altered brain function observed in long-term cannabis users. The results point to targets that could help focus development of therapies to prevent addiction to, and withdrawal from, cannabis and other formulations containing high concentrations of THC.

Publications

Hwang EK, Lupica CR. (2020). Altered corticolimbic control of the nucleus accumbens by long-term Δ-9-tetrahydrocannabinol exposure. Biol. Psychiatry. Apr 1;87(7):619-631.