Key Takeaways

  • In a double-blind, randomized, cross-over study of adults who use cannabis regularly, researchers from Massachusetts General Hospital assessed participants’ brain activity under the influence of THC (the main psychoactive component in cannabis) versus placebo.
  • Compared with placebo, THC led to reduced connections and activity within the brain’s prefrontal cortex, a region important for decision-making and self-control.
  • THC was also associated with connectivity changes that could impair the brain from efficiently adapting or reconfiguring to changing stimuli

BOSTON – A new study led by investigators from Massachusetts General Hospital, a founding member of the Mass General Brigham healthcare system, reveals that the main psychoactive component in cannabis or marijuana disrupts the normal connections and activity of the brain’s prefrontal cortex, a region that is crucial for decision-making and self-control. The findings are published in the Neuropsychopharmacology.

“We know that Δ9-tetrahydrocannabinol, or THC, in cannabis can affect thinking and behavior and potentially lead to cognitive impairment,” said senior author Jodi M. Gilman, PhD, director of Neuroscience at the Massachusetts General Hospital Center for Addiction Medicine and an associate professor in Psychiatry at Harvard Medical School. “This disruption of the prefrontal cortex may underlie cognitive impairment.”

Gilman and her colleagues conducted a double-blind, randomized, cross-over study in adults, aged 18–55 years, who use cannabis regularly. Using portable brain scanning technology, the researchers compared 128 participants’ brain activity under the influence of THC versus placebo.

THC was associated with decreased functional connectivity within the prefrontal cortex relative to placebo, with the weakest connections among those who reported greater severity of intoxication. Also, THC was associated with increased variability (or reduced stability) of functional connectivity of the prefrontal cortex, which could indicate a reduced ability of the brain to efficiently adapt or reconfigure to changing stimuli. Finally, THC was associated with lower overall activity within the prefrontal cortex.

“We were able to measures these effects of THC intoxication using  portable imaging, which could potentially be incorporated in impairment testing scenarios, for example at the roadside,” said Gilman. “We need more studies to understand how brain effects of acute THC intoxication relate to cognitive performance and operational impairment.”

Keerthana Deepti Karunakaran, Michael Pascale, Nisan Ozana, Kevin Potter, Gladys N. Pachas, A. Eden Evins, and Jodi M. Gilman.

Funding: Research support was provided by the National Institutes of Health

Paper cited: Karunakaran KD et al. “Intoxication due to Δ9-tetrahydrocannabinol is characterized by disrupted prefrontal cortex activity.” Neuropsychopharmacology DOI: 10.1038/s41386-024-01876-5


About Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. MGH is a founding member of the Mass General Brigham healthcare system.