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Translocator protein levels higher in cannabis users

Cannabis users, particularly people with cannabis use disorder, had higher 18-kDa translocator protein levels than non-cannabis users, researchers reported in JAMA Psychiatry.

“Cannabinoids may act as an immunosuppressant by inhibiting microglial activation, inhibiting the release of free radicals and reactive oxygen species from microglia, decreasing proinflammatory cytokine secretion from microglia, and increasing anti-inflammatory cytokine release,” Romina Mizrahi, MD, PhD, from the Centre for Addiction and Mental Health in Toronto, and colleagues wrote. “Although preclinical studies have investigated the association between neuroimmune function and cannabis use, clinical evidence remains sparse.”

Using a cross-sectional design, researchers compared the neuroimmune activation or 18-kDa translocator protein (TSPO) levels in 24 long-term cannabis users and 27 non-cannabis users (controls) as well as investigated the link between brain TSPO levels and behavioral measures and inflammatory blood biomarkers.

Participants underwent a positron emission tomography (PET) scan with fluorine F 18–labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl) acetamide, known as [¹⁸F]FEPPA, to quantify total distribution volume across brain regions of interest. The investigators also evaluated patients’ stress and anxiety as well as measures of inflammatory cytokines and C-reactive protein (CRP) levels.

Mizrahi and colleagues reported that cannabis users showed a 23.3% higher neuroimmune activation or translocator protein levels than controls, with a more prominent implication (31.5% higher) for participants with cannabis use disorder. The results also showed that greater brain TSPO levels were linked to chronic stress and anxiety and higher circulating CRP levels in cannabis users.

The investigators emphasized that all of these exploratory correlations must be confirmed in larger samples.

“These findings suggest that long-term cannabinoid exposure may be correlated with the cognitive and behavioral impairments associated with [cannabis use disorder], perhaps through neuroimmune contributions,” the researchers wrote. “This study emphasizes the need for more complementary preclinical systems to inform the role of cannabinoids and TSPO in neuroimmune signaling.” – by Savannah Demko

Disclosures: Mizrahi reports grants from the NIMH and from the National Alliance for Research on Schizophrenia and Depression. Please see the study for all other authors’ relevant financial disclosures.