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Impact of Inflammasome Activation in Chronic Pain Patients by Medical Marijuana (MM)

Alexandra McMahon
University of Miami

Co-Authors: Juan Pablo de Rivero Vaccari1, Alex Li2, Jennifer J Hu1, Yan Wang2
1University of Miami, 2University of Florida

Background: Chronic pain, often influenced by inflammation, is managed by some patients using Medical Marijuana (MM). The long-term effects of MM on pain and the biological mechanisms affected by MM are unclear. This pilot study aimed to assess how MM usage affects inflammasome levels and pain in patients with chronic pain.

Objective: This pilot study examined the effects of MM on inflammasome biomarker expression and pain levels among older adults with chronic pain. Specifically, we evaluated (1) the association between pain severity and inflammasome levels in plasma, and (2) the differences in pain and inflammasome levels by plasma cannabidiol (CBD) or delta-9-tetrahydrocannabinol (THC) and their metabolites.

Methods: Data from 40 chronic pain patients (mean age = 65 years old) in the Study on Medical Marijuana and its Long-Term Effects (SMILE) were analyzed. Inflammasome biomarkers included apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL-18), and the disease-associated macrophage marker Triggering receptor expressed on myeloid cells 2 (TREM2). Pain scores using Brief Pain Inventory (BPI) were collected at baseline and 3-month follow-up. T-tests and Wilcoxon tests were used to assess the relationship between MM use, inflammasomes, and pain changes. Plasma levels of THC and CBD metabolites were analyzed at baseline and 3-month follow-up.

Results: Our results show that changes in ASC levels were associated with changes in both self-reported “worst pain” (p=0.026) and “average pain” levels (p=0.037). At the 3-month follow-up, pain scores were trending lower for individuals who had detectable plasma THC or THC metabolites than those who did not, particularly for least pain present (mean=1.21, SD=2.15 vs. mean=2.13, SD= 1.85, p=0.069). TREM2 levels were trending lower for individuals who had detectable plasma CBD or CBD metabolites compared to those who did not (mean=17,003, SD= 11243 vs. mean=22,389, SD= 10091, p= 0.086).

Conclusions: Our findings suggest that lower pain severity may be associated with reduction in inflammasome activation, while THC use seems to be associated with lower pain severity and CBD use seems to be associated with lower expression of the inflammatory marker TREM2. This pilot study highlights the molecular mechanisms of MM in inhibiting inflammasome activation and inflammatory responses while improving pain scores in patients with chronic pain. Future larger internal and external studies are warranted to validate these promising findings and explore MM in pain management.