Relationships among peri-traumatic circulating endocannabinoids and long-term, negative outcomes following traumatic injury. Psychopharmacology (Berl) 2026 Feb;243(2):383-399
Date
07/11/2025Pubmed ID
40643612Pubmed Central ID
PMC12904968DOI
10.1007/s00213-025-06837-4Scopus ID
2-s2.0-105010584798 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
RATIONALE: Traumatically injured individuals can develop chronic negative psychological sequelae. Improved understanding of contributing, peri-traumatic risk factors is essential to reduce the risk of these consequences. Previous studies have found that peri-traumatic, circulating endocannabinoid concentrations are positively associated with development of post-traumatic stress disorder (PTSD), chronic pain and depression months later, particularly in members of racial/ethnic groups that have been historically marginalized.
OBJECTIVES: This replication study examined relationships among peri-trauma serum endocannabinoid concentrations and long-term consequences in a cohort comprised primarily of individuals from marginalized racial and ethnic groups.
METHODS: Participants (n = 100; 81% from marginalized racial and ethnic groups) were traumatically injured adults presenting to the ED of an urban tertiary care hospital. Endocannabinoids N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) were measured in serum collected within days (peri-trauma) and 6-10 months following injury (follow-up). Assessments, including PTSD, depression, pain and quality of life were completed. Statistical approaches, including multivariate, hierarchical regressions, were used to determine associations among serum endocannabinoid concentrations and long-term outcomes.
RESULTS: Although it did not survive correction for multiple comparisons, peri-trauma serum 2-AG concentrations. Peri-trauma serum 2-AG concentrations were also positively associated with PTSD, pain severity, and functional engagement scores at follow-up. There were no significant associations between circulating 2-AG or AEA and depression.
CONCLUSIONS: These findings generally replicate earlier studies demonstrating that serum 2-AG concentrations are biomarkers of risk for PTSD and pain and uncover an additional association with poor functional quality of life. Further studies are needed to determine the underlying mechanisms of these relationships.
Author List
Albertina EA, Tomas CW, Geier TJ, Timmer-Murillo SC, Pina IG, Jazinski-Chambers K, Sauber G, Fitzgerald JM, Larson CL, deRoon-Cassini TA, Hillard CJAuthors
Timothy J. Geier PhD Assistant Professor in the Surgery department at Medical College of WisconsinCecilia J. Hillard PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
Sydney Timmer-Murillo PhD Assistant Professor in the Surgery department at Medical College of Wisconsin
Carissa W. Tomas PhD Assistant Professor in the Institute for Health and Humanity department at Medical College of Wisconsin
Terri A. deRoon Cassini PhD Center Director, Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AdultArachidonic Acids
Chronic Pain
Cohort Studies
Depression
Endocannabinoids
Female
Follow-Up Studies
Glycerides
Humans
Male
Middle Aged
Polyunsaturated Alkamides
Quality of Life
Risk Factors
Stress Disorders, Post-Traumatic
Wounds and Injuries
Young Adult
