TitleChronic edible dosing of Δ9-tetrahydrocannabinol (THC) in nonhuman primates reduces systemic platelet activity and function.
Publication TypeJournal Article
Year of Publication2022
AuthorsReitsma SE, Lakshmanan HHara Sudha, Johnson J, Pang J, Parra-Izquierdo I, Melrose AR, Choi J, Anderson DEJ, Hinds MT, Stevens JFrederik, Aslan JE, McCarty OJT, Lo JO
JournalAm J Physiol Cell Physiol
Date Published2022 Mar 01
KeywordsAdministration, Oral, Animals, Blood Coagulation, Blood Platelets, Cannabinoid Receptor Agonists, Dronabinol, Female, Macaca mulatta, Male, Medical Marijuana, Oxylipins, Platelet Adhesiveness, Platelet Aggregation, Secretory Vesicles, Signal Transduction, Thromboxanes, Time Factors

Cannabis usage has steadily increased as acceptance is growing for both medical and recreational reasons. Medical cannabis is administered for treatment of chronic pain based on the premise that the endocannabinoid system signals desensitize pain sensor neurons and produce anti-inflammatory effects. The major psychoactive ingredient of cannabis is Δ9-tetrahydrocannabinol (THC) that signals mainly through cannabinoid receptor-1 (CBr), which is also present on nonneuron cells including blood platelets of the circulatory system. In vitro, CBr-mediated signaling has been shown to acutely inhibit platelet activation downstream of the platelet collagen receptor glycoprotein (GP)VI. The systemic effects of chronic THC administration on platelet activity and function remain unclear. This study investigates the effects of chronic THC administration on platelet function using a nonhuman primate (NHP) model. Our results show that female and male NHPs consuming a daily THC edible had reduced platelet adhesion, aggregation, and granule secretion in response to select platelet agonists. Furthermore, a change in bioactive lipids (oxylipins) was observed in the female cohort after THC administration. These results indicate that chronic THC edible administration desensitized platelet activity and function in response to GPVI- and G-protein coupled receptor-based activation by interfering with primary and secondary feedback signaling pathways. These observations may have important clinical implications for patients who use medical marijuana and for providers caring for these patients.

Alternate JournalAm J Physiol Cell Physiol
PubMed ID35080922
PubMed Central IDPMC8858671
Grant ListP51 OD011092 / OD / NIH HHS / United States
R01 AI157037 / AI / NIAID NIH HHS / United States
K12 HD000849 / HD / NICHD NIH HHS / United States
R01 HL144113 / HL / NHLBI NIH HHS / United States
HL144113 / / HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
R03 HD097116 / HD / NICHD NIH HHS / United States
P51 OD011092 / CD / ODCDC CDC HHS / United States
HL101972 / / HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI) /
R01 HL101972 / HL / NHLBI NIH HHS / United States
R01 HL146549 / HL / NHLBI NIH HHS / United States
AI157037 / / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) /