The procoagulatory effects of delta-9-tetrahydrocannabinol in human platelets.
Delta-9-tetrahydrocannabinol (THC) is increasingly used for the long-term treatment of nausea, vomiting, cachexia, and chronic pain. Recent reports, however, have indicated an increased risk of myocardial infarction and thromboangiitis obliterans after THC intake. Blood platelets have an essential role in the pathogenesis of these two diseases, but it is unclear whether platelets are potential target cells for cannabinoids. We investigated the effects of THC on human platelets and the expression of cannabinoid receptors on their cell membranes in this in vitro study. The effects of THC (final concentrations 10(-7) to 10(-5) M) on the expression of activated platelet fibrinogen receptor (glycoprotein IIb-IIIa) and P selectin were characterized by flow cytometry. Western blotting was performed with platelet membrane preparations to determine the surface expression of cannabinoid receptors on human platelets. THC increased the expression of glycoprotein IIb-IIIa and P selectin on human platelets in a concentration-dependent manner. The two known cannabinoid receptors (CB(1) and CB(2)) were both detected on the cell membrane of human platelets. Our functional results may suggest a receptor-dependent pathway of THC-induced platelet activation. However, further in vivo studies are warranted to evaluate the role of cannabinoid receptors in mediating the demonstrated procoagulatory effect of THC.
Deusch
Engelbert
E
Department of General Anesthesiology and Intensive Care B, Vienna Medical University, Vienna, Austria.
Kress
Hans Georg
HG
Kraft
Birgit
B
Kozek-Langenecker
Sibylle A
SA
D001777:Blood Coagulation / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects*; D015153:Blotting, Western; D013759:Dronabinol / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects; D043882:Receptors, Cannabinoid / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D043882:Receptors, Cannabinoid; D011956:Receptors, Cell Surface; D013759:Dronabinol