Chronic Dietary Administration of Δ9-Tetrahydrocannabinol to Primates Reduces Systemic Platelet Activity and Function
Marijuana use can lead to platelet dysfunction, according to data from a new study in non-human primates. Platelets, one of the components of blood, play an important role in keeping blood vessels and the vascular system “healthy”, and platelets also help in wound healing and placenta development during pregnancy. The article is published in the American Journal Of Physiology-Cel Physiology ahead of print.
What are platelet function tests?
Platelets (" thrombocytes“) are blood cells that circulate freely until an injury occurs, which attracts them to accumulate there and are one of the first steps in the clotting process. Healing begins with hemostasis, and platelets play a crucial initial role in the clot clotting/dissolving cycle that is part of healing.
The four main functions of platelets are:
- Adherence to each other
- synergistic involvement with other coagulation factors.
When circulating platelets are exposed to tissue, as is the case when an injury interrupts the wall that separates them, they adhere to the tissue, which activates them to secrete factors that attract other platelets to do the same . Then, circulating fibrinogen begins to bind, causing further platelet aggregation, which stabilizes the forming clot. Meanwhile, tissue exposed to vascular circulation signals other processes that trigger other cycles of the coagulation process.
When a person fails to coagulate effectively or when there is excessive platelet function that produces clots that can obstruct blood flow or cause an embolism, one or more of the above four functions are abnormal, and the platelet test is an important tool to find the cause so that you can intervene appropriately.
Although the simple act of counting platelets in a certain volume of blood is useful in identifying thrombocytopenia (i.e. an insufficient number of platelets, leading to bleeding), it does not measure their good function nor to identify their dysfunction in the body. The difficulty of assessing platelet function as it occurs inside the body, which renders the platelet count insufficient for dysfunction diagnoses, has been solved with recent technologies.
Platelet function tests are not only useful for diagnosing coagulation disorders or thromboses, but also for determining the effectiveness of treatment when antiplatelet drugs are used to treat a clotting tendency in abnormal situations.
Platelet function and THC
Cannabis use has steadily increased as acceptance increases for medical and recreational reasons. Medical cannabis is administered for the treatment of chronic pain on the premise that signals from the endocannabinoid system desensitize pain sensor neurons and produce anti-inflammatory effects. The main psychoactive ingredient in cannabis is Δ9-tetrahydrocannabinol (THC) which signals primarily through the cannabinoid 1 (CBr) receptor, which is also present on non-neuronal cells, including blood platelets in the circulatory system. In vitro, CBr-mediated signaling has been shown to acutely inhibit platelet activation downstream of platelet collagen receptor glycoprotein (GP)VI. The systemic effects of chronic THC administration on platelet activity and function remain unclear. This study examines the effects of chronic THC administration on platelet function using a non-human primate (NHP) model.
An estimated 22 million people in the United States use marijuana for recreational or medical purposes each month. The concentration of delta-9-tetrahydrocannabinol (THC) – the psychoactive component responsible for the drug's “high” – in cannabis products has increased over the years, from less than 4% to over 15% in 2018.
"Although marijuana has been used for the treatment of chronic pain, insomnia, nausea, and vomiting, studies have also suggested that marijuana use is associated with dysfunction in the cardiovascular system, including both thrombosis and compromised vascular integrity in some cases,” researchers of a new study wrote. In this study, the research team explored the effects of THC on platelet function in rhesus macaque monkeys.
Each morning, before breakfast, male and female rhesus macaques were given a cookie with THC. Over several months, the researchers gradually increased the THC levels of the biscuits intended for the animals in order to approach standard doses according to their weights and in accordance with the recommendations of the doses of medical cannabis recommended in Colorado. The research team compared samples of the macaques' blood before and after the trial and found that THC reduced plaque aggregation, an important step in the process of blood clot formation, and decreased the production of thromboxanes, a lipid involved in coagulation. On the other hand, THC did not affect clotting time.
The researchers wrote that these findings may prompt people who are having surgery or who are pregnant to undergo a thorough review of their medication history. “Our observations may have important implications for clinical health policy regarding the use of medical marijuana in the future. »
The results show that female and male NHPs consuming a THC feed daily had reduced platelet granule adhesion, aggregation, and secretion in response to certain platelet agonists. Additionally, a change in bioactive lipids (oxylipins) was observed in the female cohort after THC administration. Indicating that chronic administration of edible THC 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 marijuana for medical purposes and for the providers caring for these patients.