Date of Award
Basic Biomedical Science
Doug Martin, Ph.D.
Hong Zheng, MD
Lisa McFadden, Ph.D
Blood Pressure, Heart Rate, Synthetic Cannabinoids, Neuronal Activation, Paraventricular Nucleus, Amygdala, Autonomic Function
Cardiology | Circulatory and Respiratory Physiology | Medical Sciences | Neurosciences | Substance Abuse and Addiction | Systems and Integrative Physiology
Cannabinoids encompass natural cannabis and synthetic cannabinoids. While the synthetic cannabinoids interact with the same endogenous system as cannabis, their effects are quite different and poorly understood. In addition to psychological effects that trigger their use, these substances are linked to cardiovascular morbidity. To assess the cardiovascular effect of synthetic cannabinoids, we first tested the hypothesis that intravenous administration of a synthetic cannabinoid would increase blood pressure in conscious rats. Second, we tested the hypothesis that the sympathetic nervous system is involved by injecting a ganglion blocker to see if the cardiovascular response from synthetic cannabinoids would be blocked. Third, we tested the hypothesis that the hypothalamic paraventricular nucleus is involved by doing immunohistochemistry to check for cFos fluorescence.
We found that synthetic cannabinoid use peaked with 7,000 calls to poison control centers in 2011 and has stabilized between 1,000-2,000 calls per year in the US. In humans, cardiovascular effects account for approximately 40% of adverse responses to synthetic cannabinoids. The most frequently reported being tachycardia (50%) and hypertension (20%). To test our hypothesis, Sprague Dawley rats were fitted with chronic indwelling arterial and venous catheters to record blood pressure and heart rate. Conscious rats were given intravenous injections of vehicle (20% cyclodextrin) then incremental doses of the synthetic cannabinoid, WIN 55, 212-2 (25, 50, 100 ug/kg + 0.2 ml saline flush). We observed that injection of WIN resulted in rapid onset dose dependent increases in blood pressure and heart rate that peaked at approximately 18+/-6 mm Hg and 90+/-15 bpm. We also observed that interruption of autonomic function via ganglion blockade abolished the pressor effect of WIN. Lastly, we also used immunohistochemistry to assess the role of the PVN in the response to WIN. Collectively, the data are consistent with the view that synthetic cannabinoids, such as WIN, increase blood pressure and heart rate via autonomic mechanisms that may be controlled by the brain.
Nelson, Madeleine A., "MECHANISMS OF SYNTHETIC CANNABINOIDS ON CARDIOVASCULAR HEALTH" (2021). Honors Thesis. 167.