1. Introduction
Synthetic cannabinoids (SCs) are called ‘Spice’ in Europe and ‘K2’in the USA. The abuse of about 400 chemicals, defined as SCs, is increasing rapidly all over the world. Although generally smoked, vaporization, oral or rectal use has been reported (1). Several research have looked into using the endocannabinoid system (ECS) to treat myocardial and cerebral ischemia, hypertension, circulatory shock, atherosclerosis, metabolic syndrome, stroke, arrhythmia, and myocardial infarction, among the other vascular diseases (2-6). Furthermore, studies have shown that cannabis have both beneficial and negative effects when used to treat cardiac problems, and that there is a complex interaction between the ECS, the cardiovascular system, and the immune system (7).
For more than five decades, researchers have hypothesized that excessive use of SCs products has resulted in negative cardiovascular consequences. However, the reported frequency of cardiovascular-related problems has steadily increased during the previous decade. Young people are the most common cannabinoid users who develop these issues, and they have no underlying or hereditary relationship to cardiovascular disease. The severity of cardiovascular complications associated with SCs ranges from minor to severe, depending on the kind of issue. Cardiovascular problems have been documented in a number of ways (8). It is stated that SCs can cause death by creating vasospasm, plaque rupture, thrombus aggregation or myocardial oxygen delivery imbalance, myocardial ischemia and rhythm disturbance. The most common effects of the cardiovascular system due to the use of SCs are tachycardia and increased blood pressure (BP) (9). Cases with myocardial infarction and QT prolongation have also been reported (10-12).
It is well known that SCs interact with cannabinoid-1 (CB1) and cannabinoid-2 (CB2) receptors in body cells to mimic the effect of Δ9-tetrahydrocannabinol (THC), which is the major active ingredient in cannabis or marijuana (13). The number of new synthetic cannabinoid derivatives is increasing day after day. The presence of cannabinoid receptors has been demonstrated in the cardiovascular system, myocardial tissues, vascular endothelium, smooth muscle cells, and circulating blood cells (14-17). CB1 receptors have also been shown in the peripheral nervous system, including the vagus nerve, and can modulate cardiovascular function (18). Among the reasons for its popularity, today are the sales strategy under the name of legal marijuana, its easy accessibility, its cheap decency, and its negative results in tests developed for THC (10). During the Covid-19 pandemic, concerns about SCs use have grown (19). According to preceding reports, SCs intoxication instances had been related to chest pain, angina, arrhythmias, thrombus withinside the coronary artery, acute myocardial infarction, and minor strokes (20). Studies in which the mechanisms of these effects are investigated are quite limited.
JWH-018 is the most frequently used synthetic cannabinoid with a full agonist effect on both CB1 and CB2 receptors, with a short duration of action. While THC compound shows the partial agonistic effect on the CB1 receptor, JWH-018 shows full and potent agonistic effect (21,22). Acute cannabis exposure is well recognized to cause tachycardia, however, the effect on BP is less reliable. Chronic exposure, on the other hand, has been linked to bradycardia and a drop in blood pressure. When the CB1 receptor is activated in cardiac tissue, it causes a negative inotropic response in the heart. Although CB2 receptor expression has been found in cardiac myocytes, endothelial cells, and smooth muscle cells of coronary arteries, its function is less well understood and requires further research (23).
This study aimed to investigate the effects of the JWH-018 compound, the prototype of SCs, on the cardiovascular system in low dose (LD), and high dose (HD), acute (A) and subacute (SA) time-dependent manner. In this experimental study, JWH-018-related cardiovascular system changes were examined.