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.