What is Stroke?
Stroke is referred to as the blockade of the blood flow in different parts of the human brain. Upon its occurrence, the oxygen and necessary nutrients for the brain to function don’t reach it, causing brain dysfunction and resulting in severe brain damage, which may eventually cause death if not properly diagnosed and managed in a timely manner.
If the blockage of blood vessels in the brain occurs for just a few minutes, then the brain cells start to degenerate, causing debilitating long-term problems. Due to the high death rate, stroke is considered a medical emergency.
If the blood flow is retained quickly enough, the long-term damage to the brain can be avoided. However, it should be noted that recovery from stroke may take up to several months for the patient to retain his normal or near-normal functionality.
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Two types of Stroke
There are two types of stroke:
- Ischemic stroke:
This is the most common type of stroke, and patients with this type of stroke often have a better chance at survival with a good prognosis in the long-term.
In ischemic stroke, the blood flow to a certain part of the brain is cut off, and this can be caused by a blood clot or a cholesterol plug/plaque (atherosclerosis) that could block the cerebral arteries that are providing nutrients to the brain. Once a blood vessel is blocked, the brain region that is supplied by that vessel becomes damaged. In 2-3 minutes, the nerve cells in that region start to die, causing permanent damage that can’t be restored back to normal.
- Hemorrhagic stroke:
This type of stroke is often the severest and most serious among the different types of stroke. In hemorrhagic stroke, a blood vessel that supplies the brain becomes injuries, and the blood starts to leak outside of it. This leads to a high death rate because the blood that comes out of the injured blood vessel can’t reach the brain cells, causing them to die shortly.
The Endocannabinoid System and Stroke
Cannabinoids that are derived from marijuana are known as phytocannabinoids. They also exist inside our bodies in the form of endocannabinoids. There are many endocannabinoid compounds in our bodies, such as 2-arachidonoylglycerol (2-AG). These endocannabinoids interact with target receptors, known as cannabinoid receptors type 1 (CB1) and type 2 (CB2), in a system known as the endocannabinoid system (ECS). CB1 receptors are mainly located in the central nervous system (the brain and the spinal cord), while CB2 receptors are located primarily in the peripheral nervous system and the immune system. This ECS modulates many physiological functions, including pain perception, sleep, inflammation, and many others.
The ECS has been previously reported to regulate hypertension and several cardiovascular diseases. It has also been shown to play a very critical role in the prevention of atherosclerosis, which is a very common cause of ischemic stroke. Herein, we will discuss the various research studies that have been conducted to determine the association between the ECS and stroke.
In 2018, an animal study was conducted to determine the effects of 2-AG on blood platelet aggregation and cerebral blood flow in rats with focal ischemic strokes. It was noted that the administration of 2-AG was associated with a significant reduction in cerebral blood flow. Therefore, it was suggested that caution should be taken when administering various CB1 and CB2 receptor agonists in patients with stroke.
In another animal study, it was investigated whether or not CB2 receptor agonist (GW405833) would prevent further brain damage in rats with hypoxic-ischemic stroke. Despite the fact that previous studies indicated that CB2 agonism causes neuroprotection in models of cerebral ischemic; however, this study reports that the investigated CB2 receptor agonist reflected no promising effects in ischemic stroke.
Four research studies have been conducted to determine the correlation between CB1 receptor activation and stroke. All of them found that the altered activity at CB1 receptors leads to neuroprotection in rats with stroke.
As for CB2 receptors, two research studies indicated that the altered activity at CB2 receptors results in neuroprotection in rats with stroke. However, these findings are contradicting with the results of 2 other research studies that found no effect at all between CB2 activation and stroke neuroprotection. Meanwhile, one study found that CB2 receptor activation may be harmful to the brain (increasing brain damage) in mice with stroke.
Does CBD Have Neuroprotective Properties in Patients with Stroke?
Aside from the previous interventions, cannabidiol (CBD) has been shown to be very promising in reducing the brain damage associated with stroke. In a recent study, cannabidiol was administered to a group of rats with ischemic stroke. Surprisingly, CBD was shown to enhance morphine anti-nociception (reduces pain sensation), reduces the frequency and severity of associated seizures, and minimized the degree of stroke damage. These findings suggest that CBD provides neuroprotection against ischemic stroke. Researchers have indicated that the beneficial effects of CBD on stroke neuroprotection is warranted through the interaction with receptors called sigma-1 receptors.
Furthermore, another study investigated the effects of CBD on poststroke neuroprotection. They found that CBD was of great significance in improving post-stroke outcomes with a better prognosis. In addition, CBD, when co-administered with hypothermia in piglets with hypoxic-ischemic brain insult, was found to reduce excitotoxicity, inflammation, oxidative stress, and cellular damage. This effect was found to be better than when CBD was administered alone.
What Do Human Studies Say?
Although there are many animal and preclinical research studies that investigated the role of various cannabinoids in neuroprotection in stroke, there is a very limited number of clinical studies that investigated the effects of cannabinoids, particularly CBD, in human patients with stroke. Therefore, more research is still warranted for betting understanding of the role of CBD in ischemic brain injury, both in the context of stroke among adults and in neonates with hypoxic-ischemia.
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