stroke Cannabis use has been implicated in several cases of cerebrovascular accident (CVA) or stroke, and may also exacerbate cardiovascular ill-health that can lead to stroke, in susceptible individuals. However, there is also strong evidence that there may be a potential for cannabinoid therapies to assist in post-stroke recovery.
What is cerebrovascular accident?
Cerebrovascular accident (CVA) is the formal term for stroke, an acute condition in which blood supply to the brain is interrupted or disturbed. Around 87% of all cases of stroke are ischemic in nature; ischemic stroke (IS) is caused by ischemia, or loss of blood flow, which in turn is usually caused by a blockage in the circulatory system such as an arterial embolism, atherosclerosis or thrombosis. Stroke may also be caused by haemorrhage of blood vessels in the brain—this is termed haemorrhagic stroke (HS).
As the blood flow (and therefore supply of oxygen) to affected regions of the brain is cut off during a stroke, the affected areas are unable to function as normal, and neurological and physiological functions related to them are disturbed or halted entirely. Depending on the length of time the blood flow is interrupted, this damage may be irreversible.
As our understanding of the field increases, we are developing new and better therapies that can mitigate and reverse some of the effects of stroke. Cannabis and cannabinoid-based therapies are being rigorously assessed, due to their known neuroprotective abilities.
Prevalence & risk factors
Stroke is a serious and debilitating condition that affects up to 15 million people worldwide every year. Absolute numbers of sufferers continues to increase year-on-year—in the developing world, its prevalence is increasing as lifestyles become more westernised, while in the developed world, absolute prevalence is decreasing but cases are still becoming more frequent as the population ages.
Stroke mostly affects those in the older demographic, and as our populations continue to age throughout the world, the burden on healthcare services is increasing. Aside from old age, other factors that predispose an individual to stroke include high blood pressure or cholesterol, diabetes, ischemic heart disease and tobacco use. High blood pressure (hypertension) is the factor most strongly associated with increased risk of stroke.
Evidence that cannabis use can increase the risk of stroke both in susceptible groups and in otherwise-healthy young adult males does exist, but a causal link has not yet been definitely established. Certainly, cases of stroke that can be linked to cannabis are a tiny fraction of the whole, but as cannabis use increases in many countries, that tiny fraction may increase somewhat.
For whom does cannabis use increase stroke risk?
The existing research into the subject indicates that very few individuals that use cannabis will experience an increased risk of stroke. However, for those with certain underlying health conditions, cannabis use may increase the risk of stroke occurring—and may even directly trigger it, in extremely rare cases.
Cannabis users suffering from ischemic heart disease, hypertension, and cerebrovascular disease may develop chest pain, cardiac arrhythmia, and (in extremely rare cases) acute myocardial infarction. If an individual experiences MI, their risk of stroke is greatly elevated for the following month. Patients with a cerebrovascular disease, such as atherosclerosis, may also experience strokes caused by cannabis-related changes in blood pressure.
The risk of symptoms occurring appears to be highest immediately following cannabis use, dropping to near-normal levels within thirty minutes. Because THC has analgesic effects it may mask chest pain, delaying treatment.
CVA and cardiovascular health
Cardiovascular ill-health is very strongly linked to risk of ischemic stroke. High blood pressure (hypertension) is often seen as a cardiovascular condition in and of itself, as it puts strain on the heart and can lead to various complications. It is also a symptom of many cardiovascular disorders. However, it is viewed as an independent risk factor, particularly if it is ‘primary’ hypertension and there is no discernible underlying cause for its occurrence.
There are many other cardiovascular conditions that increase risk of stroke, including ischemic heart disease (progressive narrowing of the blood vessels), hypertensive heart disease (which is a leading cause of aneurysms) and cerebrovascular disease (a group of diseases affecting blood vessels in and towards the brain, which include atherosclerosis and transient ischemic attack).
Thrombosis & Embolism
Thrombosis and embolism are two other major factors, both of which involve obstruction to the blood vessels (thrombosis refers to blockages caused blood clots only and which occur at the site of origin, while an embolism may be a blood clot, a gas bubble or a globule of fat, and may occur in a part of the body that is remote from the point of origin).
As well as posing a direct risk, many of these diseases also cause hypertension (known as ‘secondary’ hypertension when it is a symptom of a known underlying condition), increasing the risk factor even more. Around 30-40% of all ischemic strokes have no apparent underlying physiological cause; such instances are known as ‘cryptogenic’.
The EC system, cardiovascular health and stroke
Various studies have postulated a link between cannabis use and acute myocardial infarction (MI). A study published in 2001 concluded that for a small subset of susceptible individuals, risk of heart attack increases by 4.8 times in the sixty minutes following use of cannabis. Individuals that suffer a heart attack have an increased risk of experiencing stroke during the thirty days following onset of MI.
It is also thought that cannabis smoking increases the level of carboxyhaemoglobin in the blood, decreases the rate of oxygen delivery to the heart, and increases heart rate, thereby increasing the work of the heart. These side-effects are well-known to be associated with cannabis use, but the link between cannabis use and MI itself is not fully established, and is likely to only affect those in specific high-risk brackets.
CB1 and CB2 receptors are widely distributed within the cardiovascular system. These receptors play a role in modulating the cellular activity in the walls of the blood vessels; it has been suggested that this mechanism may in some way contribute to the development of atherosclerosis, another major cause of ischemic stroke.
The CB-receptors, atherosclerosis & thrombosis
In atherosclerosis, the arterial walls typically begin to accumulate white blood cells, debris, cholesterol and fatty acids. These accumulations usually aggregate to form plaques known as atheromata. CB1 receptors have been found to express in certain white blood cells, known as macrophages, found within advanced atheromata.
It is not known what the precise mechanism at work is, but it has been noted that patients with unstable angina (irregular chest pain due to ischemia of the heart) exhibit a markedly higher expression of CB1-receptors in coronary arteries affected by atherosclerotic plaques than patients with stable angina.
The CB-receptor agonist delta-9 THC has also been shown to activate blood platelets via the CB-receptors, leading to increased expression of glycoprotein IIb/IIIa (a protein found in the platelets); this in turn causes activation of factor VII, a protein that is strongly linked to thrombogenesis (growth of blood clots) by causing aggregation of the blood platelets). Thrombosis is another major risk factor for ischemic stroke.
Cannabis Arteritis and Ischemic Stroke
There have been suggestions that cannabis can increase risk of stroke through a slightly different mechanism—the speculative disorder cannabis arteritis, which takes a form very similar to thromboangiitis obliterans (Buerger’s disease, a known consequence of long-term tobacco use).
It is thought that the recurrent inflammation of the blood vessels that characterises these diseases may occur in the brain as well as in the peripheral vessels, where it is more commonly found. If severe enough, these inflamed areas may cause obstruction of blood flow to the brain, leading to ischemic stroke.
However, it is important to note that cannabis arteritis has not been conclusively demonstrated, and many of the studies that have investigated it have involved subjects that also used tobacco. Similarly, various studies and papers describe an association between cannabis and ischemic stroke, but many of these studies have been incomplete or flawed.
Cannabis implicated in cases of stroke
In New Zealand, a study into 218 individuals suffering from IS or transient ischemic attack, twenty-five (15.6%) tested positive for cannabinoids in the urine, compared to just 8.1% of control participants.However, many of the participants also used tobacco; after adjusting for this, the researchers were unable to establish an association independent of tobacco.
In a review of medical literature conducted by Wolff, et al., fifty-nine cases of stroke believed to be related to cannabis use were documented; 83% of these cases were ischemic stroke. The average age of the fifty-nine individuals was thirty-three years, and men outnumbered women by almost five to one.
Studies have not proven a link
The evidence for cannabis use increasing risk of stroke is generally circumstantial. For example, a case study of seventeen IS patients who were exposed to marijuana justified a causal relationship by absence of other known risk factors, a temporal link between cannabis use and symptom onset, and the recurrence of symptoms with re-exposure to cannabis.
According to Wolff’s review, chronic users were more likely than occasional users to have experienced ischemic stroke. In many of the cases reported, stroke occurred during or within thirty minutes of cannabis consumption. A temporal association between cannabis consumption and IS was the main basis for suggesting a relationship.
Another review by Desbois et al. documented 71 cases of cannabis users with IS. All patients were classified as heavy marijuana smokers; in 76.5%, symptoms occurred during or within thirty minutes of consumption. While the temporal association is circumstantial, it does strongly point to cannabis’ ability to trigger stroke in specific cases. The other most notable piece of circumstantial evidence is the recurrence of symptoms on re-exposure.
THC, vasoconstriction and stenosis
It does appear that cannabis use may trigger stroke in rare cases, and there are various theories as to how this may occur. As well as potentially leading to development of atherosclerosis, presence of THC may trigger reversible cerebral vasoconstriction syndrome (RCVS). Several animal studies have shown that THC has peripheral vasoconstrictor properties.
Wolff, et al. reported the presence of multifocal intracranial stenosis (MIS) in 21% of cannabis users experiencing IS. This form of cerebral angiopathy, which manifests as severely narrowed cerebral arteries in multiple locations, was observed to reduce and ultimately disappear within three to six months following cessation of cannabis use. At least one other study has also demonstrated a link between cannabis use and MIS.
Desbois and colleagues reported MIS in 50% of patients, RCVS in 43%, and single focus stenosis in 22.6%. A review of patients with RCVS reported an incidence of 32% for cannabis use; for almost half of those, cannabis was the only drug consumed.
Acute myocardial infarction & ischemic stroke
Cardioembolic ischemic stroke, which makes up 14-30% of all cases of IS, has been associated with cannabis-related MI. Cardioembolic IS involves the occurrence of an embolism between the heart and brain, which causes disruption of the myocardial supply and demand equilibrium, leading to stroke.
Given that the endocannabinoid system is linked so deeply with cardiovascular health, it is likely that THC and other cannabinoids play a major role in cardiovascular regulatory functions. In healthy individuals with no underlying condition or predisposition, the endocannabinoid would assist in maintaining good health; however, for those in high-risk groups, where the function of the cardiovascular system is already imbalanced, malfunctioning systems could cause adverse effects.
Beyond high-risk groups, there is a small unexplained incidence of young, apparently-healthy individuals suffering from IS after cannabis use. It may be that there is no link between these cases of stroke and cannabis use, or it may be that a genetic predisposition to such phenomena exists. Presently, the sole consistent variable found in patients with cannabis-associated IS is male gender.
More work is needed to establish the relationship
Evidence supporting the link between cannabis use and ischemic stroke is increasing, but a precise causal relationship is yet to be determined. The apparent chronological relationship between cannabis use and stroke onset is the most compelling circumstantial evidence; as well as this, relapses of IS with cannabis re-exposure point to a causal relationship.
As medical cannabis becomes ever more available, and prescribed for an ever-increasing range of disorders, it is crucial that its potential side-effects are assessed. The side-effects of cannabis are apparently benevolent for the most part, and the subset of individuals that could potentially be affected is so small that it is in no way a justification to withhold cannabis medications from the wider population. Furthermore, there is great potential in cannabinoid therapies to assist those recovering from stroke.
In our next article on the relationship between cannabis and cerebrovascular accident, we will focus on the potential benefits of cannabinoid therapy to assist in post-stroke recovery.