Stroke associated with drug abuse …

Narendra Kala MD

Stroke & Vascular Disorders

Updated 09.15.2025
Released 09.23.1996
Expires For CME 09.15.2028

Stroke associated with drug abuse

Author: Narendra Kala MD

See Contributor Disclosures

Editor: Steven R Levine MD

Cite this article

Stroke associated with drug abuse

In This Article

Quick Link

Introduction

Overview

Substances taken for non-medical reasons, usually for their mind-altering effects, are considered drugs of abuse. There is a close relation of cerebrovascular disorders and drugs of abuse, with drug abuse found causal in many cases of strokes, especially in young adults. This article aims to highlight the pathophysiology and clinical features of strokes due to drug abuse.

Key points

	• Drugs of abuse increase the risk of both ischemic stroke and intracerebral hemorrhage.
	• Psychomotor stimulants (such as cocaine, amphetamines, phencyclidine, etc.) are more commonly associated with stroke. They cause a sympathetic surge with elevation of blood pressure along with possible vasospasm of cerebral and systemic arteries leading to deleterious effects.
	• Intravenous opioids (eg, heroin) are relatively less common but are noted to cause infectious complications like endocarditis and/or mycotic aneurysms.
	• There is now growing evidence that marijuana is not completely safe, and the “gateway drug” has an independent increase in stroke risk.
	• Ethnic minorities appear to be at higher risk of strokes and hemorrhages from drug abuse, especially in-and-around major cities.

Historical note and terminology

Historically, drug abuse dates back thousands of years and is not a peculiarly modern problem as often considered, with ingestion of plants having the longest reported history of abuse. Perhaps initiated in a ritualized or ceremonial context, they have been abused over time, and the annals of history in medicine and botany have numerous chapters detailing the same. Cannabis has been reported to be used by the Chinese as early as 2737 BC and in the Indian subcontinent around 500 BC as a herbal remedy. Poppy plants were a commercial trade over the medieval periods traveling across the globe. Morphine was extracted from opium by Sertuerner in 1806, and it was the first alkaloid ever to be isolated from any plant and was used as an anesthetic. Alkaloidal cocaine was first isolated by Neumann in 1859; it was introduced into a sweet tonic (Vin Mariani) in 1963 and subsequently made its way to commercial “Coca-Cola” by John Pemberton from 1884 thru 1903 (09). The abuse of herbal drugs initiated the first treaty of international drug control with the International Opium Convention and was signed in Hague by 13 countries to provide control over the distribution of morphine and cocaine in 1912. With pharmaceutical development of synthetic and semisynthetic drugs, abuse of said newer substances dates to early 20th century.

From the 1940s and evolving over time, there were case reports, letters to the editor, case series, and autopsies describing the cerebrovascular symptoms in association with illicit drug use. Many studies of stroke in the 1970s, 1980s, and 1990s revealed that approximately 6% of strokes were related to illicit drug use. However, the numbers were way higher in the young adults aged between 15 to 49 years, ranging anywhere from 13% (106) to 34% (55). The rate of detection of illicit drug use had also increased dramatically in the late 20th century from 8% to 23% (p= 0.0007) (106). At the turn of the century, there was evidence of comparative analysis among drugs, with evidence showing amphetamines’ higher risk of hemorrhage and death, and cocaine’s higher risk of ischemic strokes (119). Over the past 2 decades, there have been innumerable publications reporting and researching the deleterious effects of various drugs of abuse on the cerebrovascular health.

Table 1. Historical Publications Regarding Drug Abuse and Cerebrovascular Disorders

1945	Amphetamine overdose, subdural/intracerebral hematoma, and death
1965	Combined amphetamine and monoamine oxidase inhibitor use, intracerebral hemorrhage, and death
1968	Stroke linked to heroin addiction
1970	Demonstration on necrotizing angiitis in polysubstance intravenous drug users with cerebral infarction and hemorrhage
1971-90s	Induction of vasospasm/vasculitis in experimental animals
1970s	Initial reports of ischemic stroke and hemorrhagic stroke with amphetamines, cocaine, and phencyclidine
1980s	U.S. crack cocaine epidemic: increasing frequency of ischemic and hemorrhagic stroke related to crack, powder, and intravenous cocaine use
1990s	Case reports and series of cocaine-related stroke: observational studies of stroke and illicit drug use
Adapted from (105)

The major classes of drugs of abuse include opiates, (fentanyl, heroin, etc.), stimulants (cocaine, amphetamine, and related agents), psychotomimetics including marijuana and other hallucinogens (LSD, phencyclidine, etc.), sedatives (barbiturates, benzos, etc.), and inhalants. The two most widespread drugs of abuse—alcohol and tobacco—will not be discussed in this article to keep within its scope, but certainly should not be taken as minimizing their addictive potential or having a clear impact on stroke risk.

Each of the broad classes produces a distinct clinical intoxication and familiarity with these patterns is important to the evaluation and treatment of patients with stroke. Several difficulties arise in the discussion of the health hazards from drug abuse.

	• A variety of common street names exist to describe various drugs. As no standard definitions of these terms exist, they may sometimes mean different things to different people.
	• Also, given the illicit nature of most drugs of abuse, patients’ report of ingested drug may have limited reliability.
	• Compounds are commonly tainted and substituted with other products sometimes with a different class drug; only toxicological confirmation or direct testing of the substance itself can confirm the identity of the ingested drug.
	• Lastly, a variety of different means of administration of individual drugs exist that leads to varied effects of the drug, both desired and undesired.

The details of pathophysiology, clinical features, and management strategies will be discussed subsequently.

Table 2. Street Names and Methods of Administration for Drugs of Abuse

Agent	Administration	Street name(s)
Methamphetamine	Orally, intravenously, intranasally	Meth, speed, dexies, crystal, ice
Amphetamine derivatives	Orally, intranasally	MDMA, Ecstasy, X, molly, bath salts, plant food, jewelry cleaner, ivory wave, purple wave, zoom, cloud nine
Cocaine hydrochloride	Intranasally	Blow, nose candy, snow, dust, coke
Cocaine, alkaloidal	Inhaled or smoked; intravenously	Crack, rock, base, white pipe
Phencyclidine	Orally	PCP, angel dust, trank, DOA
Heroin	Intravenously, inhaled, or smoked	Smack, junk, skag, black tar
Cannabis	Inhaled, smoked, or ingested	Marijuana, hashish, pot, grass, weed
Synthetic cannabis	Inhaled, smoked, or ingested	Spice, K2, black mamba, Bombay blue, bliss, blaze

Etiology and pathogenesis of stroke in drug use

The mechanisms by which drug abuse causes stroke are not fully understood but are likely heterogeneous. In this regard, it is useful to distinguish stroke between a direct or an indirect medical complication of drug abuse. Direct medical complications result from the physiological action of the drug or its toxic effects. For example, it has been proposed that hemorrhagic stroke may be due to the sympathomimetic and hypertensive action of drugs like cocaine, methamphetamine, or amphetamine derivatives. The abrupt rise in sympathetic activity causes a sharp increase in blood pressure, which ruptures an intracerebral artery, causing a "hypertensive" hemorrhage or a vascular malformation or aneurysm, causing lobar or subarachnoid hemorrhage. However, this explanation is too simplistic, and other unknown factors probably play a role. The mechanisms of ischemic stroke are even less clearly defined.

Indirect complications are not immediately linked to a specific drug or its mechanism of action but, rather, to the means of its administration or to contaminants mixed in with the drug. For example, cardioembolic stroke can be secondary to bacterial endocarditis in an intravenous drug user who employs nonsterile needles (regardless of the drug being injected). Similarly, several drugs intended for intravenous use are mixed with talc or cornstarch, which have been found to occlude arteries (77). Others, such as cocaine, have been reported for many years (21; 100; 11) and cannabis recently (37) to cause myocardial infarctions, arrythmias like atrial fibrillation (AF), and cardiomyopathies, creating the potential for cardioembolic stroke. Chronic drug abuse with any stimulant agent could lead to cardiac hypertrophy and left ventricular (LV) dysfunction (02).

The biologic basis and specific proposed mechanisms by which common drugs cause cerebrovascularly injury are described below.

Cocaine. Cocaine is derived from the leaves of the shrub Erythroxylon coca, which grows in the Peruvian and Bolivian Andes. Local inhabitants have been reported to chew/suck on leaves to decrease hunger, increase endurance, and generate a sense of well-being for centuries, but addiction was not described until more concentrated forms of cocaine became available. After isolation, cocaine was first used as a local anesthetic in ophthalmic surgery due to the anesthetic effect by blocking sodium channels and intense vasoconstriction by sympathetic activation. Cocaine acts as a CNS stimulant by blocking the reuptake of norepinephrine and epinephrine after sympathetic stimulation, thus, potentiating the actions of the sympathetic nervous system. Cocaine reinforces its own use by inhibiting the reuptake of dopamine in the ventral tegmental area of the mesocorticolimbic system and nucleus accumbens. The prolongation of the actions of dopamine in this area "rewards" cocaine use and encourages its reuse. It also acts as a local anesthetic by blocking the initiation or conduction of nerve impulses following local administration (36). Cocaine is ingested in two forms: cocaine hydrochloride is injected intravenously or snorted intranasally, and alkaloidal (freebase or crack) cocaine is smoked.

Stroke following cocaine use typically occurs in the first minutes or hours after ingestion, rarely up to a week later. Patients with pseudocholinesterase deficiency may be especially vulnerable to cerebrovascular complications of cocaine because they cannot metabolize the drug efficiently (51). A systematic review in 2014 reported increase in both ischemic and hemorrhagic strokes – including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and subarachnoid hemorrhage (SAH) (107).

There does, however, appear to be a predisposition for strokes to be hemorrhagic (approximately 80%) (63). Among those undergoing angiographic evaluation, roughly 50% have an underlying aneurysm or arteriovenous malformation (64). Among patients with aneurysmal subarachnoid hemorrhage, one study reported a higher re-rupture rate (7.7% vs. 2.7%, p< 0.05) and a higher rate of in-hospital mortality (26% vs. 17%, p< 0.05) among cocaine users (15). A metaanalysis from 2023 reviewing 36 studies and identifying over 6000 cocaine users reported that cocaine users had higher risk of having vasospasm (odds ratio [OR] = 2.25), re-rupture of aneurysm (OR = 3.00), and mortality rate from any kind of stroke (OR = 5.12) (91). Many of the hemorrhages seen in patients without vascular malformations are deep, similar to hypertensive hemorrhages.

In a large, population-based case-control study of adults younger than 50 years of age, acute cocaine use, defined as use within 24 hours, was strongly associated with ischemic stroke (adjusted odds ratio [OR] = 6.4) (18). Although etiology of these infarcts was not defined in this study, there were reports that that large artery atherosclerosis is more common in cocaine user group by retrospective (44%) and case-control studies (114; 39). It is likely that cocaine might be linked to an enduring risk of cerebrovascular disease, characterized by strokes even 15 years after cocaine use (115). In addition, cocaine users are reported to have higher risk of having seizures compared to non-users (OR 1.61). Differences have been noticed in gender and ethnicity, with African-American and male predominance reported in incidence of strokes and cocaine use (91).

Several mechanisms have been proposed to explain these findings:

(1) Acute hypertension during the sudden surge of sympathetic activity could likely cause the rupture of small penetrating arterioles in patients with deep hemorrhages or with ischemic strokes in the territories of small penetrating arteries. This would also explain the rupture of existing saccular aneurysms or arteriovenous malformations.

(2) Vasospasm that is observed acutely and subacutely on angiography (35; 44; 61; 91) could be attributed to the direct effect of noradrenergic innervation of these vessels, but vasospasm has also been documented in vessels with sparse innervation (94), suggesting cocaine-induced vasospasm is mediated by endothelin-1 (33). It has been postulated that vasospasm causes ischemia of the distal vessel wall as well as the cerebral parenchyma of supply, resulting in a compensatory rise in blood flow, causing vessel rupture when the vasospasm is relieved (14).

(3) Aneurysmal formation and rupture can be another mechanism. There are reports of cocaine users presenting with more numerous aneurysms of smaller diameter compared to non-users, which are at increased risk of growth, rupture, as well as development of new aneurysms (47). Hemodynamic fluctuations from recurrent cocaine consumption could be a plausible explanation.

(4) Vasculitis has been suggested in a few cases (57; 65; 79; 73) and generally appears as a non-necrotizing small vessel angiitis involving arterioles and venules without granuloma formation or fibrinous degeneration. Controversy exists as to whether this represents a hypersensitivity angiitis or a true arteritis (13; 79; 73) or even diapedesis of leukocytes through the vessel wall. As a rule, these cases have not fulfilled rigorous pathological criteria for vasculitis, and it is not seen on angiography because of the smaller diameter of vessels involved. Adulteration of cocaine with Levamisole (an anti-helminthic agent) has been associated with vasculitis of antineutrophilic cytoplasmic antibody (ANCA) serology but is seen primarily in the systemic vasculature than cerebral (81).

(5) Cocaine directly enhances platelet aggregation through increased synthesis of thromboxane A2 and increased responsiveness to arachidonic acid (113); a procoagulant effect via depletion of protein C and antithrombin III has also been proposed (45). This may increase the likelihood of thrombus formation at the site of vasospasm (61). Furthermore, the increased shearing forces across the vessel wall may also contribute to the same (59).

(6) A moyamoya-type vasculopathy has been described in a few case reports over the years. Storen and colleagues described two patients (one with subarachnoid hemorrhage and another with bilateral strokes) having diffuse lenticulostriate formations (111). One report hypothesizes that the chronic ischemia from recurrent cocaine use could lead to VEGF pathway activation and promote auto-angiogenesis (89).

Amphetamines. Amphetamines are synthetic drugs that are known to be the most potent CNS stimulants among sympathomimetic drugs, with methamphetamine being the most potent of them, presumably due to its strong lipophilic nature crossing BBB. These drugs facilitate the release of central norepinephrine and dopamine stored in synaptic vesicles. This leads to increased wakefulness, attention, and enhanced athletic performance. At higher doses, dopamine is released in the neostriatum and the mesolimbic cortex, leading to stereotyped behaviors and “rewards” use, which encourages amphetamine reuse. At the highest doses, amphetamines trigger the release of 5-hydroxytryptamine (5-HT) in the mesolimbic cortex, or directly stimulate 5-HT receptors, leading to disturbed perception and frank psychosis. They are also anorectic through their actions on the lateral hypothalamic feeding center (36). Initially used as diet pills for their anorectic effect, they have gained prominence as mental stimulants by long-distance drivers, students, and others trying to preserve cognitive performance in the face of sleep deprivation. Athletes have used them to enhance physical performance, and the euphoriant effect of higher doses has broadened their abuse potential. Methamphetamine is typically taken orally, although it can be smoked and injected. Intravenous users crush tablets of "speed," dissolve them in a liquid, filter them through cotton, and then inject them. Cerebrovascular complications arise from the more rapid onset of sympathomimetic action, and foreign body reactions to "diluents" or filler substances like talc or cornstarch.

Methamphetamine. Stroke following methamphetamine use can occur after oral, intravenous, or inhalational use. In many cases, strokes occur within minutes to hours after last use but has been reported weeks and even months after last use (82; 62). Hemorrhagic stroke, including both intraparenchymal and subarachnoid hemorrhage, is more common than ischemic stroke, although both are possible (72; 27; 96; 62). Several mechanisms have been proposed as the cause of stroke.

1) As a sympathomimetic, methamphetamine can cause acute hypertension, and chronic use may cause long-term hypertension, which is a very well-documented risk factor for all forms of cerebrovascular disorders including ischemic and hemorrhagic strokes.

2) Vasospasm with superimposed thrombosis has also been proposed (93), perhaps due to the noradrenergic activation and local shearing. Affected vessels have been described as beaded with segmental narrowing (02) and aneurysm formation.

(3) Chronic administration of methamphetamine has been associated with a necrotizing angiitis involving arterioles and capillaries, which has been likened to polyarteritis nodosa and hypersensitivity angiitis (95; 10; 25).

(4) It is also possible that methamphetamine use may lead to accelerated atherosclerosis (43), with abnormalities seen outside CNS as well (20).

(5) Finally, there is an increased risk of myocardial infarction, severe dilated cardiomyopathy in methamphetamine users, which may represent a cardioembolic source of ischemic stroke (46; 40).

Amphetamine derivatives and other sympathomimetics. Methylphenidate is structurally related to amphetamine, with the same mechanism of action and polarity that achieves higher levels in the CNS, but has greater stimulation of mental rather than physical activities. Higher doses are associated with an increased risk of convulsions (36). Methylphenidate is ingested orally; tablets are sometimes crushed and injected intravenously.

Methylenedioxymethamphetamine, or “ecstasy,” is used both for its stimulant and euphoric properties. Other synthetic amphetamine-like substances, such as mephedrone, pyrovalerone, and methylenedioxypyrovalerone, have also gained popularity being available in drug paraphernalia stores. They are variably labeled as “bath salts” or “plant food,” and there has been a dramatic increase in calls to United States poison control centers related to these substances (52). These are ingested orally.

Ephedrine is used to treat asthma and nasal decongestion and is naturally contained in the form of ephedra in Chinese herbal preparations (ma huang), frequently sold as an herbal stimulant. It has both alpha- and beta-adrenergic agonist activity and simultaneously enhances the release of norepinephrine from sympathetic neurons, which creates its abuse potential. Pseudoephedrine is a synthetic stereoisomer of ephedrine that is used as a nasal decongestant, which also has similar properties. Over-the-counter sympathomimetics, such as phenylpropanolamine and pseudoephedrine, also by oral ingestion, have been used to treat nasal congestion or facilitate weight loss (13; 36). These are all CNS stimulants but less potent than amphetamines and also have sympathomimetic effects on the PNS. Intake is by oral ingestion. The use of pseudoephedrine in cold medications has been banned in many countries because the alkaloid is used as a precursor in the synthesis of methamphetamine. The alpha-agonist activity of these stimulant drugs causes hypertension, and this effect has been invoked to explain acute stroke occurring in some patients using these agents. Phenylpropanolamine was voluntarily withdrawn from the market in 2000 after the FDA reviewed several reports of hemorrhagic stroke associated with its therapeutic use (58).

The abuse potential and link to cerebrovascular disease associated with these drugs have been recognized since the 1980s. Intracerebral hemorrhage has been described in patients using "ecstasy", or methylenedioxymethamphetamine, and a vascular malformation was identified in at least one patient (24). Ischemic stroke due to MDMA has also been described (71). Phenylpropanolamine and pseudoephedrine have been linked to deep and lobar hemorrhages occurring a few hours after ingestion (109; 56; 106). Angiography in three cases showed the beading classically associated with amphetamine use (109; 56). A large, case-control study confirmed an association between a first use of phenylpropanolamine and hemorrhagic stroke in women; however, no association was identified with a first-use of pseudoephedrine (58). Chronic abusers of these substances may be at higher risk. Ephedrine use has been linked to subarachnoid and intracranial hemorrhage and, less commonly, ischemic stroke (122; 109; 12). Angiography disclosed an aneurysm in one patient with subarachnoid hemorrhage and vasculitic changes in two patients with intracerebral hematomas. There have been a number of reports of stroke associated with the use of herbal remedies containing ephedra (97). A case-control study did not confirm an association between ephedra use and hemorrhagic stroke, except possibly with high doses of ephedra (78).

Ischemic stroke has been reported in users of prescription amphetamines and methylphenidate for attention deficit hyperactivity disorder (101). Large population studies, however, have failed to detect an increased risk of stroke in patients receiving pharmacotherapy for attention deficit hyperactivity disorder (38; 68). These studies may be limited by healthy user bias, but nonetheless, they are reassuring that these medications appear safe when used at typical doses in otherwise healthy subjects. Similarly, case reports of ischemic stroke possibly associated with phentermine have been described (60), but a large case-control study of an obese population did not identify an association between phentermine and stroke (28). These data highlight that there may be important differences across amphetamine derivative drugs that impact whether or not they present a risk for stroke.

Opium. Opium is derived from the unripe seed capsules of the poppy plant, Papaver somniferum. Unripe capsules when incised release white latex that quickly hardens and turns brown after contact with oxygen, the hardened brown latex is called raw opium, from which alkaloid morphium is extracted. Morphine was found to play a role in post-operative pain management as well as an adjunct to general anesthesia in the mid-19th century. Heroin (diacetylmorphine) is a semisynthetic derivative of morphine, created to find a nonaddictive opiate, but it was later discovered that heroin is converted to 6-acetylmorphine and morphine by human choline-esterases. The increase of prescribing opioid medications has contributed to increased abuse of both prescription opioids and heroin. Although it is frequently injected intravenously, increases in purity have allowed for intranasal use. Opiates bind to the Mu receptors (also called Mu opioid receptors or MORs), and have effects based on location of the receptors. In the CNS, MORs are found in the limbic system and spinal cord (reduce pain perception), nucleus accumbens (pleasure, “rewards” on use), brainstem (respiratory depression), orbitofrontal cortex (decision-making), hippocampus (consolidation of new memories), amygdala (emotional processes), hypothalamus (regulation of autonomic processes), and the mammillary bodies. They are also seen in gastrointestinal tract (causing opioid-induced constipation), pupils (miosis), and in immune cells (regulation of interleukin-4 activity) (41).

Opioid use most commonly causes stroke through complications of its intravenous injection. The use of nonsterile needles causes infective endocarditis and septic embolization. The mitral, aortic, and tricuspid valves are involved with varying frequencies (13; 75). Septic embolization and the rupture of mycotic aneurysms have been associated with ischemic stroke, subarachnoid hemorrhage, and diffuse vasculitis. Opioid use has also been reported to cause a syndrome of altered mental status including potentially coma with bilateral, symmetric diffusion restriction and transient edema on magnetic resonance imaging. This syndrome is termed CHANTER (cerebellar, hippocampal, and basal nuclei transient edema with restricted diffusion) (48). The exact cause of this syndrome is uncertain, but suspicious for anoxic or toxic injury. Another peculiar form of cerebrovascular small vessel injury is seen in toxic-leukoencephalopathy by inhalation of opiates (fentanyl or heroin) called “chasing-the-dragon” (117).

Peripheral thrombophlebitis secondary to repeated use of nonsterile needles may cause stroke through paradoxical embolism in a patient with a right-to-left intracardiac shunt. Foreign body embolization of talc and cornstarch mixed with heroin has also been documented. In one case report, autopsy found deposits of talc in the small vessels in a patient with medullary infarction (77). Rare cases of what is presumed to be a hypersensitivity angiitis have been reported in heroin users. Angiography in these cases demonstrated a small vessel arteritis or diffuse angiitis (13). Ignorance regarding sterile technique and the temporal exigencies of physical addiction increase the risk of infective endocarditis and its complications, including ischemic stroke via embolism, mycotic cerebral aneurysms, and intracranial hemorrhage.

Stroke associated with heroin use (CT)

Axial noncontrast CT imaging through the brain at 2 different levels demonstrates multiple watershed areas of infarction throughout the brain in a young female having taken heroin. (Contributed by Dr. Gomez-Hassan.)
Stroke associated with heroin use (MRI)

Axial MR imaging through the brain at corresponding levels on T2- (A), FLAIR (B), T1- (C) and diffusion- (D) weighted images demonstrates multiple watershed areas of infarction throughout the brain in a young female having taken h...

Cannabis. Cannabis, from the plant Cannabis sativa, is the most widely used recreational drug in the world and has been legalized in several states in the U.S. and in Canada. Cannabis contains more than 100 different cannabinoid substances, the two most notable being delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the main psychoactive component of cannabis, and CBD is the main nonpsychoactive component. There are two known cannabinoid receptors: CB1R, located in the central nervous system, and CB2R, found peripherally, particularly within immune system tissues. CB2R are also found in the cardiac myocytes and endothelium leading to the cardiovascular effects of THC (Steffens and Pacher 2012). The amount of THC and CBD varies based on the plant, although studies have suggested increasing THC content and decreasing CBD content in recent decades (19). It causes a euphoric sensation with reduced anxiety and alertness and altered perception; however, anxiety or dysphoria can occur in some individuals. THC can cause vasodilatation independent of cannabinoid receptors by activation of calcitonin gene peptide (42). It is most often prepared as marijuana or hashish, which are subsequently smoked, inhaled, or ingested directly or by incorporation into edible substances. Potency can vary widely across preparations based on the THC content, which is generally higher in hashish than in marijuana (121). Synthetic cannabinoids (such as “Spice,” K2) are a heterogeneous group of compounds but generally act at the CB1R receptor and have similar effects as cannabis. Because they can be much more potent than cannabis, they likely have a greater risk of adverse events, including agitated psychosis, hallucinations, and seizures.

Considered nonmalicious by the general public, use of marijuana has increased tremendously over time. However, there is growing evidence of cardio-cerebrovascular disorders associated with cannabis use, with initial case reports suggesting temporal correlation of both cannabis and synthetic/cannabinoids and stroke (34; 07). Topical reviews have concluded that cannabis may increase stroke risk (121; 54). Data from the Behavioral Risk Factor Surveillance System, from the U.S. Centers for Disease Control, have found that marijuana users have significantly higher risk of coronary heart disease myocardial infarction and stroke compared to nonusers (85; 103; 50). This use was dose dependent, with higher odds of events in heavier users. A longitudinal cohort study of medical cannabis users found that cannabis users were at an increased risk of acute coronary syndrome or stroke compared to matched population-based controls (adjusted HR 1.44, 95% CI 1.08-1.93), suggesting CBD also has some risks (124).

Proposed stroke mechanisms by cannabinoids include systemic hypotension, cerebral vasospasm, arrhythmias, platelet aggregation, or oxidative stress (123; 06; 120; 19). These have been proven in many more recent studies. Cannabis and synthetic cannabis have been suggested as causes of reversible cerebral vasoconstriction syndrome, which can present with subarachnoid hemorrhage, intraparenchymal hemorrhage, and ischemic stroke (29; 92). Cannabinoids have also been reported to be highly arrhythmogenic including atrial fibrillation, which could lead to embolic strokes (87). It appears the effects may depend on route of administration, with inhalation likely to be more serious due to early peak plasma concentrations compared to oral ingestion of the drug. Another metaanalysis noted plausible causal relationships between cannabis and ASCVD risk, with proposed risk of platelet aggregation and thrombus formation (102).

Given the wide use of cannabis, frequent overlap with additional substance abuse and the methodologic limitations of existing literature like high level of heterogeneity among studies, it has traditionally been difficult to establish a direct causality between cannabis use and stroke. Multiple case-control studies have failed to detect an association between cannabis and stroke, including a large study that included 751 cases and 813 controls (05; 121; 30). Another large population-based cohort study from Sweden did not find an association between cannabis use and stroke before 45 years of age (32). A scientific statement from the American Heart Association published in 2020 found that “overall, evidence is still inconclusive for cannabis use and adverse cardiovascular outcomes” (84).

A 2024 metaanalysis found that there was a stronger association between cannabis abuse and stroke in young adults [OR = 1.21] after adjusting for confounders such as smoking and alcohol abuse (67). However, subgroup analyses revealed no significant difference in stroke risk between ischemic and hemorrhagic strokes (p = 0.43). Based on real world data systematic review, several positive associations were found between cannabis use and major adverse cardiovascular events (MACE), specifically risk ratio was estimated at 1.29 for acute coronary syndrome, 1.20 for stroke, and 2.10 for cardiovascular death (110), but there was no statistically significant association for composite outcome combining acute coronary syndrome and stroke. A systematic review and metaanalysis reported the first instance of statistically significant association between cannabinoids and ischemic stroke (pooled OR 2.05, p< 0.001), and there is a significantly elevated risk in young adults (01). A similar finding was noted in another metaanalysis where there was no significant association with cannabis use and stroke (RR: 1.38, p = 0.16), but a statistically significant association was observed between ever use of cannabis and the composite of any adverse cardiovascular events (RR: 1.48, p = 0.002) (102).

Hallucinogens.

Phencyclidine. PCP is a synthetic ketamine, which was first synthesized in 1950s and became a major drug of abuse in the 1960s and 1970s. It has multiple neurotransmitter pathways with predominantly NMDA-glutamate receptor antagonist, but also acetylcholine antagonist, and dopamine agonist, leading to a psychotic state with possible reward pathways and reuse. Complicating the picture further, PCP may have its own receptors on cerebral vessels (04). Dextromethorphan, an over-the-counter cold remedy also acts as a weak NMDA receptor antagonist and may induce PCP like symptoms at higher doses (49). It is orally ingested.

PCP-mediated strokes have been reported to be primary hemorrhagic stroke (08; 13). Data associated other hallucinogens (eg, LSD) with stroke, with suspicion of sympathomimetic side effect of hypertension as the provoking factor (76). Its effects are thought to be immediate, but spikes of blood pressure spikes have been reported hours to days after use (31).

LSD. Lysergic acid diethylamide, or LSD, is another potent hallucinogen, derived from ergot and was discovered in 1943 and isolated in 1947. It was used for alcohol addiction in the 1950s to 1960s by induced experimental psychosis and became a drug of abuse by mid-1960s (86). Ingested orally, it has a quick absorption and primarily acts as a serotonin agonist via 5-HT receptors. Activation of 5-HT2A receptors in the neocortical pyramidal cells and the hippocampal prefrontal cortex causes heightened sensory stimuli and hallucinations. Its acts on central dopaminergic receptors D1 and D2, where D2 activation is known to potentiate 5-HT2A effects. It also leads to stimulation of the central sympathetic system (via 5-HT2A receptors), which causes its cardiovascular effects like tachycardia, high blood pressure along with mydriasis, and hyperthermia. Larger recreational doses of the drug can lead to cardiovascular and cerebrovascular incidents, but chronic peripheral antagonism of 5-HT2A receptors by the drug reduces atherosclerotic and thrombotic processes due to a reduction in platelet aggregation and vascular smooth muscle cell proliferation (112).

Strokes from LSD are almost always ischemic with large artery occlusions being found frequently (66). Strokes could be from vasoconstriction and/or vasospasm of the arteries by means of its effect on serotonin receptors (03). It is postulated that reversal of vascular effects is possible by a 5-HT antagonist like methysergide.

Barbiturates, other sedatives, and inhalants. No clear data associate these agents with stroke.

Clinical manifestations

Presentation and course

Stroke can occur during the first minutes of acute intoxication with a drug, in the hours following ingestion, or weeks (rarely months) following intoxication. Recognition of the role of drug use in the pathogenesis of stroke requires familiarity with the acute effects of commonly used recreational drugs and a high index of suspicion. The signs and symptoms of a stroke are not different in the user of recreational drugs unless the user is acutely intoxicated. Rather, the physician must probe for a history of substance abuse from the patient, friends, and family. Given that drugs of abuse are typically produced illegally, there is little assurance that the patient has consumed the agent described and not some substitute drug of abuse. Thus, the clinical history alone must be considered of limited reliability. Identifying agents via toxicology screens or, rarely, analysis of drug samples themselves is important. Suspicion can be confirmed in many cases through prompt urine toxicology screening in patients who present during or soon after acute intoxication. Confirmation of the role of drug abuse as the cause of symptoms weeks and months after acute intoxication depends on a complete history and plausible mechanism of action, for example, a stroke caused by a necrotizing vasculitis due to chronic use of an amphetamine or infective endocarditis with cardioembolic stroke in an intravenous drug user who does not use sterile needles.

Identifying a stroke secondary to ingesting a specific drug permits a directed stroke work-up. For example, angiography may be indicated in patients taking drugs associated with vasculopathy or to search for vascular malformations in certain drug users with intracranial hemorrhage. Recognition that angiographic vasculopathy is due to abuse of a certain agent will prevent initiation of unnecessary treatments with possible morbidity, eg, long-term immunosuppression, which is appropriate for autoimmune but not drug-induced vasculopathy. Thus, familiarity with the cerebrovascular complications of drug abuse guides the patient’s diagnostic evaluation and determines long-term stroke prophylaxis.

Sympathomimetic drugs cause a common profile of acute intoxication. Users of amphetamines, amphetamine derivatives (MDMA, ephedrine, phenylpropanolamine, methylphenidate, etc.), and cocaine experience elation and increased alertness; motor activity, coordination, and physical endurance are increased. Orgasm is reportedly delayed and heightened. Pupils are dilated, systolic blood pressure is elevated, and reflex bradycardia is noted. Blood pressure might be normal in patients by the time they arrive for medical attention unless they are still intoxicated. Higher doses cause agitation, suspiciousness verging on paranoia, and violent acts. Palpitations and stereotyped motor behavior may be present. Chronic use causes labile mood, paranoia, and a frank psychosis resembling schizophrenia. Some users engage in "runs" of iterative drug use for several days, finally stopping because of insurmountable exhaustion, lack of funds, or because they are too disorganized to continue ingesting the drug (usually by injection) (13).

Intoxication with phencyclidine varies with the dose ingested. Lower doses heighten sensory perception and cause euphoria or dysphoria and mood lability. Higher doses increase agitation and induce a state of excited catatonia or frank paranoid psychosis with auditory hallucinations. Bizarre, potentially violent behaviors are seen. Analgesia occurs with higher doses. Phencyclidine intoxication is also associated with elevated systolic pressure, sweating, hypersalivation, miosis, burst-like nystagmus, and ataxia (08; 13).

Acute heroin intoxication causes a pleasant, dream-like euphoria with impaired concentration. Some users experience anxiety rather than drowsiness, and nausea and vomiting may occur. Pupils are small but reactive. Tone is decreased in the face and neck muscles. Dry mouth, difficulty urinating, constipation, and respiratory depression can be seen. Chronic users are often irritable and dysphoric, having developed tolerance to many of the acute effects of heroin use (13). Intradermal injections of heroin with “skin-popping” cause local skin manifestations, and wound botulism especially with “black-tar” heroin can be life threatening.

Cannabis and synthetic cannabis intoxication cause an increased sense of well-being, mild euphoria, and feelings of relaxation. High doses can cause hallucinations and paranoia. Systemic effects include mild reductions in blood pressure, increased heart rate, dry mouth, and dilation of corneal blood vessels. In certain cases, cannabis use may lead to arrhythmias, coronary artery syndrome, or myocardial infarction.

Prognosis and complications

As noted above in the mechanistic insights of drug abuse and stroke, individual drugs have individual complications. This depends on multiple factors including the dose, the route, and compounding substances at the time of drug use. For example, patients who use methamphetamine are at risk for systemic vasculopathy, and therefore, screening for other organ system dysfunction is warranted. Systemic complications of stroke in the setting of acute heroin intoxication include hypotension, increased risk for pulmonary edema, and respiratory depression with possible hypoxia. Additionally, possible septic embolization systemically could cause local abscess and organ failure, along with diseases from using unsterile needles like HBV, HCV, and HIV, which have their share of complicated health scenarios. Patients who use cocaine may have myocardial ischemia, cardiac arrhythmias, or sudden death, and a cardiac evaluation is warranted. In a series of 42 patients with cocaine-related stroke, three had HIV, three had hepatitis, two had syphilis, and one had tuberculosis (80). A similar situation is considered with marijuana use; cannabis users reported to have cardiovascular issues like arrhythmias, and evaluation is prudent. Women, especially, are noted to be at a higher risk of wide range of cardiovascular problems (115). Long-term effects include persistent white matter disease and cognitive decline. Substance-induced persisting dementia involves multiple domains of cognitive disturbance and persists beyond usual duration of substance intoxication or withdrawal (118). Additional considerations include nutritional deficiencies seen in patients with drug abuse; one study reported 18% deeply malnourished, with worse status found in relation to female sex, and disturbance of social and family networks (99).

The prognosis is largely determined by whether or not the individual user continues to use these drugs.

Simple as it may sound, this is a challenge due to many factors. Most of the substances discussed above are considered illicit, but there are some that are used in prescriptions and can still be pathogenic, if used inappropriately; a good example is the use of amphetamines and methylphenidate to treat hyperactivity and attention deficit disorder in children and adults. Many of the reported patients are "lost to follow-up," possibly due to the drugs’ addictive properties and return to use. Considering addiction medicine may be helpful in these individuals, through peer counseling (88) or group counseling (98).

Prevention

Illicit drug use appears to wax and wane in cycles as a function of many factors, including availability, perceived risk to personal health, psychosocial status of the individual drug, and treatment efficacy.

Availability refers to accessibility within a given geographical location and actual cost as a percentage of disposable income. Geographic availability means users can easily purchase a drug within their neighborhood. Theoretically, this can be reduced by interdicting drug transportation before local delivery and sale. Successful interdiction may reduce drug use through the resulting increase in cost passed on by distributors to consumers to cover losses. Popularity is also affected by the cost per dose, which may rise with reduced availability. Attempted interdiction has been stymied in many cases because drug production is ubiquitous; arresting one trafficker or destroying one region of cultivation does not sufficiently reduce availability.

Perceived risk refers to the health risks associated with drug use. The clearest example is the decline in intravenous drug use after it was linked to the intravenous transmission of HIV and AIDS. The popularity of heroin subsequently fell until the purity of street heroin was sufficient to afford a "high" with inhalational ingestion.

Psychosocial status refers to the perception of the ill effects of single or chronic use of an individual drug within the community. Crack cocaine use fell when communities saw its disastrous effects on users due to its addictive potential. Crack users seemed willing to sacrifice anything to obtain their next dose. Phencyclidine use fell when people noted the prevalence of "bad highs" characterized by paranoia and violence. Psychosocial status also refers to whether a community tolerates drug use among its members. Social stigmatization may reduce the likelihood of initial experimentation in the individual user. This is only effective when community attitudes are conveyed to the potential drug user. Initial experimentation appears to begin among preadolescents and adolescents. Community attitudes have less effect when this age group has little parental or adult supervision. When illicit drug use is assigned low psychosocial status among all age groups, the demand for these substances will decline.

Treatment efficacy refers to the availability of treatment to help illicit drug users break their habit. It entails medical care through the withdrawal syndrome (if present) and psychological counseling to deal with factors underlying psychological addiction.

Diagnostic workup

Drug use should be suspected in any young person (under 55 years of age) who presents with a stroke. It should be remembered that drug use encompasses not only illegal substances like cocaine, methamphetamine, and heroin, but also diet pills, over-the-counter decongestants, prescription drugs, synthetic cannabinoids, and amphetamine derivatives. A detailed history should be sought from the patient, friends, and family. Urine toxicology screens should be sent immediately. They can be positive as early as 1 hour after ingestion and remain positive for 2 to 3 days. Chronic users may have positive toxicology screens for longer periods. Importantly, synthetic cannabinoids and amphetamine derivatives are not tested for in routine urine toxicology screens.

In general, evaluation of the young stroke patient in the setting of drug abuse is similar to that of a patient without a history of drug use. In particular, it should be noted that patients with intracranial or subarachnoid hemorrhage associated with drug abuse are no less likely to harbor underlying vascular lesions than other patients. Head CT is done in all patients. A lumbar puncture is needed in patients with suspected subarachnoid hemorrhage when the CT scan is negative. MRI may be helpful to identify patterns of ischemic stroke. MR or CT angiography may help identify underlying vascular abnormalities (vasospasm, stenosis, occlusion, vascular malformations, aneurysms). Transcranial Doppler may also be useful in identifying vasospasm. Conventional angiography may be necessary to exclude the presence of aneurysms or vascular malformations in patients with subarachnoid or intracranial hemorrhage and may reveal evidence of vasculitis or vasospasm in patients with ischemic stroke due to cocaine, amphetamine, or amphetamine-like agents. Blood cultures and transesophageal echocardiography should be performed to exclude endocarditis in stroke patients who have used drugs intravenously. Finally, as drug abusers represent a high-risk population, patients should be tested for HIV, syphilis, and other infectious diseases for which clinical suspicion exists.

Management

Acute therapy for stroke in patients with suspected drug abuse generally should be similar to the care provided to all stroke patients, including adequate hydration, close neurologic monitoring, evaluations by physical/occupational/speech therapy teams, and attention to preventing medical complications. Very subtle differences exist compared to non-users and as such, there is no differentiation between either of these groups on national guidelines for acute stroke management (90).

In the hyperacute phase, role of intravenous thrombolytic therapy with tissue plasminogen activator or tenecteplase in ischemic stroke due to drug abuse likely depends on the presumed mechanism. Generally speaking, intravenous thrombolytic therapy should be considered if there are no contraindications otherwise but warrant special monitoring due to the varied effects of individual drugs and complications that can increase the risk of hemorrhage. In the case of stroke associated with cocaine use, evidence suggests a combination of vasospasm and superimposed thrombosis may occur; in such cases, thrombolysis may be a reasonable therapeutic option. A small cohort study comparing 29 cocaine-positive to 75 cocaine-negative patients of acute ischemic stroke treated with thrombolysis found no increased risk of treatment complications and similar outcomes between the two groups (74). In case of amphetamines with sympathomimetic effect and possible vessel wall injury in chronic users, evidence suggests predominance of hemorrhagic stroke; thrombolytics may not be applicable, and there is no evidence available to date detailing use of intravenous thrombolytic therapy in this population. One case report mentions the increased risk of hemorrhage with tPA in a cannabis user, citing likely augmenting properties of the latter (104); therefore, caution is warranted. Ischemic stroke due to infective endocarditis, on the other hand, is associated with a high risk of hemorrhagic transformation, and tissue plasminogen activator is not recommended in this setting. Mechanical thrombectomy should be considered in acute stroke due to drug abuse when a large vessel occlusion is present, even in cases with infective endocarditis. Recent guidelines recommend avoidance of intravenous thrombolytic therapy in patients with infective endocarditis but encourage mechanical thrombectomy if expertise is available (23). One scoping review suggested that there could be reperfusion hemorrhagic injury in cocaine users based on their pooled analysis data that indicated hemorrhagic conversion in 3.2% intravenous thrombolytic therapy patients and 50% mechanical thrombectomy patients (22).

In hemorrhagic stroke associated with acutely elevated blood pressure due to drug use, it may be reasonable to be somewhat more aggressive than usual in reducing blood pressure. Ideal therapy for ongoing vasculitis among users of methamphetamine has not been identified, partly because the pathogenesis of the vasculitis is unclear. Steroid therapy has been used in some patients on a short-term basis, but there is little evidence to suggest if this is beneficial. Calcium channel blockers, in particular the dihydropyridine agents (nifedipine, amlodipine, isradipine), have been advocated for the treatment of stroke in cocaine users, but no formal data exist regarding efficacy (53). Vascular malformations and aneurysms should be treated similarly to those occurring in patients without a history of drug abuse.

Complications of drug abuse and stroke should be managed simultaneously. Patients should be closely monitored for symptoms of drug withdrawal and appropriate therapy instituted if necessary (eg, methadone in opiate addiction). As many abusers of illicit drugs also abuse alcohol, a low threshold should exist for initiating benzodiazepines for symptoms suggestive of alcohol withdrawal. Post-stroke seizures must be managed similar to non-drug users but with attention to overlapping side effects. Similarly, no difference exists in conservative care like avoidance of bed sores, therapy for regaining function, and management of mood disorders.

For secondary prevention of ischemic stroke in drugs, strategies should obviously include cessation of the abused drug in addition to control of other traditional risk factors like hypertension, diabetes, smoking cessation along with lifestyle changes to include better diet and exercise. There is no evidence to support or object use of antithrombotic therapies. Most randomized control trials assessing the effect of antiplatelets or anticoagulants have excluded patients with drugs of abuse to avoid confounders and due to risk of other systemic complications. At this time, consensus is to proceed with standard antiplatelet/anticoagulant management in drug abuse patients with close monitoring for risk of hemorrhagic complications. Only one case report has been identified discussing this and notes safety of heparin use in amphetamine user, but this cannot be generalized (69).

References

01: Abdullah FT, Al-Dulaimi AA, Vaghela KHM, et al. Cannabis use in different ethnicity/race populations and risk of ischemic stroke: A systematic review and meta-analysis. J Ethn Subst Abuse 2025:1-19. PMID 40397400
02: Akasaki Y, Ohishi M. Cerebrovascular and cardiovascular diseases caused by drugs of abuse. Hyperten Research 2020;43(5):363-71. PMID 31801994
03: Altura BM, Alttura BT, Carella A, Turlapaty PD. Hypomagnesemia and vasoconstriction: possible relationship to etiology of sudden death ischemic heart disease and hypertensive vascular diseases. Artery 1981;9(3):212-31. PMID 7305671
04: Altura BT, Quirion R, Pert Altura BM. Phencyclidine (“angel dust”) analogs and sigma opiate benzomorphans cause cerebral arterial spasm. Proc Natl Acad Sci U S A 1983;80(3):865-9. PMID 6298779
05: Barber PA, Pridmore HM, Krishnamurthy V, et al. Cannabis, ischemic stroke, and transient ischemic attack: a case-control study. Stroke 2013;44(8):2327-9. PMID 23696547
06: Barnes D, Palace J, O’Brien MD. Stroke following marijuana smoking. Stroke 1992;9:1381. PMID 1519298
07: Bernson-Leung ME, Leung LY, Kumar S. Synthetic cannabis and acute ischemic stroke. J Stroke Cerebrovasc Dis 2014;23(5):1239-41. PMID 24119618
08: Bessen HA. Intracranial hemorrhage associated with phencyclidine abuse. JAMA 1982;248:585. PMID 7097906
09: Beyer J, Drummer OH, Maurer HHH. Herbal drugs of abuse. In: Ramawat K (editor). Herbal drugs: Ethnomedicine to modern medicine. Berlin: Springer, 2009.
10: Bostwick DG. Amphetamine induced cerebral vasculitis. Hum Pathol 1981;12(11):1031-3. PMID 7319490
11: Brown E, Prager J, Lee HY, Ramsey RG. CNS complications of cocaine abuse: prevalence, pathophysiology, and neuroradiology. AJR Am J Roentgenol 1992;159:137-47. PMID 1609688
12: Bruno A, Nolte KB, Chapin J. Stroke associated with ephedrine use. Neurology 1993;43:1313-6. PMID 8327131
13: Brust JC. Drug dependence. In: Baker AB, editor. Clinical neurology. Philadelphia: Harper & Row, 1986.
14: Caplan L. Intracerebral hemorrhage revisited. Neurology 1988;38:624-7. PMID 3352921
15: Chang TR, Kowalski RG, Caserta F, Carhuapoma JR, Tamargo RJ, Naval NS. Impact of acute cocaine use on aneurysmal subarachnoid hemorrhage. Stroke 2013;44(7):1825-9. PMID 23652270
16: Chasnoff IJ, Bussey ME, Savich R, Stack CM. Perinatal cerebral infarction and maternal cocaine use. J Pediatr 1986;108:456-9. PMID 3950828
17: Chasnoff IJ, Griffith DR, MacGregor S, Dirkes K, Burns KA. Temporal patterns of cocaine use in pregnancy. Perinatal outcome. JAMA 1989;261:1741-4. PMID 2918671
18: Cheng YC, Ryan KA, Qadwai SA, et al. Cocaine use and risk of ischemic stroke in young adults. Stroke 2016;47(4):918-22. PMID 26965853
19: Choi SH, Mou Y, Silva AC. Cannabis and cannabinoid biology in stroke: controversies, risks, and promises. Stroke 2019;50(9):2640-5. PMID 31366312
20: Citron BP, Halpern M, McCarron M, et al. Necrotizing angiitis associated with drug abuse. N Engl J Med 1970;283:1003-11. PMID 4394271
21: Cregler LL, Mark H. Medical complications of cocaine abuse. N Engl J Med 1986;315:1495-9. PMID 3537786
22: Dabhi N, Mastorakos P, Sokolowski JD, Kellogg RT, Park MS. Effect of drug use in the treatment of acute ischemic stroke: A scoping review. Surg Neurol Int 2022;13:367. PMID 36128166
23: Delgado V, Ajmone Marsan N, de Waha S, et al. 2023 ESC guidelines for the management of endocarditis: developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM). Euro Heart J 2023;44(39):3948-4042. PMID 37622656
24: De Silva RN, Harries DP. Ecstasy [letter]. BMJ 1992;305:310. PMID 1356545
25: De Silva DA, Wong MC, Lee MP, Chen CL, Chang HM. Amphetamine-associated ischemic stroke: clinical presentation and proposed pathogenesis. J Stroke Cerebrovasc Dis 2007;16(4):185-6. PMID 17689416
26: de los Rios F, Kleindorfer DO, Khoury J, et al. Trends in substance abuse preceding stroke among young adults: a population based study. Stroke 2012;43:3179-83. PMID 23160887
27: Delaney P, Estes M. Intracranial hemorrhage with amphetamine abuse. Neurology 1980;30:1125-8. PMID 7191505
28: Derby LE, Myers MW, Jick H. Use of dexfenfluramine, fenfluramine, and phentermine and the risk of stroke. Br J Clin Pharmacol 1999;47(5):565-9. PMID 10336582
29: Ducros A, Boukobza M, Porcher R, Sarov M, Valade D, Bousser MG. The clinical and radiological spectrum of reversible cerebral vasoconstriction syndrome. A prospective series of 67 cases. Brain 2007;130(Pt 12):3091-101. PMID 18025032
30: Dutta T, Ryan KA, Thompson O, et al. Marijuana use and the risk of early ischemic stroke: the stroke prevention in young adults study. Stroke 2021;52(10):3184-90. PMID 34266309
31: Esse K, Fossati-Bellani M, Traylor A, Martin-Schild S. Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard. Brain Behav 2011;1(1):44-54. PMID 22398980
32: Falkstedt D, Wolff V, Allebeck P, Hemmingsson T, Danielsson AK. Cannabis, tobacco, alcohol use, and the risk of early stroke: a population based cohort study of 45,000 Swedish men. Stroke 2017;48(2):265-70. PMID 28028147
33: Fandino J, Sherman JD, Zuccarello M, Rapoport RM. Cocaine-induced endothelin-1-dependent spasm in rabbit basilar artery in vivo. J Cardiovasc Pharmacol 2003;41(2):158-61. PMID 12548074
34: Freeman MJ, Rose DZ, Myers MA, Gooch CL, Bozeman AC, Burgin WS. Ischemic stroke after use of the synthetic marijuana “spice.” Neurology 2013;81(24):2090-3. PMID 24212384
35: Golbe LI, Merkin MD. Cerebral infarction in a user of free-base cocaine ("crack"). Neurology 1986;36:1602-4. PMID 3785675
36: Goodman Gilman A, Rall TW, Nies AS, Taylor P. Goodman and Gilman's the pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press, 1990.
37: Goyal H, Awad HH, Ghali JK. Role of cannabis in cardiovascular disorders. J Thoracic Dis 2017;9(7):2079. PMID 28840009
38: Habel LA, Cooper WO, Sox CM, et al. ADHD medications and risk of serious cardiovascular events in young and middle-aged adults. JAMA 2011;306(24):2673-83. PMID 22161946
39: Hall JP, Grewal P, Asthana A, et al. Abstract WMP69: Recreational drug use and ischemic stroke: Demographics, stroke mechanism, and outcomes. Stroke 2023;54(Suppl_1):AWMP69.
40: Hawley LA, Auten JD, Matteucci MJ, et al. Cardiac complications of adult methamphetamine exposures. J Emerg Med 2013;45:821-7. PMID 24054881
41: Herman T, Cascella M, Muzio MR. Mu receptors. In: StatPearls [Internet]. Treasure Island (FL): StatsPearls Publishing, 2024. PMID 31855381
42: Hiley CR, Ford WR. Cannabinoid pharmacology in the cardiovascular system: potential protective mechanisms through lipid signalling. Biol Rev Camb Philos Soc 2004;79:187-205. PMID 15005177
43: Ho EL, Josephson SA, Lee HS, Smith WS. Cerebrovascular complications of methamphetamine abuse. Neurocrit Care 2009;10(3):295-305. PMID 19132558
44: Huang QF, Gebrewold A, Altura BT, Altura BM. Cocaine-induced cerebral vascular damage can be ameliorated by Mg2+ in rat brain. Neurosci Lett 1990;109:113-6. PMID 2314626
45: Isner JM, Chokshi SK. Cocaine and vasospasm. N Engl J Med 1989;321:1604-6. PMID 2586556
46: Ito H, Yeo KK, Wijetunga M, Seto TB, Tay K, Schatz IJ. A comparison of echocardiographic findings in young adults with cardiomyopathy: with and without a history of methamphetamine abuse. Clin Cardiol 2009;32:E18-22. PMID 19330818
47: Jabbarli R, Dinger TF, Oppong MD, et al. Risk factors for and clinical consequences of multiple intracranial aneurysms: a systematic review and meta-analysis. Stroke 2018;49(4):848-55. PMID 29511128
48: Jasne AS, Alsherbini KH, Smith MS, Pandhi A, Vagal A, Kanter D. Cerebellar hipppocampal and basal nuclei transient edema with restricted diffusion (CHANTER) syndrome. Neurocritical Care 2019;31(2):288-96. PMID 30788708
49: Javitt DC, Avissar M. Disorders due to substance use: phencyclidine. In: Tasman’s psychiatry. Cham: Springer International Publishing, 2024:2805-23.
50: Jeffers AM, Glantz S, Byers AL, Keyhani S. Association of cannabis use with cardiovascular outcomes among US adults. J Am Heart Assoc 2024;13(5):e030178. PMID 38415581
51: Jatlow P, Barash PL, van Dyke C, Byck F. Impaired hydrolysis of cocaine in plasma from succinylcholine sensitive patients. AFCR Clin Pharm 1976;24:255A.
52: Jerry J, Collins G, Streem D. Synthetic legal intoxicating drugs: the emerging ‘incense’ and ‘bath salt’ phenomenon. Clev Clin J Med 2012;79(4):258-64. PMID 22473725
53: Johnson BA, Devous MD Sr, Ruiz P, Ait-Daoud N. Treatment advances for cocaine-induced ischemic stroke: focus on dihydropyridine-class calcium channel antagonists. Am J Psychiatry 2001;158(8):1191-8. PMID 11481148
54: Jouanjus E, Raymond V, Lapeyre-Mestre M, Wolff V. What is the current knowledge about the cardiovascular risk for users of cannabis-based products? A systemic review. Curr Atheroscler Rep 2017;19(6):26. PMID 28432636
55: Kaku DA, Lowenstein DH. Emergence of recreational drug abuse as a major risk factor for stroke in young adults. Ann Intern Med 1990;113:821-7. PMID 2240897
56: Kase CS, Foster TE, Reed JE, Spatz EL, Girgis GN. Intracerebral hemorrhage and phenylpropanolamine use. Neurology 1987;37:399-404. PMID 3822132
57: Kaye BR, Fainstat M. Cerebral vasculitis associated with cocaine abuse. JAMA 1987;258:2104-6. PMID 3656626
58: Kernan WN, Viscoli CM, Brass LM, et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med 2000;343:1826-32. PMID 11117973
59: Kim ST, Park T. Acute and chronic effects of cocaine on cardiovascular health. Internation J Mol Sci 2019;20(3):584. PMID 30700023
60: Kokkinos J, Levine SR. Possible association of ischemic stroke with phentermine. Stroke 1993;24:310-3. PMID 8421834
61: Konzen JP, Levine SR, Garcia JH. Vasospasm and thrombus formation as possible mechanisms of stroke related to alkaloidal cocaine. Stroke 1995;26:1114-8. PMID 7762031
62: Lappin JM, Darke S, Farrell M. Stroke and methamphetamine use in young adults: a review. J Neurol Neurosurg Psychiatry 2017;88(12):1079-91. PMID 28835475
63: Levine SR, Brust JC, Futrell N, et al. Cerebrovascular complications of the use of the "crack" form of alkaloidal cocaine [comment]. New Engl J Med 1990;323(11):699-704. PMID 2388668
64: Levine SR, Brust JC, Futrell N, et al. A comparative study of the cerebrovascular complications of cocaine: alkaloidal vs. hydrochloride: a review. Neurology 1991;41:1173-7. PMID 1866000
65: Levine SR, Welch KM, Brust JC. Cerebral vasculitis associated with cocaine abuse or subarachnoid hemorrhage. (letter to the editor). JAMA 1988;259:1648.
66: Lieberman AN, Bloom W, Kishore PS, Lin JP. Carotid artery occlusion following ingestion of LSD. Stroke 1974;5(2):213-5. PMID 4816136
67: Liu D, Yang L, Liu P, Wang Y, Gao L. Impact of cannabis abuse on the occurrence of stroke in young people: a systematic review and meta-analysis. Front Neurol 2024;15:1426023. PMID 39502388
68: Liu H, Feng W, Zhang D. Association of ADHD medications with the risk of cardiovascular disease: a meta-analysis. Eur Child Adolesc Psychiatry 2019;28(10):1283-93. PMID 30143889
69: Loewenhardt B, Bernhard M, Pierskalla A, Neumann-Haefelin T, Hofmann E. Neurointerventional treatment of amphetamine-induced acute occlusion of the middle cerebral artery by intracranial balloon angioplasty. Clin Neuroradiol 2013;23:137-43. PMID 22173373
70: Madsen TE, Cummings OW, De Los Rios La Rosa F, et al. Substance use and performance of toxicology screens in the Greater Cincinnati Northern Kentucky Stroke Study. Stroke 2022;53(10):3082-90. PMID 35862206
71: Manchanda S, Connolly MJ. Cerebral infarction in association with ecstasy abuse. Postgrad Med J 1993;69:874. PMID 7904748
72: Margolis MT, Newton TH. Methamphetamine ("speed") arteritis. Neuroradiology 1971;2:179-82. PMID 5164222
73: Martin K, Rogers T, Kavanaugh A. Central nervous system angiopathy associated with cocaine abuse. J Rheumatol 1995;22:780-2. PMID 7791183
74: Martin-Schild S, Albright KC, Misra V, et al. Intravenous tissue plasminogen activator in patients with cocaine-associated acute ischemic stroke. Stroke 2009;40:3635-7. PMID 19745181
75: Mathew J, Addai T, Arnand A, Morrobel A, Maheshwari P, Freels S. Clinical features, site of involvement, bacteriologic findings, and outcome of infective endocarditis in intravenous drug users. Arch Intern Med 1995;155:1641-8. PMID 7618988
76: McCarron MM, Schulze BW, Thompson GA, Conder MC, Goetz WA. Acute phencyclidine intoxication: incidence of clinical findings in 1,000 cases. Ann Emerg Med 1981;10(5):237-42. PMID 7224271
77: Mizutani T, Lewis RA, Gonatas NK. Medial medullary syndrome in a drug abuser. Arch Neurol 1980;37:425-8. PMID 7387487
78: Morgenstern LB, Viscoli CM, Kernan WN, et al. Use of Ephedra-containing products and risk for hemorrhagic stroke. Neurology 2003;60(1):132-5. PMID 12525737
79: Morrow PL, McQuillen JB. Cerebral vasculitis associated with cocaine abuse. J Forensic Sci 1993;38:732-8. PMID 8515225
80: Nanda A, Vannemreddy P, Willis B, Kelley R. Stroke in the young: relationship of active cocaine use with stroke mechanism and outcome. Acta Neurochir Suppl 2006;96:91-6. PMID 16671433
81: Nolan AI, Kuang-Yu J. Pathologic manifestations of levamisole-adulterated cocaine exposure. Diagn Pathol 2015;10:48. PMID 25943359
82: Ohta K, Mori M, Youritaka A, et al. Delayed ischemic stroke associated with methamphetamine use. J Emerg Med 2005;28:165-7. PMID 15707812
83: Omran SS, Chatterjee A, Chen ML, Lerario MP, Merkler AE, Kamel H. National trends in hospitalizations for stroke associated with infective endocarditis and opioid use between 1993 and 2015. Stroke 2019;50(3):577-82. PMID 30699043
84: Page RL, Allen LA, Kloner RA, et al. Medical marijuana, recreational cannabis, and cardiovascular health: a scientific statement from the American Heart Association. Circulation 2020;142(10):e131-52. PMID 32752884
85: Parekh T, Pemmasani S, Desai R. Marijuana use among young adults (18-44 years of age) and risk of stroke: a Behavioral Risk Factor Surveillance System Survey analysis. Stroke 2020;51(1):308-10. PMID 31707926
86: Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A. The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci Therapeutics 2008;14(4):295-314. PMID 19040555
87: Paulraj S, Upreti P, Tamirisa K, Batnyam U. Arrhythmias and cannabis use: A comprehensive overview. Heart Rhythm 2025;6(1):78-85. PMID 40224259
88: Pautina MR, Tuasikal JM, Sari P, Lakdjo MA, Idris I. Implementation peer counselors of anti-drug to prevent drug abuse in students. KONSELI: Jurnal Bimbingan dan Konseling (E-Journal) 2024;11(1):121-6.
89: Polineni SP, Karp A. Autoangiogenesis secondary to chronic cocaine use mimicking Moya‐Moya. Stroke Vasc Intervent Neurol 2023;3:e12823_110.
90: Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2019;50(2):e344-e418. PMID 31662037
91: Rendon LF, Malta S, Leung J, Badenes R, Nozari A, Bilotta F. Cocaine and ischemic or hemorrhagic stroke: a systematic review and meta-analysis of clinical evidence. J Clin Med 2023;12(16):5207. PMID 37629248
92: Rose DZ, Guerrero WR, Mokin MV, et al. Hemorrhagic stroke following use of the synthetic marijuana “spice”. Neurology 2015;85(13):1177-9. PMID 26320200
93: Rothrock JF, Rubenstein R, Lyden PD. Ischemic stroke associated with methamphetamine inhalation. Neurology 1988;38:589-92. PMID 3352918
94: Rowley HA, Lowenstein DH, Rowbotham MC, Simon RP. Thalamomesencephalic strokes after cocaine abuse. Neurology 1989;39:428-30. PMID 2927656
95: Rumbaugh CL, Bergeron RT, Scanlan RL, et al. Cerebral vascular changes secondary amphetamine abuse in the experimental animal. Radiology 1971;101:345. PMID 5000427
96: Sachdeva K, Woodward KG. Caudal thalamic infarction following intranasal methamphetamine use. Neurology 1989;39:305-6. PMID 2915804
97: Samenuk D, Link MS, Homoud MK, et al. Adverse cardiovascular events temporally associated with ma huang, an herbal source of ephedrine. Mayo Clin Proc 2002;77(1):12-6. PMID 11795249
98: Sampurna AS, Mulyani MA, Putra BJ. The effect of group counseling using DHIKR therapy to reduce aggressive behavior in drug addicts. Jurnal Konseling Pendidikan Islam 2025;6(2):401-10.
99: Santolaria-Fernández FJ, Gomez-Sirvent JL, González-Reimers CE, et al. Nutritional assessment of drug addicts. Drug Alcohol Dependence 1995;38(1):11-8. PMID 7648992
100: Sauer CM. Recurrent embolic stroke and cocaine-related cardiomyopathy. Stroke 1991;22:1203-5. PMID 1926265
101: Schteinschnaider A, Plaghos LL, Garbugino S, et al. Cerebral arteritis following methylphenidate use. J Child Neurol 2000;15:265-7. PMID 10805196
102: Sebastian SA, Shah Y, Arsene C, Krishnamoorthy G. Cannabis use and atherosclerotic cardiovascular disease outcomes: A meta-analysis of multinational cohort data. Disease Mon 2025;71(3):101849. PMID 39800612
103: Shah S, Patel S, Paulraj S, Chaudhuri D. Association of marijuana use and cardiovascular disease: a behavioral risk factor surveillance system data analysis of 133,706 US adults. Am J Med 2021;134(5):614-20. PMID 33181103
104: Shere A, Goyal H. Cannabis can augment thrombolytic properties of rtPA: Intracranial hemorrhage in a heavy cannabis user. Am J Emerg Med 2017;35(12):1988-e1. PMID 28987516
105: Sloan MA. Illicit drug use/abuse and stroke. Handbook Clin Neurol 2008;93:823-40. PMID 18804682
106: Sloan MA, Kittner SJ, Rigamonti D, Price TR. Occurrence of stroke associated with use/abuse of drugs. Neurology 1991;41:1358-64. PMID 1891081
107: Sordo L, Indave BI, Barrio G, Degenhardt L, de la Fuente L, Bravo MJ. Cocaine use and risk of stroke: a systematic review. Drug Alcohol Depend 2014;142:1-13. PMID 25066468
108: Steffens S, Pacher P. The activated endocannabinoid system in atherosclerosis: driving force or protective mechanism? Curr Drug Targets 2015;16(4):334-41. PMID 25469884
109: Stoessl AJ, Young GB, Feasby TE. Intracerebral haemorrhage and angiographic beading following ingestion of catecholaminergics. Stroke 1985;16:734-6. PMID 4024187
110: Storck W, Elbaz M, Vindis C, Deguilhem A, Lapeyre-Mestre M, Jouanjus E. Cardiovascular risk associated with the use of cannabis and cannabinoids: a systematic review and meta-analysis. Heart 2025:heartjnl-2024-325429. PMID 40527600
111: Storen EC, Wijdicks EF, Crum BA, Schultz G. Moyamoya-like vasculopathy from cocaine dependency. AJNR 2000;21:1008-10. PMID 10871003
112: Suleria A, Verma S, Arya K, et al. Lysergic acid diethylamide (LSD) and the heart: exploring the potential impacts of LSD on cardiovascular function. Cureus 2025;17(7):e87356. PMID 40765607
113: Togna G, Tempesta E, Togna AR, Dolci N, Cebo B, Caprino L. Platelet responsiveness and biosynthesis of thromboxane and prostacyclin in response to in vitro cocaine treatment. Haemostasis 1985;15:100-7. PMID 3924789
114: Toossi S, Hess CP, Hills NK, Josephson SA. Neurovascular complications of cocaine use at a tertiary stroke center. J Stroke Cerebrovasc Dis 2010;19(4):273-8. PMID 20444626
115: Ukah UV, Potter BJ, Paradis G, Low N, Ayoub A, Auger N. Cocaine and the long-term risk of cardiovascular disease in women. Am J Med 2022;135(8):993-1000. PMID 35472377
116: US Department of Health and Human Services. Substance Abuse and Mental Health Services Administration. Results from the 2019-2020 National Survey on Drug Use and Health: national findings. https://www.samhsa.gov/data/report/2019-2020-nsduh-state-prevalence-estimates. Accessed June 14, 2021.
117: van Lanen, Rick HGJ, et al. Should neurosurgeons ‘chase the dragon’? A case report. Interdisciplin Neurosurg 2025;40:102012.
118: Vik PW, Cellucci T, Jarchow A, Hedt J. Cognitive impairment in substance abuse. Psychiatric Clinics 2004;27(1):97-109. PMID 15062633
119: Westover AN, McBride S, Haley RW. Stroke in young adults who abuse amphetamines or cocaine: a population-based study of hospitalized patients. Arch Gen Psychiatry 2007;64(4):495-502. PMID 17404126
120: White D, Martin D, Geller T, Pittman T. Stroke associated with marijuana abuse. Pediatr Neurosurg 2000;32:92-4. PMID 10838508
121: Wolff V, Armspach JP, Lauer V, et al. Cannabis-related stroke: myth or reality. Stroke 2013;44:558-63. PMID 23271508
122: Wooten MR, Khangure MS, Murphy MJ. Intracerebral hemorrhage and vasculitis related to ephedrine abuse. Ann Neurol 1983;13:337-40. PMID 6342508
123: Zachariah SB. Stroke after heavy marijuana smoking. Stroke 1991;22:406. PMID 2003312
124: Zongo A, Lee C, Dyck JRB, et al. Medical cannabis authorization and the risk of cardiovascular events: a longitudinal cohort study. BMC Cardiovas Disord 2021;21(1):426. PMID 34507536

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Narendra Kala MD

Dr. Kala of Temple University, Philadelphia, has no relevant financial relationships to disclose.
See Profile

Editor

Steven R Levine MD

Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.
See Profile

Former Authors

Birgitte H Bendixen MD PhD
Scott Eric Kasner MD
Brett Cucchiara MD
Michael T Mullen MD

Patient Profile

Age range of presentation: 0-01 month, 6-65+ years
Sex preponderance: male>female, >1:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-10: Drug dependence syndrome: F11.2, F13.2, F14.2

Harmful use of drugs: F11.1, F13.1, F14.1

Occlusion and stenosis of other cerebral artery: I66.8

Occlusion and stenosis of unspecified cerebral artery: I66.9

Cerebral atherosclerosis: I67.2

Intracerebral haemorrhage, unspecified: I61.9

Subarachnoid haemorrhage, unspecified: I60.9

Vertebro-basilar artery syndrome: G45.0

Cerebrovascular accident NOS: I64
ICD-11: Hazardous drug use: QE11, including QE11.0, 11.1, 11.2, 11.3, 11.4, 11.7, 11.8, 11.Y, 11.z

Transient ischemic attack: 8B10

Cerebral ischemic stroke: 8B11.0, 11.1, 11.2, 11.3, 11.4, 11.5

Intracerebral hemorrhage: 8B00.0, 00.1, 00.2, 00.3, 00.4, 00.5, 00.Z

Subarachnoid hemorrhage: 8B01.0, 01.2, 0.2

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Stroke associated with drug abuse

Differential Diagnosis

premature atherosclerosis
arterial dissection
cardioembolism
prothrombotic states
infection

Also Relevant

Cerebral embolism
Cerebral venous thrombosis
Coma due to drug intoxication
Congenital cocaine syndrome
Drug-induced seizures
- Illicit drug use: neurologic complications
- Ischemic stroke
- Spinal epidural abscess
- Stroke in young adults

Drug	12 to 17 years	18 to 25 years	26 years or older
Marijuana Cocaine Heroin Prescription pain reliever Methamphetamine	11.7 0.4 * 1.9 0.1	35.0 4.8 0.2 4.6 0.7	15.8 1.7 0.3 3.4 0.9
* Low precision; no estimate reported.

Stroke associated with drug abuse

Cite this article

Introduction

Overview

Key points

Historical note and terminology

Table 1. Historical Publications Regarding Drug Abuse and Cerebrovascular Disorders

Table 2. Street Names and Methods of Administration for Drugs of Abuse

Etiology and pathogenesis of stroke in drug use

Clinical manifestations

Presentation and course

Prognosis and complications

Epidemiology

Table 3. Types of Illicit Drug Use in the Past Month (Percentages) 2019-2020

Prevention

Differential diagnosis

Diagnostic workup

Management

Special considerations

Pregnancy

Anesthesia

Media

References

Contributors

Author

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Stroke associated with cerebral angiography

Fibromuscular dysplasia

Brainstem hemorrhage

Cardiac catheterization: neurologic complications

Intracranial atherosclerosis

Cerebellar infarction and cerebellar hemorrhage

Lobar hemorrhage

Nontraumatic intracerebral hemorrhage

This is an article preview.
Start a Free Account
to access the full version.