Clinical Toxicology

ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: https://www.tandfonline.com/loi/ictx20

Cannabis use and acute coronary syndrome

John R. Richards, Mary L. Bing, Aimee K. Moulin, Joshua W. Elder, Robert T.

Rominski, Phillip J. Summers & Erik G. Laurin

To cite this article: John R. Richards, Mary L. Bing, Aimee K. Moulin, Joshua W. Elder, Robert T.
Rominski, Phillip J. Summers & Erik G. Laurin (2019): Cannabis use and acute coronary syndrome,
Clinical Toxicology, DOI: 10.1080/15563650.2019.1601735

To link to this article: https://doi.org/10.1080/15563650.2019.1601735

Published online: 09 Apr 2019.

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CLINICAL TOXICOLOGY
https://doi.org/10.1080/15563650.2019.1601735

REVIEW

Cannabis use and acute coronary syndrome

John R. Richards , Mary L. Bing, Aimee K. Moulin, Joshua W. Elder , Robert T. Rominski, Phillip J.
Summers and Erik G. Laurin
Department of Emergency Medicine, University of California Davis Medical Center, Sacramento, CA, USA

ABSTRACT ARTICLE HISTORY

Introduction: Cannabis smoking can result in elevation of heart rate and blood pressure immediately Received 9 December 2018
after use, possibly from sympathetic nervous system stimulation and parasympathetic nervous system Revised 8 February 2019
inhibition. Vascular inflammation, platelet activation, and carboxyhemoglobin generation have also Accepted 25 March 2019
been proposed as potential side effects of cannabis smoking. As such, an association between canna- Published online 2 2 2
bis use and acute coronary syndrome has been postulated. KEYWORDS
Objective: The objective of our study was to analyze systematically the medical literature pertaining Acute coronary syndrome;
to this putative association. cannabis; chest pain;
Methods: PubMed, Google Scholar, and OpenGrey were queried using a unique search string. All marijuana; myocar-
human trials, case series, or case reports of cannabis use and acute coronary syndrome in any lan- dial infarction
guage were considered in the literature search. The definition of acute coronary syndrome represented
a penumbra that included chest pain, angina pectoris, unstable angina, myocardial infarction, myocar-
dial ischemia, and cardiac arrest. Preferred Reporting Items for Systematic Reviews and Meta-analyses
(PRISMA) guidelines were followed. Our final search strategy included free-text words (TW):
(“cannabis”[TW] OR "marijuana"[TW]) AND ("acute coronary syndrome"[TW] OR “myocardial” OR
“ischemia”[TW] OR “infarction”[TW] OR “chest pain”[TW] OR “cardiac arrest”[TW] OR “angina”[TW]). To
remain consistent over a span of five decades, we specifically did not include any publications with
non-phytogenic, non-smoked cannabis as the sole etiology, as these are relatively recent and may pos-
sess additional pharmacologic characteristics compared to phytogenic cannabinoids. Therefore, for the
purpose of this review, the term “cannabis” refers to the smoked phytogenic form. The search resulted
in 325 articles. References in each selected publication were carefully hand-searched for any additional
reports having relevance, and a total of 12 publications were identified in this manner. Following com-
parison and discussion amongst the co-authors, duplicate and non-relevant publications were
removed, and a total of 85 publications involving 541,518 human subjects were selected for inclusion.
Results were synthesized and reviewed by the authors for relevance. Clinical trials, observational stud-
ies, retrospective studies, case series, and case reports were graded using Oxford Centre for Evidence-
based Medicine guidelines.
Results: There were no Level I randomized blinded controlled studies specifically addressing the can-
nabis/acute coronary syndrome association. However, there were five Level I systematic reviews, 14
Level II studies with 83,961 subjects, and 14 Level III studies with 457,495 subjects. Conclusions from
28 of these 33 studies highlighted an increased risk of both acute coronary syndrome and chronic car-
diovascular disease from cannabis use. The systematic reviews were wide-ranging in topic and scale,
and none specifically focused on the association between cannabis use and acute coronary syndrome.
The dissenting studies included two systematic reviews, one concluding there was limited and weak
evidence for association of cardiovascular disease and acute coronary syndromes with cannabis use,
and another citing the evidence was inconclusive. The other dissenting articles were two longitudinal
prospective studies and a retrospective review concluding cannabis users had lower post-myocardial
infarction mortality. There were 51 case series (Level IV) and case reports (Level V) with 62 subjects.
Six cases were female (10%). Average age was 31 ± 12 years, reported maximum heart rate was 88 ±
21 bpm, systolic blood pressure was 125 ± 32 mmHg, and diastolic blood pressure was 80 ± 17
mmHg. ST-segment elevation was documented on 37 (60%) electrocardiograms, and the most com-
mon angiographic finding was left anterior descending coronary arterial occlusion and/or stenosis in
22 (35%) patients. Concomitant cardiomyopathy was described in 21 (34%) cases. There were 14
(23%) deaths attributed to acute coronary syndrome associated with cannabis use.
Conclusion: There were five Level I systematic reviews, 14 Level II studies with 83,961 subjects, and
14 Level III studies with 457,495 subjects. All but five Level I–III publications highlighted an increased
risk of both acute coronary syndrome and chronic cardiovascular disease associated with cannabis use.

CONTACT John R. Richards jrrichards@ucdavis.edu Department of Emergency Medicine, PSSB 2100, U.C. Davis Medical Center, 2315 Stockton Boulevard,
Sacramento, CA 95817, USA
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 J. RICHARDS ET AL.
Introduction
Cannabis is one of the most commonly-used drugs world-
wide, with 192 million people using cannabis at least once in
the past year according to the most recent United Nations’
2018 World Drug Report [1]. The rate of global cannabis use
has risen by 16% over the current decade, and this trend is
predicted to continue as legalization for recreational and
medical use continues to spread [1].
The authors of several clinical studies, reviews, case series
and reports over the past five decades have suggested a
nexus between cannabis use and cardiovascular diseases
[2,3]. This potential association was first recognized in the
early 1970s, when three small prospective studies high-
lighted the significant increase in heart rate and blood
pressure directly after smoking cannabis [4–6]. These hypera-
drenergic effects could be mitigated with beta-blocker pre-
treatment, suggesting cannabis activation of the sympathetic
nervous system [7].
In 1974 Aronow and Cassidy [8] reported cannabis smok-
ing significantly decreased time to angina pectoris during
exercise in 10 subjects with coronary artery disease. The fol-
lowing year the same authors published a comparison study
between cannabis versus tobacco smoking in 10 subjects
with coronary artery disease and found cannabis smoking
significantly decreased exercise time until angina compared
to tobacco [9]. In 1975 this study group went on to publish
the effects of cannabis smoking on the hemodynamics of
subjects with coronary artery disease, confirming increased
heart rate and blood pressure, but decreased left ventricular
end-diastolic volume, ejection fraction, and cardiac index
[10]. The authors postulated these physiologic effects were
directly caused by delta 9-tetrahydrocannabinol (THC), the
major psychoactive compound in cannabis, and/or the carb-
oxyhemoglobin induced from cannabis smoking.
Cannabinoid agonists such as THC interact with the endo-
cannabinoid system via G protein-coupled membrane recep-
tors, CB1 and CB2, which are found throughout the body.
The CB1 receptors are distributed within the central nervous
system and modulate allostasis and autonomic nervous sys-
tem signaling [11,12]. These receptors are also located in the
myocardium and vascular endothelium [4,13]. The CB2 recep-
tors are found in immune cells, and activation results in anti-
inflammatory effects [14]. Cannabis use most commonly
results in tachycardia and hypertension through sympathetic
nervous system activation and parasympathetic nervous sys-
tem inhibition, which is the primary mechanism thought to
be responsible for its provocation of acute coronary syn-
drome from increased myocardial oxygen demand [2,3]. This
effect may be further worsened if cannabis is smoked, which
results in elevated concentrations of carboxyhemoglobin that
is higher than measured from smoking tobacco [15].
The activation of CB1 receptors is proatherogenic, with
downregulation of Th1 immune response cells in atheroscler-
otic lesions [16]. The expression of CB1 receptors was found
to be higher in coronary atheromas of patients with unstable
angina compared with those with stable angina [17]. Other
proposed mechanisms of cannabis-induced acute coronary
syndrome include angiotensin I receptor activation, creation
of reactive oxygen species, endothelial dysfunction, and
regional coronary vasospasm resulting in coronary arterial
occlusion and/or thrombosis [2,3,18,19]. Cannabis-mediated
activation of CB1 and CB2 receptors may also lead to pro-
coagulant effects, such as increased platelet membrane
glycoprotein IIb-IIIa and P-selectin, lipopolysaccharide-stimu-
lated tissue factor protein expression in activated monocytes,
and platelet activation [2,3,19–21]. In addition to acute cor-
onary syndrome, atrial and ventricular dysrhythmias have
been directly associated with cannabis use [22–24].
Objective
The objective of our study was to analyze systematically the
medical literature pertaining to the putative association
between cannabis use and acute coronary syndrome, a spec-
trum of clinical presentations that includes angina pectoris,
unstable angina, ST-segment elevation myocardial infarction,
non-ST-segment myocardial infarction, and witnessed/unwit-
nessed cardiac arrest. The emphasis of our objective differs
from previously published systematic reviews, which cover a
broader scope of cardiovascular pathologies, risk factors,
morbidity, and mortality.
Methods
Peer-reviewed publications were retrieved from an extensive
query of PubMed, Google Scholar, and OpenGrey from incep-
tion to March 1, 2019. All human trials, case series, or case
reports of cannabis use and acute coronary syndrome in any
language were considered in the literature search. The defin-
ition of acute coronary syndrome represented a penumbra
that included chest pain, angina pectoris, unstable angina,
myocardial infarction, myocardial ischemia, and cardiac
arrest. Preferred Reporting Items for Systematic Reviews and
Meta-analyses (PRISMA) guidelines were followed [25]. Our
final search strategy included free-text words (TW):
(“cannabis”[TW] OR "marijuana"[TW]) AND ("acute coronary
syndrome"[TW] OR “myocardial” OR “ischemia”[TW] OR
“infarction”[TW] OR “chest pain”[TW] OR “cardiac arrest”[TW]
OR “angina”[TW]). To remain consistent over a span of five
decades, we specifically did not include any publications
with non-phytogenic, non-smoked cannabis as the sole eti-
ology, as these are relatively recent and may possess add-
itional pharmacologic characteristics compared to
phytogenic cannabinoids. Therefore, for the purpose of this
review, the term “cannabis” refers to the smoked phytogenic
form. Differentiation between acute and chronic cannabis
use was not possible as most articles reviewed did not men-
tion this distinction.
The search resulted in 325 articles. References in each
selected publication were carefully hand-searched for any
additional reports having relevance, and a total of 12 publi-
cations were identified in this manner. Following comparison
and discussion amongst the co-authors, duplicate and non-
relevant publications were removed, and a total of 85 publi-
cations involving 541,518 human subjects were selected for
inclusion. Examples of non-relevant publications included

animal studies, general reviews, and pathologies other than
acute coronary syndrome, such as hypertension, stroke, and
peripheral arterial disease.
A complete and meaningful meta-analysis with measures
of bias and heterogeneity was not possible due to the wide
variety of protocols, limited number and quality of trials, and
study durations. Data were, therefore, analyzed in a qualita-
tive manner. Because of the small number of high-quality
(Level I, II) eligible studies, case series and reports detailing
treatments and outcomes were also included and discussed.
Articles were graded using the Oxford Centre for Evidence-
Based Medicine (CEBM) levels of evidence [26]. These levels
are essentially designated as: I ¼ properly powered and con-
ducted randomized clinical trial, systematic review, or meta-
analysis; II ¼ well-designed controlled trial without random-
ization; prospective comparative cohort; III ¼ case-control
studies, retrospective cohort studies; IV ¼ case series with or
without intervention, cross-sectional studies; V ¼ opinion of
authorities, case reports.
Results
There were five Level I systematic reviews, 14 Level II studies
with 83,961 subjects, and 14 Level III studies with 457,495
subjects (Table 1) [3,8–10,27–55]. Conclusions from all but
five Level I–III publications highlighted an increased risk of
both acute coronary syndrome and chronic cardiovascular
disease associated with cannabis use. The exceptions were a
systematic review highlighting limited and weak evidence for
association of acute coronary syndrome with cannabis use,
another systematic review that was inconclusive, two longitu-
dinal prospective studies and a retrospective review conclud-
ing cannabis users had lower post-myocardial infarction
mortality [29–31,40,52].
Level I studies
There were no Level I randomized blinded controlled studies
specifically addressing the cannabis/acute coronary syndrome
association, only wide-ranging systematic reviews of varying
focus and scale. There were no systematic reviews that spe-
cifically addressed the association between cannabis use and
acute coronary syndrome.
In 2011 Nawrot and colleagues [27] published the first
systematic review and meta-analysis of what they termed
“triggers” of non-fatal myocardial infarction, which included
environmental, emotional, and substance-induced etiologies.
They reported cannabis smoking was the third highest-rank-
ing associated variable (odds ratio 4.8, 95% confidence inter-
val [2.9–9.5]) after cocaine and eating a heavy meal. In 2013
Desbois and Cacoub [28] reviewed systematically the litera-
ture regarding cannabis-associated generalized arterial dis-
ease and concluded cannabis use was associated with
myocardial infarction, stroke, and peripheral arteritis.
Jouanjus et al. [3] performed a 2017 systematic review
regarding the overall cardiovascular risks of cannabis and
concluded the risk of stroke was higher than other cardiovas-
cular disease, such as myocardial infarction.
CLINICAL TOXICOLOGY 3
There were two systematic reviews which differed from
the aforementioned studies in their conclusion regarding a
harmful association between cannabis use and cardiovascular
disease. Pradhan et al. [29] narrowly focused on cannabis use
and in-hospital mortality following myocardial infarction.
Based on only four studies selected, the authors concluded
in-hospital mortality from myocardial infarction was reduced
among cannabis users compared to non-users in retrospect-
ive studies, but not in cohort studies, and that a direct causal
relationship between cannabis and acute coronary syndrome
was inconclusive [34,35,46,52]. In contrast to this study, the
association between cannabis use and acute coronary syn-
drome was not specifically queried, and no case series or
reports were included in their review. Ravi et al. [30]
addressed cannabis use and overall cardiovascular risks and
outcomes and concluded the evidence from 24 articles was
hampered by poor-to-moderate quality data, and thus insuf-
ficient. Specific limitations mentioned by the authors
included recall bias, inadequate exposure assessment, min-
imal cannabis exposure, and a predominance of low-risk
cohorts. In contrast to this study, their systematic review did
not focus specifically on acute coronary syndrome and
included no mention of case series or reports.
Level II studies
In addition to the previously discussed prospective studies
from the 1970s, there were several important Level II studies
identified in our review. In their prospective case-crossover
Determinants of Myocardial Infarction Onset Study (MIOS) of
2001, Mittleman et al. [33] reported a significantly increased
relative risk (4.8, [2.4–9.5]) of myocardial infarction within
one hour of smoking cannabis. This risk was no longer
increased after the first hour, suggesting an acute effect of
cannabis itself. Mukamal et al. [34] conducted an inception
cohort study and revealed that cannabis was associated with
three-fold higher total mortality after myocardial infarction,
and a graded increase in the risk of myocardial infarction
with more frequent cannabis use. In a subanalysis of MIOS,
Frost et al. [35] found that the mortality rate was 29% higher
among cannabis users with myocardial infarction compared
to non-users.
Reece et al. [36] studied radial arterial pulse wave tonom-
etry, an objective measurement of cardiovascular ageing, in
1553 subjects and determined cannabis use significantly
accelerated cardiovascular age and hence risk for acute cor-
onary syndrome. James et al. [32] published a case-control
study of 54 adolescents presenting with chest pain, and one-
quarter of both case (n ¼ 7) and control (n ¼ 7) subjects
tested positive for cannabis metabolite on quantitative toxi-
cology testing followed by ephedrine (n ¼ 5) in the case
subjects. Only three of the case subjects admitted to canna-
bis use, with two stating their chest pain followed immedi-
ately after cannabis use. The authors noted cannabis was the
most common drug detected in the study population. In a
consecutive drug overdose cohort study of 3739 patients, 70
patients with phytogenic cannabis overdose had associated
cardiotoxicity [37]. From the Coronary Artery Risk
4 J. RICHARDS ET AL.

Table 1. Summary of relevant studies.

Level of No. of articles
Year Authors Study type evidence or subjects Summary
2011 Nawrot et al. [27] Systematic review, I 36 Odds ratio 4.8 for cannabis as a potential trigger for MI
meta-analysis
2013 Desbois et al. [28] Systematic review I 147 Cannabis use is associated with MI, peripheral arterial dis-
ease, and stroke
2017 Jouanjus et al. [3] Systematic review I 29 Association between cannabis use and cardiovascular dis-
ease less than for stroke
a
2018 Pradhan et al. [29] Systematic review I 4 Inconclusive as to whether cannabis use increases risk
of ACS
2018 Ravi et al. [30]a Systematic review I 24 Limited evidence for association of cannabis use with ACS
and other cardiovascular diseases
1974 Aronow & Cassidy [8] Prospective cohort II 10 Cannabis versus placebo smoking decreased time to angina
during exercise, increased heart rate and blood pressure
1975 Aronow & Cassidy [9] Prospective cohort II 10 Cannabis versus tobacco smoking decreased time to
angina during exercise, increased rate-pressure product
1975 Prakash et al. [10] Prospective double- II 10 Cannabis versus placebo smoking decreased cardiac index,
blind cohort ejection fraction, increased heart rate and
blood pressure
1997 Sidney et al. [31]a Prospective longitudinal II 65,171 No significant increase in relative risk of cardiovascular
mortality in cannabis users versus non-users
1998 James et al. [32] Prospective cohort II 54 Cannabis smoking reported in 25% of adolescents present-
ing with chest pain
2001 Mittleman et al. [33] Prospective case-crossover II 3,882 Risk of ACS elevated in the 60 minutes after canna-
bis smoking
2008 Mukamal et al. [34] Prospective inception cohort II 1,913 Cannabis use associated with increased hazard ratios for
cardiovascular mortality
2013 Frost et al. [35] Prospective longitudinal II 2,097 22 of 109 MI patients reporting cannabis use died; mortal-
ity rate was 29% higher than non-users
2016 Reece et al. [36] Prospective longitudinal II 1,163 Cannabis use accelerated cardiovascular ageing via radial
artery pulse wave
2016 Zaurova et al. [37] Prospective cohort II 70 Three of 70 phytogenic cannabis users diagnosed with
myocardial injury (4.3%)
2017 Auer et al. [38] Prospective longitudinal II 3,117 Cannabis and concurrent tobacco use increased athero-
sclerosis risk
2017 Draz et al. [39] Prospective cross-sectional II 138 Cannabis smoking potential risk factor for developing ST-
elevation myocardial infarction, single coronary vessel
atherosclerosis
2017 Reis et al. [40]a Prospective longitudinal II 5,113 Cannabis use not associated with cardiovascular disease
and associated deaths compared with non-users
2017 Yankey et al. [41] Prospective longitudinal II 1,213 Cannabis use and duration increases risk for hypertension
mortality, which includes MI
2011 Jouanjus et al. [42] Retrospective review III 200 Seven subjects with MI associated with cannabis use
2014 Jouanjus et al. [43] Retrospective review III 1,979 1.8% of cannabis-related reports were cardiovascular com-
plications; 20 with ACS, 9 deaths
2014 Thankavel et al. [44] Retrospective review III 32 Seven pediatric patients with vasospasm and MI from pre-
ceding cannabis use
2015 Dines et al. [45] Retrospective review III 2,198 36 cannabis-only toxicity cases from Euro-DEN network;
one fatality from cardiac arrest
2017 Desai et al. [46] Retrospective review III 35,771 Lifetime odds for acute MI were increased in recreational
cannabis users but not mortality
2017 Lee et al. [47] Retrospective review III 200 Cannabis users patients with MI were younger and had
less history of CAD than non-users
2017 Lorenz et al. [48] Retrospective review III 558 Cannabis use increases risk of MI, angina pectoris, and
other cardiovascular events in HIV positive patients
2017 Sharma et al. [49] Retrospective review III 10 Cannabis users with MI; LAD pathology most commonly
seen on angiograpy
2017 Abouk & Adams [50] Retrospective review III 1,275 Database review and fixed effects modeling: cardiac death
significantly higher in states with liberal cannabis laws
2018 DeFillipis et al. [51] Retrospective review III 125 2.13 adjusted hazard ratio for cardiovascular death in can-
nabis users
a
2018 Johnson-Sasso et al. [52] Retrospective review III 3,854 Cannabis use was not associated with increased risk of
adverse short-term outcomes following acute MI
2018 Kalla et al. [53] Retrospective review III 31,397 Cannabis use associated with higher rate cardiovascular
events such as sudden cardiac death
2018 Patel et al. [54] Retrospective review III 3,79,843 Admissions for cannabis use and associated acute MI rising,
morbidity, mortality and cost also
2019 Ramphul et al. [55] Retrospective review III 53 Odds ratio of acute MI was 5.033 with cannabis use
in teenagers
a
indicates no harm and/or benefit from cannabis use.
ACS: acute coronary syndrome; CAD: coronary artery disease; HIV: human immunodeficiency virus; LAD: left anterior descending coronary artery; MI: myocar-
dial infarction.
Table 2. Summary of relevant case series and reports.
Age HR SBP DBP ECG CAD
Year Authors (years) Gender (bpm) (mmHg) (mmHg) findings history Summary
1979 Charles et al. [56] 25 Male 96 100 70 T wave inversion V3-V6, aVL No Chest pain and dyspnea after smoking cannabis; pulmonary edema on
chest radiograph
1984 MacInnes & Miller [57]a 32 Male 100 "normal" "normal"  Unknown Chest pain, agitation, cardiac arrest, death after smoking cannabis; autopsy
showed LAD thrombus, cardiomyopathy, CAD
1985 Collins et al. [58] 35 Female 96 110 70 STE II, III, aVFSTD V2-V6 No Chest pain after smoking cannabis; ventricular fibrillation; cardioversion
1989 Choi & Pearl [59] 17 Male 75 116 80 STE II, III, aVF, STD V1-V3 No Chest pain morning after cannabis smoking; THC and caffeine also
detected on toxicology screen
1990 Podczeck et al. [60] 20 Male    Q waves III, aVF V6 No Acute MI in a chronic cannabis smoker; treated with recombinant tissue
plasminogen activator
2001 Bachs et al. [61]a 39 Male     No Shoulder pain preceding unwitnessed cardiac arrest, death; autopsy
showed MI, CAD, cardiomyopathy; THC detected on toxicology testing
40 Male     No Unwitnessed cardiac arrest, death; autopsy showed LAD narrowing and
sparse CAD; THC detected on toxicology testing
43 Male     Yes Unwitnessed cardiac arrest, death; autopsy showed MI, CAD, and cardiomy-
opathy; THC detected on toxicology testing
37 Male     No Unwitnessed cardiac arrest, death; autopsy showed CAD; THC and 0.04%
ethanol detected on toxicology testing
17 Male     No Unwitnessed cardiac arrest, death; autopsy showed "slightly enlarged
heart"; THC detected on toxicology testing
42 Male     Unknown Witnessed cardiac arrest, death; autopsy showed MI, "slight" CAD; THC
detected on toxicology testing
2002 McLeod et al. [62] 41 Male  112 86 Inferior lead infarct pattern No Chest pain morning after cannabis smoking and sildenafil use; treated
with aspirin, beta-blocker, heparin
2003 Rezkalla et al. [63] 34 Male 82 162 96 Ventricular tachycardia No Chest pain, palpitations, and dyspnea after smoking cannabis; ventricular
tachycardia; cardioversion; angiography: slow-flow
2005 Caldicott et al. [64] 21 Male    STE II, III, aVF No Chest pain morning after cannabis smoking; angiography: LAD occlusion
2005 Fisher et al. [65] 35 Female 150 233 120 Rapid atrial flutter No Chest pain and palpitations after smoking cannabis; adenosine and fleca-
nide treatment
2005 Lindsay et al. [66] 48 Male    Ventricullar fibrillation Yes Cardiac arrest after smoking cannabis; angiography: left main
artery occlusion
22 Male    STE V1-V5 STD reciprocal No Chest pain after smoking cannabis; thrombolysis; angiography: LAD plaque
2006 Taher et al. [67] 24 Male 84 130 80 STE V2-V6, STD II, III, aVF No Chest pain after smoking cannabis; received streptokinase; angiography:
LAD occlusion
2007 Tatli et al. [68] 24 Male   New RBBB, STE V2-V5 No Chest pain after smoking cannabis; angiography: left coronary thrombosis
2008 Cappelli et al. [69] 30 Male    STE V2-V6, aVL No Chest pain after smoking cannabis, ventricular fibrillation, cardioversion;
angiography: LAD occlusion
2008 Dwivedi et al. [70] 23 Male    T wave inversion II, III, aVL No Chest pain after smoking cannabis; refused angiography
50 Male    STE V2-V5 aVL No Chest pain after smoking cannabis; thrombolyic treatment
2009 Basnet et al. [71] 17 Male    STE V3-V6 No Chest pain morning after cannabis smoking; resolved with nitroglycerin;
echocardiography: apical hypokinesis
2009 Sattout & Nicol [72] 15 Male 86 115 86 Normal No Cardiac arrest after cannabis smoking; intubated; toxicology screening posi-
tive for THC
2010 Bailly et al. [73] 36 Female 66 119 75 STE V1-V5 STD II, III No Chest pain after smoking cannabis; angiography: interventricular
artery occlusion
2010 Bilbault et al. [74] 23 Male    STE V2-V4 recriprocal changes No Chest pain after smoking cannabis; cardiac arrest; angiography:
LAD occlusion
29 Male    STE V2-V4 No Chest pain after smoking cannabis; angiography: LAD occlusion
2010 Karabulut & Cakmak [75] 35 Male 69 140 100 STE and Q waves II, III No Chest pain after smoking cannabis; angiography: slow coronary flow
2011 Çanga et al. [76] 28 Male 85 135 80 STE and Q waves V1-V4 No Chest pain after smoking cannabis; angiography: LAD occlusion; echocardi-
ography: anterior, apical hypokinesis, ejection fraction 35%
CLINICAL TOXICOLOGY

2011 De Silva & Perera [77] 51 Male 74 125 70 STE V1, aVR STD II, III, aVF No Chest pain in a chronic cannabis smoker; angiography: left main
artery occlusion
(continued)
5
 6

Table 2. Continued.
Age HR SBP DBP ECG CAD
Year Authors (years) Gender (bpm) (mmHg) (mmHg) findings history Summary
2012 Arora et al. [78] 37 Male 102 112 86 STE I, aVL No Chest pain after smoking cannabis; angiography: normal; distant sildena-
fil use
2012 Biyik et al. [79] 19 Male    "Acute anterior MI" No Chest pain after smoking cannabis; angiography: LAD occlusion
2012 Dahdouh et al. [19] 20 Male     No Sudden cardiac arrest; echocardiography: ejection fraction 10%, left apical
thrombus; angiography: left main artery occlusion; heart transplant
2012 Safaa et al. [80] 40 Male 78 110 69 T wave changes V3, V4 No Chest pain after smoking cannabis; angiography and echocardio-
J. RICHARDS ET AL.

gram: normal
2012 Yurtdas & Aydin [81] 26 Male 60 100 60 STE II, III, aVF No Chest pain after smoking cannabis; angiography: right coronary
artery occlusion
a
2013 Casier et al. [82] 52 Male    STE anterior inferior Yes Cardiac arrest after smoking cannabis; angiography: vasospasm of
LAD; death
23 Male    STE anterior inferior posterior No Cardiac arrest after smoking cannabis; angiography: LAD and right artery
occlusion; cardiac transplant
28 Male    STE anterior lateral No Cardiac arrest after smoking cannabis; angiography: LAD thrombus, ejec-
tion fraction 26%; required ECLS; death from multiple organ failure
2013 Deharo et al. [83] 24 Male    STE III, aVF No Chest pain with chronic cannabis smoking; angiography: right artery occlu-
sion; echocardiography: basal hypokinesis, ejection fraction 55%
2013 Ghannem et al. [84] 24 Male    STE V2-V4 No Chest pain with chronic cannabis smoking; angiography: left interventricu-
lar arterial occlusion
2013 Lee et al. [85] 42 Male 130 110 60 STE V1-V3 No Chest pain after cannabis smoking and sildafenil use; angiography: myo-
cardial bridging with systolic LAD compression
2013 Sayin et al. [86] 30 Male    Q waves III, aVF R wave V2 No Chest pain with chronic cannabis smoking; angiography: right artery occlu-
sion, LAD slow-flow
2014 Gunawardena et al. [87] 29 Male    STE inferior and lateral No Chest pain with chronic cannabis smoking; angiography: LAD slow-flow
2014 Hartung et al. [88]a 23 Male     No Cardiac arrest, death; toxicology positive for THC; autopsy: cardiomyopathy
and coronary arterial thrombus
28 Male     No Cardiac arrest, death; toxicology positive for THC; autopsy: normal heart
2014 Hodcroft et al. [89] 21 Male    STE V2-V6, inverted T wave III No Chest pain after exercise with chronic cannabis smoking; angiography: LAD
artery thrombus
2014 Rodr
ıguez-Castro et al. [90] 29 Male 69 115 65 STE II, III, aVF PR depression No Chest pain with chronic cannabis smoking; echocardiography: moderate
concentric hypertrophy
2015 Jehangir et al. [91] 27 Female 98 132 89 STE II, III; inverted T waves V1-V3 No Chest pain with chronic cannabis smoking; angiography: 99% LAD occlu-
sion; echocardiogram: anterior akinesis, ejection fraction 40%
a
2015 Marchetti et al. [92] 50 Male     No Cardiac arrest, death in a chronic cannabis user; autopsy: right
artery occlusion
2015 Velibey et al. [93] 27 Male 53 125 75 STD V5-V6 No Chest pain with chronic cannabis smoking; angiography: left main artery
occlusion; echocardiography: left ventricle hypokinesis
2016 Hayiroglu et al. [94] 18 Male 90 142 75 New RBBB No Chest pain after smoking cannabis; angiography: LAD thrombus
2016 Keskin et al. [95] 15 Male 104 84 47 STE II, III, aVL new RBBB No Chest pain after smoking cannabis; angiography: normal; echocardiog-
raphy: left ventricle hypokinesis, ejection fraction 40%; concomi-
tant stroke
2016 Orsini et al. [96]a 40 Male 104 "undetectable" "undetectable" STE II, III, aVF V1-V5 No Cardiac arrest, death, toxicology positive for THC, ethanol; echocardiogram:
global hypokinesis, ejection fraction 20%; autopsy: acute MI
2016 Pierard & Hantson [97] 41 Male    STE V1-V4 No Chest pain and concomitant cannabinoid hyperemesis; aniography: 40%
LAD stenosis; echo: takotsubo cardiomyopathy
a
2017 Del Buono et al. [98] 23 Female    STE V5-V6 STD V1-V2 No Cardiac arrest, death; chronic cannabis smoking; echocardiography: left
ventricle dysfunction, ejection fraction 20%, takotsubo pattern; angiog-
raphy: normal
2017 Hsu et al. [99] 16 Male 93 116 75 New RBBB No Chronic cannabis smoking, normal cardiac magnetic resonance imaging
2018 Toce et al. [100] 16 Male  70  STE II,III,V4-V6 STD V1-V3 No Chest pain after smoking cannabis, angiography normal, developed dilated
cardiomyopathy
(continued)
 CLINICAL TOXICOLOGY 7

Development in Young Adults (CARDIA) study of 3498 sub-

Chest pain after smoking cannabis; angiography: LAD occlusion; intra-aortic

Chest pain after smoking cannabis; angiography: stenting of LAD; intra-aor-

CAD: coronary artery disease; DBP: diastolic blood pressure; ECG: electrocardiogram; HR: heart rate; LAD: left anterior descending coronary artery; MI: myocardial infarction; RBBB: right bundle branch block; SBP: systolic
ease and takotsubo cardiomyopathy, required intra-aortic balloon pump
Toxicology screen positive for THC, angiography: mild coronary artery dis-

Angiography: stenosis in the proximal LAD artery with distal embolization

jects, Auer et al. [35] reported that cannabis plus tobacco
use was associated with subclinical atherosclerosis.

balloon pump placement; Serial rising quantitative THC levels

Draz et al. [39] conducted a prospective cross-sectional

tic balloon pump placement; echo: ejection fraction 20-25%

study of 138 patients, of whom 23 were cannabis users, and
reported increased proportions of ST-segment elevation
Chest pain after smoking cannabis; angiography: normal

myocardial infarction, cardiomyopathy, and coronary artery

disease in cannabis users compared to non-users, which
were both clinically and statistically significant. Yankey et al.
Summary

[41] utilized the National Health and Nutrition Examination

Survey (NHANES) data to assess cannabis use and association
with cardiovascular mortality of 1213 subjects and found
cannabis use was significantly associated with increased
hypertension mortality, such as from myocardial infarction
and stroke. The authors of two Level II studies concluded
there was no harm from cannabis use with regard to cardio-
vascular disease. In 1997 Sidney et al. [31] reported a pro-
spective longitudinal cohort of 65,171 people (age 15–49
years) and determined the relative risk of cardiovascular dis-
ease was not increased in cannabis users (1.12, [0.9–1.4] for
men and 1.09, [0.8–1.5] for women). Reis et al. [40] per-
history

formed a second CARDIA subanalysis to examine the associ-

CAD

Yes
No

No
No

No

ation between cumulative lifetime cannabis use and

cardiovascular mortality and found no significant association.
blood pressure; STD: ST-segment depression; STE: ST-segment elevation; THC: tetrahydrocannabinol or other cannabis metabolite.
STE V1-V2, Brugada type I

Level III studies

Diffuse T wave inversions

STE anterolateral leads

findings

STE II, III, aVF, V3-V6

There were several Level III retrospective studies, all of which

ECG

except one suggested an association of cannabis use with

acute coronary syndrome. The one dissenting study was by
STE V1-V4

Johnson-Sasso et al. [52] from 2018, a review of 3854 acute

myocardial infarction patients who were cannabis users (n ¼
1,273,897). No association between cannabis use and acute
myocardial infarction was detected (p ¼ .53). Interestingly, a
(mmHg)

potential benefit of cannabis was observed, in that the in-

DBP

95

114


hospital mortality rate was lower for cannabis users com-

pared to non-users (odds ratio 0.79, p ¼ .016), and cannabis
users were less likely to experience shock (odds ratio 0.74, p
¼ .001). The authors postulated this benefit may represent a
(mmHg)
SBP


122

184

younger population age of cannabis users with fewer cardio-

vascular disease risk factors. Other Level III studies of interest
include two by Jouanjus et al. [42,43] detailing cardiovascular
(years) Gender (bpm)
76

72

84


complications and deaths associated with acute cannabis

HR

use, with seven of 200 patients having myocardial infarction

Female

in their first study [42]. In their second study [43], there were
Male
Male
Male

Male

20 acute coronary syndrome cases and nine cardiac arrests

resulting in death out of 1979 patients. The authors noted
Age

62

36
22
30

63

this ratio was much higher than the general population of

their region, which had incidence rates for acute coronary
syndrome and coronary deaths of 57/100,000 among men
2018 Wengrofsky et al. [104]

and 13/100,000 among women [43].

2018 Kariyanna et al. [102]

2019 Richards et al. [105]

2018 Opolski et al. [103]

The risk in younger patients was highlighted in two stud-

2018 Khalid et al. [101]
Authors

ies: Thankavel et al. [44] detailed seven pediatric patients of

Table 2. Continued.

32 total with vasospasm and myocardial infarction associated

indicates fatality

with prior cannabis use, followed by a study of 333 teen-

agers with acute myocardial infarction by Ramphul et al.
[55], who calculated an odds ratio of 5.03 [3.5–7.3] for myo-
Year

cardial infarction after cannabis use. In a large-scale study by

a
8 J. RICHARDS ET AL.
Desai et al. (n ¼ 35,771) [46], the odds of developing myo-
cardial infarction increased by 8% in patients with recre-
ational cannabis use.
Lorenz et al. [48] studied 558 male patients with human
immunodeficiency virus infection and found heavy cannabis
users had an odds ratio of 2.5 [1.3–5.1] for cardiovascular
events compared to those who were occasional or non-users,
which was independent from tobacco use. Abouk and
Adams [50] analyzed data from the U.S. National Vital
Statistics System for 1990–2014 and determined states with
more liberal rules on dispensing cannabis showed higher car-
diac-related mortality rates for both genders that increased
with age. De Filippis et al. [51] studied patients younger than
50-years-old without risk factors such as diabetes, dyslipide-
mia, or hypertension who experienced a type I myocardial
infarction. Among 2097 patients, 125 were cannabis users
and had higher all-cause mortality and morbidity compared
to non-users. Out-of-hospital cardiac arrest was more com-
mon in cannabis users. Kalla et al. [53] identified 31,397
patients who used cannabis during the years 2009–2010, and
after adjusting for other risk factors such as tobacco smok-
ing, determined the use of cannabis remained an independ-
ent predictor of acute cardiovascular events, in particular
heart failure.
Case series and reports
The inclusion of Level IV and V case series and reports
enabled analysis of demographic, hemodynamic, and post-
mortem findings in cannabis users with acute coronary syn-
drome (Table 2). We were also able to assess electrocardio-
gram, angiography, and echocardiography characteristics to
determine if there were unique patterns.
There were 51 case series (Level IV) and case reports
(Level V) with 62 subjects (Table 2) [19,56–105]. Only six
cases were female (10%). Average age of the Level IV and V
cases was 31 ± 12 years, with a range of 15 to 63 years. Only
smoking, and not oral cannabis use was reported in any of
the cases. In only four cases (7%) was there a known history
of coronary arterial disease. The reported maximum heart
rate was 88 ± 21 bpm, systolic blood pressure was 125 ± 32
mmHg, and diastolic blood pressure was 80 ± 17 mmHg.
With regard to reported vital signs, it was often impossible
to ascertain if these were taken upon arrival or later unless
explicitly stated in the article. Although acute tachycardia
and hypertension have been shown to occur directly after
cannabis smoking, this was rarely reported.
Elevation of the ST-segment was documented on 37
(60%) electrocardiograms [19,58,59,64,66–69,73–79,81–85,87,
89–91,95–98,100,102–105]. The most common angiographic
finding was left anterior descending coronary arterial occlu-
sion and/or stenosis in 22 (35%) patients [64,66,67,69,74,76,
79,82, 84–87,89, 91,97,103–105]. Concomitant cardiomyopathy
was described in 21 (34%) cases [19,56,71,76,82,83,88,90,91,
93,95–98,100,101,104].
There were 14 (23%) deaths in subjects who were canna-
bis users [57,61,82,88,92,96,98]. In this subgroup cannabis
use was determined from toxicological screening in 11 cases
and from patient history in the remaining three cases.
Average age was 34 ± 10 years with a range of 17 to 52
years, and there was only one female case (7%). Only two
cases (14%) had a known history of coronary artery disease.
Autopsy revealed acute myocardial infarction in nine cases,
coronary artery disease in six cases, and cardiomyopathy in
eight cases. Ethanol was detected at non-toxic levels in 2
cases. The authors of these case series and reports empha-
sized the adverse effects of cannabis as a potential etiology
for acute coronary syndrome, and ultimately death.
Discussion
Cannabis use has been associated with an increased risk of
acute coronary syndrome in 25 of 28 published epidemio-
logical studies and three of five systematic reviews. The two
dissenting systematic reviews were a narrowly-focused study
of outcomes after myocardial infarction that included only
four articles and was inconclusive [29], and a broadly-focused
study of 24 articles concluding the published evidence was
weak [30]. This association is supported by plausible physio-
logical mechanisms and a large number of published case
series and reports. Yet, it is impossible to ascribe acute can-
nabis use as the sole precipitant of acute coronary syndrome
based on these cases and the higher-level studies included
in this review. The presence of known or occult coronary
artery disease, cardiomyopathy, hypertension, dysrhythmia,
stress, exercise, cold air, or sudden vasospasm could have
resulted in acute coronary syndrome. With regard to canna-
bis smoking, the act of inhaling and breath-holding may lead
to a Valsalva maneuver, with increased intrathoracic pressure,
systolic blood pressure, and tachycardia, and decreased cor-
onary artery blood flow, venous return, and cardiac output
[106]. Cannabis users may also smoke tobacco, which is a
risk factor for acute coronary syndrome.
Clinicians and nurses should inquire about acute and
chronic cannabis use by their patients presenting with chest
pain, dysrhythmia, and/or unexplained syncope. Information
regarding this possible deleterious association should be
imparted to patients who are chronic or occasional users of
recreational or medical cannabis. As the use of cannabis con-
tinues to increase yearly, high quality prospective studies are
greatly needed to further define the role of cannabis in the
precipitation of acute coronary syndrome as well as other
cardiovascular diseases.
Limitations
Our review has several potential limitations. No large,
randomized, multi-center studies regarding the association of
cannabis use with acute coronary syndrome exist. As such,
there was a significant risk of bias associated with the design
or methodology of the identified studies, which could have
influenced the results of our review. Publication bias is a
concern, and in anticipation of this, we used a broad search
strategy and a low inclusion threshold for any relevant publi-
cations. We also included retrospective studies, case series,
and case reports to be as comprehensive as possible.

No search strategy, however thorough, can guarantee all
relevant publications are identified.
The significant differences in the studies with regard to
protocol, subject selection, precise cannabis exposure time
frame, and measured outcomes precluded a meta-analysis.
Bias of the reviewers is also a potential limitation, and as
such we chose to pay special attention to any studies or
reports which detailed no detriment or potential benefit
associated with cannabis use. Another limitation was that
route of administration and specific type of cannabis was
not defined in many of the publications included in this
review. For articles which did not specify route and type of
cannabis use, we assumed a default of smoked phytogenic
cannabis, and articles which detailed non-phytogenic, non-
smoked cannabis were excluded. This represents another
limitation as recall bias, as patient history regarding cannabis
use was equated with qualitative or quantitative toxicological
testing.
It is also important to note that the current THC potency
of phytogenic cannabis is significantly higher than past due
to cultivation practices and chemical isolation [107]. This
increasing ratio of THC relative to other cannabinoids such
as CBD, otherwise known as the “entourage effect,” may also
be a factor with regard to potential benefit or harm [108].
Finally, the preponderance of male subjects may not accur-
ately reflect the cardiovascular risks for females.
Conclusions
There were five Level I systematic reviews, 14 Level II studies
with 83,961 subjects, and 14 Level III studies with 457,495
subjects. All but five Level I–III publications highlighted an
increased risk of both acute coronary syndrome and chronic
cardiovascular disease associated with cannabis use.
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
John R. Richards http://orcid.org/0000-0003-1251-3877
Joshua W. Elder http://orcid.org/0000-0001-7422-5825
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