Cardiol Ther (2018) 7:45–59 https://doi.org/10.1007/s40119-017-0102-x REVIEW Cardiovascular Complications of Marijuana and Related Substances: A Review . . . . Amitoj Singh Sajeev Saluja Akshat Kumar Sahil Agrawal . . Munveer Thind Sudip Nanda Jamshid Shirani Received: August 21, 2017 / Published online: December 7, 2017 The Author(s) 2017. This article is an open access publication established cardiovascular disease are at even ABSTRACT higher danger of such events following expo- sure to cannabis. The pathophysiological basis The recreational use of cannabis has sharply of these events is not fully understood and increased in recent years in parallel with its likely encompasses a complex interaction legalization and decriminalization in several between the active ingredients (particularly the countries. Commonly, the traditional cannabis major cannabinoid, D -tetrahydrocannabinol), has been replaced by potent synthetic and the endo-cannabinoid system, autonomic cannabinoids and cannabimimetics in various nervous system, as well as other receptor and forms. Despite overwhelming public perception non-receptor mediated pathways. Other com- of the safety of these substances, an increasing plicating factors include opposing physiologic number of serious cardiovascular adverse events effects of other cannabinoids (predominantly have been reported in temporal relation to cannabidiol), presence of regulatory proteins recreational cannabis use. These have included that act as metabolizing enzymes, binding sudden cardiac death, vascular (coronary, cere- molecules, or ligands, as well as functional bral and peripheral) events, arrhythmias and polymorphisms of target receptors. Tolerance to stress cardiomyopathy among others. Many of the effects of cannabis may also develop on the victims of these events are relatively young repeated exposures at least in part due to men with few if any cardiovascular risk factors. receptor downregulation or desensitization. However, there are reasons to believe that older Moreover, effects of cannabis may be enhanced individuals and those with risk factors for or or altered by concomitant use of other illicit drugs or medications used for treatment of Enhanced content To view enhanced content for this established cardiovascular diseases. Regardless article go to http://www.medengine.com/Redeem/ of these considerations, it is expected that the 68FCF06068C10492. current cannabis epidemic would add signiﬁ- Electronic supplementary material The online cantly to the universal burden of cardiovascular version of this article (https://doi.org/10.1007/s40119- diseases. 017-0102-x) contains supplementary material, which is available to authorized users. A. Singh S. Saluja A. Kumar S. Agrawal Keywords: Autonomic nervous system; M. Thind S. Nanda J. Shirani (&) Cannabis; Endocannabinoid system; Department of Cardiology, St. Luke’s University Marijuana; Myocardial infarction; Stress Health Network, Bethlehem, PA, USA e-mail: email@example.com 46 Cardiol Ther (2018) 7:45–59 cardiomyopathy; Stroke; Tetrahydrocannabinol; arteritis’’, ‘‘stress cardiomyopathy’’ and ‘‘ar- Vasculopathy rhythmia’’. All referenced material in selected articles were also reviewed carefully for poten- tially relevant reports. The results were thor- INTRODUCTION oughly examined for accuracy of content. The available literature was then categorized Cannabis sativa, the plant known as the original according to both relevance and the clarity of marijuana, was likely ﬁrst cultivated in Central the presented data. Care was particularly taken Asia, and subsequently brought to other parts of to avoid inclusion of studies with designs that the world. Currently, cannabis grows naturally deviated from usual manners that cannabis is in many countries and is also cultivated indoors used recreationally. The ﬁnal count of the through the use of hydroponic systems and manuscripts and documents used was 135 that artiﬁcial lighting [1, 2]. The plant has been long included 55 case reports, eight case series, 20 used as a medicinal herb or as a mood altering human experimental studies, 11 animal or substance . More recently, a rise in recre- ex vivo studies, 20 databases or guidelines as ational use of cannabis has paralleled that of well as 22 review articles. legislations that have legalized or decriminal- ized the possession, sales, and cultivation of the Compliance with Ethics Guidelines plant . According to the United Nations ofﬁce on drugs and crime, the global recre- This article does not contain any new studies ational use of cannabis increased by 27% from with human or animal subjects performed by 1998 to 2009 . In 2014, it was estimated that any of the authors. * 183 million people use cannabis worldwide with a steady rise since 2007 . Today, can- nabis is the most frequently used psychoactive NATURAL FORMS OF CANNABIS substance after alcohol and tobacco . The recreational cannabis ‘‘epidemic’’ has been In general, three naturally growing strains of accompanied by an increased number of case Cannabis (sativa, indica, and ruderalis) have been reports of serious cardiovascular complications recognized although interbreeding has pro- from across the globe. A recent systematic duced many more ‘‘hybrid’’ strains of the plants. review has identiﬁed 116 such cases published These strains differ in the content and propor- between January 2011 and March 2016 . In tion of the two best recognized active ingredi- the context of the rising popularity of recre- ents, namely D -tetrahydrocannabinol (THC) ational cannabis (and its synthetic analogues) and cannabidiol (CBD). Additionally, the effects we aim to review potential cardiovascular of various cannabis strains may differ based on adverse events associated with the use of these the varying concentration and composition of substances. Furthermore, the potential patho- terpene resins . The sativa strain contains the physiological mechanisms responsible for the highest level of THC, the psychoactive most serious cardiovascular events in users of cannabinoid that produces the euphoric effect cannabis are discussed. and has a relatively low content of CBD, the cannabinoid that may mitigate the euphoric and psychotropic effects of THC. The leaves and METHODS buds of the female plants have the highest content of THC and can be dried for smoking or To prepare this literature review, we performed made into other forms of consumable cannabis searches of PUBMED, MEDLINE and EMBASE including edibles, waxes, oils, liquid incense or databases using the phrases ‘‘marijuana’’, ‘‘can- vapor for both medical and recreational uses. nabis’’, ‘‘cannabinoids’’, ‘‘THC’’, ‘‘D -tetrahydro- Medically, cannabis has been used effectively cannabinol’’, ‘‘cardiovascular disease’’, ‘‘cardiac for treatment of otherwise refractory nausea disease’’, ‘‘heart disease’’, ‘‘stroke’’, ‘‘cannabis and vomiting following chemotherapy and Cardiol Ther (2018) 7:45–59 47 neuropathic pain associated with advanced SYNTHETIC CANNABINOIDS neurologic disorders and cancer, among others AND CANNABIMIMETICS [2, 7, 8]. It is important to note that in the United States, cannabis (marijuana) is still listed Synthetic THC compounds, dronabinol and by the Drug Enforcement Administration as a nabilone, have been marketed as capsules in the Schedule I substance, alongside hallucinogens United States since 1985 for treatment of nau- and heroin, according to the section 202 of the sea, vomiting and weight loss associated with Controlled Substances Act of 1970. Schedule I cancer chemotherapy and acquired immunod- drugs are substances with high potential for eﬁciency syndrome. A liquid form of dronabi- abuse, no currently established medical use, and nol has also been approved recently as an oral no accepted safety for use under medical solution by the United States Food and Drug supervision. Despite this, 42 states and the Administration for anorexia and weight loss District of Columbia have either legalized or associated with acquired immunodeﬁciency decriminalized medical uses of cannabis and syndrome and refractory nausea/vomiting related approved medications. associated with cancer chemotherapy. Illegally An important consideration in the uses of manufactured synthetic cannabinoids and cannabis has been the unpredictability of the cannabimimetics have been also mass produced dosage of the active ingredients of variously for recreational uses and have found appeal prepared forms. Accordingly, similar amounts among users because they are higher in potency of dried leaves/ﬂowers, waxes/oils, or ingestible and conventional drug screening tests are forms of cannabis may contain vastly different unable to identify them. These substances quantities of active compounds. Additionally, include a family of more than 700 synthetic the route of administration may inﬂuence the compounds made by various chemical alter- absorption, bioavailability and serum concen- ations of THC to enhance its afﬁnity for tration of the active compounds. In a study of cannabinoid receptors, augment downstream healthy volunteers, plasma THC concentration signal transduction and increase its duration of and clinical effects were similar after smoking action. Many synthetic compounds also have and intravenous injection while ingestion highly active metabolites . Synthetic resulted in less predictable, delayed and lower cannabinoids are commonly sprayed onto dried peak plasma THC concentration . Similar leaves and marketed under various names trends have been found for the psychotropic including Spice and K2. effects of inhaled versus orally ingested THC . The potential physiologic effects of THC are also affected by concomitant use of other CARDIOVASCULAR PHYSIOLOGIC illicit drugs, smoking tobacco, and drinking EFFECTS OF CANNABINOIDS alcohol. The interaction of cannabis with med- ications used for prevention or treatment of The physiologic effects of cannabis are primarily cardiovascular diseases is largely unknown. mediated through the interaction of THC with There has been an ongoing attempt to stan- the endocannabinoid system, an endogenous dardize the shelf life, dosage and bioavailability signaling network involved in a wide range of of the active compounds contained in naturally processes including endothelial function, derived medical cannabis preparations. One metabolism, inﬂammation, and immunity. At such preparation, nabiximols, a botanical least 2 G protein-coupled membrane cannabi- metered dose oral spray that contains both THC noid receptors, CBR1 and CBR2, have been and CBD, has been approved in several coun- identiﬁed. CBR1 is extensively expressed within tries for treatment of spasticity, pain, and uri- the central, peripheral sensory and autonomic nary dysfunction in multiple sclerosis . nervous systems and is the primary target of 48 Cardiol Ther (2018) 7:45–59 THC. A signiﬁcant proportion of the cardiovas- cannabinoids used, duration of exposure and cular effects of cannabinoids are thus mediated other external and physiological factors that through activation of the sympathetic nervous affect vascular tone. Under controlled experi- system, as well as inhibition of the parasympa- mental conditions, cannabis is believed pre- thetic autonomic nervous system . Smoking dominantly to cause an acute vasodilatory cannabis results in an immediate increase in response possibly through activation of tran- heart rate that may last more than 1 h after sient receptor potential ankyrin type-1 exposure . This is followed by a substantial (TRPA1) ion channels on perivascular sensory rise in serum norepinephrine level at 30 min neurons . However, this arteriolar vasodi- . Further support for the role of CBR1-me- lation is not universal to all vascular beds as diated modulation of the autonomic nervous vasoconstriction has been seen in the coro- system in the chronotropic response to exoge- nary, cerebral and peripheral arterial systems nous cannabinoids is provided by studies that and has been directly responsible for many have demonstrated effectiveness of pretreat- instances of acute myocardial infarction (AMI), ment with propranolol, atropine, and rimona- stroke and peripheral arteriopathy [15, 31]. It bant (an inverse agonist of CBR1) in preventing has been shown that the contrasting effect of such a response [12, 14–17]. Additionally, cannabinoids (including THC) in various vas- inhibition of the parasympathetic activity is cular territories is primarily due to differing suggested by an exaggerated heart rate response endothelial vasodilator mechanisms that exist to atropine following cannabis smoking . in these vascular beds [12, 32]. With respect to Acute exposure to cannabis may also result in coronary circulation, myocardial blood ﬂow, as elevation of supine systolic blood pressure assessed by N-ammonia positron emission [18, 19] and may induce atrial ﬁbrillation tomographic imaging during cold pressor test [20–22]. An epidemiological study has demon- and after pharmacologic vasodilation, is strated an association between elevated systolic shown to correlate inversely with circulating pressure and recent use of cannabis . Along plasma levels of endocannabinoids . In with tachycardia and hypertension [12, 24, 25], addition, cannabis has been shown to be a enhanced left ventricular systolic function as potent source of cellular oxidative stress assessed by circumferential ﬁber shortening through formation of reactive oxygen species (primarily driven by tachycardia) has been . The latter may then contribute to reported following the use of cannabis . The pathogenesis of endothelial dysfunction and summative result of autonomic nervous system promote regional arterial vasospasm through modulation by cannabis is an increase in car- CBR1 receptor-mediated pathway while inhi- diac workload and myocardial oxygen demand. bition of CBR1 is associated with decreased For those who use cannabis by smoking, oxygen oxidative stress and improved endothelial delivery to the heart and other vital organs may function . also be compromised by an elevation in blood More recently, it was shown that THC carboxyhemoglobin levels . The impaired prolongs lipopolysaccharide-stimulated tissue myocardial oxygen demand to supply ratio fol- factor protein expression in activated mono- lowing cannabis smoking has been shown to cytes that results in a dose-dependent proco- reduce the time to onset of symptoms during agulant effect . This ex vivo observation exercise in patients with stable angina [25, 28]. has been supported by reports of thrombotic Ventricular ﬁbrillation and appropriate coronary artery occlusion in young individuals implantable cardioverter deﬁbrillator shock has without underlying atherosclerosis [36–38]. In been reported in a patient with ischemic car- addition, both CBR1 and CBR2 are present on diomyopathy shortly after smoking cannabis the cell membrane of human platelets and . exposure to THC is shown to increases the The direct effects of cannabis on regional surface expression of glycoprotein IIb–IIIa and and organ-level blood ﬂow is complex and P selectin in a concentration-dependent man- likely affected by type and dosage of ner . Researchers have further established Cardiol Ther (2018) 7:45–59 49 Fig. 1 Flow diagram demonstrating pathophysiologic negative inotropic effect on cardiomyocytes and together pathways to common major adverse cardiovascular events with catecholamine surge may precipitate stress cardiomy- reported in users of cannabis and related chemicals. opathy. For those individuals who use cannabis by Although non-receptor and non-endocannabinoid recep- smoking, elevation of blood carboxyhemoglobin levels tor-mediated pathways have been identiﬁed, most patho- may contribute to reduction in oxygen supply to vital logic effects of cannabis are mediated through CBR1. organs including the heart. AMI acute myocardial infarc- Autonomic nervous system is a major contributor to the tion; CBR1 cannabinoid receptor 1, CVA cerebrovascular pathogenesis of most complications while oxidative stress, accident, MVO myocardial oxygen consumption (de- hypercoagulability and increased platelet aggregation mand), O oxygen, ROS reactive oxygen species potentiate such effects. CBR1 activation also has a direct that cannabinoids exert their effects on pla- CARDIOVASCULAR telets through non-receptor mediated path- COMPLICATIONS ways as their effect persists in the presence of OF CANNABINOID USE cannabinoid receptor antagonists . Figure 1 summarizes the cardiovascular Adverse cardiovascular effects of cannabis have physiologic effects of cannabinoids based on been suspected for the last 45 years while the human studies and case reports of cardiovascu- last decade has witnessed a sharp rise in the lar events observed in temporal relation to reported incidence of such complications. marijuana use. Individual major adverse car- Between 2006 and 2010, 2% of all cannabis diovascular events are subsequently discussed in related events reported to the French Addic- more detail. Deviations from the scheme pro- tovigilance Network were cardiovascular in posed in Fig. 1 have been shown in animal nature . Furthermore, the cardiovascular studies and in some clinical trials that have used complication rate rose from 1.1% in 2006 to large doses of cannabinoids often administered 3.6% in 2010 and the mortality rate from those by unnatural routes. In addition, counter-regu- complications was 25% . Cannabis users latory mechanisms and tolerance to the effects presenting with cardiovascular emergencies are of cannabinoids exist and may play a role in often young and frequently have no other risk variable individual responses to these agents. factors for cardiovascular disease . These 50 Cardiol Ther (2018) 7:45–59 Table 1 Reported adverse cardiovascular events associated Table 1 continued with cannabis, synthetic cannabinoids and Vasculopathy cannabimimetics S54–S57 Cannabis arteritis Acute coronary syndrome S58 Migratory thrombophlebitis S1–S3 Coronary thrombosis without atherosclerosis S59 Renal artery dissection S4 Recurrent coronary thrombosis S60 Central retinal vein occlusion Acute myocardial infarction Fetal cardiovascular complications S5–S8 Non-fatal S61 Maternal use and single ventricle physiology S4 Fatal S62 Maternal use and transposition of great arteries S10–S12 Worsening of stable angina Paternal use and membranous ventricular septal S13–S18 Coronary vasospasm S63 defects S19 Recurrent coronary vasospasm S64 Intra-uterine growth retardation S20,S21 Coronary no reﬂow Miscellaneous Cerebrovascular disease S65 Rhabdomyolysis S22–S28 Ischemic stroke Superscript notations refer to references listed in Supple- S29 Recurrent stroke with re-challenge mentary Appendix 1 S30, S31 Stroke with posterior circulation predilection S32–S33 growing concerns have lead other researchers to Cerebral vasospasm call for a registry in the United States similar to S34, S35 Reversible cerebral vasoconstriction syndrome the efforts of the French Addictovigilance Net- work discussed above [43, 44]. The most com- Synthetic cannabinoid and acute cerebrovascular S36 monly reported cardiovascular complications of event cannabis use have ranged from acute coronary Congestive heart failure syndrome (ACS) to cardiac arrhythmias, stroke, S37, S38 peripheral arteriopathy, stress cardiomyopathy Transient left ventricular regional ballooning (SC) and sudden death (Table 1). Although S39 Acute congestive heart failure these adverse events are primarily reported in recreational users of cannabis they have also Synthetic cannabinoids and acute congestive heart S40, S41 been observed in those using the cannabis for failure medically approved reasons. S42 Diastolic dysfunction Rhythm disturbances Acute Coronary Syndrome S43 Asystole and atrioventricular block The risk of AMI increases nearly ﬁvefold within S44 Increase in premature ventricular contractions an hour of exposure to cannabis compared to S45 nonusers . The population-attributable fac- Ectopic atrial rhythm tor for triggering an AMI by cannabis was found S46, S47 Atrial ﬁbrillation to be relatively low in a meta-analysis of epi- S48 Ventricular tachycardia demiological studies published between 1960 S49 and 2010 . However, the growing burden of Ventricular ﬁbrillation cannabis use and availability of potent syn- S50–S53 Sudden cardiacdeath thetic cannabis will likely impact the overall risk of AMI attributable to cannabis. Cardiol Ther (2018) 7:45–59 51 Over the last four decades many case reports use has been linked to several adverse cardio- have temporally linked cannabis use to devel- vascular events, the evidence is strongest for opment of AMI . In some instances, reintro- ischemic stroke . Neurological symptoms duction of marijuana has also been associated were the most common reasons (44%) for hos- with recurrence of myocardial ischemia . pitalization of cannabis users in French health- Many, but not all, cannabis users presenting care facilities from 2004 to 2007 . with AMI have been young men with no pre- Additionally, ischemic stroke is the most com- existing coronary artery disease (CAD) and have monly reported adverse cardiovascular effect of had normal coronary angiograms [5, 48]. Toxi- cannabis use . In a study of young individuals cology in such cases has often been positive for (age 18–44 years) admitted with stroke and cannabis only [31, 47–56], although routine substance abuse, cannabis was associated with urine toxicology may be negative in those using ischemic but not hemorrhagic events, while synthetic cannabinoids [57–59]. The latter may amphetamines were associated with predomi- have led to signiﬁcant underestimation of the nantly hemorrhagic events . A general cannabinoid associated AMI in the young. The population survey of Australians aged pathophysiology of marijuana induced coro- 20–64 years (n = 7455), past year cannabis use nary events is shown in Fig. 1 and involves a was associated with a 2.3-fold higher risk of series of interactions that lead to increased cerebrovascular ischemic events after adjust- myocardial oxygen demand [60–64], reduced ment for covariates related to stroke including oxygen supply [28, 61, 64], and a pro-coagulant tobacco smoking . The risk was increased to  or pro-thrombotic [36–39] state. In many 4.7-fold if the participant used cannabis weekly instances, microvascular [54, 62] or epicardial or more often . Similar results were reported coronary artery spasm [55, 56, 63] in the from the United States Nationwide Inpatient absence of atherosclerotic coronary artery dis- Sample, where cannabis use was found to be an ease have been described. In other cases, acute independent predictor of acute stroke and coronary thrombosis in the absence of angio- associated with a 2.26-fold increased likelihood graphic atherosclerosis as conﬁrmed by of hospitalization with acute Ischemic stroke intravascular ultrasonography has been among those aged 25–34 years . responsible for AMI [36, 37]. An extreme case of Further support for a causal relationship thrombotic total occlusion of the left main between cannabis use and ischemic stroke requiring emergent coronary artery bypass graft comes from numerous case reports over the last surgery has also been reported . The three decades [73–75]. A recent series has threshold for precipitation of acute myocardial described 17 cases (age 15–63 years) of ischemic ischemia is likely lower in cannabis users with stroke temporally related to cannabis use . established atherosclerotic CAD [28, 64, 65]. In Among the latter, ﬁve individuals had recur- general, AMI in cannabis users may be associ- rence of cerebrovascular ischemic symptoms on ated with higher short-term mortality . The resuming cannabis use after hospital discharge latter may in part be related to the potential . Interestingly, the ischemic strokes showed delay in seeking medical attention in young a predilection (53%) for the posterior cerebral individuals with impaired judgement due to circulation . These observations have been drug use or to the analgesic effect of cannabis corroborated by other investigators [77, 78]. that may mask symptoms . Although atherosclerosis may be responsible for stroke in some cannabis users, the primary mechanism of stroke in this setting has been Cerebrovascular Disease reversible cerebrovascular spasm (RCVS) [79, 80]. RCVS is characterized by severe head- Reports of acute neurovascular events related to ache often associated with nausea, vomiting, cannabis use have appeared as early as 1964 photophobia, confusion and blurred vision and . A recent systemic review of the literature a ‘‘string and beads’’ appearance of cerebral has ﬁrmly concluded that although cannabis arteries on angiography . In a prospective 52 Cardiol Ther (2018) 7:45–59 study of 67 consecutive patients with angio- mellitus, hypertension, CAD, tobacco use, and graphically conﬁrmed RCVS, 32% showed pos- alcohol use . An association between can- itive toxicology for cannabis . In another nabis use and SC has been shown in case reports prospective study of acute ischemic stroke, [92, 98] and in hospitalized patients . multifocal narrowing of cerebral arteries (pre- Among the latter, cannabis use was found to be dominantly in posterior circulation) was highly an independent predictor of SC, particularly predictive of cannabis use . Reversibility of among younger men, after adjustment for other cerebral vasoconstriction has been demon- known risk factors for the disease . Impor- strated by angiography within days to months tantly, cannabis users with SC frequently suf- after cessation of cannabis use [82, 83]. It should fered from serious adverse events including be noted that similar to AMI, vasospasm is not cardiac arrest . the sole etiology of ischemic stroke in cannabis The pathophysiology of SC in cannabis users users. Transcranial Doppler has demonstrated remains poorly deﬁned although the associated persistently elevated cerebral vascular resistance catecholamine surge may be largely responsible in cannabis users even long after monitored for the association. However, evidence for a abstinence . In a study of 334 of young primary role of the endocannabinoid system in (age\45 years) patients admitted with canna- pathogenesis of stress cardiomyopathy has been bis related stroke, intracranial arterial stenosis mounting. As discussed previously, cannabi- was demonstrated in 45% . The etiology of noids exert cardiovascular effects and a hyper- stroke in the remaining patients was deter- adrenergic state through receptor-mediated and mined to be cardio-embolic (14%), presumed receptor-independent mechanisms paradoxical embolism through an isolated [12, 95, 100]. Endogenous cannabinoids have a patent foramen ovale (3%), carotid artery dis- CBR1-mediated negative inotropic effect on section or atherosclerosis (10%), hypercoagula- cardiac muscle  and inhibition of CBR1 with ble state (3%) or small vessel disease (2%) while rimonabant results in prevention of myocardial the etiology of stroke remained undetermined dysfunction and myocyte apoptosis after expo- in nearly one-fourth of the patients . Other sure to doxorubicin . It should be noted that potential causes of stroke in cannabis users are the presence of pre-existing myocardial dys- cardioembolic events associates with AMI or function may particularly predispose individu- atrial ﬁbrillation [86, 87]. Left ventricular apical als to deterioration of left ventricular systolic thrombus has been reported as the etiology of function particularly with the use of potent stroke in a young patient with AMI following synthetic cannabinoids . synthetic cannabinoid use . Rhythm Disturbances and Sudden Cardiac Left Ventricular Systolic Dysfunction Death The endocannabinoid system is implicated in An association between cannabis use and pal- myocardial stunning associated with acute pitation was suggested by an epidemiologic neurological events, stress (takotsubo) car- study reported nearly three decades ago . A diomyopathy, sepsis and hemorrhagic shock multitude of case reports have also documented [89–92]. Cannabinoids are also shown to reduce a range of rhythm abnormalities in cannabis myocardial contractility through CBR1-medi- users from sinus tachycardia to ectopic atrial or ated effects [93, 94]. Myocardial dysfunction ventricular rhythms, and atrial or ventricular may also result from persistent tachycardia, ﬁbrillation [20–22, 29, 103–110]. Logically, atrial ﬁbrillation or induction of ischemia in these cardiac tachyarrhythmias are explainable those with pre-existing CAD [12, 21, 25, 95, 96]. by the presence of a hyperadrenergic state fol- Cannabis use is shown to be an independent lowing exposure to cannabis and related sub- predictor of hospitalization with heart failure stances. In fact, electrophysiology study after after adjustment for age, gender, diabetes cannabis use has demonstrated increased Cardiol Ther (2018) 7:45–59 53 burden of inducible premature ventricular and cannabimimetics has further complicated contractions . Myocardial ischemia caused the ﬁeld. Although seriously underestimated by microvascular spasm, AMI, or pre-existing and underreported, cardiovascular adverse CAD may accompany serious ventricular events are being described at an alarming rate in arrhythmias and may result in dizziness, syn- users of cannabis and its related chemicals. cope, cardiac arrest or sudden cardiac death Many of these serious events have occurred in [29, 103–110, 112]. children and young adults who are increasingly Atrial ﬁbrillation has been reported in can- driven to use these substances due to the false nabis users as young as 14 years old and without notion of their safety and rapidly moving structural heart disease shortly after smoking decriminalization and legalization processes. cannabis [22, 113]. Cannabis use may also be The pathophysiology of these adverse cardio- the sole precipitating factor for atrial ﬁbrillation vascular events in temporal relation to cannabis in the younger (\45 years old) individuals and is far from established. Yet, the current evidence recurrence may occur upon repeated exposure points to a major role for the endocannabinoid . Atrial ﬁbrillation following cannabis use system and its interaction with the autonomic may be complicated by adverse events due to nervous system. Human data is generally deﬁ- delayed recognition of the condition in young, cient and most available studies in humans otherwise healthy, individuals with altered have been performed decades ago with mental status . methodology and resources of the time. While well conducted controlled studies are sorely needed in this area, current data should alert Cannabis Arteritis physicians and legislators across the world to the potentially harmful effects of unregulated Cannabis vasculopathy was ﬁrst described use of cannabis in children, young adults and nearly seven decades ago . Since then, a those with underlying cardiovascular risk fac- large number of cases [116–119] and two com- tors or established heart disease. prehensive reviews [120, 121] have appeared in the literature. The disease is clinically indistin- guishable from thromboangiitis obliterans ACKNOWLEDGEMENTS [122–127], but tends to occur at an earlier age in those who use both cannabis and tobacco . The typical angiographic appearance is that of Funding. No funding or sponsorship was segmental narrowing of distal arteries with received for this study or publication of this minimal if any collateral vessels [127–129]. article. Subacute and progressive ischemia of upper and lower extremities affected by arteritis may then Authorship. All named authors meet the lead to serious complications including tissue International Committee of Medical Journal necrosis and gangrene with worsening during Editors (ICMJE) criteria for authorship for this periods of heavy cannabis use . Other manuscript, take responsibility for the integrity vascular complications of cannabis use have of the work as a whole, and have given ﬁnal included migratory thrombophlebitis  and approval for the version to be published. renal artery dissection . A rare form of vasculopathy involving occlusion of the central Disclosures. A Singh, S. Saluja, A. Kumar, S. retinal vein has also been reported . Agrawal, M. Thind, S. Nanda and J. Shirani have nothing to disclose. CONCLUSIONS Compliance with Ethics Guidelines. This article does not contain any new studies with Cannabis use has rapidly reached epidemic human or animal subjects performed by any of proportions in the world. Appearance of highly the authors. potent and unregulated synthetic cannabinoids 54 Cardiol Ther (2018) 7:45–59 clinical effects after oral and intravenous adminis- Open Access. This article is distributed tration and smoking. Clin Pharmacol Ther. under the terms of the Creative Commons 1980;28:409–16. Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/ 10. Grotenhermen F. Pharmacokinetics and pharma- codynamics of cannabinoids. Clin Pharmacokinet. by-nc/4.0/), which permits any noncommer- 2003;42:327–60. cial use, distribution, and reproduction in any medium, provided you give appropriate credit 11. Gurney SMR, Scott KS, Kacinko SL, Presley BC, to the original author(s) and the source, provide Logan BK. Pharmacology, toxicology, and adverse effects of synthetic cannabinoid drugs. Forensic Sci a link to the Creative Commons license, and Rev. 2014;26:53–78. indicate if changes were made. 12. Benowitz NL, Rosenberg J, Rogers W, Bachman J, Jones RT. Cardiovascular effects of intravenous delta-9-tetrahydrocannabinol: autonomic nervous REFERENCES mechanisms. Clin Pharmacol Ther. 1979;25:440–6. 13. Gash A, Karliner JS, Janowsky D, Lake CR. Effects of 1. United Nations Ofﬁce on Drugs and Crime smoking marihuana on left ventricular performance (UNODC). World drug report 2016. New York: and plasma norepinephrine studies in normal men. United Nations Publication; 2016 [Accessed 26 July Ann Intern Med. 1978;89:448–52. 2017] p. 174. http://www.unodc.org/doc/wdr2016/ WORLD_DRUG_REPORT_2016_web.pdf. 14. Kanakis C Jr, Pouget JM, Rosen KM. The effects of delta-9-tetrahydrocannabinol (cannabis) on cardiac 2. Iversen LL. The science of marijuana. Br J Clin performance with and without beta blockade. Cir- Pharmacol. 2009;67:268. culation. 1976;53:703–7. 3. Center for Behavioral Health Statistics and Quality. 15. Beaconsﬁeld P, Ginsburg J, Rainsbury R. Marihuana 2015 National survey on drug use and health: smoking: cardiovascular effects in man and possible detailed tables prevalence estimates. 2016. https:// mechanisms. M Engl J Med. 1972;287:209–12. www.samhsa.gov/data/sites/default/ﬁles/NSDUH- DetTabs-2016/NSDUH-DetTabs-2016.pdf. 16. Sulkowski A, Vachon L, Rich E. Propranolol effects on acute marihuana intoxication in man. Psy- 4. Substance Abuse and Mental Health Services chopharmacology. 1977;52:47–53. Administration. Results from the 2011 national survey on drug use and health: summary of national 17. Huestis MA, Boyd SJ, Heishman SJ, Preston KL. ﬁndings, NSDUH series H-44, HHS publication no. Single and multiple doses of rimonabant antagonize (SMA) 12-4713. Rockville, Maryland: Substance acute effects of smoked cannabis in male cannabis Abuse and Mental Health Services Administrations, users. Psychopharmacology. 2007;194:505–15. 18. Karschner EL, Darwin WD, McMahon RP, Liu F, 5. Jouanjus E, Raymond V, Lapeyre-Mestre M, Wolff V. Wright S, Goodwin RS, et al. Subjective and physi- What is the current knowledge about the cardio- ological effects after controlled Sativex and oral vascular risk for users of cannabis-based products? A THC administration. Clin Pharmacol Ther. systematic review. Curr Atheroscler Rep. 2011;89:400–7. 2017;19:26. 19. Jicha CJ, Lofwall MR, Nuzzo PA, Babalonis S, Elayi 6. Booth JK, Page JE, Bohlmann J. Terpene synthases SC, Walsh SL. Safety of oral dronabinol during from Cannabis sativa. PLoS One. 2017;12:e0173911. opioid withdrawal in humans. Drug Alcohol Depend. 2015;157:179–83. 7. Koppel BS, Brust JC, Fife T, Bronstein J, Youssof S, Gronseth G, Gloss D. Efﬁcacy and safety of medical 20. Charbonney E, Sztajzel JM, Poletti PA, Rutschmann marijuana in selected neurologic disorders. Report O. Paroxysmal atrial ﬁbrillation after recreational of the Guideline Development Subcommittee of the marijuana smoking: another ‘‘holiday heart’’? Swiss American Academy of Neurology. Neurology. Med Wkly. 2005;135:412–4. 2014;82:1556–63. 21. Kosior DA, Filipiak KJ, Stolarz P, Opolski G. Parox- 8. Iversen L. Cannabis and the brain. Brain. ysmal atrial ﬁbrillation following marijuana intox- 2003;126:1252–70. ication: a two-case report of possible association. Int J Cardiol. 2001;78:183–4. 9. Ohlsson A, Lindgren JE, Wahlen A, et al. Plasma delta-9 tetrahydrocannabinol concentrations and Cardiol Ther (2018) 7:45–59 55 22. Singh GK. Atrial ﬁbrillation associated with mari- 35. Williams JC, Klein TW, Goldberger BA, Sleasman juana use. Pediatr Cardiol. 2000;21:284. JW, Mackman N, Goodenow MM. D(9)-Tetrahy- drocannabinol (THC) enhances lipopolysaccharide- 23. Ponto LL, O’Leary DS, Koeppel J, et al. Effect of stimulated tissue factor in human monocytes and acute marijuana on cardiovascular function and monocyte-derived microvesicles. J Inﬂamm (Lond). central nervous system pharmacokinetics of 2015;12:39. (15) [ O]water: effect in occasional and chronic users. J Clin Pharmacol. 2004;44:751–66. 36. Dahdouh Z, Roule V, Lognone T, Sabatier R, Grollier G. Cannabis and coronary thrombosis: what is the 24. Alshaarawy O, Elbaz HA. Cannabis use and blood role of platelets? Platelets. 2012;23:243–5. pressure levels: United States National Health and Nutrition Examination Survey, 2005–2012. J Hyper- 37. Hodcroft CJ, Rossiter MC, Buch AN. Cannabis-as- tens. 2016;34:1507–12. sociated myocardial infarction in a young man with normal coronary arteries. J Emerg Med. 25. Prakash R, Aronow WS, Warren M, et al. Effects of 2014;47:277–81. marihuana and placebo marihuana smoking on hemodynamics in coronary disease. Clin Pharmacol 38. Velibey Y, Sahin S, Tanık O, Keskin M, Bolca O, Eren M. Ther. 1975;18:90–5. Acute myocardial infarction due to marijuana smok- inginayoungman:guiltyshould not be underesti- 26. Tashkin DP, Levisman JA, Abbasi AS, Shapiro BJ, mated. Am J Emerg Med. 2015;33:1114.e1–3. Ellis NM. Short-term effects of smoked marihuana on left ventricular function in man. Chest. 39. Deusch E, Kress HG, Kraft B, Kozek-Langenecker SA. 1977;72:20–6. The procoagulatory effects of delta-9-tetrahydro- cannabinol in human platelets. Anesth Analg. 27. Wu TC, Tashkin DP, Djahed B, Rose JE. Pulmonary 2004;99:1127–30. hazards of smoking marijuana as compared with tobacco. N Engl J Med. 1988;318:347–51. 40. Brantl SA, Khandoga AL, Siess W. Mechanism of platelet activation induced by endocannabinoids in 28. Aronow WS, Cassidy J. Effect of marihuana and blood and plasma. Platelets. 2014;25:151–61. placebo-marihuana smoking on angina pectoris. N Engl J Med. 1974;291:65–7. 41. Jouanjus E, Lapeyre-Mestre M, Micallef J. Cannabis use: signal of increasing risk of serious cardiovas- 29. Baranchuk A, Johri AM, Simpson CS, Methot M, cular disorders. J Am Heart Assoc. 2014;3:e000638. Redfearn DP. Ventricular ﬁbrillation triggered by marijuana use in a patient with ischemic car- 42. Lindsay AC, Foale RA, Warren O, Henry JA. Can- diomyopathy: a case report. Cases J. 2008;1:373. nabis as a precipitant of cardiovascular emergencies. Int J Cardiol. 2005;104:230–2. 30. Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Ho¨gesta¨tt ED, Meng ID, Julius D. 43. Rezkalla S, Kloner RA. Recreational marijuana use: is Mustard oils and cannabinoids excite sensory nerve it safe for your patient? J Am Heart Assoc. ﬁbres through the TRP channel ANKTM1. Nature. 2014;3:e000904. 2004;427:260–5. 44. Rezkalla S, Stankowski R, Kloner RA. Cardiovascular 31. Dines AM, Wood DM, Galicia M, Yates CM, Hey- effects of marijuana. J Cardiovasc Pharmacol Ther. erdahl F, Hovda KE, et al. Presentations to the 2016;21:452–5. emergency department following cannabis use—a multi-centre case series from ten European coun- 45. Mittleman MA, Lewis RA, Maclure M, Sherwood JB, tries. J Med Toxicol. 2015;11(4):415–21. Muller JE. Triggering myocardial infarction by marijuana. Circulation. 2001;103:2805–9. 32. O’Sullivan SE, Kendall DA, Randall MD. Further characterization of the time-dependent vascular 46. Nawrot TS, Perez L, Ku¨nzli N, Munters E, Nemery B. effects of delta9-tetrahydrocannabinol. J Pharmacol Public health importance of triggers of myocardial Exp Ther. 2006;317:428–38. infarction: a comparative risk assessment. Lancet. 2011;377:732–40. 33. Quercioli A, Pataky Z, Vincenti G, et al. Elevated endocannabinoid plasma levels are associated with 47. Safaa AM, Markham R, Jayasinghe R. Marijuana-in- coronary circulatory dysfunction in obesity. Eur duced recurrent acute coronary syndrome with Heart J. 2011;32:1369–78. normal coronary angiograms. Drug Alcohol Rev. 2012;31:91–4. 34. Lipina C, Hundal HS. Modulation of cellular redox homeostasis by the endocannabinoid system. Open 48. Caldicott DG, Holmes J, Roberts-Thomson KC, Biol. 2016;6:150276. Mahar L. Keep off the grass: marijuana use and 56 Cardiol Ther (2018) 7:45–59 acute cardiovascular events. Eur J Emerg Med. 62. Rezkalla SH, Sharma P, Kloner RA. Coronary no-ﬂow 2005;12:236–44. and ventricular tachycardia associated with habitual marijuana use. Ann Emerg Med. 2003;42:365–9. 49. Tatli E, Yilmaztepe M, Altun G, et al. Cannabis-in- duced coronary artery thrombosis and acute ante- 63. Basnet S, Mander G, Nicolas R. Coronary vasospasm rior myocardial infarction in a young man. Int J in an adolescent resulting from marijuana use. Cardiol. 2007;120:420–2. Pediatr Cardiol. 2009;30:543–5. 50. Cappelli F, Lazzeri C, Gensini GF, et al. Cannabis: a 64. Aronow WS, Cassidy J. Effect of smoking marihuana trigger for acute myocardial infarction? A case report. and of a high-nicotine cigarette on angina pectoris. J Cardiovasc Med (Hagerstown). 2008;9:725–8. Clin Pharm Therap. 1975;17:549–54. 51. Yurtdas¸ M, Aydın MK. Acute myocardial infarction 65. Gottschalk LA, Aronow WS, Prakash R. Effect of in a young man; fatal blow of the marijuana: a case marijuana and placebo-marijuana smoking on psy- report. Korean Circ J. 2012;42:641–5. chological state and on psycho-physiological car- diovascular functioning in anginal patients. Biol 52. Pratap B, Korniyenko A. Toxic effects of marijuana Psychiatry. 1977;12:255–66. on the cardiovascular system. Cardiovasc Toxicol. 2012;12:143–8. 66. Mukamal KJ, Maclure M, Muller JE, Mittleman MA. An exploratory prospective study of marijuana use and mortality following acute myocardial infarc- 53. Arora S, Goyal H, Aggarwal P, Kukar A. ST-segment tion. Am Heart J. 2008;155:465–70. elevation myocardial infarction in a 37-year-old man with normal coronaries—it is not always 67. Hall W, Solowij N. Adverse effects of cannabis. cocaine! Am J Emerg Med. 2012;30:2091.e3. Lancet. 1998;352:1611–6. 54. Karabulut A, Cakmak M. ST segment elevation 68. Mohan H, Sood GC. Conjugate deviation of the myocardial infarction due to slow coronary ﬂow eyes after Cannabis indica intoxication. Br J Oph- occurring after cannabis consumption. Kardiol Pol. thalmol. 1964;48:160–1. 2010;68:1266–8. 69. Jouanjus E, Leymarie F, Tubery M, et al. Cannabis- 55. Casier I, Vanduynhoven P, Haine S, Vrints C, Jorens related hospitalizations: unexpected serious events PG. Is recent cannabis use associated with acute coronary syndromes? An illustrative case series. identiﬁed through hospital databases. Br J Clin Acta Cardiol. 2014;69:131–6. Pharmacol. 2011;71:758–65. 56. Gunawardena MDVM, Rajapakse S, Herath J, 70. Westover AN, McBride S, Haley RW. Stroke in Amarasena N. Myocardial infarction following young adults who abuse amphetamines or cocaine: cannabis induced coronary vasospasm. BMJ Case a population-based study of hospitalized patients. Rep. 2014;2014. https://doi.org/10.1136/bcr-2014- Arch Gen Psychiatry. 2007;64:495–502. 71. Hemachandra D, McKetin R, Cherbuin N, Anstey 57. Mir A, Obafemi A, Young A, Kane C. Myocardial KJ. Heavy cannabis users at elevated risk of stroke: infarction associated with use of the synthetic evidence from a general population survey. Aust N cannabinoid K2. Pediatrics. 2011;128:e1622–7. Z J Public Health. 2016;40:226–30. 58. Atik SU, Dedeoglu R, Varol F, Cam H, Eroglu AG, 72. Rumalla K, Reddy AY, Mittal MK. Recreational Saltik L. Cardiovascular side effects related with use marijuana use and acute ischemic stroke: a popu- of ‘‘bonzai’’: two case reports. Turk Arch Pediatr. lation-based analysis of hospitalized patients in the 2015;50:61–4. United States. J Neurol Sci. 2016;364:191–6. 59. McKeever RG, Vearrier D, Jacobs D, LaSala G, Oka- 73. Phillips MC, Leyden JM, Chong WK, et al. Ischae- neku J, Greenberg MI. K2—not the spice of life; mic stroke among young people aged 15 to 50 years synthetic cannabinoids and ST elevation myocar- in Adelaide, South Australia. Med J Aust. dial infarction: a case report. J Am Coll Med Toxi- 2011;195:610–4. col. 2015;11:129–31. 74. de los Rıos F, Kleindorfer DO, Khoury J, et al. Trends 60. Jones RT. Cardiovascular system effects of mari- in substance abuse preceding stroke among young juana. J Clin Pharmacol. 2002;42(11 Suppl): adults: a population based study. Stroke. 58S–63S. 2012;43:3179–83. 61. Ashton CH. Pharmacology and effects of cannabis: 75. Wolff V, Armspach JP, Lauer V, et al. Cannabis-related a brief review. Br J Psychiatry. 2001;178:101–6. stroke: myth or reality? Stroke. 2013;44:558–63. Cardiol Ther (2018) 7:45–59 57 76. Singh NN, Pan Y, Muengtaweeponsa S, Geller TJ, myocardial infarction and left ventricular apical Cruz-Flores S. Cannabis-related stroke: case series thrombus. Int J Cardiol. 2016;215:129–31. and review of literature. J Stroke Cerebrovasc Dis. 2012;21:555–60. 89. Wagner JA, Varga K, Ellis EF, Rzigalinski BA, Martin BR, Kunos G. Activation of peripheral CB1 77. Finsterer J, Christian P, Wolfgang K. Occipital stroke cannabinoid receptors in hemorrhagic shock. Nat- shortly after cannabis consumption. Clin Neurol ure. 1997;390:518–21. Neurosurg. 2004;106:305–8. 90. Varga K, Wagner JA, Bridgen DT, Kunos G. Platelet- 78. Santos AF, Rodriguez M, Mare R, Ferreira C, Soares- and macrophage-derived endogenous cannabinoids Fernandes J, Rocha J. Recurrent stroke in a young are involved in endotoxin-induced hypotension. cannabis user. J Neuropsychiatry Clin Neurosci. FASEB J. 1998;12:1035–44. 2014;26:41–2. 91. Godlewski G, Malinowska B, Schlicker E. Presynap- 79. Mouzak A, Agathos P, Kerezoudi E, Mantas A, tic cannabinoid CB(1) receptors are involved in the Vourdeli-Yiannakoura E. Transient ischemic attack inhibition of the neurogenic vasopressor response in heavy cannabis smokers—how ‘‘safe’’ is it? Eur during septic shock in pithed rats. Br J Pharmacol. Neurol. 2000;44:42–4. 2004;142:701–8. 80. Melki E, Denier C, The´audin-Saliou M, Sachet M, 92. Kaushik M, Alla VM, Madan R, Arouni AJ, Mohiuddin Ducreux D, Saliou G. External carotid artery bran- SM. Recurrent stress cardiomyopathy with variable ches involvement in reversible cerebral vasocon- regional involvement: insights into etiopathogenetic striction syndrome. J Neurol Sci. 2012;313:46–7. mechanisms. Circulation. 2011;124:e556–7. 81. Ducros A, Boukobza M, Porcher R, Sarov M, Valade ¨ 93. Bonz A, Laser M, Kullmer S, et al. Cannabinoids D, Bousser MG. The clinical and radiological spec- acting on CB1 receptors decrease contractile per- trum of reversible cerebral vasoconstriction syn- formance in human atrial muscle. J Cardiovasc drome. A prospective series of 67 patients. Brain. Pharmacol. 2003;41:657–64. 2007;130:3091–101. 94. Mukhopadhyay P, Batkai S, Rajesh M, et al. Phar- 82. Wolff V, Lauer V, Rouyer O, Sellal F, Meyer N, Raul macological inhibition of CB1 cannabinoid recep- JS, et al. Cannabis use, ischemic stroke, and multi- tor protects against doxorubicin-induced focal intracranial vasoconstriction a prospective cardiotoxicity. J Am Coll Cardiol. 2007;50:528–36. study in 48 consecutive young patients. Stroke. 2011;42:1778–80. 95. Pacher P, Ba´tkai S, Kunos G. Cardiovascular phar- macology of cannabinoids. Handb Exp Pharmacol. 83. Uhegwu N, Bashir A, Hussain M, Dababneh H, 2005;168:599–625. Misthal S, Cohen-Gadol A. Marijuana induced reversible cerebral vasoconstriction syndrome. 96. Sidney S. Cardiovascular consequences of mari- J Vasc Interv Neurol. 2015;8:36–8. juana use. J Clin Pharmacol. 2002;42(S1):64S–70S. 84. Herning RI, Better WE, Tate K, Cadet JL. Cere- 97. Kalla A, Krishnamoorthy P, Gopalakrishnan A, Garg brovascular perfusion in marijuana users during a J, Figueredo V. Cannabis use predicts risks of heart month of monitored abstinence. Neurology. failure and cerebrovascular accidents: results from 2005;64:488–93. the national inpatient sample. J Am Coll Cardiol. 2017;69(11(Suppl)):1784 (abstract). 85. Wolff V, Zinchenko I, Quenardelle V, Rouyer O, Geny B. Characteristics and prognosis of ischemic 98. Nogi M, Fergusson D, Chiaco JM. Mid-ventricular stroke in young cannabis users compared with non- variant takotsubo cardiomyopathy associated with cannabis users. J Am Coll Cardiol. 2015;66:2052–3. cannabinoid hyperemesis syndrome: a case report. Hawaii J Med Public Health. 2014;73:115–8. 86. Renard D, Taieb G, Gras-Combe G, Labauge P. Can- nabis-related myocardial infarction and cardioem- 99. Singh A, Agrawal S, Fegley M, Manda Y, Nanda S, bolic stroke. J Stroke Cerebrovasc Dis. 2012;21:82–3. Shirani J. Marijuana (cannabis) use is an indepen- dent predictor of stress cardiomyopathy in younger 87. Volpon LC, Sousa CLMM, Moreira SKK, Teixeira SR, men. Circulation. 2016;134:A14100. Carlotti APCP. Multiple cerebral infarcts in a young patient associated with marijuana use. J Addict 100. Pacher P, Mukhopadhyay P, Mohanraj R, Godlewski Med. 2017;11:405–7. G, Ba´tkai S, Kunos G. Modulation of the endo- cannabinoid system in cardiovascular disease: 88. Shah M, Garg J, Patel B, Guthier J, Freudenberger therapeutic potential and limitations. Hyperten- RS. Can your heart handle the spice: a case of acute sion. 2008;52:601–7. 58 Cardiol Ther (2018) 7:45–59 101. Elsheshtawy M, Sriganesh P, Virparia V, Patel F, 114. Korantzopoulos P. Marijuana smoking is associated Khanna A. Synthetic marijuana induced acute with atrial ﬁbrillation. Am J Cardiol. nonischemic left ventricular dysfunction. Case Rep 2014;113:1085–6. Cardiol. 2016;2016:4. https://doi.org/10.1155/ 2016/9625758. 115. Sterne J, Ducasting G. Les arte´rites du Cannabis indica. Arch Mal Cœur. 1960;53:143–7. 102. Petronis KR, Anthony JC. An epidemiologic inves- tigation of marijuana- and cocaine-related palpita- 116. Bucci F, Redler A, Fiengo L. Critical limb ischemia in tions. Drug Alcohol Depend. 1989;23:219–26. a young man: saddle embolism or unusual presen- tation of thromboangiitis obliterans? Case Rep Vasc 103. Kiplinger GF, Manno JE. Dose-response relation- Med. 2013;2013:4. https://doi.org/10.1155/2013/ ships to cannabis in human subjects. Pharmacol 830540. Rev. 1971;23:339–47. 117. Broz P, Jaeger KA. Images in vascular medicine— 104. Daisley H, Jones-Le Cointe A, Hutchinson G, Sim- Buerger’s disease. Vasc Med. 2012;17:366–7. mons V. Fatal cardiac toxicity temporally related to poly-drug abuse. Vet Hum Toxicol. 1998;40:21–2. 118. Ibrir M, Ouadahi N, Hamzaoui N, Zemmour D, Ghita DH, Habouchi A, et al. Peripheral arteritis 105. Bachs L, Mørland H. Acute cardiovascular fatalities disease and ischemic strokes in cannabis use: a case following cannabis use. Forensic Sci Int. report. Thromb Res. 2014;133:S115–6. 2001;124:200–3. 119. Roberts JA, Meyer J-P. Buerger’s disease presenting 106. Montisci M, Thiene G, Ferrara SD, Basso C. Canna- as a testicular mass: a rare presentation of an bis and cocaine: a lethal cocktail triggering coronary uncommon disease. Urol Ann. 2016;8:249–51. sudden death. Cardiovasc Pathol. 2008;17:344–6. 120. Combemale P, Consort T, Denis-Thelis L, Estival JL, 107. Ferna´ndez- Ferna´ndez FJ, Caı´nzos-Romero T, Mesı´as Dupin M, Kanitakis J. Cannabis arteritis. Br J Der- Prego A, Sesma P. Ectopic atrial rhythm associated matol. 2005;152:166–9. with cannabis use. Minerva Cardioangiol. 2011;59:119–20. 121. Cottencin O, Karila L, Lambert M, Arveiller C, Benyamina A, Boissonas A, Goudemand M, Rey- 108. Hartung B, Kauferstein S, Ritz-Timme S, Daldrup T. naud M. Cannabis arteritis: review of the literature. Sudden unexpected death under acute inﬂuence of J Addict Med. 2010;4:191–6. cannabis. Forensic Sci Int. 2014;237:e11–3. 122. Leithauser B, Langheinrich AC, Rau WS, Tillmanns 109. Korantzopoulos P, Liu T, Papaioannides D, Li G, H, Matthias FR. A 22-year-old woman with lower Goudevenos JA. Atrial ﬁbrillation and marijuana limb arteriopathy: Buerger’s disease, or metham- smoking. Int J Clin Pract. 2008;62:308–13. phetamine or cannabis-induced arteritis? Heart Vessels. 2005;20:39–43. 110. Krishnamoorthy S, Lip GY, Lane DA. Alcohol and illicit drug use as precipitants of atrial ﬁbrillation in 123. Peyrot I, Garsaud AM, Saint-Cyr I, Quitman O, young adults: a case series and literature review. Am Sanchez B, Quist D. Cannabis arteritis: a new case J Med. 2009;122:851–6. report and a review of the literature. J Eur Acad Dermatol Venereol. 2007;21:388–91. 111. Miller RH, Dhingra RC, Kanakis C, Amat-y-Leon F, Rosen KM. The electrophysiological effects of delta- 124. Nahas GG. Cannabis arteritis. N Engl J Med. 9-tetrahydrocannabinol (cannabis) on cardiac con- 1971;284:113. duction in man. Am Heart J. 1977;94:740–7. 125. Cazalets C, Laurat E, Cador B, et al. Arteriopathies 112. Orsini J, Blaak C, Rajayer S, Gurung V, Tam E, Morante du cannabis: quatre nouveaux cas [Cannabis J, Shamian B, Malik R. Prolonged cardiac arrest com- arteritis: four new cases]. Rev Med Intern. plicating a massive ST-segment elevation myocardial 2003;24:127–30. infarction associated with marijuana consumption. J Community Hosp Intern Med Perspect. 2016;. 126. Martin-Blondel G, Koskas F, Cacoub P, Se`ne D. Is https://doi.org/10.3402/jchimp.v6.31695. thrombangitis obliterans presentation inﬂuenced by cannabis addiction? Ann Vasc Surg. 113. Fisher BAC, Ghuran A, Vadamalai V, Antonios TF. 2011;25:469–73. Cardiovascular complications induced by cannabis smoking: a case report and review of the literature. 127. Noel B, Ruf I, Panizzon RG. Cannabis arteritis. J Am Emerg Med J. 2005;22:679–80. Acad Dermatol. 2008;58(Suppl 1):S65–7. Cardiol Ther (2018) 7:45–59 59 128. Schneider F, Abdoucheli-Baudot N, Tassart M, et al. 131. Lee C, Moll S. Migratory superﬁcial throm- Cannabis and tobacco: cofactors favoring juvenile bophlebitis in a cannabis smoker. Circulation. obliterative arteriopathy. J Mal Vasc. 2014;130:214–5. 2000;25:388–9. 132. Lou JY, Randhawa MS, Hornacek D, Bajzer C. 129. Santos RP, Resende CI, Vieira AP, Brito C. Cannabis Spontaneous renal artery dissection in a cannabis arteritis: ever more important to consider. BMJ Case user. Vasc Med. 2015;20:379–80. Rep. 2017;2017. https://doi.org/10.1136/bcr-2016- 219111. 133. Corvi F, Querques G, Lattanzio R, Preziosa C, Parodi MB, Bandello F. Central retinal vein occlusion in a 130. Disdier P, Granel B, Serratrice J, et al. Cannabis young patients following cannabis smoke inhala- arteritis revisited—ten new case reports. Angiology. tion. Eur J Ophthalmol. 2014;24(3):437–40. 2001;52:1–5.
Cardiology and Therapy – Springer Journals
Published: Dec 7, 2017
It’s your single place to instantly
discover and read the research
that matters to you.
Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.
All for just $49/month
Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly
Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.
Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.
Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.
All the latest content is available, no embargo periods.
“Hi guys, I cannot tell you how much I love this resource. Incredible. I really believe you've hit the nail on the head with this site in regards to solving the research-purchase issue.”Daniel C.
“Whoa! It’s like Spotify but for academic articles.”@Phil_Robichaud
“I must say, @deepdyve is a fabulous solution to the independent researcher's problem of #access to #information.”@deepthiw
“My last article couldn't be possible without the platform @deepdyve that makes journal papers cheaper.”@JoseServera