Atrial fibrillation and Marijuana Smoking

P. Korantzopoulos; T. Liu; D. Papaioannides; G. Li; J. A. Goudevenos


Int J Clin Pract. 2008;62(2):308-313. 

In This Article


Compelling evidence is accumulating that cannabis has significant haemodynamic and electrophysiological effects on the cardiovascular system.[6,7] It has been suggested that these effects are mediated mainly by Δ9-tetrahydrocannabinol (THC), although other substances may also be implicated.[6,7] It should further be acknowledged that the route of administration, the preparation of cannabis, and the content in THC, affect the biological responses (possibly because of variable pharmacokinetics of the active substances). For instance, marijuana smoking, oral intake of hashish or hashish oil and intravenous administration of cannabis, may have a different physiological impact.

The acute cardiovascular effects of marijuana smoking in humans have been carefully examined, but it should be underlined that only healthy young males have been involved in most of the experimental protocols. These effects include a marked increase in heart rate, lesser increases in supine blood pressure and frequent occurrence of postural hypotension.[7] On the one hand, these effects seem to be dose dependent, but on the other hand, the frequent use over a relatively short period of time results in tolerance.[7]

Specifically, marijuana smoking in relative small doses leads to a slight blood pressure elevation in the supine position and a moderate decrease while standing. At the same time the cardiac output and the cardiac work increases. The increase in cardiac output is due to increased heart rate and to peripheral vasodilation. These changes along with a decreased oxygen carrying capacity, owing to elevated carboxyhaemoglobin concentration, imply a disturbance in the balance between myocardial oxygen supply and demand.[6,7] As a result, the triggering of angina attacks or acute coronary syndromes is facilitated, especially in older individuals who have increased atherosclerotic burden. Smoking of higher doses of marijuana provokes an exacerbated postural or orthostatic hypotension and associated vasovagal reactions. These reactions may result in dizziness, syncope, falls and even injuries. The presumed decrease in peripheral vascular resistance is not uniform across the vascular beds. Despite individual variations, the constriction of small vessels in toes and fingers that often leads to a subjective sensation of cold has been well characterised.[10] Notably, a more serious reaction (a form of local arteritis) which can result in gangrene has been described. This inflammatory vasculitis in conjunction with marked vasospastic responses have been recently implicated in neurologic complications such as headache, transient ischaemic attacks and stroke.[12,13]

The electrophysiological effects of marijuana smoking are more complex. The most consistent finding is the rapid increase in heart rate that lasts 2-3 h after cessation of smoking. This tachycardia is believed to be of sinus origin and it has been attributed to enhanced sinus node automaticity.[23] At low and moderate doses, consistent with ordinary marijuana smoking, the THC leads to an increase in sympathetic and a reduction in parasympathetic activity.[6] Beaconsfield et al.[24] were the first who demonstrated the implication of beta-adrenergic stimulation in marijuana-induced sinus tachycardia in humans. In specific, tachycardia could be prevented by orally administered propranolol, but it could still be induced with marijuana even after subcutaneous administration of atropine.[24] Further support to the concept of sympathetic activation was provided by studies that demonstrated an increased urinary excretion of epinephrine after THC use,[25] and also increased plasma norepinephrine levels in conjunction with the acute cardiovascular changes observed after marijuana smoking.[26] With respect to electrical conduction in the heart, Miller et al.[23] showed a significant decrease in the A-H interval and in the atrioventricular refractoriness in humans, induced by intravenous administration of THC. Of note, this facilitation of atrioventricular conduction was contrary to previous animal experiments. Moreover, intra-atrial and intraventricular conduction seems to be unaffected by THC.[23] Despite their scientific interest, the clinical significance of the latter findings regarding electrical conduction is not clearly evident. However, more rapid ventricular rates during AF could be observed in this setting.

Even though the aforementioned effects of marijuana in humans are predominantly mediated by the autonomic alterations, modulation of the cannabinoid receptor system may also be operative. The exact role of cannabinoid receptors CB1 and CB2 is still under intensive investigation. Central and peripheral CB1 receptors possibly have a regulatory function in the cardiovascular system affecting centres in the brain as well as the peripheral autonomic system.[7,21] Furthermore, experimental studies in animals indicate that CB1 antagonists decrease heart rate and blood pressure and facilitate vasodilation. Given that the latter effects are rather different to those of marijuana, the role of cannabinoid receptors in AF seems to be very complicated.

The impact of marijuana smoking on clinical arrhythmias has not been well studied. Palpitations are commonly experienced after marijuana smoking and are usually ascribed to the sinus tachycardia or more rarely to premature ventricular contractions.[6,27] Petronis and Anthony,[28] in a large epidemiological study, clearly showed that marijuana smoking is independently associated with increased incidence of palpitations, although the underlying cause of this finding was not clarified. Interestingly, case reports describing a temporal association between marijuana use and ventricular arrhythmias often implicate myocardial ischaemia as the underlying cause.[9,14] Rezkalla et al.[14] have also proposed that besides the stimulation of sympathetic nervous system and the associated decrease in the parasympathetic tone, cannabis might have detrimental effects on the coronary microcirculation and induce the triggered activity in the Purkinje fibres.[14]

During the past few years an increasing number of case reports indicate an association between marijuana smoking and the development of AF. In this brief review, we concisely analysed all the relative reported cases. Despite the small number of these reports, the observed close temporal relationship between marijuana smoking and AF occurrence, especially in young people without structural heart disease or other precipitating factors for AF, strongly supports an association between the two conditions. The clinical relevance of such an association appears to be important, given that even short self-terminating episodes of AF imply an increased thromboembolic risk particularly when other risk factors for thromboembolism are also present.[15,16] As already mentioned, an increasing body of evidence relates marijuana smoking to stroke events. Although vasospastic responses of cerebral vessels and vasculitis are the most plausible mechanisms, the implication of a cardioembolic cause such as AF cannot be excluded.[13] Moreover, AF could contribute to the haemodynamic abnormalities observed in marijuana smokers. In fact, the well-described orthostatic/postural hypotension that often takes place may be markedly aggravated by an excessive tachycardia leading to syncope, and falls. Remarkably, half of the patients that we described experienced such an event, fortunately without any subsequent serious injury.

With respect to the underlying mechanisms of marijuana-induced AF, it could be speculated that most of the above-mentioned mechanisms are also operative in this setting. The pathogenic role of the autonomic nervous system in AF is well documented.[29] Adrenergic stimulation reduces action potential duration and alters the electrophysiological properties of myocardium favouring automaticity, triggered activity and micro-reentry.[20,29] Although adrenergic-induced AF usually occurs in the presence of heart disease,[29] a subset of healthy individuals sensitive to the catecholamine surge may be prone to AF development.[17] Moreover, disturbances in atrial coronary or microvascular flow (atrial ischaemia) caused by marijuana might contribute to AF pathogenesis.[30] Collectively, sympathetic system activation, ischaemia, and impaired coronary microcirculation, may facilitate AF development and perpetuation possibly because of increased pulmonary vein ectopy, enhanced atrial electrical remodelling (shortening of effective refractory period) and increased dispersion of refractoriness (anisotropic conduction) (Figure 1).

Figure 1.

Proposed pathogenesis of marijuana-induced atrial fibrillation. AF, atrial fibrillation; ERP, effective refractory period.

The exact incidence of AF related to marijuana smoking is difficult to be estimated. Although many patients describe palpitations, the relative frequency of sinus tachycardia, premature ventricular beats and AF during these circumstances remains elusive. Given the euphoric and neuropsychological effects of marijuana that may alter or cover the palpitations or other symptoms suggestive for AF, this issue becomes more complicated. It should also be borne in mind that because of social or legal reasons most users of illicit drugs avoid seeking medical attention. In addition, many short episodes of AF may pass without symptoms. Taking into consideration all these notions, it could be reasonable to conclude that the burden of the problem is possibly underestimated. However, the potential adverse effects of AF in this setting may be different to those derived from studies in other populations. Whether AF increases mortality in this situation remains to be proved. Clearly, the repeated episodes of the arrhythmia may lead to atrial remodelling resulting in AF perpetuation.


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