Table 2.

Cardiac effects of acute cannabinoid administration in humans.

Number (Characterization, Age in Years)	Agonist	Dose (mg) *	Application	Cardiac Effects	Comments/Suggested Mechanisms and Involvement of CB1-Rs	References
10 healthy volunteers (21–33)	THC	1–40	cigarette	dose-dependent ↑HR; ↑BP	changes in BP better correlated to HR than to doses; antagonists not studied	[104]
16 healthy volunteers (18–42)	THC	25	cigarette	↑HR; ↓BP: normotensive < hypertensive persons	n.a.	[105]
6 healthy volunteers (18–30)	THC	10	cigarette	↑HR; ↑BP	tachycardia resulting from β-AR activation (diminished by propranolol 120 mg p.o.)	[107]
10 healthy volunteers(30–40)	THC	10	cigarette	↑HR; ECG: ↑amplitude and ↓width of P wave in Lead 2 and inversion of T wave in Lead 3	tachycardia is mediated via β-ARs, since it was prevented by propranolol (40 mg/kg p.o.) but not by atropine (0.6 mg/kg s.c.)	[108]
14 healthy volunteers (20–31)	THC	6	cigarette	↑HR and ↑left ventricular performance (mean rate of internal diameter shortening)	tachycardia not accompanied by ↑plasma NA levels, since the respective maximal increases took place at 10 and 30 min, respectively	[110]
21 experienced users of cannabis (21–45)	THC	20–60	1 to 3 cigarettes	↑HR; ↑cardiac output ↔stroke volume ↔ejection fraction	marijuana has no significant effect on myocardial contractility independent of its effect on HR	[113]
91 cannabis users (19–25); double-blind, placebo-controlled, parallel-group randomized clinical trial	THC	94	cigarette	↑HR; peak HR (~40 beats/min) and plasma THC concentration (~55 ng/mL) at 5 min; ↑HR different until +4 h	n.a.	[112]
42 volunteers (mean age of 29); randomized, double blind, parallel group design	cannabis	2.8% THC	cigarette	↑HR	acute tachycardia depends on CB1-Rs since it was diminished by acute rimonabant (90 mg/kg p.o.) or its chronic application (40 mg/kg for 8 and 15 days)	[109]
16 healthy volunteers (mean age of 28)	THC UR-144	1, 1.5 10, 20	joints (smoking)	↑HR, ↑BP ↑HR, ↑BP	(THC and the preferential CB2-R agonist UR-144 were administered in joints containing tobacco.)	[114]
16 healthy volunteers (mean age of 30)	JWH-122 JWH-210	1 1.25	joints (smoking)	↑HR, ↑BP ↔HR, ↔BP	(compounds with high potency at CB1-/CB2-Rs, respectively)	[128]
17 healthy volunteers (mean age of 27)	THC	10 25	smoked or vaporized	↑HR ↑HR	THC-induced tachycardia slightly higher in the case of vaporization	[106]
36 healthy volunteers (18–31)	THC	2, 4 and 6	inhalation by vaporizer	↑HR in a dose-dependent manner	THC-induced tachycardia inhibited by the CB1-R antagonist AVE1625 (20, 60, 120 mg p.o.)	[116]
30 healthy volunteers (18–45); double-blind, placebo-controlled, randomized, four-period six-sequence crossover study	THC	2, 4 and 6	inhalation by vaporizer	↑HR	THC-induced tachycardia was inhibited by the CB1-R antagonist surinabant 20 and 60 mg p.o.	[118]
12 healthy volunteers (21–27)	THC	2, 4, 6 and 8	vaporized	sharp ↑HR and rapid decline	THC-induced tachycardia is dose-dependent	[115]
12 healthy volunteers	THC	2, 4, 6 and 8	vaporized	↑HR	different sites of action for cardiac and CNS responses suggested: average population equilibration half-life for HR 8 min and for CNS 39–85 min	[117]
11 frequent and 9 occasional cannabis smokers (mean age of 27 and 29, respectively)	THC	~54	smoked vaporized oral	↑HR; ↑carbon monoxide ↑HR ↑HR	smoking produced higher increase in carbon monoxide compared to vaporization	[129]
84 healthy volunteers (mean age of 32), naturalistic, ad libitum use	THC	average 51 average 16	smoked or vaporized (flower cannabis), oral (edible cannabis)	↑HR ↑HR	the flower group started with lower basal HR than the edible group at pre-use but had higher average HR at post-use	[111]
16 healthy volunteers (mean age of 26)	THC CBD	10 600	capsules	↑HR ↔HR	tachycardia induced by THC but not by CBD (has low affinity to CB1-Rs)	[119]
14 healthy volunteers (21–45); randomized, double-blind design	nabilone Cesamet® dronabinol Marinol®	4, 6, 8 10, 20	capsules capsules	dose-dependent ↑HR, ↓systolic BP ↔HR, ↓systolic BP	nabilone has better bioavailability than dronabinol (THC)	[121]
37 healthy volunteers (18–35)	THC	7.5, 15	capsules	↑HR, ↓heart rate variability, ↔pre-ejection period, ↔BP	tachycardia results from parasympathetic inhibition; no changes in sympathetic tone	[120]
9 healthy volunteers (mean age of 21.4)	THC (Namisol®)	6.5 and 8.0	tablets	slight ↑HR (by about 5 beats/min)	n.a.	[130]
11 healthy volunteers (≥65)	THC (Namisol®)	3, 5 or 6.5	tablets	no clinically relevant changes in HR and ECG parameters	n.a.	[131]
5 volunteers (22–29); regular marijuana smokers (at least once a day)	THC	30 μg/kg	i.v.	↑HR	tachycardia results from sympathetic stimulation and parasympathetic inhibition (diminished by i.v. propranolol and atropine 0.2 and 0.04 mg/kg, respectively)	[122]
20 healthy male volunteers (22–30)	THC	25 μg/kg ≈ 5 mg in one marijuana cigarette	i.v.	↑HR, ↑total electromechanical systole; ↑left ventricular ejection time; ↓pre-ejection period	THC-induced changes in cardiac performance via the autonomic nervous system: partially diminished by propranolol 0.1 mg/kg i.v. and totally by propranolol 0.1 mg/kg plus atropine 2 mg/kg i.v.	[123,124]
21 healthy volunteers	THC CBD	0.2 mg/min 1.8 mg/min	i.v.	↑HR ↑HR	CBD increases HR only at a much higher dose than THC	[126]
6 patients undergoing diagnostic ECG evaluation	THC	25 μg/kg	i.v.	↓sinus length; ↓mean sinus node recovery, ↓maximal sinus node recovery times; ↓mean calculated sinoatrial conduction; ↓mean A-V nodal effective and functional refractory periods	(25 µg/kg i.v. correspond to ≈5 mg in one marijuana cigarette) enhancement of sinus automaticity and facilitation of sinoatrial and A-V nodal conduction	[125]
9 cannabis users	THC Sativex®: THC: CBD	5, 15 16.2:15.0	oromucosal sprays	comparable ↑HR induced by THC and Sativex®	CBD fails to diminish the THC-induced tachycardia	[127]

This table does not include individual case reports because of the marked heterogeneity in terms of dose, concomitant diseases or concurrent drugs and stimulants (which, in turn, might lead to adverse cardiac reactions). * if not stated otherwise; A-V, atrioventricular; β-AR, β-adrenergic receptor; BP, blood pressure; CB₁-R, CB₂-R, cannabinoid CB_1, CB₂ receptor; CBD, cannabidiol; CNS, central nervous system; ECG, electrocardiography; HR, heart rate; i.v., intravenous(ly); NA, noradrenaline; n.a., not applicable; p.o., per os; s.c., subcutaneous(ly); THC, Δ⁹-tetrahydrocannabinol.