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Studies of the overall cardiovascular impact of smoked marijuana have been inconsistent. Some suggest a benefit[m-beni] while others suggest the opposite[m-detr]. In contrast, studies of individual cannabis compounds have tended to get consistent results.
The following topics outline the various kinds of cardiovascular impairment: hypertension, dyslipidemia, and atherosclerosis; myocardial ischemia and myocarditis; heart failure, ischemic strokes, and heart attacks.
In human studies, CBD reduced blood pressure, and the results were more pronounced in people who had high blood pressure to begin with[1]. Prolonged THC use lowered blood pressure and heart rate; The first study to report these results is from 1975[2]. Eucalyptol has lowered blood pressure in rats[bp-euca1][bp-euca2].
Dyslipidemia involves abnormal blood levels of lipids — such as cholesterol and triglycerides. It can involve HDL levels that are too low or LDL levels that ae too high. The primary concern is with LDL levels.
Cholesterol-lowering alternatives to statins are of interest because statins block a primary metabolic pathway. They block not only cholesterol but 30,000 other molecules, including heme, vitamin K, coenzyme Q10, and all steroid hormones[3].
Linalool and eucalyptol synergistically inhibit the production of cholesterol in a manner competitive with statins, judging from their effect on liver cells[4]. Camphene is comparable to lovastatin in its ability to lower cholesterol, at least in rats[5]. THCV and CBD may also be useful as they reduce lipid levels in liver and fat cells[6]. These results are significant in that they reduce the incidence of fatty liver disease and help avoid obesity.
While LDL cholesterol has been tied to cardiovascular problems, oxidized LDL is a much stronger predictor of coronary heart disease[7][8][9]. LDL particles pose a risk for cardiovascular disease when they enter blood vessel walls and become oxidized[10]. In an in vitro study, terpinolene and γ-terpinene inhibited oxidation of LDL cholesterol[11].
Atherosclerosis is a buildup of abnormal fatty deposits and fibrous tissue in the inner layer of the arteries. In a word, clogged arteries.
Treatment with the terpene β‑caryophyllene reduces cardiac lipid content and improves the antioxidant/oxidant ratio in heart tissue of hypercholesterolemic rats[12]. Low‑dose oral THC reduces the progression of atherosclerosis in mice via a role similar to that of β‑caryophyllene[13][14].
CBD is of substantial benefit in myocardial ischemia (reduced blood flow to the heart)[16], and it reduces associated ventricular arrhythmias[17]. β-Caryophyllene may also be of value due to its anti-inflammatory and antioxidant properties[mi-bcp]. These results are based on animal and cellular studies.
In an animal study, CBD reduced inflammation of the heart muscle[myoc-cbd].
Heart failure occurs when the heart cannot pump sufficiently to maintain blood flow to meet the body's needs. The condition is associated with poor tolerance to exercise, and IL-1β makes that worse. In mice, blocking IL-1β brings improvement[hf-il1]. As noted in the article, Taming Inflammatory Cytokines, CBD, β-caryophyllene nerolidol, d-limonene, eucalyptol, d-humulene, and geraniol all lower IL-1.
Ischemic strokes reduce blood flow to the brain and are often triggered by blood clots. The reduced blood flow kills neurons, and dying neurons kill more neurons. CBD can reduce this cascade of dying neuros, but only at moderate doses[18]. It increases cerebral flow and reduces cell death in the area of the stroke[19]. CBD provides potent, long-lasting neuroprotection in mice, whether administered before or after an induced stroke. The protection is mainly due to CBD's anti‑inflammatory properties[20].
After an ischemic stroke, the blood-brain barrier is weakened by a lack of glucose and oxygen, thus allowing an influx of substances toxic to the brain. CBD inhibits this weakening of the blood-brain barrier[st-cbd].
In animal studies, preventive treatment with CBD was effective. Moreover, repeated treatment continued to be effective without developing tolerance[21]. Treatment with β-caryophyllene before a stroke decreased swelling, brain damage, and mitochondrial dysfunction after the stroke[23][24][st-bcp].
Perillyl alcohol, a metabolite of the terpene d-limonene, protected against cell death from reactive oxygen species after a stroke[st-peri]. Linalool was neuroprotective[st-lina]. α-Bisabolol was neuroprotective, probably due to its anti-inflammatory capability[st-abis]. Eucalyptol limited the damage after a stroke due to its anti-oxidative effect[st-euca].
A heart attack is a sudden blockage of blood flow to a part of the heart muscle.
Marijuana consumers are more likely to survive a heart attack[m-beni].
IL-1β contributes to long-term damage after a heart attack, and blocking IL-1 limits damage[ha-il1a]. As noted above, CBD, β-caryophyllene, nerolidol, d-limonene, eucalyptol, d-humulene, and geraniol all lower IL-1.
α-Bisabolol protects heart muscle following a heart attack through its free-radical scavenging capabilities in rats[ha-free].
m-beni. Marijuana use and short-term outcomes in patients hospitalized for acute myocardial infarction [large-scale study]. Article. Cecelia P Johnson-Sasso, Christine Tompkins, David P Kao, Lori A Walker. Plos One. 2018 July 11.
m-detr. Cannabis use predicts risk of heart failure and cerebrovascular accidents: results from the national inpatient sample. Extended abstract. Aditi Kalla, Parasuram Krishnamoorthy, Akshaya Gopalakrishnan. Jornal of the American College of Cardiology. 2017 March.
1. A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study. Article. Jadoon K, Tan G, O'Sullivan S. The Journal of Clinical Investigation: Insight. Published 2017 June 15.
2. Cardiovascular effects of prolonged delta‑9‑tetrahydrocannabinol ingestion [Small-scale study]. Abstract. N L Benowitz, R T Jones. Clinical Pharmacology & Therapeutics. Published September 1975.
bp-euca1. Cardiovascular effects of 1,8-cineole, a terpenoid oxide present in many plant essential oils, in normotensive rats. Abstract. Saad Lahlou, André Fernandes Figueiredo, et al. Canadian journal of physiology and pharmacology. 2002 December.
bp-euca2. Effects of 1,8-cineole on hypertension induced by chronic exposure to nicotine in rats. Abstract. Hea Kyung Moon, Purum Kang, et al. The Journal of pharmacy and pharmacology. 2014 May.
3. Mevalonate pathway. Article. WikiProject Medicine. Wikipedia. Upated 25 March 2021.
4. Synergistic antiproliferative and anticholesterogenic effects of linalool, 1,8‑cineole, and simvastatin on human cell lines. Abstract. Rodenak‑Kladniew B, Polo M, Montero‑Villegas S, et al. Elsevier Chemico‑Biological Interactions. Published 2014 March 12.
5. Camphene, a Plant‑Derived Monoterpene, Reduces Plasma Cholesterol and Triglycerides in Hyperlipidemic Rats Independently of HMG‑CoA Reductase Activity. Article. Vallianou I, Peroulis N, Pantazis P, et al. PLOS ONE. 2011 November 3.
6. Two non‑psychoactive cannabinoids reduce intracellular lipid levels and inhibit hepatosteatosis [animal study]. Abstract. Silvestri C, Paris D, Martella A, et al. Journal of Hepatology. Published January 13, 2015.
7. The oxidation ratio of LDL: a predictor for coronary artery disease. Article. Huang H, Mai W, Liu D, et al. Disease Markers. Published August 1, 2008.
8. Circulating Oxidized LDL Is a Useful Marker for Identifying Patients With Coronary Artery Disease. Article. Holvoet P, Mertens A, Verhamme P, et al. Arteriosclerosis, Thrombosis, and Vascular Biology. Published 1 May 2001.
9. Plasma Oxidized Low‑Density Lipoprotein, a Strong Predictor for Acute Coronary Heart Disease Events in Apparently Healthy, Middle‑Aged Men From the General Population. Article. Meisinger C, Baumert J, Khuseyinova N, et al. Circulation. 25 Jul 2005.
10. Low‑density lipoprotein. Article. WikiProject Molecular and Cell Biology. Wikipedia. Updated 2019 March 9.
11. The monoterpene terpinolene from the oil of Pinus mugo L\. in concert with alpha‑tocopherol and beta‑carotene effectively prevents oxidation of LDL [in vitro study]. Abstract. Grassmann J, Hippeli S, Spitzenberger R, Elstner E. Phytomedicine. Published 2005 June 15.
12. β‑caryophyllene reduces atherogenic index and coronary risk index in hypercholesterolemic rats: The involvement of cardiac oxidative damage. Abstract. Baldissera M, Souza C, Grando T. Chemico-Biological Interactions. 2017 April 12.
13. Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Abstract. Steffens S, Veillard N, Arnaud C, et al. Nature. Published 2005 April 7.
14. Atheroprotection via cannabinoid receptor-2 is mediated by circulating and vascular cells in vivo. Abstract. Hoyer F, Steinmetz M, Zimmer S, et al. Journal of Molecular and Cellular Cardiology. Published 2011 August 19.
ha-il1a. Interleukin-1 Blockade With Anakinra to Prevent Adverse Cardiac Remodeling After Acute Myocardial Infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot Study). Article. Antonio Abbate, MD, PhD; Michael C Kontos; et al. American Journal of Cardiology. 2013 February 27.
ha-free. α-Bisabolol abrogates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and intrinsic pathway of apoptosis in rats. Abstract. Mohamed Fizur Nagoor Meeran, Farah Laham, et al. Molecular and Cellular Biochemistry. 2018 August 29.
hf-il1. Enhanced Interleukin-1 Activity Contributes to Exercise Intolerance in Patients with Systolic Heart Failure. Article. Benjamin W Van Tassell, Ross A Arena, et al. Plos One. Published 2012 March 16.
myoc-cbd. Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation [animal study]. Full text. Wen-Shin Lee, Katalin Erdelyi, et al. Molecular Medicine. Published 2016 January 8.
16. Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury [animal study]. Article. Durst R, Danenberg H, Gallily R, et al. American Journal of Physiology - Heart and Circulatory Physiology. Published 2007 December 1.
17. Acute administration of cannabidiol in vivo suppresses schaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion [animal study]. Article. Walsh S, Hepburn C, Kane K, et al. British Journal of Pharmachology. Published 2010 July.
mi-bcp. Antioxidant Activity [in The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene β-Caryophyllene from the Essential Oil of Aquilaria crassna]. Article section. Saad S Dahham, Yasser M Tabana, et al. Molecules. 2015 July.
18. Post-ischemic treatment with cannabidiol prevents electroencephalographic flattening, hyperlocomotion and neuronal injury in gerbils. Abstract. Braida D, Pegorini S, Arcidiacono M, et al. Neuroscience Letters. Published 2003 June 11.
19. Cannabidiol prevents cerebral infarction via a serotonergic 5-hydroxytryptamine1A receptor-dependent mechanism [animal study]. Abstract. Mishima K, Hayakawa K, Abe K, et al. Stroke. Published 2005 April 21.
20. Delayed treatment with cannabidiol has a cerebroprotective action via a cannabinoid receptor-independent myeloperoxidase-inhibiting mechanism [animal study]. Article. Hayakawa K, Mishima K, Nozako M, et al. Journal of Neurochemistry. Published 2007 March 9.
st-cbd. Cannabidiol protects an in vitro model of the blood–brain barrier from oxygen‐glucose deprivation via PPARγ and 5‐HT1A receptors. Article. William H Hind, Timothy J England, Saoirse E O'Sullivan. British Journal of Pharmacology. Published 2016 February 3.
21. Repeated treatment with cannabidiol but not Δ9‑tetrahydrocannabinol has a neuroprotective effect without the development of tolerance [animal study]. Abstract. Hayakawa K, Mishima K, Nozako M, et al. Neuropharmacology. Published February 21.
23. β-Caryophyllene Pretreatment Alleviates Focal Cerebral Ischemia-Reperfusion Injury by Activating PI3K/Akt Signaling Pathway [animal study]. Abstract. Zhang Q, An R, Tian X, et al. Neurochemical Research. Published February 24.
24. Protective effect of β-caryophyllene, a natural bicyclic sesquiterpene, against cerebral ischemic injury [animal study]. Abstract. Chang H, Kim J, Lee J, et al. Journal of Medicinal Food. Published 2013 June 14.
st-bcp. Activation of cannabinoid CB2 receptor-mediated AMPK/CREB pathway reduces cerebral ischemic injury [animal study]. Abstract. In-Young Choi, Chung Ju, et al. The American Journal of Pathology. 2013 March.
st-peri. Perillyl alcohol improves functional and histological outcomes against ischemia–reperfusion injury by attenuation of oxidative stress and repression of COX-2, NOS-2 and NF-κB in middle cerebral artery occlusion rats. Abstract. RizwanaTabassum, KumarVaibhava, et al. European Journal of Pharmacology. 22015 January 15.
st-lina. Neuroprotective effects of (−)-linalool against oxygen-glucose deprivation-induced neuronal injury [in vitro study]. Abstract. Hyeon Park, Geun Hee Seol, et al. Archives of pharmacal research. 2016 April.
st-abis. (-)-α-bisabolol prevents neuronal damage and memory deficits through reduction of proinflammatory markers induced by permanent focal cerebral ischemia in mice. Abstract. Mara Yone Dias Fernandes, Marta Regina Santos doCarmo, et al. European journal of pharmacology. 2019 January.
st-euca. 1,8-Cineole ameliorates oxygen-glucose deprivation/reoxygenation-induced ischaemic injury by reducing oxidative stress in rat cortical neuron/glia. Abstract. Sangwoo Ryu, Hyeon Park, et al. Journal of Phrmacy and Pharmacology. Published 2014 August 3.