Hypertension - Medical Marijuana Research Papers Worldwide - 2000- 2017
The verdict is in; Marijuana increases heart rate, reduces blood pressure by dilating blood vessels reducing inflammation and protects nerve and brain cells in the event of stroke or heart attack.
1 Our knowledge of the pharmacodynamics of phyto-cannabinoids, that is, “the research of the biochemical and physiologic effects of drugs and their mechanisms of action”, has increased considerably within the past ten years due to the discovery of the endogenous (body's) cannabinoid system with specific receptors and their endogenous (body's own) ligands.
1 d9THC (tetrahydrocannabinol-D9), is the main source of the pharmacological effects caused by the use of marijuana, including the medical benefits of the herb-plant, is an agonists (binds to receptor) to both the Cannabinoid-1 and the Cannabinoid-2 subtypes of these receptors.
1 Its acid metabolite of THC-COOH, and the non-psychotropic cannabidiol - CBD, analogues of these natural compounds, are antagonists antagonist (dampens biological response) at the cannabinoid receptors and are modulators of the endogenous (body's own) cannabinoid system make these phyto-cannabinoids promising candidates for clinical research and clinical uses.
1 Cannabinoid receptors are distributed throughout the central nervous system and many peripheral tissues - in the spleen, leukocytes;reproductive, urinary and gastrointestinal tracts; endocrine glands, arteries and heart, etc.. Moreover, there is appreciable evidence for non-receptor dependent mechanisms of phyto-cannabinoids.
1 Five endogenous (body's own) cannabinoids, anandamide, 2-arachidonoylglycerol, noladin ether, virodhamine, and NADA, have been discovered, detected. There is evidence that besides the two cannabinoid receptor subtypes cloned so far, additional cannabinoid receptor subtypes and vanilloid receptors are involved in the complex physiological functions of endocannabinoids (body's own) that include:motor coordination, memory procession, pain modulation and neuroprotection. Strategies to modulate their activity include inhibition of reuptake into cells and inhibition of their degradation to increase concentration and duration of action.
2 CANNABIS CANNABINOIDS REDUCES HYPERTENSION IN RODENTS BY DIALING DOWN BLOOD PRESSURE
2 Background— endocannabinoids (body's own) are new lipid mediators with hypotensive and cardiodepressant activity. Here, we examined the possible role of the endocannabinoid system in cardiovascular regulation in hypertension.
2 In spontaneously hypertensive rodents-SHR, cannabinoid-1 receptor (CB1) antagonist (dampens biological response) to increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid (body`s own) anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rodents, and these effects are prevented by Cannabinoid-1 (dampens biological response). Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rodents, the same parameters remain unaffected by any of these treatments.
2 Cannabinoid-1 agonists (binds to receptor) diminished blood pressure much more in spontaneously hypertensive rodents - SHR than in normotensive Wistar-Kyoto rats, and the expression of Cannabinoid-1 is increased in heart and aortic endothelium of spontaneously hypertensive rodents - SHR compared with Wistar-Kyoto rats.
2 We conclude that endocannabinoids -body's own tonically suppress cardiac contractility in hypertension and that enhancing the Cannabinoid-1-mediated cardiac depressor and vasodilator effects of endogenous (body's own) anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers new clinical strategies in the treatment of hypertension.
3 CANNABINOIDS - CANNABIS HAS POWERFUL CARDIO-ACTIVE EFFECTS
3 Cannabinoids and their endogenous (body's own) and synthetic analogs exert powerful hypotensive and cardiodepressant effects by complex mechanisms involving direct and indirect effects on myocardium and vasculature. On the one hand, endocannabinoids -body's own and cannabinoid receptors have been implicated in the hypotensive state associated with hemorrhagic, endotoxic and cardiogenic shock, and advanced liver cirrhosis.
3 On the other hand, there is emerging evidence suggesting that the endocannabinergic system plays an important role in the cardiovascular regulation in hypertension. This review is aimed to discuss the in vivo hypotensive and cardiodepressant effects of phytocannabinoids mediated by cannabinoid and TRPV1 receptors, and concentrates on the new clinical strategies offered by targeting the endocannabinoid system in the treatment of hypertension.
4 THC ACTIVATES RECEPTORS IN MICE THAT CONTROL NERVOUS SYSTEM ACTIVITY
4 The biologically active principal of cannabis, d9THC is a partial agonists (binds to receptor) of a G protein-coupled receptor. This receptor, named the Cannabinoid-1 receptor, is selectively activated by d9-THC and other phytocannabinoids. The Cannabinoid-1 receptor has been characterized at a molecular level and is expressed in high amounts in the central nervous system-CNS. (dampens biological response) studies and studies using Cannabinoid-1 receptor KO rodents provides evidence that most of the biological effects of intravenous doses of 10 mg/kg or less of d9-THC are mediated by the Cannabinoid-1 receptor.
5 CANNABIS CANNABINOIDS CAN REPLACE BODY'S OWN CANNABINOIDS
5 Phyto-cannabinoids, the bioactive constituents of the cannabis herb-plant and their synthetic and endogenous (body's own) analogs cause not only neurobehavioral, but also cardiovascular effects. The most important component of these effects is a profound decrease in blood pressure and heart rate.
5 Although multiple lines of evidence indicate that the hypotensive and bradycardic effects of anandamide and other phyto-cannabinoids are mediated by peripherally located CB1 cannabinoid receptors, anandamide can also elicit vasodilation in certain vascular beds, which is independent of Cannabinoid-1 or Cannabinoid-2 receptors. Possible cellular mechanisms underlying these effects and the cellular sources of vasoactive anandamide are discussed.
6 CAUTION - OCCASIONAL ADVERSE EFFECTS FROM CANNABIS IN HEART DISEASE
6 Cannabis's cardiovascular effects are not associated with serious health problems for most young,, healthy users, although occasional myocardial infarction, stroke, and other adverse cardiovascular events are reported. Cannabis smoking by people with cardiovascular disease poses health risks because of the consequences of the resulting increased cardiac work, increased catecholamine levels, carboxyhemoglobin, and postural hypotension.
7 BENEFICIAL EFFECTS DELIVERED BY CANNABINOIDS - AFTER SURGERY AND INJURY
7 Cardiac effects of phyto-cannabinoids were described with respect to their probable participation to the well-studied preconditioning phenomenon. Beneficial effects of post-infarction phyto-cannabinoids administration against ischemia-reperfusion injury were also reported. Concerning their vascular effects the situation is more complex, some studies reporting pressor effects, while others depressor ones. The clinical use of cannabinoid receptors agonists (binds to receptor) or (dampens biological response) will depend on the development of non psychoactive compounds.
8 NO PROBLEMS WITH SYNTHETIC THC IN CARDIAC PATIENTS - RISK OVERSTATED
8 The observation that cardiotoxicity has never been reported in cancer patients taking dronabinol, the synthetic form of d9THC, tends to suggest that animal-rodent studies may have overstated the cardiovascular risk, which is probably comparable to that of smoking cigarettes.
9 The associations between cannabis use and systolic blood pressure and triglycerides disappeared, having been mainly confounded by greater alcohol use in cannabis users. In conclusion, although cannabis use was not independently associated with cardiovascular risk factors, it was associated with other unhealthy behaviors, such as high caloric diet, tobacco smoking, and other illicit drug use, which all have long-term detrimental effects on health.
10 The authors have demonstrated recently that oral treatment with low dose d9THC inhibits atherosclerosis progression in rodents through pleiotropic immunomodulatory effects on inflammatory cells. All these effects were mediated via the cannabinoid receptor Cannabinoid-2, the main cannabinoid receptor expressed on immune cells. However, these promising results are in conflict with the known health risks of smoking cannabis, as d9THC binds to and activates both cannabinoid receptors,Cannabinoid-1 and Cannabinoid-2. The identification and characterization of cannabinoid derivative that selectively activate Cannabinoid-2 receptors and are devoid of adverse effects might offer a new clinical plan for the treatment of atherosclerosis.
11 CANNABIS IS GOOD FOR RATS WITH CARDIOVASCULAR ISSUES
11 In both human and rodent atherosclerotic plaques. Lymphoid cells isolated from d9THC-treated rodents showed diminished proliferation capacity and decreased interferon-gamma secretion. Macrophage chemotaxis, which is a crucial step for the development of atherosclerosis 1, was also inhibited in vitro by d9THC.
11 All these effects were completely blocked by a specific Cannabinoid-2 receptor (dampens biological response). Our data demonstrate that oral treatment with a low dose of d9THC inhibits atherosclerosis progression in the apolipoprotein E KO rodent model, through pleiotropic immunomodulatory effects on lymphoid and myeloid cells. Thus, d9THC or phyto-cannabinoids with activity at the Cannabinoid-2 receptor may be valuable targets for treating atherosclerosis.
12 CANNABINOIDS MAY BE A KEY IN ALL INFLAMMATORY DISORDERS - INCLUDING HYPERTENSION
12 The immunomodulatory capacity of phyto-cannabinoids are now well established and suggests a broad clinical potential of phyto-cannabinoids for a variety of conditions, including atherosclerosis. New strategies based on nonpsychotropic cannabinoid receptor ligands or compounds modulating endocannabinoid synthesis or stability might solve the problem of the unwanted side effects associated with phyto-cannabinoid administration.
13 Anti-inflammatory agents may become increasingly important in the treatment of atherogenesis, atherosclerosis, and possibly even acute coronary or ischemic syndromes. This presentation reviews two types of molecules associated with the diagnosis, development, or treatment of atherosclerosis: C-reactive protein -CRP, and marijuana.
14 Cannabis is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, marijuana is now legal for medical purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it's important that cardiologists be made aware of the potential for cannabis-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency.
14 In this report, the investigators concentrate on the known cardiovascular, cerebrovascular, and peripheral effects of cannabis inhalation. Temporal associations between cannabis use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and marijuana arteritis have been described. In conclusion, the potential for increased use of cannabis in the changing legal landscape suggests the need for the community to intensify research regarding the safety of cannabis use and for cardiologists to maintain an awareness of the potential for adverse effects.
15 Smoking marijuana can increase your heart rate by as much as two times for up to 3 hours. That’s why some people have a heart attack right after they use cannabis. It can increase bleeding, diminished blood pressure, and affect your blood sugar, too.
16 Yes, stick to the indica. I have smoked for 40 some years and until a few years ago I didn't know about "The 2 different kinds of weed" Indica and Sativa.... I always wondered why some pot was "Motor weed" and some laid you back. Hmmmm, well now, i know.I can't handle Sativa. i never liked to be paranoid,but i just thought some weed did that.
16 Well, now i know.I only smoke Indica now. Look up on a seed catalog site and they will tell what's what as far as different strains go.When i think of so many friends that quit smoking and went on to be drinkers.All because they got "weirded out"by smoking pot.Well it was that sativa they were smoking... I now tell them to try it again but with %100 percent Indica. They laughed and smiled !!! and enjoyed it. So all you with high blood pressure -myself included stick to Indica and see if it helps. - Happy trails, Red.
17 Marijuana increases heart rate in users, although tolerance develops to this effect. Phyto-cannabinoids can also reduce blood pressure via arteriolar dilatation in a variety of tissues, although the effect on blood flow varies at a local level, with some organs or brain regions experiencing vasoconstriction, others vasodilation.In the withdrawal phase following cessation of chronic use, cerebral blood flow may be significantly reduced.
17 Marijuana use has been implicated as a causative factor in a small number of patients suffering strokes or transient ischaemic attacks, and may represent a risk factor to susceptible individuals.
17 However phyto-cannabinoids, in particular Cannabinoid-1-receptor agonists (binds to receptor), have been shown to protect against nerve cell death following stroke, and dexanabinol at an advanced stage of the licensing process as a drug to be administered to victims of stroke or closed-head injuries to minimise the long-term brain insult caused by such events, and to improve survival and recovery prospects.
420EVALUATIONSONLINE: We provide Cannabis ID Cards, California Licensed Medical Doctor`s Recommendations, Cultivation Permits and Renewals, all 100% online, quickly and affordably. Documents are used to purchase marijuana and cannabis based medicines at dispensaries, cannabis clubs, cooperatives, delivery services, and compassion clubs. In 2018, when recreational marijuana goes on sale, medical marijuana card holders will pay about 35% off as they are sales tax exempt.
1 (R)-methanandamide: A chiral new anandamide possessing higher potency & metabolic stability. J Med Chem 37:1889–1893. Abadji V- Lin S- Taha G- Griffin G- Stevenson LA- Pertwee RG- Makriyannis A year 1994
2 Biosynthesis- release & degradation of the new endogenous (body's own) cannabimimetic metabolite 2-arachidonoylglycerol in rodent neuroblastoma cells. Biochem J 322:671–677. Bisogno T- Sepe N- Melck D- Maurelli S- De Petrocellis L- Di Marzo V year 1997
3 The endothelial component of cannabinoid-induced relaxation in rabbit mesenteric artery depends on gap junctional communication. J Physiol -Lond 520:539–550. Chaytor AT- Martin PE- Evans WH- Randall MD- Griffith TM year 1999
4 Production & physiological actions of anandamide in the vasculature of the rat kidney. J Clin Invest 100:1538–1546. Deutsch D- Goligorsky MS- Schmid PC- Krebsbach RJ- Schmid HHO- Das SK- Dey SK- Arreaza G- Thorup C- Stefano G- Moore LC year 1997
5 Mandelbaum A- Etinger A- Mechoulam R year 1992 Isolation & structure of a brain constituent that binds to the cannabinoid receptor. Science -Wash DC 258:1946–1949. Devane WA- Hanus L- Breuer A.- Pertwee RG- Stevenson LA- Griffin G- Gibson D-
6 Cannabinoid pharmacology. Pharmacology Rev 38:151–178.Abstract Dewey WL year 1986 Di Marzo V- Bisogno T- De Petrocellis L- Melck D- Orlando P- Wagner JA- Kunos G year 1999 Biosynthesis & inactivation of the endocannabinoid 2-arachidonoylglycerol in circulating & tumoral macrophages. European J Biochem 264:258–267 CB-1
7 Biosynthesis of anandamide & related acyl ethanolamides in rodent J774 macrophages & N18 neuroblastoma cells. Biochem J 316:977–984. Di Marzo V- De Petrocellis L- Sepe N- Buono A year 1996
8 Formation & inactivation of endogenous (body's own) cannabinoid anandamide in central neurons. Nature -Lond 372:686–691. Di Marzo V- Fontana A- Cadas H- Schinelli S- Cimino G- Schwartz JC- Piomelli D year 1994
9 The synthesis & pharmacological evaluation of the cannabinoid (dampens biological response) SR141716A. Med Chem Res 5:54–62. Dutta AK- Sard H- Ryan W- Razdan RK- Compton DR- Martin BR year 1994
10 Human platelets & polymorphonuclear leukocytes synthesize oxygenated derivatives of arachidonylethanolamide -anandamide: Their affinities for cannabinoid receptors & pathways of inactivation. Mol Pharmacology 54:180–188. Edgemond WS- Hillard CJ- Falck JR- Kearn CS- Campbell WB year 1998
11 LY 320135- a new cannabinoid CB1 receptor (dampens biological response)- unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J Pharmacol Experimental Therapy 284:291–297. Felder CC- Joyce KE- Briley EM- Glass M- Mackie KP- Fahey KJ- Cullinan GJ- Hunden DC- Johnson DW- Chaney MO- Koppel GA- Brownstein M year 1998
12 Morphine & anandamide stimulate intracellular calcium transients in human arterial endothelial cells: Coupling to nitric oxide release. Cell Signal 11:189–193. Fimiani C- Mattocks D- Cavani F- Salzet M- Deutsch DG- Pryor S- Bilfinger TV- Stefano GB year 1999
13 Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current. Am J Physiol 276:H2085–H2093. Gebremedhin D- Lange AR- Campbell WB- Hillard CJ- Harder DR year 1999
14 General pharmacological actions of some synthetic tetrahydrocannabinol derivatives. Pharmacology Rev 23:295–315. Hardman HF- Domino EF- Seevers MH year 1971
15 Biochem & pharmacology of arachidonylethanolamide- a putative endogenous (body's own) cannabinoid. J Lipid Res 38:2383–2398.Abstract Hillard CJ- Campbell WB year 1997
16 Cannabinoid CB1 receptors fail to cause relaxation- but couple via Gi/Go to the inhibition of adenylyl cyclase in carotid artery smooth muscle. British J Pharmacology 128:597–604. Holland M- John Challiss RA- Standen NB- Boyle JP year 1999
17 Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid Cannabinoid-1 receptors on peripheral sympathetic nerves. British J Pharmacology 118:2023–2028. Ishac EJ- Jiang L- Lake KD- Varga K- Abood ME- Kunos G year 1996
18 A role for N-arachidonoylethanolamine -anandamide as the mediator of sensory nerve-dependent Ca2+-induced relaxation. J Pharmacology Experimental Therapy 289:245–250. Ishioka N- Bukoski RD year 1999
19 Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from Cannabinoid-1 or Cannabinoid-2 receptors. Proc Natl Acad Sci USA 96:14136–14141. Jarai Z- Wagner JA- Varga K- Lake KD- Compton DR- Martin BR- Zimmer AM- Bonner TI- Buckley NE- Mezey E- Razdan RK- Zimmer A- Kunos G year 1999
20 Cannabinoid-induced hypotension & bradycardia in rodents mediated by Cannabinoid-1-like cannabinoid receptors. J Pharmacology Experimental Therapy 281:1030–1037. Lake KD- Compton DR- Varga K- Martin BR- Kunos G year 1997
21 Acute changes in cerebral blood flow after smoking cannabis. Life Sci 52:757–767. Matthew R- Wilson W year 1993
22 Anandamide-induced mobilization of cytosolic Ca2+ in endothelial cells. British J Pharmacology 126:1593–1600. Mombouli JV- Schaeffer G- Holzmann S- Kostner GM- Graier WF year 1999
23 Effect of the cannabinoid receptor agonists (binds to receptor)WIN 55212-2 on sympathetic cardiovascular regulation. British J Pharmacology 126:457–466. Niederhoffer N- Szabo B year 1999
24 Pharmacology of cannabinoid receptor ligands. Curr Med Chem 6:635–664. Pertwee RG year 1999
25 Anandamide synthesis is induced by arachidonate mobilizing agonists (binds to receptor) in cells of the immune system. Biochim Biophys Acta 1394:249–260. Pestonjamasp VK- Burstein SH year 1998
26 Evidence that anandamide & EDHF act via different mechanisms in rat isolated mesenteric arteries. British J Pharmacology 121:1509–1511. Plane F- Holland M- Waldron GJ- Garland CJ- Boyle JP year 1997
27 N-arachidonylethanolamide relaxation of bovine coronary artery is not mediated by CB1 cannabinoid receptor. Am J Physiol 274:H375–H381. Pratt PF- Hillard CJ- Edgemond WS- Campbell WB year 1998
28 An endogenous (body's own) cannabinoid as an endothelium-derived vasorelaxant. Biochem Biophys Res Comm 229:114–120. Randall MD- Alexander SPH- Bennett T- Boyd EA- Fry JR- Gardiner SM- Kemp PA- McCulloch AI- Kendall DA year 1996
29 SR141716A- a potent & selective (dampens biological response) of the brain cannabinoid receptor. FEBS Lett 350:240–244. Rinaldi-Carmona M- Barth F- Heaulme M- Shire D- Calandra B- Congy C- Martinez S- Maruani J- Neliat G- Caput D- Ferrara P- Soubrie P- Breliere JC- LeFur G year 1994
30 Cannabinoid receptor agonists (binds to receptor) inhibit glutamatergic synaptic transmission in rat hippocampal cultures. J Neurosci 16:4322–4334. Shen M- Piser TM- Seybold VS- Thayer SA year 1996
31 A second endogenous (body's own) cannabinoid that modulates long-term potentiation. Nature -Lond 388:773–778. Stella N- Schweitzer P- Piomelli D year 1997
32 Is the cannabinoid CB1 receptor a 2-arachidonoylglycerol receptor? Structural requirements for triggering a Ca2+ transient in NG108-15 cells. J Biochem -Tokyo 122:890–895. Sugiura T- Kodaka T- Kondo S- Nakane S- Kondo H- Waku K- Ishima Y- Watanabe K- Yamamoto I year 1997
33 Detection of an endogenous (body's own) cannabimimetic molecule- 2-arachidonoylglycerol- & cannabinoid CB1 receptor mRNA in human vascular cells: Is 2-arachidonoylglycerol a possible vaso modulator? Biochem Biophys Res Commun 243:838–843. Sugiura T- Kodaka T- Nakane S- Kishimoto S- Kondo S- Waku K year 1998
34 Evidence that the cannabinoid CB1 receptor is a 2-arachidonoylglycerol receptor. Structure-activity relationship of 2-arachidonoylglycerol- ether-linked analogues- & related compounds. J Biol Chem 274:2794–2801. Sugiura T- Kodaka T- Nakane S- Miyashita T- Kondo S- Suhara Y- Takayama H- Waku K- Seki C- Baba N- Ishima Y year 1999
35 Novel (dampens biological response) implicates the CB1 cannabinoid receptor in the hypotensive action of anandamide. European J Pharmacology 278:279–283. Varga K- Lake K- Martin BR- Kunos G year 1995
36 Mechanism of the hypotensive action of anandamide in anesthetized rodents. Hypertension 28:682–686. Varga K- Lake KD- Huangfu D- Guyenet PG- Kunos G year 1996
37 Platelet- & macrophage-derived endogenous (body's own) cannabinoids are involved in endotoxin-induced hypotension. FASEB J 12:1035–1044. Varga K- Wagner JA- Bridgen DT- Kunos G year 1998
38 Role of the central autonomic nervous system in the hypotension & bradycardia induced by -−-delta9-trans-tetrahydrocannabinol. J Pharm Pharmacology 26:186–192. Vollmer R- Cavero I- Ertel R- Solomon T- Buckley J year 1974
39 Activation of peripheral CB1 cannabinoid receptors in haemorrhagic shock. Nature -Lond 390:518–521. Wagner JA- Varga K- Ellis EF- Rzigalinski BA- Martin BR- Kunos G year 1997
40 Mesenteric vasodilation mediated by endothelial anandamide receptors. Hypertension 33:429–434. Wagner JA- Varga K- Jarai Z- Kunos G year 1999
41 A comparison of EDHF-mediated & anandamide-induced relaxations in the rat isolated mesenteric artery. British J Pharmacology 122:1573–1584. White R- Hiley CR year 1997
42 Increased mortality- hypoactivity- & hypoalgesia in cannabinoid CB1 receptor KO rodents. Proc Natl Acad Sci USA 96:5780–5785. Zimmer A- Zimmer AM- Hohmann AG- Herkenham M- Bonner TI year 1999
43 Studies on the effects of anandamide in rat hepatic artery. British J Pharmacology 122:1679–1686.Zygmunt PM- Hogestatt ED- Waldeck K- Edwards G- Kirkup AJ- Weston AH year 1997
44 Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature -Lond 400:452–457.Zygmunt PM- Petersson J- Andersson DA- Chuang H- Sorgard M- Di Marzo V- Julius D- Hogestatt ED year 1999
.png)
