Cannabinoids Lower Blood Pressure to Normal Levels

Published by Jan

 

HYPERTENSION-(High Blood Pressure)


High blood pressure (HBP) or hypertension means high pressure (tension) in the arteries. Arteries are vessels that carry blood from the pumping heart to all the tissues and organs of the body.  High blood pressure does not mean excessive emotional tension, although emotional tension and stress can temporarily increase blood pressure. Normal blood pressure is below 120/80; blood pressure between 120/80 and 139/89 is called "pre-hypertension", and a blood pressure of 140/90 or above is considered high.
The top number, the systolic blood pressure, corresponds to the pressure in the arteries as the heart contracts and pumps blood forward into the arteries.  The bottom number, the diastolic pressure, represents the pressure in the arteries as the heart relaxes after the contraction.  The diastolic pressure reflects the lowest pressure to which the arteries are exposed.
An elevation of the systolic and/or diastolic blood pressure increases the risk of developing heart (cardiac) disease, kidney (renal) disease, hardening of the arteries (atherosclerosis or arteriosclerosis), eye damage, and stroke(brain damage).  These complications of hypertension are often referred to as end-organ damage because damage to these organs is the end result of chronic (long duration) high blood pressure.  For that reason, the diagnosis of high blood pressure is important so efforts can be made to normalize blood pressure and prevent complications.
It was previously thought that rises in diastolic blood pressure were a more important risk factor than systolic elevations, but it is now known that in people 50 years or older systolic hypertension represents a greater risk.
The American Heart Association estimates high blood pressure affects approximately one in three adults in the United States - 73 million people.  High blood pressure is also estimated to affect about two million American teens and children, and the Journal of the American Medical Association reports that many are under-diagnosed.  Hypertension is clearly a major public health problem.


Causes:


Essential hypertension
Essential hypertension is the most prevalent hypertension type, affecting 90–95%  of hypertensive patients  Although no direct cause has been identified, there are many factors such as sedentary lifestyle,  smoking, stress, visceral obesity, potassium deficiency (hypokalemia),  obesity  (more than 85% of cases occur in those with a body mass index greater than 25),  salt (sodium) sensitivity,  alcohol intake,  and vitamin D deficiency that increase the risk of developing hypertension.   Risk also increases with aging,  some inherited genetic mutations,  and having a family history of hypertension.    An elevated level of renin, a hormone secreted by the kidney, is another risk factor,  as is sympathetic nervous system overactivity.  Insulin resistance, which is a component of syndrome X (or the metabolic syndrome), is also thought to contribute to hypertension.  Recent studies have implicated low birth weight as a risk factor for adult essential hypertension.


Secondary hypertension
 

Secondary hypertension by definition results from an identifiable cause.  This type is important to recognize since it is  treated differently than  essential hypertension, by treating the underlying cause of the elevated blood pressure.  Hypertension results in the compromise or imbalance of the pathophysiological mechanisms, such as the hormone-regulating endocrine system, that regulate blood plasma volume and heart function.  Many conditions cause hypertension.  Some are common, well-recognized secondary causes such as Cushing's syndrome,  ( a condition where the adrenal glands overproduce the hormone cortisol).  Hypertension is also caused by other conditions that cause hormone changes, such as hyperthyroidism,  hypothyroidism , and certain tumors of the adrenal medulla (e.g., pheochromocytoma).  Other common causes of secondary hypertension include kidney disease, obesity/metabolic disorder, pre-eclampsia during pregnancy, the congenital defect known as coarctation of the aorta, and certain prescription and illegal drugs.


Prevention:


• The degree to which hypertension can be prevented depends on a number of features including current blood pressure level, sodium/potassium balance, detection and omission of environmental toxins, changes in end/target organs (retina, kidney, heart, among others), risk factors forcardiovascular diseases  and the age at diagnosis of prehypertension or at risk for hypertension.  A prolonged assessment that involves repeated blood pressure measurements provides the most accurate blood pressure level assessment. Following this, lifestyle changes are recommended to lower blood pressure, before the initiation of prescription drug therapy.  Managing Prehypertension:

 

  • • Weight reduction and regular aerobic exercise (e.g., walking):  Regular exercise improves blood flow and helps to reduce the resting heart rate and blood pressure.
  • • Reduce dietary sugar
  • • Reduce sodium (salt) in the body by disuse of condiment sodium and the adoption of a high potassium diet which rids the renal system of excess sodium.  Many people use potassium chloride salt substitute to reduce their salt intake.
  • • Additional dietary changes beneficial to reducing blood pressure include the DASH diet (dietary approaches to stop hypertension) which is rich in fruits and vegetables and low-fat or fat-free dairy products.  .  In addition, an increase in dietary potassium, which offsets the effect of sodium has been shown highly effective in reducing blood pressure.
  • • Discontinuing tobacco use and alcohol consumption has been shown to lower blood pressure.  The exact mechanisms are not fully understood, but blood pressure (especially systolic) always transiently increases following alcohol or nicotine consumption.  Abstaining from cigarette smoking reduces the risks of stroke and heart attack associated with hypertension.
  • • Vasodialators such as niacin.
  • • Limiting alcohol intake to less than 2 standard drinks per day can reduce systolic blood pressure by between 2-4mmHg.
  • • Reducing stress, for example with relaxation therapy, such as meditation and other mindbody relaxation techniques,  by reducing environmental stress such as high sound levels and over-illumination can also lower blood pressure.  Jacobson's Progressive Muscle Relaxation and biofeedbackare also beneficial,  such as device-guided paced breathing,  although meta-analysis suggests it is not effective unless combined with other relaxation techniques. 
  • Increasing omega 3 fatty acids can help lower hypertension.  Fish oil lowers blood pressure in hypertensive individuals.  The fish oil may increase sodium and water excretion.
  • Treatment:
  • Lifestyle modifications
  • The first line of treatment for hypertension—which are the same as the recommended preventative lifestyle changes— include:
  • • Dietary changes
  • • Physical exercise
  • • Weight loss

These have all been shown to significantly reduce blood pressure in people with hypertension.  If hypertension is high enough to justify immediate use of medications, lifestyle changes are still recommended in conjunction with medication.  Drug prescription should take into account the patient's absolute cardiovascular risk (including risk of myocardial infarction and stroke) as well as blood pressure readings, in order to gain a more accurate picture of the patient's cardiovascular profile.  Different programs aimed to reduce psychological stress such as biofeedback, relaxation or rmeditation are advertised to reduce hypertension. 
Regarding dietary changes, a low sodium diet is beneficial;  A Cochrane review published in 2008 concluded that a long term (more than 4 weeks) low sodium diet in Caucasians has a useful effect to reduce blood pressure, both in people with hypertension and in people with normal blood pressure.  Also, the DASH diet (Dietary Approaches to Stop Hypertension) is a diet promoted by the National Heart, Lung, and Blood Institute (part of the NIH, a United States government organization) to control hypertension.  A major feature of the plan is limiting intake of sodium,  and it also generally encourages the consumption of nuts, whole grains, fish, poultry, fruits and vegetables while lowering the consumption of red meats, sweets, and sugarThe DASH diet is  rich in potassium, magnesium, and calcium, as well as protein


Medications:


Several classes of medications, collectively referred to as antihypertensive drugs, are currently available for treating hypertension.  Reduction of the blood pressure by 5 mm Hg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.  The aim of treatment should be to reduce blood pressure to <140/90 mm Hg for most individuals, and lower for individuals with diabetes or kidney disease.
The first line antihypertensive supported by the best evidence is a low dose thiazide-based diuretic.
Often multiple medications in combination  are needed to achieve the goal blood pressure.  Commonly used prescription drugs include:   ACE inhibitors, alpha blockers, angiotensin II receptor antagonists , beta blockers , calcium channel blockers, diuretics (e.g. hydrochlorothiazide), direct renin inhibitors.

Some examples of commonly  combined prescription drug treatments include:
A fixed combination of an ACE inhibitor and a calcium channel blocker.  One example of this is the combination of perindopril and amlodipine, the efficacy of which has been demonstrated in individuals with glucose intolerance or metabolic syndrome.
A fixed combination of a diuretic and an ARB.
Combinations of an ACE inhibitor or angiotensin II–receptor antagonist, a diuretic and an NSAID (including selective COX-2 inhibitors and non-prescribed drugs such as ibuprofen) should be avoided whenever possible due to a high documented risk of acute renal failure.  The combination is known colloquially as a "triple whammy" in the Australian health industry.
In the elderly:
Treating moderate to severe high blood pressure decreases death rates in those under 80 years of age.  In those over 80 years,  there was a decrease in morbidity but no decrease in mortality.  The recommended BP goal is <140/90 mm Hg with thiazide diuretics being the first line medication.


Complications:

Hypertension is the most important risk factor for death in industrialized countries.  It increases hardening of the arteries thus predisposes individuals to heart disease, peripheral vascular disease,  and strokes.   Types of heart disease that may occur include:  myocardial infarction,  heart failure, and left ventricular hypertrophy.  Other complications include:

 

  • • Hypertensive retinopathy
  • • Hypertensive nephropathy
  • • If blood pressure is very high hypertensive encephalopathy may result.

 

Silent stroke is a type of stroke (infarct) that does not have any outward symptoms (asymptomatic), and the patient is typically unaware they have suffered a stroke.  Despite not causing identifiable symptoms a silent stroke still causes damage to the brain, and places the patient at increased risk for a major stroke in the future.  Hypertension is the major treatable risk factor associated with silent stokes


In children:
The prevalence of high blood pressure in the young is increasing.  Most childhood hypertension, particularly in preadolescents, is secondary to an underlying disorder.  Kidney disease is the most common (60–70%) cause of hypertension in children.  Adolescents usually have primary or essential hypertension, which accounts for 85–95% of cases.

 

History:


Some cite the writings of Sushruta in the 6th century BC as being the first mention of symptoms like those of hypertension.   Others propose even earlier descriptions dating as far as 2600 BCE.  Main treatment for what was called the "hard pulse disease" consisted in reducing the quantity of blood in a subject by the sectioning of veins or the application of leeches.   Well known individuals such as The Yellow Emperor of China, Cornelius Celsus, Galen, and Hipocrates advocated such treatments
Our modern understanding of hypertension began with the work of physician William Harvey (1578–1657), who was the first to describe correctly the systemic circulation of blood being pumped around the body by the heart in his book "De motu cordis".  The basis for measuring blood pressure were established by Stephen Hales in 1733.  Initial descriptions of hypertension as a disease came among others from Thomas Young in 1808 and specially Richard Bright in 1836.  The first ever elevated blood pressure in a patient without kidney disease was reported by Frederick Mahomed (1849–1884).  It was not until 1904 that sodium restriction was advocated while a rice diet was popularized around 1940.
Studies in the 1920s demonstrated the public health impact of untreated high blood pressure;  treatment options were limited at the time, and deaths from malignant hypertension and its complications were common.  A prominent victim of severe hypertension leading to cerebral hemorrhage was Franklin D. Roosevelt (1882–1945).  The Framingham Heart Study added to the epidemiological understanding of hypertension and its relationship with coronary artery disease.  The National Institutes of Health also sponsored other population studies, which additionally showed that African Americans had a higher burden of hypertension and its complications.   Before pharmacological treatment for hypertension became possible, three treatment modalities were used,  all with numerous side-effects:  strict sodium restriction, sympathectomy (surgical ablation of parts of the sympathetic nervous system), and pyrogen therapy (injection of substances that caused a fever, indirectly reducing blood pressure).  The first chemical for hypertension, sodium thiocyanate, was used in 1900 but had many side effects and was unpopular.  Several other agents were developed after the Second World War, the most popular and reasonably effective of which were tetramethylammonium chloride and its derderivative hexamethonium, hydralazine and reserpine (derived from the medicinal plant Rauwolfia serpentina).  A randomized controlled trial sponsored by the Veterans Administration using these drugs had to be stopped early because those not receiving treatment were developing more complications and it was deemed unethical to withhold treatment from them.  These studies prompted public health campaigns to increase public awareness of hypertension and the advice to get blood pressure measured and treated. These measures appear to have contributed at least in part to the observed 50% fall in stroke and ischemic heart disease between 1972 and 1994.
A major breakthrough was achieved with the discovery of the first well-tolerated orally available agents. The first was chlorothiazide, the first thiazide and developed from the antibiotic sulfanilamide, which became available in 1958.   It  increased salt excretion while preventing fluid accumulation.  In 1975, the Lasker Special Public Health Award was awarded to the team that developed chlorothiazide.  The British physician James W. Black developed beta blockers in the early 1960s.   These were initially used for angina, but turned out to lower blood pressure.  Black received the 1976 Lasker Award and in 1988 the Nobel Prize in Physiology or Medicine for his discovery.   The next class of antihypertensives to be discovered was that of the calcium channel blockers.   The first member was verapamil, a derivative of papaverine that was initially thought to be a beta blocker and used for angina, but then turned out to have a different mode of action and was shown to lower blood pressure.   ACE inhibitors were developed through rational drug design.  The renin-angiotensin system was known to play an important role in blood pressure regulation, and snake venom from Bothrops  jararaca could lower blood pressure through inhibition of ACE.  In 1977 captopril, an orally active agent, was described.   T his led to the development of a number of other ACE inhibitors.
The National Heart, Lung, and Blood Institute (NHLBI),  estimated in 2002,  that hypertension cost the United States $47.2 billion.

 

Cannabinoids reduce hypertension to normal levels:

 

Cannabis is known to reduce hypertension to normal levels with regular use and to maintain normal levels with continued use in some cases.  Because of repeated threats by the federal government, only a few physicians have elected to recommend medical marijuana in cases of severe high blood pressure.
Recent research indicates that the body's internal cannabinoid system plays an important role in regulating blood pressure, but a full understanding of the exact mechanisms awaits further research.  Animal studies have demonstrated that annadamide and other endocannabinoids suppress hypertension.
Emerging research indicates that the endogenous cannabinoid system plays a role in regulating blood pressure, though its mechanism of action is not well understood.  Animal studies demonstrate that anandamide and other endocannabinoids profoundly suppress cardiac contractility in hypertension and can normalize blood pressure, leading some experts to speculate that the manipulation of the endocannabinoid system “may offer novel therapeutic approaches in a variety of cardiovascular disorders.”

The administration of natural cannabinoids has yielded conflicting cardiovascular effects on humans and laboratory animals.  The vascular response in humans administered cannabis in experimental conditions is typically characterized by a mild increase in heart rate and blood pressure.  However, complete tolerance to these effects develops quickly and potential health risks appear minimal.

In animals, cannabinoid administration in animals is typically associated with vasodilation, transient bradycardia and hypotension, as well as an inhibition of atherosclerosis (hardening of the arteries) progression.  The administration of synthetic cannabinoids have also been shown to lower blood pressure in animals and have not been associated with cardiotoxicity in humans.

At this time, research assessing the clinical use of cannabinoids for hypertension is in its infancy though further investigation appears warranted.
Furthermore, the (Phase III) hypotensive properties of anandamide and some other CB1 receptor agonists have led to the proposal that the cannabinoid system could offer therapeutic targets for hypertension, particularly since Kunos and co-workers have demonstrated that cannabinoid-induced falls in blood pressure are enhanced in chronically hypertensive rats, including spontaneous hypertensive rats (SHR). (Lake et al., 1997a; Batkai et al.,  In summary, we have shown that anandamide induced a dose-dependent, delayed hypotension, which was associated with peripheral vasodilatation in conscious, acutely hypertensive rats.  The synthetic cannabinoid, WIN55212-2 also caused depressor and enhanced vasodilator effects in acute hypertension.  While these data extend previous observations relating to the ability of cannabinoids to lower blood pressure in hypertension, the results clearly show that the mechanisms of action involved depend on the cannabinoids, and it remains unclear whether modulators of the endocannabinoid system are sufficient to normalize cardiovascular variables in hypertension.


Smoking is certainly deleterious to the cardiovascular system.  Nevertheless, chronic smoking of cannabis has been associated with lower blood pressure and with symptomatic hypotension.


Lowering Of Blood Pressure Achieved Through Use Of Hashish-Like Drug  (cannabigerol)


The cannabinoid CB1 and CB2 receptors and endocannabinoid degrading enzymes are present in cardio-vascular tissues. Activation of cardiovascular CB1 receptors leads to hypotension and decreased cardiac contractility. However, the role of myocardial CB2 receptors is still elusive. The ECS plays a limited role in cardiovascular regulation under normal physiological conditions. In various forms of shock and heart failure, the ECS may become overactivated and contribute to depressed cardiovascular function, which can be prevented or attenuated by CB1 antagonists.


  Cannabis is known to reduce hypertension to normal levels with regular use and to maintain normal levels with continued use in some cases. Because of repeated threats by the federal government, only a few physicians have elected to recommend medical marijuana in cases of severe high blood pressure.


Recent research indicates that the body's internal cannabinoid system plays an important role in regulating blood pressure, but a full understanding of the exact mechanisms awaits further research.  Animal studies have demonstrated that annadamide and other endocannabinoids suppress hypertension.


In summary, we have shown that anandamide induced a dose-dependent, delayed hypotension, which was associated with peripheral vasodilatation in conscious, acutely hypertensive rats.  The synthetic cannabinoid, WIN55212-2 also caused depressor and enhanced vasodilator effects in acute hypertension. While these data extend previous observations relating to the ability of cannabinoids to lower blood pressure in hypertension, the results clearly show that the mechanisms of action involved depend on the cannabinoids, and it remains unclear whether modulators of the endocannabinoid system are sufficient to normalize cardiovascular variables in hypertension.
 

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References:


[2] Batkai et al. 2004. Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation 110: 1996-220.
[3] Pacher et al. 2005. Blood pressure regulation by endocannabinoids and their receptors (PDF). Neuropharmacology 48: 1130-1138.
[4] Ibid.
The British Pharmacological Society References
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[xxxiv] Mathew

 

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