cbd and blood pressure regulationDecember 15, 2021
Prices can be high: a 500mg bottle of CBD oil oral drops could set you back as much as £45. Not that this has put people off: over the past two years, sales of CBD have almost doubled in the UK, putting regular users at an estimated quarter of a million.
Since 2016, any CBD product that is presented as having medicinal value must be licensed and regulated as a medicine, regardless of whether it is actually effective. Manufacturers must follow very specific and robust rules around production, packaging and the information provided.
CBD, or cannabidiol, is a chemical that’s extracted from the leaves and flowers of the cannabis plant. Cannabis itself is an illegal class B drug, as is the compound THC (tetrahydrocannabinol) which it contains. But pure CBD isn’t illegal, as it doesn’t cause the intoxicating effects of cannabis.
What CBD products are available?
However, it also notes that this research is still in the early stages, and that more studies are needed before conclusions can be drawn on whether CBD is effective.
“It’s clear that CBD has potential,” says Professor Sumnall, “but we’re at a very early stage of that research.”
“In terms of the products found in shops, there’s virtually no evidence to support the claims made for a lot of them.” Harry Sumnall, Professor in Substance Use at Liverpool John Moores University.
There is ongoing research into the use of purer forms of CBD for a variety of conditions, including heart and circulatory diseases and, in particular, diseases of the heart muscle, including myocarditis and some types of cardiomyopathy.
Professor Sumnall argues that while it could be effective for some people, in some of these cases the results could be caused by the placebo effect (where the patient’s belief in a treatment makes them feel better). The placebo effect can be powerful, but Professor Sumnall warns that if people try CBD oil instead of speaking to their doctor, it could cause a problem.
CBD’s popularity has been given a boost by the fact that two CBD-containing medicines have been approved for prescription use by the NHS in England: Epidyolex, which has been found to reduce the number of seizures in children with severe epilepsy, and Sativex, which contains a mixture of CBD and THC, and is licensed for treatment of muscle stiffness and spasms in people with MS.
Does CBD work?
But so far, Professor Sumnall points out, CBD products in shops are marketed as food supplements, not medicines, so none of them have gone through this process.
CBD is the latest health craze to sweep the high street, with claims it can help everything from chronic pain and inflammation to anxiety. But what is CBD, and can it really help the heart? Emily Ray finds out.
Inflammation is part of the process that leads to many diseases, including coronary heart disease, high blood pressure and stroke, and there is some evidence that CBD has anti-inflammatory properties. Other studies have suggested that CBD can have a protective effect on the heart: this has been proven in rats after a heart attack and in mice with some of the heart damage associated with diabetes. But because these studies are often based on findings in a lab or in animals, not in humans, we cannot yet be confident that CBD will benefit the human heart.
The choice of CBD products has exploded recently: you can buy oils, capsules, muscle gels, sprays and oral drops, as well as beer, tea, sweets, hummus and even CBD-infused clothing.
What is CBD, and is it legal in the UK?
Harry Sumnall, Professor in Substance Use at Liverpool John Moores University, says: “In terms of the products found in shops, there’s virtually no evidence to support the claims made for a lot of them. There’s a lot of marketing that says CBD is a ‘miracle of the modern age’; however, the marketing has actually overtaken the evidence of what it’s effective for.”
Many of these can be easily picked up from reputable high street stores, such as Holland & Barrett or Boots.
The biggest difference between CBD used in clinical trials and in stores is the dose. Research has shown that some products contain very little CBD (or even none at all). Others contain THC or other illegal drugs, or even alcohol instead of CBD. By contrast, in clinical trials the CBD is purified, manufactured to a very high standard and given at a much higher dose. It is also taken regularly and under medical supervision.
Some of this work is still in animals, and much more research is needed before we can definitively say that CBD can help in this area.
A 2018 report by the World Health Organization suggested that CBD may help treat symptoms relating to conditions such as cancer, Parkinson’s disease, multiple sclerosis (MS), anxiety, depression, insomnia and Alzheimer’s disease.
On the other hand, cannabidiol does not directly bind to the CB1 and CB2 receptors. Instead, it causes a number of indirect actions leading to therapeutic benefits, such as activating TRPV1 receptors that regulate pain, body temperature, and inflammation.
All of the forms of CBD that you can buy over the counter are not generic products. Their effectiveness depends largely on the quality of the manufacturer producing it, and the type of CBD that’s used.
No prescription or documentation is needed for CBD oil. The only exceptions are the marijuana-derived CBD oil sold in dispensaries (in medical marijuana states, you’ll need a patient card to buy it) and a medication called Epidiolex, a CBD medication only available by prescription to patients suffering from some forms of childhood epilepsy.
How CBD Can Help With Hypertension.
In a 2018 study, researchers found that a dose of 300 mg was most effective for reducing anxiety in a simulated public speaking trial. Participants who took 150 mg or 600 mg did not receive the same benefit.
The best way to determine how effective a dose of CBD will be for you is to start small and frequently check your blood pressure using an electronic cuff. Write down the dose you took and the time you took it, as well as your blood pressure reading. Over time, you should be able to obtain a clearer picture of what dose will help you achieve low blood pressure.
The sample size of these studies was small and further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders, but the results are promising.
As CBD reduces stress, you may see an increase in your quality of sleep and general wellness.
High blood pressure can lead to cardiovascular complications such as heart disease, heart attack, stroke, aneurysm and heart failure. The condition is exacerbated by type 2 diabetes, stress, anxiety, inflammation, high cholesterol levels, insomnia, a diet high in salt, and alcohol and tobacco use.
According to federal law, hemp-derived CBD oil is classified as having less than 0.3% THC, making it legal to purchase and use. And since hemp has minuscule amounts of THC content, CBD oil from this type of cannabis plant does not cause any of THC’s intoxicating side effects. Marijuana-derived CBD oil, whether it’s derived from sativa or indica-dominant plants, contains more than 0.3% THC as its primary active ingredient, and may make you high. It is only legal in states with recreational or medical marijuana legalization.
Hypertension is the medical term for high blood pressure. As blood is pumped through your blood vessels, they undergo a degree of force. If you have high blood pressure, this force can damage the walls of your blood vessels, veins and arteries.
CBD Improves Sleep.
Many CBD oils come in dropperful (1 ml) doses of 10 mg/ml. Cannabidiol affects different people, particularly based on the weight, metabolism and body type. However, Park said the effective therapeutic dose is usually in the range of 20 mg to 300 mg, or 2 to 30 dropperfuls.
Park noted that, “If CBD works for you, without the use of other medications, I would say it is a great and safe alternative.” CBD may not be a replacement for exercise and a healthy diet, but it is nice to know you might be able to lower your blood pressure with a few drops of oil under the tongue.
This system has two main endocannabinoid receptors, called CB1 and CB2. THC binds directly to the CB1 receptors, affecting areas of the brain that influence memory, motor coordination and time perception, and to the CB2 receptors which affect the pain centers in your brain and manage inflammation in the body. The interaction between THC and the endocannabinoid system is what causes the psychoactive side effects that marijuana is best known for.
CBD oil has been shown to reduce anxiety in animal studies by the National Institute for Drug Abuse (NIDA). This study demonstrated that symptoms that accompany anxiety, like high blood pressure and rapid heart rate, were improved by use of CBD.
Called a “vasorelaxant” by researchers, CBD oil’s anti-inflammatory properties may lower blood pressure by allowing the free flow of blood through your heart, arteries and veins.
Sarah Polansky, owner and developer of the CBD brand Prismatic Plants, told Public Goods that “The more you take CBD and help to regulate your adrenals, the less likely you’ll feel fatigued as your body returns to a state of balance rather than constant stress.”
Some cannabidiol delivery methods work more slowly than others.
In a famous 2017 randomized crossover study led by British doctor Khalid Jadoon and published in the Journal of Clinical Investigation (JCI), a single dose of 600 mg of CBD oil or a placebo was administered to nine healthy volunteers. The resulting data showed that acute administration of CBD reduced resting blood pressure compared to placebo dosing.
When you visit the doctor, you’ll usually hear your blood pressure described by two numbers, like 120/70.
Does CBD oil lower blood pressure, or is it an unfounded claim? Is it possible to skip the burdensome doctors’ visits and expensive trips to the pharmacy?
“CBD lowers blood pressure by reducing cortisol levels and dilating blood vessels, allowing more blood flow and leading to lower blood pressure,” Park said.
KAJ helped with study design, researched data, wrote the manuscript, and reviewed/edited the manuscript. GDT reviewed/edited the manuscript. SEO was involved in study design and reviewed/edited the manuscript.
The cold pressor test caused a rise in SBP (placebo P < 0.01, CBD P < 0.05; Figure 5A ) and MAP (placebo P < 0.001, CBD P < 0.05; Figure 5C ) in both groups and a rise in DBP only with placebo ( P < 0.01; Figure 5B ). An equal rise in SBP and MAP was seen with both CBD and placebo in the first half of this stress test. However, while the blood pressure (SBP and MAP) continued to rise in the placebo group, it plateaued in volunteers who had taken CBD, and therefore both SBP and MAP were significantly lower in volunteers after CBD (mean difference –8 mmHg [95% CI, –4 to –12, P < 0.01] and –6 mmHg [95% CI, –2 to –11, P < 0.01]). Post-hoc analysis showed that DBP was also significantly lower in those who had taken CBD in the latter half of the stress period ( Figure 5B ; P < 0.001).
The cold pressor test caused a significant rise in TPR (as expected) in the placebo group only ( Figure 5H ; P < 0.01) and rise in forearm skin blood flow with both CBD and placebo ( Figure 5I ; P < 0.05). The overall trend was for lower TPR and forearm skin blood flow in those who had taken CBD, with post-hoc analysis showing a reduction in both just before and in the latter half of cold stress ( Figure 5H [ P < 0.05 to < 0.0001] and Figure 5I [ P < 0.001]).
Ten healthy young male volunteers, mean age 24 years (range 19–29), with no underlying cardiovascular or metabolic disorders, were recruited for this study, which was approved by the University of Nottingham Faculty of Medicine Ethics Committee (study reference E18102012). Written informed consent was obtained according to the Declaration of Helsinki. Exclusion criteria included any significant cardiovascular or metabolic disorder or use of any medication. All the volunteers were nonsmokers and had taken no prescribed or over-the-counter medication within a week prior to randomization. No volunteers had ever used cannabis.
CBD has multiple desirable effects on the cardiovascular system. It attenuates high glucose–induced proinflammatory changes in human coronary artery endothelial cells (7) and myocardial dysfunction associated with animal models of diabetes (8), and it preserves endothelial integrity in diabetic retinal microvasculature (9). In vivo administration of CBD before cardiac ischemia and reperfusion also reduces ventricular arrhythmias and infarct size. CBD also causes both acute and time-dependent vasorelaxation in isolated arteries in rats and humans (10–12). There is also evidence from animal studies that CBD modulates the cardiovascular response to stress. Resstel and colleagues (13) showed in rats that i.p. injection of CBD (10 and 20 mg/kg, –30 min) reduced restraint stress–induced cardiovascular response and behavior. Both these effects were blocked by preadministration of WAY100635 (0.1 mg/kg), a 5-hydroxytryptamine 1A (5HT 1A ) antagonist. These effects appear to be mediated centrally and involve the bed nucleus of the stria terminalis (BNST), a limbic structure that modulates neuroendocrine responses to acute stress (14).
We have shown for the first time that to our knowledge that, in humans, acute administration of CBD reduces resting blood pressure, with a lower stroke volume and a higher heart rate. This response may be secondary to the known anxiolytic properties of CBD (16) and may account for the lack of anticipatory rise in blood pressure seen with placebo. These findings are in contrast to previous studies in humans, where CBD at the same dose did not affect baseline cardiovascular parameters (17–19), although changes in the cardiovascular system were not the primary outcome of these studies. In the present study, CV parameters were measured continuously, while in previous studies, monitoring for SBP, DBP, and HR were performed manually at only 1, 2, or 3 hours after drug delivery. Additionally, our subjects were cannabis naive, while the subjects of other studies had used cannabis in the past. Since tolerance may develop to the hemodynamic response to CBs in humans, this may explain the differences between studies.
CBD was well tolerated, and there were no adverse events on the day of stress tests. None of the subjects reported any adverse events over the following week.
Mental arithmetic has been shown to cause a rise in MAP and muscle sympathetic nerve activity (MSNA) (25) and vasodilatation in forearm skeletal muscle (26). In our study, none of the cardiovascular parameters other than HR, DBP, and SV were affected, suggesting that the level of stress to this test was minimal. This could be because of the added visual stimulus of a computer screen, which would have helped volunteers perform the task. Overall, there was trend for lower SBP, DBP, MAP, SV, TPR, and forearm skin blood flow in subjects who had taken CBD, particularly in the pre– and post–stress test periods. Like resting cardiovascular parameters, these changes may indicate anxiolytic effects of CBD and/or generalized sympathoinhibition.
RESULTS. CBD reduced resting systolic BP (–6 mmHg; P < 0.05) and stroke volume (–8 ml; P < 0.05), with increased heart rate (HR) and maintained cardiac output. Subjects who had taken CBD had lower BP (–5 mmHg; P < 0.05, especially before and after stress), increased HR (+10 bpm; P < 0.01), decreased stroke volume (–13 ml; P < 0.01), and a blunted forearm skin blood flow response to isometric exercise. In response to cold stress, subjects who had taken CBD had blunted BP (–6 mmHg; P < 0.01) and increased HR (+7 bpm; P < 0.05), with lower total peripheral resistance.
CBD increased HR during the latter part of mental stress and in the poststress period ( Figure 3D ; P < 0.05 to < 0.0001), with a corresponding decline in EJT ( Figure 3G ; P < 0.05 to < 0.0001). Although CBD reduced SV ( Figure 3E ; P < 0.05 to < 0.0001), there was no difference in CO between CBD and placebo ( Figure 3F ).
Subjects who had taken CBD had increased HR (mean difference 10 bpm; 95% CI, 5–14, P < 0.01, Figure 4D ) and decreased SV (mean difference –13 ml; 95% CI, –4 to –22, P < 0.01, Figure 4E ) and EJT (mean difference –0.01 sec, 95% CI, –0.001 to –0.03, P < 0.05, Figure 4G ) during the exercise stress. There was no difference in CO during the exercise stress ( Figure 4F ).
THC, the major psychoactive component of cannabis, is known to cause tachycardia and orthostatic hypotension in humans (20), a hemodynamic response similar to that observed to CBD in the present study. THC is a partial agonist at both CB 1 and CB 2 receptors (21), and the effects of THC on heart rate are mediated through CB 1 receptors (20). CBD does not bind with any great affinity to CB 1 , but it can interact indirectly by augmenting CB 1 receptors’ constitutional activity or endocannabinoid tone, the so called indirect agonism (22). We recently showed that CBD also causes endothelium-dependent vasorelaxation in isolated human mesenteric arteries through CB 1 activation (11). Therefore, it is possible that the changes in hemodynamics brought about by CBD are mediated through CB 1 .
Cold stress causes intense sympathoexcitation, producing a tachycardic and pressor response, and an increase in MSNA (32, 33). The pressor response is due to an initial rise in CO, in response to increased HR and a later increase in MSNA, causing vasoconstriction. Both MAP and TPR show a linear correlation with MSNA during cold stress (34). In our study, cold stress produced a pressor response in both groups, but, interestingly, while SBP and MAP continued to rise with placebo throughout the test period, the pressor response to cold was blunted in subjects who had taken CBD, and SBP and MAP were significantly lower. In keeping with this, TPR was lower with CBD than placebo, suggesting a possible inhibition of sympathetic outflow. This could also be due to analgesic properties of CBD (35), reducing cold stress and therefore minimizing the sympathetic response (also explaining why the cold pressor test was affected more by CBD than the exercise test). In the animal study of Resstel and colleagues (13), the authors suggested that the modulation of cardiovascular response was most likely secondary to attenuation of emotional response to stress. However, given our findings that CBD produced similar changes in cardiovascular parameters — though to a variable degree — during rest and stress, this may indicate that CBD also has direct cardiovascular effects.
CONCLUSIONS. This data shows that acute administration of CBD reduces resting BP and the BP increase to stress in humans, associated with increased HR. These hemodynamic changes should be considered for people taking CBD. Further research is required to establish whether CBD has a role in the treatment of cardiovascular disorders.
The effects of placebo (closed square) and CBD (open square) on systolic blood pressure (SBP) ( A ), diastolic blood pressure (DBP) ( B ), mean arterial blood pressure (MAP) ( C ), heart rate (HR) ( D ), stroke volume (SV) ( E ), cardiac output (CO) ( F ), ejection time (EJT) ( G ), total peripheral resistance (TPR) ( H ), and forearm blood flow ( I ), measured continuously just before, during, and after cold pressor test (dotted line denotes stress test period), except for forearm blood flow. Measurements for forearm blood flow were made over a 2-minute window just before, during, and after the stress test. Repeated measures 2-way ANOVA; mean ± SEM (*/ + / # P < 0.05, **/ ++ P < 0.01, ***/ +++ P < 0.001, **** P < 0.0001 using Bonferroni post-hoc analysis; + and # denote significant change in a parameter during the stress period seen with placebo and CBD, respectively).
Effect of CBD on cardiovascular parameters in response to exercise stress.
BACKGROUND. Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans.
Looking at the individual response to the cold pressor test, 8 of 9 subjects had a lower SBP during the cold stress and in the recovery period after taking CBD ( Figure 2 ). Six of 9 subjects had a lower DBP during the cold pressor, and 7 of 9 subject had a lower DBP in the recovery period after taking CBD ( Figure 2 ).
Our data show that a single dose of CBD reduces resting blood pressure and the blood pressure response to stress, particularly cold stress, and especially in the post-test periods. This may reflect the anxiolytic and analgesic effects of CBD, as well as any potential direct cardiovascular effects. CBD also affected cardiac parameters but without affecting cardiac output. Giving the increasing use of CBD as a medicinal product, these hemodynamic changes should be considered for people taking CBD. Further research is also required to establish whether CBD has any role in the treatment of cardiovascular disorders such as a hypertension.
Mental stress caused a rise in HR ( P < 0.05; Figure 3D ) and a decline in SV ( P < 0.01; Figure 3E ), which was seen in both the CBD and placebo groups. There was a rise in DBP ( P < 0.05; Figure 3B ) and a decline in EJT ( P < 0.05; Figure 3G ), seen only in those who had taken CBD.
CBD treatment reduced resting systolic blood pressure (SBP) (mean difference –6 mmHg; 95% CI, –1 to –12, P < 0.05, Figure 1A ). Although there was no overall difference in diastolic blood pressure (DBP) and mean arterial blood pressure (MAP) between the 2 groups, post-hoc analysis showed that both DBP and MAP were lower with CBD treatment ( Figure 1, B and C , respectively; P < 0.01), particularly in the latter time points (120–160 min).
During an initial visit, subjects were familiarized with the stress tests and with noninvasive cardiovascular (CVS) monitoring, and an electrocardiogram (ECG) was done to rule out any preexisting cardiac conditions. Subjects were advised to fast overnight, to avoid beverages containing caffeine or alcohol, and to avoid strenuous exercise for 24 hours before each of the 2 study visits. Two hours after CBD/placebo was administered, subjects performed various stress tests (36). Noninvasive cardiovascular monitoring using Finometer and laser Doppler flowmetry was carried out during the 2 hours to assess changes in baseline parameters and during the stress test periods.
2 The NIHR Oxford Biomedical Research Centre, Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
Safety and tolerance.
There was a trend toward reduction in total peripheral resistance (TPR, Figure 1H ) with CBD in the latter half of the resting period, and a significant reduction in forearm skin blood flow before the start of the stress tests ( Figure 1I ; P < 0.01).
The effects of placebo (closed square) and CBD (open square) on systolic blood pressure (SBP) ( A ), diastolic blood pressure (DBP) ( B ), mean arterial blood pressure (MAP) ( C ), heart rate (HR) ( D ), stroke volume (SV) ( E ), cardiac output (CO) ( F ), ejection time (EJT) ( G ), total peripheral resistance (TPR) ( H ), and forearm blood flow ( I ), measured continuously over 2 hours after drug ingestion, except for forearm blood flow. Forearm blood was measured over a time period of 2 minutes just before the start and in between the stress tests. Dotted line denotes baseline values between the stress tests. Repeated measures 2-way ANOVA; mean ± SEM (*/ + / # P < 0.05, **/ ++ / ## P < 0.01 using Bonferroni’s post-hoc analysis; + and # represent significant change in any parameter over time seen with placebo and CBD, respectively; denotes overall significant difference between 2 treatments).
1 Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.
The study was a randomized, crossover design with each subject given CBD (BN: K12067A) or placebo (both gifts from GW Pharmaceuticals) in a capsule in a double-blind fashion, with a minimum time interval of at least 48 hours (range 3–16 days), taking place at the Division of Medical Sciences, School of Medicine, Royal Derby Hospital. Allocation was decided by a coin toss, and block randomization was employed by S.E. O’Sullivan, who assigned participants. K.A. Jadoon carried out all study visits, and data analysis was blinded.
METHODS. Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler.
A rise in forearm cutaneous blood flow in response to exercise (as would be expected) was only seen in volunteers who had taken placebo ( P < 0.05; Figure 4I ). Post-hoc analysis showed significantly lower forearm skin blood flow in those who had taken CBD ( Figure 4I ; P < 0.001 to < 0.0001), during the early and latter parts of the stress test. This was associated with reduced TPR ( Figure 4H ; P < 0.05 to < 0.001) before, after, and in the latter half of exercise stress.
Upon arrival, subjects were rested for 10–15 minutes, and their baseline blood pressure and heart rate were recorded using a digital blood pressure (BP) monitor. Participants were given a standardized breakfast, and 15 minutes later, they were given either oral CBD (600 mg) or placebo in a double-blind fashion. This is a dose known to cause anxiolytic effects in humans and is comparable with what is used clinically (19, 37–39). Study medication consisted of capsules containing either 100 mg of CBD or excipients, which were a gift from GW Pharmaceuticals. There was no difference between the 2 formulations in color, taste, or smell.
GT is supported by the NIHR Oxford Biomedical Research Centre Programme. The views expressed are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health.