CBD is one of the fastest growing trends that is currently taking the health and wellness industry by storm. The natural substance, which derives from the hemp plant, has emerged as a great way to control a number of medical problems while simultaneously promoting great overall health. Pure Craft CBD offers CBD Oil 1000mg & 2000mg flavored CBD tinctures, CBD Gummy Bears, CBD Oil for Dogs and more! Discover Pure Craft CBD PURE CRAFT BLOG A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study 1 Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal
Can you use CBD if you have low blood pressure?
CBD is one of the fastest growing trends that is currently taking the health and wellness industry by storm. The natural substance, which derives from the hemp plant, has emerged as a great way to control a number of medical problems while simultaneously promoting great overall health. An increasing number of people around the world have begun to make use of the substance to control what were once seen as untreatable problems and conditions. It has especially become popular in the United States as many states have continued to lessen restrictions on cannabis and hemp related products.
One demographic that CBD has been particularly attracting attention from are those with high blood pressure. The condition, which can be caused by a number of both genetic and environmental factors, can make it hard to live life to the fullest. It is this that makes the potential of CBD to lower blood pressure so exciting.
What causes high blood pressure?
It is pretty much impossible to point to one single factor as being the cause for someone’s high blood pressure. The body is a complex system and can be impacted by a combination of things. When it comes to this condition, there are a variety of risk factors that increase the likelihood of blood pressure issues. These factors can be split into two different categories: underlying conditions and risk factors that have been induced by lifestyle choices.
Risk factors caused by underlying conditions
- Kidney disease
- Thyroid disorders
- Sleep apnea
- Adrenal tumors/disease
Risk factors caused by lifestyle choices
- Diets high in sodium
- Sedentary lifestyles
- Chronic stress/stress in general
- Excessive alcohol use
How does CBD help lower blood pressure?
Just like there are a complex combination of factors that cause blood pressure to increase, it takes a combination of factors to lead to a solution that can lower blood pressure as well. CBD is able to achieve this because of how it works with neurotransmitters in the body. The properties of the substance connect with these transmitters to target a range of problems in the body that worsen the effects of high blood pressure. As a result, the CBD lowers blood pressure and allows you to return to a healthier state of being. Here are some specific areas that can be improved upon by CBD:
Stress is a natural reaction that is meant to alert the body in potentially dangerous situations and trigger it into defensive mode. Unfortunately, in our modern world, stress is a problem that doesn’t alert and protect, but rather sends our health spiraling and causes a range of issues. Parts of our everyday life push stress on our bodies that result in chronic problems that worsen over time. This leads to an increase in the release of cortisol in the bloodstream which leads to hypertension (also known as high blood pressure). CBD has been shown to be able to lessen these effects because of its ability to reduce the levels of cortisol in the body.
Another reason that CBD is so popular with people who suffer from high blood pressure is due to its anti-inflammatory capabilities. Although it is often used in the sense of controlling inflammation that causes arthritis and joint pain, it can also work to reduce this problem to improve the efficiency of the body’s immune system. Inflammation can cause plaques to build up which narrow the blood vessels and detracts from the cardiovascular system’s ability to work how it’s supposed to. CBD oil and other CBD infused products can target this problem by reducing this inflammation and improving the functionality of the blood vessels.
Where can I buy CBD?
Now that you know how CBD can help reduce your blood pressure, the next step is finding out where to get some. Currently, CBD products that contain no THC (or those that contain levels of THC below 0.3%) are legal on a federal level. Despite this, it can sometimes be difficult to find a wide selection of it in brick and mortar stores. Because of this, it is a great idea to get your CBD products from online stores that offer wide selections and great accessibility.
CBD & Low Blood Pressure: Yea Or Nay?
We hear a lot about high blood pressure — almost half of all American adults are afflicted with this.(1) But what about low blood pressure?
It’s hard to nail down an exact percentage of the population that has low blood pressure, aka hypotension. This is largely because it’s often a silent or transient condition. However, experts agree that some degree of low blood pressure is common — maybe even about 50% of people experience a hypotensive episode.(2)
Given the prevalence of low blood pressure and popularity of CBD, people want to know if the two mix. They’re interested in understanding things like:
- How does CBD affect blood pressure?
- Can CBD lower blood pressure?
- Can you take CBD if you have low blood pressure?
Hypotension — What’s That?
The optimal range for healthy blood pressure (BP) between 90/60 and 120/80 (systolic/diastolic). For most healthy adults, their BP is somewhere in this ballpark. (3,4,5)
Hypotension is the medical name for low blood pressure, or a BP that’s below 90/60.
Types Of Hypotension
A person can have occasional low blood pressure that’s pretty much NBG and requires no treatment. It’s likely that everyone experiences a bout of hypotension at some point in their lives. Low BP gets to be a concern if it’s persistent or causing other problems (like fainting and falling).
Not all hypotension is the same. There are different sorts of low blood pressure, including:
- Orthostatic or Postural Hypotension
- Neurally Mediated Hypotension
- Postprandial Hypotension
- Shock-Related Hypotension
Low Blood Pressure Symptoms
Hypotension can be symptomatic or asymptomatic. But, if low BP were to rear its head, it might look something like this:
- Distorted vision
- Shallow, fast breathing
- Trouble concentrating
- Unusual behavior
Causes of Low Blood Pressure
This condition has lots of potential causes, including:
- Allergic reactions
- Being on bed rest
- Body position
- Breathing rhythm
- Nervous system diseases
- Certain medications
- Drugs and alcohol
- Exposure to extreme temperatures
- Heart and lung conditions
- Losing a lot of blood
- Metabolic or endocrine conditions
- Severe infections
- Some supplements or home remedies
Not all of these causes are associated with all types of hypotension. Each kind of low blood pressure has its own subset of possible causes and triggers.
Age, sex, time of day, and other factors can impact the likelihood of low BP, too.
The treatment protocol is different for each form of low blood pressure and each person. If your doctor determines it’s necessary for intervention, he or she could recommend a variety of lifestyle changes and medical therapies. These could include:
- Dietary changes
- Relaxation techniques
- Physical movement
- Compression stockings
- Hormone therapy
- IV fluids
- Blood transfusion
If the hypotension is brought on by and underlying condition, your healthcare provider will work to help you resolve that.
CBD & Blood Pressure
So, you’re probably wondering how CBD impacts blood pressure and if it’s a viable therapeutic or recreational option right about now.
As a quick refresher, CBD is the common name for the cannabinoid cannabidiol. CBD is non-psychoactive and is well-reputed for its many potential mental and physical wellness benefits. It may help with various health concerns that relate to blood pressure.
How CBD Impacts Blood Pressure
According to research, CBD appears to move the dial on blood pressure in a few ways.
Studies show that CBD lowers blood pressure and diminishes the blood pressure response to increased heart rate.(6) A double whammy to hypertension!
Besides these direct methods, CBD can indirectly act on blood pressure. It does this by affecting levers like psychological and emotional, lifestyle, and other contributors to high BP. For example, CBD could help reduce stress and anxiety — and with lower stress and anxiety levels, a person may have better blood pressure trends.
And again, CBD has a rep for supporting general well-being. People with more robust health tend to have lower risk factors for cardiovascular, metabolic, and other disorders that may lead to blood pressure problems. Their bodies stay closer to that healthy balanced zone: homeostasis.
CBD & Hypotension
Bluntly, there seems to be little existing research on this. Most of the focus is on CBD and high blood pressure (hypertension).
Fortunately, we can glean a lot of useful info from those investigations into cannabinoids and blood pressure. (For an in-dept look at CBD and high BP, check out Does CBD Oil Raise Blood Pressure? next.)
Here’s what the clinical data and academic papers are finding:
- THC — a fellow cannabinoid often found in CBD oil products — can either lower or raise blood pressure. The effect hinges on a number of things like how much THC was consumed and how a person’s body metabolizes the cannabinoid.(7)
- CBD opens up blood vessels, which can lead to improved blood flow and lower BP.(8)
Researchers continue to delve into the effects of cannabinoids on blood pressure and contributing conditions. However, many clinical trials exclude patients with hypotension, so it may make it difficult to derive direct insights.
Using CBD With Low Blood Pressure
As always, it’s advisable to talk to your doctor before using CBD if you have pre-existing medical conditions or take medications or supplements. Your doc will be able to tell you if CBD is a no-go based on your health profile — including considerations related to your blood pressure.
You physician can evaluate and diagnose hypotension and hypertension. If you have blood pressure issues, your physician can discuss all your options with you. There are likely to be natural solutions you can incorporate in your care plan. CBD may or may not be on that list….
Assuming your care provider, gives the two-thumbs-up signal for you to try CBD:
- Be sure to use the purest, highest-quality CBD products around. You’ll up your chances of having better results!
- And, you may want to opt for full-spectrum CBD or broad-spectrum CBD products. They contain at least trace amounts of THC, which may help modulate the blood-pressure altering effects of the CBD.
Can You Take CBD If You Have Low Blood Pressure? Maybe…
There are different kinds of hypotension (low blood pressure). Depending upon your body, your variety of low blood pressure, and the type of CBD you consume — CBD may lower your blood pressure even more.
Consult with your doctor prior to taking CBD, especially if you have hypotensive experiences. Your physician is in a position to help you better address health concerns and advise on whether or not CBD is appropriate for you.
A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study
1 Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.
Garry D. Tan
2 The NIHR Oxford Biomedical Research Centre, Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
Saoirse E. O’Sullivan
1 Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.
1 Division of Medical Sciences & Graduate Entry Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom.
2 The NIHR Oxford Biomedical Research Centre, Oxford Centre for Diabetes, Endocrinology & Metabolism, Churchill Hospital, Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
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.
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.
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.
Epidemiological studies have shown a positive relationship between long-term stress and the development of cardiovascular disease (1). Factors like social isolation, low socioeconomic status, depression, stressful family and work life, and anxiety are associated with an increased risk of the development and accelerated progression of existing cardiovascular disease. Current European guidelines on the prevention of cardiovascular disease have emphasized the importance of tackling these factors (2). Mental stress induces myocardial ischaemia in patients with stable coronary artery disease, and this appears to be mediated by adrenal release of catecholamines (3).
Cannabinoids (CBs) are compounds that bind to CB receptors or are structurally similar to compounds that bind to CB receptors. They include endogenously produced compounds (called endocannabinoids), synthetic compounds and phytocannabinoids obtained from the Cannabis sativa plant. There are over 80 known types of phytocannabinoids, the most widely studied of which is Δ 9 tetrahydrocannabinol (Δ 9 -THC or THC), which is responsible for the psychoactive properties of cannabis (4). The other major phytocannabinoid is cannabidiol (CBD), which does not have psychoactive properties. CBD is currently the focus of much research due to its potential in a number of therapeutic areas, as it has been shown to have antiinflammatory, anticonvulsant, antioxidant, anxiolytic, antinausea, and antipsychotic properties (5). A number of preclinical studies have also shown beneficial effects of CBD in a range of disorders of the cardiovascular system (6). A CBD/THC combination (Sativex/Nabiximols, GW Pharmaceuticals) is licensed for the treatment of spasticity in multiple sclerosis, and CBD alone (Epidiolex, GW Pharmaceuticals) has entered an expanded access program in children with intractable epilepsies (Dravet syndrome and Lennox-Gastaut syndrome). Epidiolex has also received orphan designation status for the treatment of neonatal hypoxia-ischaemic encephalopathy.
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 (5HT1A) 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).
Our recent systematic review showed us that there are no dedicated studies in humans to date, to our knowledge, looking at the effect of CBD on either resting cardiovascular measurement or on the responses to stress, with continuous monitoring of CV parameters (15). Therefore, the aim of the present study was to investigate whether CBD decreases the cardiovascular response to stress after the administration of a single dose of CBD (600 mg) in healthy volunteers, with the hypothesis that blood pressure would be reduced by CBD. Noninvasive cardiovascular measurements were used along with stress tests in the form of mental arithmetic, isometric exercise, and the cold pressor test.
Ten male subjects were recruited, but 1 withdrew for personal reasons. The mean age, weight, and height of the volunteers were 23.7 ± 3.2 years, 77.5 ± 6.4 kg, and 178.6 ± 4.5 cm (mean ± SD).
Effect of CBD on resting cardiovascular parameters.
Changes in resting cardiovascular parameters after a single dose (600 mg) of cannabidiol (CBD) in healthy volunteers (n = 9).
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).
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).
Effect of CBD on cardiovascular parameters mental stress.
The individual blood pressure responses of healthy volunteers to the stresses are presented in Figure 2 , showing the average baseline systolic or diastolic blood pressure in the 4 minutes preceeding the stress test, the peak response during stress, and the average recovery response in the 4 minutes after the stress test.
Individual systolic and diastolic blood pressure responses to all stress tests after a single dose (600 mg) of cannabidiol (CBD) or placebo in healthy volunteers (n = 9).
Green color coding shows subjectS who had a reduced (compared with placebo) blood pressure response to stress after taking CBD, and red color coding shows an increased blood pressure response to stress after taking CBD.
Mental stress test.
Cardiovascular response to mental stress after a single dose (600 mg) of cannabidiol (CBD) in healthy volunteers (n = 9).
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 mental arithmetic 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 (+ and # denote significant change in a parameter during the stress period seen with placebo and CBD, respectively). + / # P < 0.05, ++ /# # P < 0.01.
Exercise stress test.
Cardiovascular parameters in response to exercise stress after a single dose (600 mg) of cannabidiol (CBD) in healthy volunteers (n = 9).
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 isometric exercise 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).
Cold stress test.
Cardiovascular response to cold stress after a single dose (600 mg) of cannabidiol (CBD) in healthy volunteers (n = 9).
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).
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 ).
Based on preclinical evidence, the aim of this study was to test the hypothesis that CBD would reduce the cardiovascular response to stress in healthy volunteers. We found that resting blood pressure was lower after subjects had taken CBD and that CBD blunted the blood pressure response to stress, particularly in the pre- and poststress periods. Post-hoc analysis showed an overall trend of lower SBP, MAP, DBP, SV, TPR, forearm skin blood flow, and left ventricular EJT and a higher HR in subjects who had taken CBD. These hemodynamic changes should be considered for people taking CBD and suggest that further research is warranted to establish whether CBD has any role in the treatment of cardiovascular disorders.
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.
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 CB1 and CB2 receptors (21), and the effects of THC on heart rate are mediated through CB1 receptors (20). CBD does not bind with any great affinity to CB1, but it can interact indirectly by augmenting CB1 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 CB1 activation (11). Therefore, it is possible that the changes in hemodynamics brought about by CBD are mediated through CB1.
CBD may cause sympathoinhibition (through CB1 or some other mechanism), thereby preventing an increase in blood pressure and cardiac output, causing a compensatory rise in heart rate to maintain cardiac output. Indeed, the changes in SBP preceded any changes in HR. Another possibility is that CBD inhibits cardiac vagal tone, thereby increasing heart rate (despite any potential sympathoinhibition). A recent study in male Sprague-Dawley rats showed that GPR18 activation in the rostral ventrolateral medulla (RVLM) by abnormal CBD (Abn-CBD) resulted in reduced blood pressure and increased heart rate (23) (similar to that observed in the present study). The same study showed that pretreatment with atropine and propranolol fully abrogated the HR response, suggesting a role for the autonomic nervous system. CBD is a weak partial agonist at GPR18 (24).
Effect of CBD on cardiovascular parameters in response to mental stress.
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.
Effect of CBD on cardiovascular parameters in response to exercise stress.
Isometric exercise produces a pressor response, via sympathoexcitation, originating in the contracting muscle and relayed to the RVLM via the nucleus of solitary tract. The end result is a rise in heart rate and cardiac output and vasoconstriction in nonexercising organs (27–29). There is increased skeletal muscle blood flow in the nonexercising limb, which is sensitive to atropine and propranolol (30). A similar response was seen in our study, where isometric exercise caused a significant rise in SBP, DBP, MAP, and HR and an increase in forearm blood flow, although this was significant in the placebo group only. Subjects who had taken CBD had reduced blood pressure during the exercise stress test, and this was most pronounced in the pre- and posttest period. Before the exercise stress, HR was higher and SV lower in volunteers when they had taken CBD, and this trend continued throughout exercise stress and in the poststress period. There was also a significant reduction in EJT with CBD, which represents a reciprocal change to increased HR. The rise in cutaneous blood flow was only seen with placebo and not with CBD, possibly suggesting reduced β2 adrenergic–mediated vasodilatation, which could be a result of general sympathoinhibition or a specific effect at the β2 adrenoceptors. The tissue distribution of β2 adrenoceptors and CB1 receptors overlaps in many tissues, including in the cardiovascular system (31). At the cellular level, a complex physical and functional interaction between these 2 receptors has been demonstrated; there is evidence of cointernalization of β2 adrenoceptors with CB1 receptors, leading to desensitisation of β2 adrenoceptors (31).
Effect of CBD on cardiovascular parameters in response to cold stress.
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.
Safety and tolerance.
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.
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.
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.
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.
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.
Two hours afterward, subjects were asked to perform the stress tests (36). Timing of the tests was chosen to coincide with peak plasma levels for CBD (18). All the experiments were performed in a sitting position under ambient temperature conditions. Maximum voluntary contraction for the isometric hand grip test was assessed for each subject prior to administering study medication.
After administration of CBD or placebo, subjects remained seated, either doing nothing, reading, or using a computer. During this time, subjects were connected to a calibrated Finometer (Finapres Medical Systems), which uses a finger-clamp method to detect beat-to-beat changes in digital arterial diameter using an infrared photoplethysmograph (40). The Finometer gives a continuous signal of beat-to-beat changes in blood pressure and blood flow, and it uses this signal to derive other parameters, including systolic, diastolic, and mean blood pressure; interbeat interval; heart rate and left ventricular ejection time; stroke volume; cardiac output; and systemic peripheral resistance. Baseline cardiovascular data was recorded for 2 hours following administration of CBD or placebo. Forearm blood flow was measured using a calibrated laser Doppler flowmeter (Perimed) (41). For each recording, 5 images of microcirculation were taken, over an area 19 mm × 19 mm, using the upper third of the left forearm under high resolution. After 2 hours, subjects underwent the cardiovascular stress tests in the following order: mental arithmetic, isometric exercise, and cold pressor test.
The mental arithmetic test consisted of calculating a sum every 2 second for 2 minutes. Subjects were seated in front of a computer screen, and a PowerPoint presentation delivered a slide with a simple mathematical sum of a 3-digit number minus a smaller number (e.g., 317 – 9, 212 – 11, 185 – 7) every 2 seconds; the subject had to give the answer verbally. In the isometric exercise stress test, using a dynamometer, handgrip was maintained at 30% of maximum voluntary contraction (MVC) for 2 min. For the cold pressor test, subjects immersed their left foot (up to ankle) in ice slush (temperature 4°C–6°C) for 2 minutes. Cardiovascular parameters were measured continuously using the Finometer, while skin blood flow measurements were taken just before, during, and 5 minutes after each test. Each stress test lasted for 2 minutes, and there was a recovery period of at least 10 minutes.
Data were analyzed using repeated measures ANOVA to determine the effect of treatment and time on different variables using GraphPad PRISM version 6.02. Level of significance was set at α = 0.05 and values presented as mean ± SEM. Sidak’s post-hoc test was used to see treatment affect at various time points. Data were not unblinded until after statistical analysis.
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.
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.
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.
Conflict of interest: GW Pharma supplied the cannabidiol (CBD) and placebo but did not fund the study.
Reference information:JCI Insight. 2017;2(11):e93760. https://doi.org/10.1172/jci.insight.93760.
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