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 CBD Oil for Blood Pressure: Research and Best CBD Oils
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.
1. Figueredo VM. The time has come for physicians to take notice: the impact of psychosocial stressors on the heart. Am J Med. 2009; 122 (8):704–712. doi: 10.1016/j.amjmed.2009.05.001. [PubMed] [CrossRef] [Google Scholar]
2. Perk J, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts) Eur Heart J. 2012; 33 (13):1635–1701. doi: 10.1093/eurheartj/ehs092. [PubMed] [CrossRef] [Google Scholar]
3. Goldberg AD, et al. Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) Circulation. 1996; 94 (10):2402–2409. doi: 10.1161/01.CIR.94.10.2402. [PubMed] [CrossRef] [Google Scholar]
4. Costa B. On the pharmacological properties of Delta9-tetrahydrocannabinol (THC) Chem Biodivers. 2007; 4 (8):1664–1677. doi: 10.1002/cbdv.200790146. [PubMed] [CrossRef] [Google Scholar]
5. Mechoulam R, Parker LA, Gallily R. Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol. 2002; 42 (11 Suppl):11S–19S. [PubMed] [Google Scholar]
6. Stanley CP, Hind WH, O’Sullivan SE. Is the cardiovascular system a therapeutic target for cannabidiol? Br J Clin Pharmacol. 2013; 75 (2):313–322. doi: 10.1111/j.1365-2125.2012.04351.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
7. Rajesh M, et al. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am J Physiol Heart Circ Physiol. 2007; 293 (1):H610–H619. doi: 10.1152/ajpheart.00236.2007. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
8. Rajesh M, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol. 2010; 56 (25):2115–2125. doi: 10.1016/j.jacc.2010.07.033. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
9. El-Remessy AB, Al-Shabrawey M, Khalifa Y, Tsai NT, Caldwell RB, Liou GI. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am J Pathol. 2006; 168 (1):235–244. doi: 10.2353/ajpath.2006.050500. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
10. O’Sullivan SE, Sun Y, Bennett AJ, Randall MD, Kendall DA. Time-dependent vascular actions of cannabidiol in the rat aorta. Eur J Pharmacol. 2009; 612 (1-3):61–68. doi: 10.1016/j.ejphar.2009.03.010. [PubMed] [CrossRef] [Google Scholar]
11. Stanley CP, Hind WH, Tufarelli C, O’Sullivan SE. Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation. Cardiovasc Res. 2015; 107 (4):568–578. doi: 10.1093/cvr/cvv179. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
12. Walsh SK, Hepburn CY, Kane KA, Wainwright CL. Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion. Br J Pharmacol. 2010; 160 (5):1234–1242. doi: 10.1111/j.1476-5381.2010.00755.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
13. Resstel LB, Tavares RF, Lisboa SF, Joca SR, Corrêa FM, Guimarães FS. 5-HT1A receptors are involved in the cannabidiol-induced attenuation of behavioural and cardiovascular responses to acute restraint stress in rats. Br J Pharmacol. 2009; 156 (1):181–188. doi: 10.1111/j.1476-5381.2008.00046.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
14. Choi DC, Furay AR, Evanson NK, Ostrander MM, Ulrich-Lai YM, Herman JP. Bed nucleus of the stria terminalis subregions differentially regulate hypothalamic-pituitary-adrenal axis activity: implications for the integration of limbic inputs. J Neurosci. 2007; 27 (8):2025–2034. doi: 10.1523/JNEUROSCI.4301-06.2007. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
15. Sultan SR, Millar SA, England TJ, O’Sullivan SE. A Systematic Review and Meta-Analysis of the Haemodynamic Effects of Cannabidiol. Front Pharmacol. 2017; 8 :81. [PMC free article] [PubMed] [Google Scholar]
16. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology (Berl) 1982; 76 (3):245–250. doi: 10.1007/BF00432554. [PubMed] [CrossRef] [Google Scholar]
17. Martin-Santos R, et al. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers. Curr Pharm Des. 2012; 18 (32):4966–4979. doi: 10.2174/138161212802884780. [PubMed] [CrossRef] [Google Scholar]
18. Fusar-Poli P, et al. Distinct effects of
19. Bergamaschi MM, et al. Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients. Neuropsychopharmacology. 2011; 36 (6):1219–1226. doi: 10.1038/npp.2011.6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
20. Sidney S. Cardiovascular consequences of marijuana use. J Clin Pharmacol. 2002; 42 (11 Suppl):64S–70S. [PubMed] [Google Scholar]
21. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol. 2008; 153 (2):199–215. doi: 10.1038/sj.bjp.0707442. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
22. McPartland JM, Duncan M, Di Marzo V, Pertwee RG. Are cannabidiol and Δ(9) -tetrahydrocannabivarin negative modulators of the endocannabinoid system? A systematic review. Br J Pharmacol. 2015; 172 (3):737–753. doi: 10.1111/bph.12944. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
23. Penumarti A, Abdel-Rahman AA. The novel endocannabinoid receptor GPR18 is expressed in the rostral ventrolateral medulla and exerts tonic restraining influence on blood pressure. J Pharmacol Exp Ther. 2014; 349 (1):29–38. doi: 10.1124/jpet.113.209213. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
24. McHugh D, Page J, Dunn E, Bradshaw HB. Δ(9) -Tetrahydrocannabinol and N-arachidonyl glycine are full agonists at GPR18 receptors and induce migration in human endometrial HEC-1B cells. Br J Pharmacol. 2012; 165 (8):2414–2424. doi: 10.1111/j.1476-5381.2011.01497.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
25. Schwartz CE, Durocher JJ, Carter JR. Neurovascular responses to mental stress in prehypertensive humans. J Appl Physiol. 2011; 110 (1):76–82. doi: 10.1152/japplphysiol.00912.2010. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
26. Barcroft H, Brod J, Hejl BZ, Hirsjarvi EA, Kitchin AH. The mechanism of the vasodilatation in the forearm muscle during stress (mental arithmetic) Clin Sci. 1960; 19 :577–586. [PubMed] [Google Scholar]
27. Lind AR, Taylor SH, Humphreys PW, Kennelly BM, Donald KW. THE CIRCULATIORY EFFECTS OF SUSTAINED VOLUNTARY MUSCLE CONTRACTION. Clin Sci. 1964; 27 :229–244. [PubMed] [Google Scholar]
28. Delius W, Hagbarth KE, Hongell A, Wallin BG. Manoeuvres affecting sympathetic outflow in human muscle nerves. Acta Physiol Scand. 1972; 84 (1):82–94. doi: 10.1111/j.1748-1716.1972.tb05158.x. [PubMed] [CrossRef] [Google Scholar]
29. Sander M, Macefield VG, Henderson LA. Cortical and brain stem changes in neural activity during static handgrip and postexercise ischemia in humans. J Appl Physiol. 2010; 108 (6):1691–1700. doi: 10.1152/japplphysiol.91539.2008. [PubMed] [CrossRef] [Google Scholar]
30. Ishii K, et al. Differential contribution of ACh-muscarinic and β-adrenergic receptors to vasodilatation in noncontracting muscle during voluntary one-legged exercise. Physiol Rep. 2014; 2 (11):e12202. [PMC free article] [PubMed] [Google Scholar]
31. Hudson BD, Hébert TE, Kelly ME. Physical and functional interaction between CB1 cannabinoid receptors and beta2-adrenoceptors. Br J Pharmacol. 2010; 160 (3):627–642. doi: 10.1111/j.1476-5381.2010.00681.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]
32. Victor RG, Leimbach WN, Seals DR, Wallin BG, Mark AL. Effects of the cold pressor test on muscle sympathetic nerve activity in humans. Hypertension. 1987; 9 (5):429–436. doi: 10.1161/01.HYP.9.5.429. [PubMed] [CrossRef] [Google Scholar]
33. Mathias CJ, Bannister R. Investigation of autonomic disorders. In: Bannister R, Mathias CJ, eds. Autonomic Failure. A textbook of clinical disorders of the autonomic nervous system. Oxford:Oxford University Press;1992:255–290. [Google Scholar]
34. Yamamoto K, Iwase S, Mano T. Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test. Jpn J Physiol. 1992; 42 (2):239–252. doi: 10.2170/jjphysiol.42.239. [PubMed] [CrossRef] [Google Scholar]
35. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008; 4 (1):245–259. [PMC free article] [PubMed] [Google Scholar]
36. O’Sullivan SE, Bell C. Training reduces autonomic cardiovascular responses to both exercise-dependent and -independent stimuli in humans. Auton Neurosci. 2001; 91 (1-2):76–84. doi: 10.1016/S1566-0702(01)00288-0. [PubMed] [CrossRef] [Google Scholar]
37. Tzadok M, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure. 2016; 35 :41–44. doi: 10.1016/j.seizure.2016.01.004. [PubMed] [CrossRef] [Google Scholar]
38. Fusar-Poli P, et al. Modulation of effective connectivity during emotional processing by Delta 9-tetrahydrocannabinol and cannabidiol. Int J Neuropsychopharmacol. 2010; 13 (4):421–432. doi: 10.1017/S1461145709990617. [PubMed] [CrossRef] [Google Scholar]
39. O’Connell BK, Gloss D, Devinsk O. Cannabinoids in treatment-resistant epilepsy: A review. Epilepsy Behav. doi: 10.1016/j.yebeh.2016.11. [published online ahead of print February 8, 2017]. https://doi.org/10.1016/j.yebeh.2016.11.012. [PubMed] [CrossRef] [Google Scholar]
40. Schutte AE, Huisman HW, van Rooyen JM, Malan NT, Schutte R. Validation of the Finometer device for measurement of blood pressure in black women. J Hum Hypertens. 2004; 18 (2):79–84. doi: 10.1038/sj.jhh.1001639. [PubMed] [CrossRef] [Google Scholar]
41. Johnson JM, Taylor WF, Shepherd AP, Park MK. Laser-Doppler measurement of skin blood flow: comparison with plethysmography. J Appl Physiol Respir Environ Exerc Physiol. 1984; 56 (3):798–803. [PubMed] [Google Scholar]
CBD Oil for Blood Pressure: Research and Best CBD Oils
Disclaimer: This post contains affiliate links. We may be compensated for sales.
High blood pressure, or hypertension, is a common condition that can lead to heart disease and stroke. While there are many medications available to treat hypertension, some people may prefer to try CBD oil first.
This article will explore the research on CBD oil for high blood pressure and list the best CBD oils for this purpose.
Best CBD Oils for Blood Pressure
How CBD Might Lower Your Blood Pressure
There are many non-intoxicating cannabinoids found in cannabis and hemp, but CBD stands out. Unlike THC which produces an intoxicating high (the type associated with feelings like pain relief or mood), this one acts on serotonergic (5HT) or vanilloid TRP sites to regulate bodily processes such as inflammation without providing any sort of feeling at all.
CBD has been shown to lower blood pressure, but it’s not clear if this happens because of the mood elevating effect or some other property. Studies indicate that CBD reduces stress and leads people who use them feel lighter overall which could be responsible for their reduced heart rates.
There is a possibility that CBD’s activity in your brain might reduce stress by improving mood, which could also be linked to reduced hypertension. Future research will reveal more information on how it relates specifically for blood pressure.
Does CBD Oil Lower Blood Pressure?
There is a lot of research regarding how CBD affects blood pressure, but the results are not always clear. It could end up being good news for those looking into natural remedies as an alternative treatment option if it turns out that lower readings were seen with increased consumption rates than higher ones!
With more and more people sharing their experiences online, it’s clear that CBD can help with high blood pressure. The relaxing feeling provided by this cannabinoid is enough to make anyone feel better!
Many people with high blood pressure have shared stories online regarding how CBD helped them get their disease under control. One of the most common effects that those who use this cannabinoid report is a body-wide relaxing feeling, and it’s easy to see why individuals would say using CBD oil lowers your resting heartbeat.
Is CBD Safe to Use for High Blood Pressure?
CBD can make your blood pressure low, but it may also interact badly with prescription medicines. If you take any “grapefruit warning” medications then talk to a doctor before adding CBD supplements into the mix!
The most commonly reported side effects of CBD oil for blood pressure includes sleepiness, nausea, and dry mouth but many users do not experience any negative reactions at all in spite of its popularity for treating hypertension among other things
The benefits seem to outweigh these insignificant issues making it worth considering as an option beyond traditional medicine options.
What Research Says About CBD and Blood Pressure
In the last few years, CBD has been shown to have a number of health benefits. One such benefit is its ability to reduce blood pressure levels which could be useful for people who suffer from hypertension or high cholesterol and heart disease risks associated with it.
A recent study shows that this isn’t just theory anymore–cannabis oil seems real potential when looking at reducing your chances against developing these conditions in the future.
The research into CBD’s potential as an overall treatment for heart health was first introduced in 2012. The study started the conversation on this subject within medical science and provided some insight into how it could be useful with managing different conditions such as high blood pressure or chronic pain
This passage details when scientists began discussing whether there is evidence that backs up claims made by those who say cannabis can treat cardiovascular issues like angina pectoris, strokes, etc.,
The first hard evidence of the usefulness of CBD for blood pressure was most recently published in 2017. This small study found this cannabinoid to maintain low pressures even when participants were exposed to stressful stimuli, leading researchers from various institutions to declare that “CBD does seem like a promising alternative or supplement.”
Researchers have yet to uncover the secrets of CBD for blood pressure, but they continue their research into this area. In 2020 researchers performed extensive experiments on animal and human tissue samples in order to determine how it affects vessel relaxation properties among other things- discovering more about this potential treatment’s ability may be fruitful indeed.
What Type of CBD Is Best for Blood Pressure?
If you’re trying to manage your high blood pressure with CBD, then the best types of products are oils and gummies. They have been proven in clinical trials as being more effective than other forms like soft gels or topicals. Still, let’s discuss the various options of CBD oil for blood pressure:
CBD oils are also referred to as CBD tinctures. These are the more popular types of CBD products you’ll find online. Their popularity is mostly a testament to the ease of use and discreet ability to get your CBD Oil for blood pressure in liquid form.
CBD users often take oil tinctures whenever they experience pain or other ailments in life. Besides offering a higher potency and quick absorption time, these CBD oils are better for managing blood pressure than other types of orally consumed CBD options.
The benefits of CBD oil are diverse, but one thing that you might not have known about them is how they can be consumed. Tinctures typically come in bottles and need to be taken sublingually while gummies offer the convenience factor because it means no more carrying around vials with yourself everywhere!
When using CBD to manage blood pressure, it’s important that you avoid eating excessive sweets. This could make your condition worse so only choose gummies with natural ingredients and minimal sweeteners for the best results.
Another venetian option to take CBD oil for blood pressure is CBD soft gels. These are just as easy to take orally and can provide you with an easy way to swallow and forget about your CBD oil treatment.
While soft gels may be the simpler option to get your intake of CBD oil, they’re much like CBD gummies in that they’re less potent than CBD tinctures. However, soft gels may be better than CBD gummies as they don’t have the sugar content found in the gummies. Thus making CBD soft gels are a doable option for blood pressure patients.
CBD Topicals and Creams
Topically applied CBD creams, lotions and balms won’t be very useful for reducing high blood pressure. Hypertension is a cardiovascular condition with its central origin being the heart, inside the body. So treating the peripheral areas of your body will not help unlock symptoms associated with CBD oil for blood pressure.
The use of this cannabinoid must extend beyond just topical applications if you want adequate success rates when it comes down to effectively controlling your blood pressure with CBD oils.
Best CBD Oil for Blood Pressure
With all of the options available for CBD oil, it’s hard to know which brand will work best. We scoured product descriptions and reviews from customers who tried different brands in order to find out how well each one reduced blood pressure levels when compared against others.
Below is an overview comparing some popular CBD oils for blood pressure available on the market as of today.
1. Colorado Botanicals
Image courtesy Colorado Botanicals
With a lack of federal regulation, Colorado Botanicals has taken upon themselves to offer high-tech and terpene-rich CBD hemp extractions. The company uses pharmaceutical-grade equipment for the production process without any metal toxins or pesticides in order to make sure their customers get what they need with all natural ingredients.
What makes the Colorado Botanicals CBD oil so special? It’s organic, non-GMO, and full of synergistic effects. This means that when taken together with other cannabinoids like THC or terpenes it becomes more potent than before! Reviewers rave about how this product has helped them in their medical treatments but also claims to be ideal for those who have hypertension as well – because they know what comes first: Your health matters most too.
2. Penguin CBD – Best CBD Oil for Blood Pressure
Image courtesy Penguin CBD
This brand is on-trend and it would be safe to say they are becoming popular among consumers looking for quality products at reasonable prices without sacrificing performance or terpenes like those found in Colorado Botanicals extractions.
However-aside from being less attentive about choosing specific cannabinoids over others based solely on their desired effects. Penguin out does an excellent job offering high standard tinctures that you can try.
The company, Penguin CBD has a variety of products available with different flavors and potencies. They use third-party lab reports to ensure the safety of their product which is free from THC but contains natural ingredients such as terpenes found in cannabis during extraction rather than introducing them after seeping through cotton fibers or other methods commonly employed by manufacturers who produce isolates instead of curing whatever mixture might have been used before planting.
3. R+R Medicinals
Image courtesy R+R Medicinals
The all-natural approach taken by R+R Medicinals is a step further than practically any other company we’ve seen. Their labeling is little outdated, their CBD tinctures contain just full-spectrum extracts with no additional ingredients besides those found in traditional medicine – which is often very beneficial when it comes to blood pressure control!
R+R Medicinals is one of the only companies that uses supercritical CO2 extraction to produce CBD tinctures. The company provides batch-specific, third-party lab tests for all its products and has no reviews available online except for their own website which does not provide any insight into how well these blends work or what benefits may arise when taken as directed with other medications/supplements, etc., so we recommend proceeding cautiously if you’re interested in trying them out.
Image courtesy Everest
For all you dessert lovers out there, Everest has the perfect CBD oil for your sweet tooth. Their blueberry mint full-spectrum cannabis concentrate is mouthwateringly good and can be taken under tongue or blended into hot cocoa to create that signature warm feeling in an instant.
Everest’s CBD oil is so powerful that each bottle contains 1,500mg of the cannabinoid. With 50mg per dose and an 5:1 ratio to other helpful cannabinoids like THC it normally costs $125 but you can get your hands on this great product for just $100 with their subscribe discounted plan.
Image courtesy CBDfx
With products that look like they’d be right at home locked up behind the counter, CBDfx is taking a mainstream approach to consumer packaged goods. Offering an array of different types for low prices and with a huge variety in every product line; CBD fans will surely find something relevant!
CBDfx is a brand that focuses heavily on natural ingredients but includes some added terpenes in their products. However, all of these goods are produced through artificial processing with unnatural additives or sweeteners which give them an unpleasant taste for many people’s tastes buds- including ours.
6. Royal CBD
Image courtesy Royal CBD
When it comes to high-quality CBD, Royal is the brand you need. They offer more than just their competition when considering cost and benefit for blood pressure treatment with products that are available in 500 mg through 2000mg options under this overpriced company’s label!
The information available on Royal CBD is not as extensive or impressive. The lab tests and ingredients are hard to find, which leaves room for improvement in this area of their brand promise.
What to Look for When Buying CBD Oil
We’ve done the hard work for you, but it will be up to each person individually as they search through all of these products vying for their attention. Somewhere out there is likely a perfect match-a tincture that suits your needs and takes into account some criteria such as blood pressure levels or symptoms associated with chronic pain management warrants consideration before making any final decisions about what might simply feel good enough.
Full Spectrum vs. Broad Spectrum CBD Oil
There is a big difference between full-spectrum and broad spectrum CBD. The THC content in some brands can be as high as 0.3%, while others have tiny traces that are undetectable to human senses (or even if they exist).
One of the only downsides to using broad-spectrum CBD is that delicate hemp compounds such as terpenes often get damaged during extraction. Luckily, Penguin CBD has found a way around this by taking their time and ensuring all plant material remains intact while producing high-quality extracts without any significant breakdown in flavors or effects.
Testing is an important step in the quality assurance of any business, but it’s even more crucial for CBD companies. The lack of inadequate regulation by federal agencies has made many consumers nervous about what they’re purchasing and how much risk there may be involved with their purchase, especially when dealing directly from brands online without physically seeing products before buying them.
By having tests done on your product(s), CBD oil brands can show customers that not only do they care about providing trustworthy items as per request; testing also helps them prove validity so everyone knows exactly where each bottle came from!
FDA Warning Letters and Lawsuits
It’s important to stay away from CBD hemp manufacturers that have been specifically targeted by the FDA for wrongdoing. The agency sends out warning letters from time to time, and an up-to-date list of all their correspondence can be found on their website.
Transparency is important for any CBD manufacturer, but it’s especially vital when you are trying to sell your product. When potential customers know what they’re getting and how their purchase will benefit them, there’s no reason not to make things clear with the people who helped create this natural healing herb.
CBD is no longer a new thing, but it has been gaining momentum. With more and more brands founded all the time, however, there are plenty of reliable players who have had their turn at accumulating customer reviews
The internet can be an overwhelming place for new CBD oil consumers, but that doesn’t mean you should give up on finding a product before it’s even tried. Brands with fewer than 100 reviews may not have been properly tested by those who are critical about their work – so make sure to do additional research.
Is CBD Oil Safe to Use with Blood Pressure Medications?
CBD has been shown to interact with certain common prescription drugs that utilize the cyp3a4 metabolic enzyme. One 2017 review of available evidence concluded that when you consume CBD, it can cause a change in blood pressure medication concentrations leading some doctors to determine contraindications for these medications before prescribing them exclusively or primarily depending on their own experiences treating patients who take both types combined.
On the contrary, it’s not CBD that you should be worried about but rather prescription drugs in your blood. Elevated levels of these can no longer leave as they’re blocked by metabolic enzymes and instead cause problems for other bodily functions like heart health or brain function which may lead to increased risk-taking behaviors – something we don’t want!
However with a doctor’s consenting permission if using oil together then go ahead knowing extreme caution is still necessary when taking both simultaneously because there could potentially be an adverse reaction.
When to Contact a Doctor
You should always be in touch with your doctor when it comes to CBD. Ask them if you can try the product and make sure that they are excited about its potential heart health benefits, but also watch out for any negative side effects or interactions between other medications/intervention programs where there could potentially be more harmful than helpful outcomes.
While CBD’s apparent ability to reduce blood pressure may be the desired effect in some individuals, it can also lead them to a side of complacency and neglect other aspects of their health. The cardiovascular system is remarkably delicate, so always take caution when trying this natural method to reduce blood pressure.
You should never wait until your symptoms are severe before contacting a doctor. CBD can make the blood pressure too low, so if you’re concerned about this and need help reaching out ask anyone who knows how! Staying in touch with them will keep you safe while treating your condition.
Final Thoughts: CBD for Blood Pressure
While cannabidiol has been shown to reduce blood pressure, the potential health benefits of CBD are worthy of further study. At this point in time, there’s no evidence that it will cause any serious side effects and many people have reported success using it for high blood pressure or other types of heart disease
A lot more research needs doing before we know what kind exactly but probably something similar like how marijuana helps fight off certain cancers and epilepsy and bipolar and schizophrenia in adults and kids to see if CBD oil can do the same.
The body is designed to keep your system delicately balanced, and high-quality CBD oil acts as a natural balancer. The lack or inclusion of THC in these products means that they will not get you high even if used incorrectly; however, it can still have many health benefits without harming anyone’s blood pressure levels.
While CBD is not an intoxicant, it does have promising effects on blood pressure. The scientists of today and tomorrow will determine whether or not this cannabinoid lowers the reading in individuals with higher levels of risk for cardiovascular disease- but there’s no doubt that research has already begun exploring its possibilities as a cure-all around town.
For now, feel free to use one of our CBD oil for blood pressure recommendations featured above. As long as you take CBD oil under the guidance of a doctor, you’ll find that these natural products will assist in helping you feel better quickly. All in all, we feel if you’re on the hunt for CBD oil for blood pressure, our list is the best place to start for high-quality, trusted CBD oil brands to lower blood pressure.