Fewer studies have investigated the vascular effects of CBD. incidents such as acute myocardial infarction, heart failure and stroke [43–45]. Despite the considerable research in this field, the benefits of cannabis and its . of diseases such as stroke, atherosclerosis, restenosis, MI and heart failure. CBD, a cannabinoid from the cannabis plant, has been studied for its heart disease, stroke, and diseases of the arteries, arterioles, and.
Failure Cannabidiol Studies & Congestive Heart
Similarly, in a different model of ischaemia-reperfusion, CBD has been shown to reduce infarct size and increase blood flow in animal models of stroke, sensitive to 5HT 1A receptor antagonism. Although acute or chronic CBD treatment seems to have little effect on haemodynamics, CBD reduces the cardiovascular response to models of stress, applied either systemically or intracranially, inhibited by a 5HT 1A receptor antagonist. In blood, CBD influences the survival and death of white blood cells, white blood cell migration and platelet aggregation.
Taken together, these preclinical data appear to support a positive role for CBD treatment in the heart, and in peripheral and cerebral vasculature.
However, further work is required to strengthen this hypothesis, establish mechanisms of action and whether similar responses to CBD would be observed in humans. Cannabidiol CBD is an abundant, non psychoactive, plant derived cannabinoid phytocannabinoid whose stereochemistry was first described in by Mechoulam and colleagues [ 1 ]. Since its isolation, a range of synthetic analogues have been synthesized based on the classic cannabinoid dibenzopyran structure, including abnormal CBD Abn-CBD , O and O [ 2 , 3 ].
CBD is reported to have a diverse pharmacology which is reviewed in depth elsewhere [ 4 ]. As well as a rich pharmacology, CBD is suggested to have therapeutic potential in a vast range of disorders including inflammation, oxidative stress, cancer, diabetes, gastrointestinal disturbances, neurodegenerative disorders and nociception [ 8 — 12 ].
Evidence is also now accumulating that there are positive effects of CBD in the vasculature. It is the aim of this review to examine this evidence and establish whether or not the cardiovascular system is a potential therapeutic target for CBD. A recent review of the safety and side effects of CBD concluded that CBD appears to be well tolerated at high doses and with chronic use in humans [ 13 ], and thus has the potential to be taken safely into the clinic.
The acute vascular effects of cannabinoid compounds have been well studied in a range of models. In a variety of in vivo and in vitro models, phytocannabinoids and endogenous cannabinoids endocannabinoids have been shown to cause vasorelaxation.
However, the potency, efficacy and mechanisms of action often differ. For example, early work in rabbit cerebral arteries showed that THC and the endocannabinoid anandamide AEA caused vasorelaxation that was dependent on cyclooxygenase COX activity [ 14 ]. Later, Randall et al. The vasorelaxant effects of AEA in rat arteries are also dependent on the vessel size in that the maximal response to AEA is greater in small resistance vessels and includes an endothelial-dependent component that is not observed in larger arteries [ 16 ].
Further differences in cannabinoid effects can be found when comparing the same arterial bed of differing species. It has also been shown that cannabinoid responses are dependent on the cannabinoid compound used.
For example, the endocannabinoids AEA and N -arachidonoyl-dopamine NADA cause similar degrees of vasorelaxation in rat aortae, but by different mechanisms [ 17 ]. These studies highlight the complexity of acute vasodilator actions of cannabinoids on the vasculature for a full review see [ 19 ].
The potential therapeutic uses of cannabinoids other than CBD in cardiovascular diseases, including cardioprotection, stroke, arrhythmias and atherosclerosis, have been reviewed elsewhere [ 22 — 24 ]. Work to date investigating the vascular effects of cannabinoids has primarily concentrated on the response to endocannabinoids, THC and synthetic ligands, with only limited studies conducted using CBD. The effects of Abn-CBD were inhibited by high. The findings of endothelial dependent and independent components of Abn-CBD-induced vasorelaxation is in agreement with a similar study of the same year showing that in rat mesenteric arteries, vasorelaxation to Abn-CBD was inhibited by PTX incubation and incubation with another CBD anologue, O, and indeed this was dependent on the endothelium [ 28 ].
More recently it has been shown that Abn-CBD causes vasorelaxation in the human pulmonary artery through similar mechanisms [ 29 ]. Fewer studies have investigated the vascular effects of CBD.
However, in arterial segments taken from the rat mesenteric vascular bed that have been mounted onto a Mulvany-Halpern myograph and constricted with phenylephrine, CBD causes a concentration-dependent near-maximal vasorelaxation [ 28 ].
Unfortunately, this study did not probe the mechanisms underlying this vasorelaxant effect of CBD in rat mesenteric arteries. In human mesenteric arteries, CBD-induced vasorelaxation has a p E C 50 in the mid-micromolar range which is similar to that observed in rat mesenteric arteries. Direct vascular effects of CBD measured in isolated arteries. It is interesting to note that Ruiz-Valdepenas et al. LPS has been suggested to cause hypotension through activation of a novel as yet unidentified cannabinoid receptor which could be inhibited by SRA but not AM [ 35 ].
Increasing evidence has indicated that cannabinoids are capable of binding to, activating and causing PPAR—mediated responses [ 39 ]. However, it should be noted that recent work has suggested the use of TZDs may lead to decreases in cardiovascular function and could prompt incidents such as acute myocardial infarction, heart failure and stroke [ 43 — 45 ]. Few studies to date have examined the haemodynamic responses to CBD.
However, other studies do not report any acute effects of in vivo treatment with CBD on baseline heart rate or blood pressure in animal studies [ 48 , 49 ]. In a recent review, Bergamaschi et al. Thus, the majority of evidence suggests there is no effect of CBD on haemodynamics. However, as has been observed with other cannabinoid compounds, the potential hypotensive effects of CBD may need to be revealed in models of raised blood pressure.
Additionally, any change in haemodynamics that might occur may be rapid [ 47 ] and therefore not observed in chronic treatment studies. CBD is known to be anxiolytic. CBD treatment reduces anxiety related to public speaking or fearful stimuli in humans [ 10 ]. A number of studies have now also shown that CBD reduces the cardiovascular response to anxiety or stressful situations.
This effect appears to be mediated in the brain, as the same effect of CBD on cardiovascular responses could be mimicked when CBD was injected into the bed nucleus of the stria terminalis a limbic structure [ 50 ].
The potential ability of CBD treatment in humans to reduce the cardiovascular as well as behavioural response to stress could have significant effects on the development of atherosclerosis and hypertension, which are known to be accelerated by stress [ 51 , 52 ]. Several studies have shown that CBD is beneficial in preventing ischaemia-reperfusion damage in the liver [ 53 , 54 ] and brain [ 55 ].
Furthermore, they showed that this cardioprotective effect of CBD could not be mimicked in vitro , and suggested that the cardioprotective effects of CBD are due to a systemic immunomodulatory effect rather than a direct effect on the heart [ 56 ]. This was also associated with a reduction in ventricular ectopic beats, suggesting an additional anti-arrhythmic role for CBD. Together, these data suggest that in vivo treatment with CBD has significant cardioprotective effects, which may be through a direct action on the heart or via a general anti-inflammatory, anti-oxidant mechanism see Table 1.
The current body of evidence supporting a therapeutic role for CBD in cardiovascular disorders. There is a growing body of evidence that administration of CBD can ameliorate the negative effects of conditions associated with endothelial dysfunction.
The high glucose conditions associated with diabetes have been reported as a causal factor in endothelial dysfunction. These effects were all reduced when the cells were co-incubated with CBD compared with high glucose alone. CBD also decreased monocyte adhesion and trans-endothelial migration, which are key elements in the progression of atherosclerosis.
Using an in vivo model of diabetic retinopathy, El-Remessy et al. Thus, CBD-mediated protection of the vasculature in a model of diabetes may lead to a reduction in complications such as retinopathy, although this could also be driven by the neuroprotective effects of CBD. We have carried out some preliminary experiments examining the ability of CBD to modulate vasodilator responses. We have similarly shown that incubation with CBD enhances the vasorelaxant response to acetylcholine in the spontaneously hypertensive rat O'Sullivan, unpublished data.
Taken together these studies show that in vitro and in vivo , using cell culture, isolated tissue and animal models, CBD has been demonstrated to reduce the negative effects of high glucose, diabetes and inflammation on the vasculature and on vascular hyperpermeability. As yet, the receptor sites of action for CBD in some of these studies remain unclear, but a common theme is the reduction in inflammatory markers see Table 1.
Administration of endogenous, synthetic or phytocannabinoids has been shown to provide neuroprotection using a variety of in vivo and in vitro disease models, including stroke [ 65 ].
Similarly, post ischaemic administration of CBD 1. CBF is reduced or completely abolished in certain areas of the brain during ischaemic stroke, thus, restoring CBF to provide adequate perfusion is of great importance. Exposing newborn piglets to hypoxia-ischaemia, Alvarez and colleagues [ 72 ] also demonstrated the ability of CBD 0. BBB disruption is an important facet in the pathophysiology of ischaemic stroke [ 73 ]. Therefore, CBD-mediated preservation of this barrier, as demonstrated in other disease models could represent another mechanism of CBD-mediated protection in ischaemic stroke.
Improvement is associated with reduced inflammation which is a probable mechanism of recovery, and, importantly, improvement is seen whether TZDs are administered before or after MCAO [ 75 , 77 ]. However, the current evidence suggests that the analgesia is mediated by THC and it is unclear whether CBD contributes to the therapeutic effects. However, the anti-inflammatory properties of CBD discussed above could be predicted to play a role in the analgesic effects of nabiximols.
Recent research has also suggested that cannabinoids and opioids have different mechanisms for reducing pain and that their effects may be additive, which suggests that combination therapies may be developed that may have reduced risks compared to current opioid therapies.
However, this work is very preliminary. In addition to the research on the use of cannabinoids in palliative treatments for cancer—reducing pain and nausea and in increasing appetite—there are also several pre-clinical reports showing anti-tumor effects of CBD in cell culture and in animal models.
There are multiple industry sponsored clinical trials underway to begin to test the efficacy of CBD in human cancer patients. Marijuana can produce acute psychotic episodes at high doses, and several studies have linked marijuana use to increased risk for chronic psychosis in individuals with specific genetic risk factors.
Research suggests that these effects are mediated by THC, and it has been suggested that CBD may mitigate these effects. CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological e. CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task.
Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphine xxxviii and reduced cue-induced heroin seeking xxxix in animal models. NIDA is supporting multiple ongoing clinical trials in this area. A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages, including acute and chronic dose regimens, using various modes of administration.
Because of this, there is extensive information available with regard to its metabolism, toxicology, and safety. However, additional safety testing among specific patient populations may be warranted should an application be made to the Food and Drug Administration. Studies have demonstrated that inflammatory molecules stimulate the cycle leading to atherosclerotic lesions.
The CB2 receptor is also stimulated by plant-based cannabinoids. Reduced Risk of Cancer Could cannabidiol help prevent tumors and other cancers before they grow? A study showed that animals treated with CBD were significantly less likely to develop colon cancer after being induced with carcinogens in a laboratory.
Continuing research is focused on the best ratio of CBD to THC and the most effective dose level in cancer prevention and treatment. Cannabinoids are neuroprotective, meaning that they help maintain and regulate brain health. The effects appear to be related to several actions they have on the brain, including the removal of damaged cells and the improved efficiency of mitochondria.
Extra glutamate, which stimulates nerve cells in the brain to fire, causes cells to become over-stimulated, ultimately leading to cell damage or death. Thus, cannabinoids help protect brain cells from damage, keeping the organ healthy and functioning properly. CBD has also been shown to have an anti-inflammatory effect on the brain.
As the brain ages, the creation of new neurons slows down significantly. In order to maintain brain health and prevent degenerative diseases, new cells need to be continuously created. A study showed that low doses of CBD- and THC-like cannabinoids encouraged the creation of new nerve cells in animal models, even in aging brains. Cannabinoids are facilitative of the process of bone metabolism—the cycle in which old bone material is replaced by new at a rate of about 10 percent per year, crucial to maintaining strong, healthy bones over time.
CBD in particular has been shown to block an enzyme that destroys bone-building compounds in the body, reducing the risk of age-related bone diseases like osteoporosis and osteoarthritis. In both of those diseases, the body is no longer creating new bone and cartilage cells. CBD helps spur the process of new bone-cell formation, which is why it has been found to speed the healing of broken bones and, due to a stronger fracture callus, decrease the likelihood of re-fracturing the bone bones are 35—50 percent stronger than those of non-treated subjects.
Protects and Heals the Skin The skin has the highest amount and concentration of CB2 receptors in the body. When applied topically as an infused lotion, serum, oil, or salve, the antioxidant a more powerful antioxidant than vitamins E and C  in CBD oil has many benefits and can repair damage from free radicals like UV rays and environmental pollutants.
Cannabinoid receptors can be found in the skin and seem to be connected to the regulation of oil production in the sebaceous glands. In fact, historical documents show that cannabis preparations have been used for wound healing in both animals and people in a range of cultures spanning the globe and going back thousands of years.
The use of concentrated cannabis and CBD oils to benefit and treat skin cancer is gaining popularity with a number of well-documented cases of people curing both melanoma and carcinoma-type skin cancers with the topical application of CBD and THC products. Best known is the case of Rick Simpson, who cured his basal cell carcinoma with cannabis oil and now has a widely distributed line of products.
Cannabis applied topically is not psychoactive. Cannabinoids have been proven to have an anti-inflammatory effect in numerous studies.
CBD engages with the endocannabinoid system in many organs throughout the body, helping to reduce inflammation systemically. The therapeutic potential is impressively wide-ranging, as inflammation is involved in a broad spectrum of diseases. The oral use of cannabis and CBD for anxiety appears in a Vedic text dated around BCE, and it is one of the most common uses of the plant across various cultures.
While THC can increase anxiety in some patients, it lowers it in others. However, CBD effects have been shown to consistently reduce anxiety when present in higher concentrations in the cannabis plant. On its own, CBD has been shown in a number of animal and human studies to lessen anxiety. The stress-reducing effect appears to be related to activity in both the limbic and paralimbic brain areas. A research review assessed a number of international studies and concluded that CBD has been shown to reduce anxiety , and in particular social anxiety, in multiple studies and called for more clinical trials.
It is suggested that patients work with a health care practitioner experienced in recommending cannabidiol or medicinal cannabis so that dosage and delivery methods can be developed and fine-tuned on an individual basis. At the same time, educated and aware patients can be their own highly informed health consultants. For anxiety, CBD products with a ratio of High-CBD cannabinoids can be very effective in reducing chronic anxiety, treating temporary stress, and protecting the body from the physiological effects of both.
Varieties high in linalool, a terpene shared with lavender, are known to be effective for relieving anxiety. Always start with the micro dose to test sensitivity and go up as needed within the dosing range, before going to the next, until symptoms subside. The micro to standard dose is usually recommended to treat stress and anxiety with CBD. For relief of immediate symptoms, as in a panic or anxiety attack, vaporizing or smoking work well.
The medication lasts one to three hours, whereas most ingested products, including CBD oil, take thirty to sixty minutes before taking effect and last six to eight hours. Herbal vaporizers that use the whole plant are also an effective delivery method. Sublingual sprays or tinctures taken as liquid drops take effect quickly and last longer than inhaled products.
The Cannabis Health Index CHI is an evidence-based scoring system for cannabis in general, not just CBD oil effects and its effectiveness on various health issues based on currently available research data. Using this rubric and based on eleven studies, cannabis rated in the possible-to-probable range of efficacy for treatment of anxiety. Elixinol Organic High Potency CBD Capsules Elixinol offers a highly concentrated, high-potency, organic whole-hemp plant CBD oil , which is naturally extracted with carbon dioxide and free of all synthetics and chemicals.
Whole-hemp plant extracts contain synergistic compounds that are believed to enhance the effectiveness and benefits of CBD. Clinical depression is a serious mood disorder characterized by persistent sadness and loss of interest, sometimes leading to decreased appetite and energy and suicidal thoughts. Commonly used pharmaceuticals for depression often target serotonin, a chemical messenger that is believed to act as a mood stabilizer. The neural network of the endocannabinoid system works similarly to the way that serotonin, dopamine, and other systems do, and, according to some research, cannabinoids have an effect on serotonin levels.
Whereas a low dose of THC increases serotonin, high doses cause a decrease that could worsen the condition. CBD products with a ratio of Specifically, products made with Valentine X or Electra 4 are more energizing, helping relieve depression.
When low energy is an issue, sativa or other stimulating strains can be helpful for improving energy and focus when THC can be tolerated.
Is the cardiovascular system a therapeutic target for cannabidiol?
A collection of published research articles and other educational resources about heart disease, arrhythmia, and CBD (cannabidiol). Official Title: Phase I, Single Center, Open-label Study of Cannabidiol in Patients With Heart Failure in AHA/ACC Stages A-C. Estimated Study. Cannabidiol (CBD) is an active ingredient in cannabis derived from the hemp plant. To date, there is no evidence of public health related problems associated with the use of pure CBD. In numerous studies, CBD was able to reduce the number of seizures, and .. Executive Editor, Harvard Heart Letter.