Table 2 Therapeutic effects of CBD and the ECS on vascular disease

CAD

Human; Subjects of white, black, and Asian ancestry (n = 2667);

FAAH cDNA polymorphism

FAAH 385 A/A missense polymorphism is a risk factor for overweight/obesity, which are also risk factors for CAD.

[45]

Human; Individuals from the German MI family study (n = 1968);

CNR2 (encoding CB2) variations

Common CNR2 variations confer no susceptibility to CAD.

[46]

Human; Overweight/obese patients (n = 6897);

Rimonabant (CB1 antagonist)

In overweight/obese patients, rimonabant induced weight loss and significant improvements in multiple cardiometabolic risk factors.

[47]

Mouse; ApoE-/- mice (n = 48);

Exercise and rimonabant treatments

Both exercise and rimonabant treatments induced plaque regression and promoted plaque stability.

[48]

Mouse; type I diabetic cardiomyopathy mouse model;

CBD

CBD could have a high therapeutic potential in the management of cardiovascular disorders by attenuating oxidative/nitrative stress, inflammation, cell death, and fibrosis.

[53]

Cell; Mouse microglial cells;

CBD

CBD exerted its anti-inflammatory effects on microglia via its intrinsic antioxidant properties, which are amplified by the inhibition of glucose-dependent NADPH synthesis.

[50]

Cell; BV-2 microglial cells;

CBD

CBD affected genes involved in the regulation of stress response and inflammation, mainly via the Nrf2/Hmox1 axis and the Nrf2/ATF4-Trib3 pathway.

[51]

Hypertension

Human; Healthy participants (n = 12);

CBD and TurboCBD™

TurboCBD™ 90 mg was associated with a slight reduction in BP.

[64]

Human; Healthy male participants (n = 26);

CBD

CBD reduced BP at rest after a single dose, but the effect was lost after seven days of treatment.

[66]

Human; Healthy male participants (n = 9);

CBD

Acute administration of CBD reduces resting BP and stress-induced hypertension.

[71]

Rat; Spontaneously and deoxycorticosterone hypertensive rats;

CBD

Chronic CBD administration did not exert an antihypertensive effect in primary and deoxycorticosterone hypertension model.

[65]

Rat; Male Wistar rats;

CBD

CBD showed anxiolytic-like properties similar to those of diazepam in a rat model of conditioned fear to context.

[70]

DRVD

Human; Noninsulin-treated type 2 diabetes patients (n = 62);

CBD

CBD decreased insulin resistance and increased glucose-dependent insulinotropic peptide levels.

[73]

Rat; Zucker D\diabetic fatty rats

CBD

Increased circulating endocannabinoids could alter the vascular function in type 2 diabetes, possibly due to endothelium-dependent vasorelaxation improvement.

[77]

Cell; Human coronary artery endothelial cell;

CBD

CBD could have significant therapeutic benefits against diabetic complications and atherosclerosis.

[74]

Cell; Type I diabetic cardiomyopathy mouse model;

CBD

CBD could have a high therapeutic potential in the treatment of cardiovascular disorders, by attenuating oxidative/nitrative stress, inflammation, cell death, and fibrosis.

[53]

I/R injury

Rat; Ischemic rat hearts model;

CBD

CBD exerted a substantial in vivo cardioprotective effect.

[78]

Rat; Male rats;

CBD

CBD showed a therapeutic effect against I/R injury-induced arrhythmias via the activation of adenosine A1 receptor.

[79]

Rat;

CBD

CBD demonstrated a therapeutic effect against CI, possibly by diminishing TNFR1/NF-κB-induced neurotoxicity.

[81]

Rat; Neonatal Wistar rats;

CBD

CBD administration after middle cerebral artery occlusion led to long-term functional recovery, neuronal loss and astrogliosis reduction, and modulation of apoptosis, metabolic derangement, excitotoxicity and neuro-inflammation.

[82]

Piglet; Hypoxic-ischemic newborn piglets

CBD

The combined effect of hypothermia and CBD on excitotoxicity, inflammation, oxidative stress, and cell damage is greater than the effects of either hypothermia or CBD alone.

[83]

Piglet; Hypoxic-ischemic newborn piglets

CBD

CBD administration after hypoxia-ischemia in piglets showed neuroprotective effects.

[84]