Edible THC causes chronic restricted blood flow, damaged endothelial cells, & strokes, like a chronic smoker

 Endocannabinoid CB1 receptor activation increases dopamine levels in the brain, particularly in the nucleus accumbens, by acting on the mesolimbic pathway. CB1 receptors, located on inhibitory GABAergic terminals, reduce GABA release (disinhibition), which allows dopamine neurons in the midbrain to become more active...inhibiting GABA (gamma-aminobutyric acid) signaling typically increases dopamine levels. GABA acts as a major inhibitory neurotransmitter in the brain, often providing "tonic inhibition" that suppresses dopamine release. Activating CB1 receptors reduces the amount of GABA released. Fewer GABA molecules act on the dopamine neuron, causing a "disinhibition" of the VTA dopamine neurons. This leads to increased firing and dopamine release in the nucleus accumbens... 

While traditionally attributed to

-endorphins, modern research indicates that endocannabinoids (specifically anandamide) are primarily responsible for the runner's high, not

-endorphins. Endorphins have a limited role because they cannot cross the blood-brain barrier, whereas endocannabinoids readily cross it to produce euphoric effects

. 

Exercise increases levels of both

-endorphin (an opioid) and anandamide (an endocannabinoid), but modern research suggests that anandamide, not

-endorphin, is the primary driver of the "runner’s high". While

-endorphins are released, they are large molecules that cannot cross the blood-brain barrier. In contrast, anandamide is lipophilic and easily enters the brain to promote euphoria, reduced anxiety, and calmness

The main cause of natural beta-endorphin release is

physical exercise (specifically aerobic activity). Often associated with a "runner's high," intense or sustained physical activity stimulates the brain and pituitary gland to release these neurotransmitters, which function as natural painkillers, improve mood, and combat stress...endorphins are released during exercise and can stop peripheral muscle soreness that results from exercise, they cannot be the source of the runners’ high [5,6,7,8]....Participants who were given the opioid-receptor blocking naltrexone still experienced exercise-induced euphoria and anxiolysis [15]. The findings of this study indicate that RH in humans does not depend on opioid signaling but depends on endocannabinoids, similar to the results obtained in mice [15]. The Endocannabinoid System and Physical Exercise (2023)

Alcohol acts as a positive allosteric modulator of GABAA receptors, increasing the inhibitory effects of GABA, which explains the initial calming effect. However, alcohol also acts on other systems (e.g., endorphins, nicotinic receptors) to cause the indirect release of dopamine, and it can inhibit GABA interneurons, which disinhibits the dopamine neurons. 

Alcohol inhibits neurons that would normally stop dopamine release, including blocking KCNK13 potassium channels.

Opioid System Involvement: Alcohol triggers the release of endorphins (endogenous opioids), which indirectly prompts dopamine-releasing neurons to fire, says a report from the National Institutes of Health...  Low to moderate amounts of alcohol increase beta-endorphins, but high doses do not,

Beta-endorphin is the main endorphin released.

Brain Regions: The release occurs in the nucleus accumbens (reward center) and orbitofrontal cortex.

Effect: These chemicals bind to opioid receptors,...Repeated alcohol consumption can lead to a deficiency in natural endorphins, creating a dependency....

The Result: Similar to THC, alcohol increases dopamine release in the mesolimbic pathway, specifically through actions in the VTA and the nucleus accumbens

THC and alcohol increase dopamine through a shared mechanism known as

disinhibition in the ventral tegmental area (VTA) of the brain. While they interact with GABA in different ways, both drugs ultimately prevent GABA from restraining dopamine-producing neurons

THC (tetrahydrocannabinol) is known to act as a vasodilator, meaning it relaxes and widens blood vessels

. This action frequently leads to reduced blood pressure and increased heart rate, contributing to effects like lightheadedness or "red eye". However, regular, chronic use may lead to reduced vascular function and potential heart risks... https://www.health.harvard.edu/heart-health/marijuana-and-heart-health-what-you-need-to-know

 complex effects cannabinoids have on the cardiovascular system, including raising resting heart rate, dilating blood vessels, and making the heart pump harder. Research suggests that the risk of heart attack is several times higher in the hour after smoking marijuana...While THC is known for its immediate vasodilating (widening) effects on blood vessels, which can lower blood pressure temporarily, the restriction of endothelial cells is a separate, chronic process driven by cellular inflammation, oxidative stress, and the overactivation of cannabinoid receptors....

 THC binds to CB1 receptors found on endothelial cells (the inner lining of blood vessels). While acute use may cause vasodilation, frequent activation of these receptors by THC leads to a damaging cascade... JAMA Cardiol . 2025 Aug 1;10(8):851-855.

Association of Endothelial Dysfunction With Chronic Marijuana Smoking and THC-Edible Use

Acute (Short-term): THC acts as a vasodilator by acting on smooth muscle cells and increasing nitric oxide, which makes vessels widen.

Chronic (Long-term): Frequent use, particularly in high doses, causes endothelial dysfunction, which is the inability of vessels to function properly. This leads to a paradoxical state where the vessels are "stiff" or dysfunctional despite having once dilated.

Research Evidence: A UCSF study found that chronic cannabis users (both smokers and edible users) had an arterial flow-mediated dilation (FMD)—a measure of how well vessels open—that was roughly half as good as non-users

Inflammation and Oxidative Stress: THC triggers the production of Reactive Oxygen Species (ROS) and pro-inflammatory cytokines, which directly harm endothelial cells.

Reduced Nitric Oxide (NO): Healthy endothelial cells produce nitric oxide to keep vessels flexible and dilated. Chronic THC exposure reduces the production of nitric oxide, leading to impaired, stiff vessels.

Atherosclerosis Acceleration: Laboratory studies show THC promotes the early markers of atherosclerosis (plaque build-up) in human endothelial cells

“The vessels just don’t grow in diameter in real time when they need to pass more blood, indicating an unhealthy vessel wall that presages later cardiovascular disease,” he said.

Prior studies have found strong links between marijuana use and later cardiovascular disease. A February 2024 study found smoking, vaping or eating marijuana led to a significantly higher risk of heart attack and stroke,

vascular function was reduced by 42% in marijuana smokers and by 56% in THC-edible users compared to nonusers,” lead study author Dr. Leila Mohammadi, an assistant researcher in cardiology at the University of California, San Francisco, said in an email.

 “Using strict inclusion and exclusion criteria to avoid confounding effects of other potential exposures, we found that chronic marijuana smoking and THC-edible use were both associated with reductions in FMD compared with nonuser controls,” the group explained. “The reduction in FMD was similar to what we have reported previously for chronic tobacco smokers.” Overall, mean arterial flow-mediated dilation (FMD) measurements were lower for marijuana smokers (6%) and edible users (4.6%) than nonusers (10.4%)

Smoking weed and consuming THC-laced edibles linked to early heart disease, study finds

https://cardiovascularbusiness.com/topics/clinical/heart-health/marijuana-use-linked-blood-vessel-damage-impact-seen-smoking-and-edibles 

 THC might possess direct toxic effect on arterial vessels and could exert a synergistic effect with tobacco smoking (52). THC induced peripheral vasoconstriction could also contribute to this phenomenon

THC restricts endothelial blood flow and impairs vessel function by causing endothelial dysfunction, reducing nitric oxide production, and promoting inflammation

. Chronic THC exposure increases oxidative stress and damages the endothelial barrier, which can lead to hypertension and arterial stiffness

THC activates cannabinoid receptor 1 (

), triggering vascular inflammation and oxidative stress that impairs the inner lining of blood vessels.

Reduced Nitric Oxide: THC lowers the production of nitric oxide, a compound necessary for proper endothelial cell function and blood vessel relaxation.

Method of Intake Differences: Both smoked marijuana and edible THC use result in significant endothelial impairment. However, they may damage vascular function through different processes, as blood from smoked marijuana users tends to be more damaging to lab-grown endothelial cells than blood from edible users.

Cardiovascular Risks: Endothelial dysfunction causes vessels to act as if they are roughly 30 years older, accelerating risks for atherosclerosis and heart disease.

 

 

THC restricts blood flow primarily by

causing inflammation in endothelial cells, which line blood vessels, leading to constriction and reduced blood flow. While acute use can sometimes cause vasodilation, chronic THC exposure is associated with reduced cerebral blood flow and can cause vascular spasms, promoting atherosclerosis—the narrowing of arteries—and increasing cardiovascular strain

https://www.cnn.com/2025/05/28/health/marijuana-edibles-heart-damage-wellness