Medical Cannabis and Metabolic Syndrome

Metabolic syndrome is a term used for when a person suffers from a combination of diabetes, hypertension (high blood pressure), and obesity. This puts a person at greater risk of coronary heart disease, stroke, kidney disease, and other health problems. Non-alcoholic fatty liver disease (NAFLD) is also associated with metabolic syndrome.

Medical cannabis has a complicated relationship with metabolic syndrome, as phytocannabinoids like cannabidiol (CBD), cannabigerol (CBG), and tetrahydrocannabivarin (THCV) may help manage weight and reduce insulin resistance. Tetrahydrocannabinol (THC) has been shown to elevate and decrease blood pressure, leading some to suggest that cannabis use (especially smoking cannabis) can lead to a heightened risk of stroke and lower blood pressure pressure in the long term. To complicate matters further, cannabinoids in cannabis also display neuroprotective properties, helping protect against brain damage caused by stroke.

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What is Metabolic Syndrome?

Metabolic syndrome is the term given to a person diagnosed with a combination of diabetes, high blood pressure (hypertension), and obesity. Metabolic syndrome is defined as having at least three of the following components:

An elevated waist circumference equal to or greater than 88 cm (34.65 inches) for women or 102 cm (40.16 inches) for men.
Elevated triglycerides equal to or greater than 150 mg/dL. Triglycerides are fat (lipid) made from the conversion of unused calories. Triglycerides are the main constituents of body fat in humans.
Low levels of high-density lipoprotein (HDL)— less than 40 mg/dL for men and less than 50 mg/dL for women. HGL is sometimes called “good cholesterol,” as it absorbs cholesterol and carries it back to the liver. High HDL cholesterol lowers the risk of heart disease and stroke.
Elevated blood pressure equal to or greater than 130 mm Hg systolic or 85 mm Hg diastolic.
Elevated fasting glucose equal to or greater than 100 mg/dL.

Being on medications to manage any of the above is also considered a component of metabolic syndrome.

Metabolic syndrome is estimated to affect more than 30% of people in the United States. Over two-thirds of U.S. adults are overweight or obese. The prevalence of obesity has increased steadily since the 1990s, as has the bulk of type-2 diabetes and hypertension. Metabolic syndrome is a substantial public health problem with huge costs. In 2016, obesity or being overweight accounted for $480.7 billion in direct health costs and $1.24 trillion in indirect costs due to lost economic production.

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Brief Summary of Current Treatments

The most common first-line treatments for metabolic syndrome include:

Following a healthy, flavonoid-rich diet.
Regulating calorie intake and meal times.
Regular physical activity. Experts recommend getting at least 30 minutes of moderate exercise, such as brisk daily walking.
Reducing and managing stress.
Stopping smoking.
Reducing or eliminating alcohol intake.

Medications that are prescribed for metabolic syndrome include:

Antidiabetics: Biguanides such as metformin (Axpinet, Diagemet, Glucient, Glucophage, Metabet).
Antidiabetics: Thiazolidinediones such as pioglitazone (Actos).
Lipid-Lowering Agents: Statins like atorvastatin (Lipitor) or fluvastatin (Lescol).
Lipid-lowering Agents: Non-Statin, such as cholestyramine (Locholest, Prevalite, Questran), colesevelam (WelChol), and colestipol (Colestid).
ACE Inhibitors such as quinapril (Accupril) and benazepril (Lotensin).
Angiotensin II Receptor Blockers (ARBs) such as irbesartan (Avapro) and Azilsartan (Edarbi).
Antiplatelet Agents: Cardiovascular, such as acetylsalicylic acid (Aspirin, Asaphen, Entrophen, Novasen), clopidogrel (Plavix), prasugrel (Effient) and ticagrelor (Brilinta).
For those suffering from nerve pain due to diabetic neuropathy, anticonvulsants like gabapentin may be prescribed.

How Might Medical Cannabis Help?

There are several aspects of metabolic disorder that cannabinoids could help treat. THCV, CBD, and CBG could all help treat diabetes, as they have been shown to improve metabolism and decrease blood glucose levels in human and animal models of diabetes.

Low doses of THCV combined with CBD, CBG, and terpene humulene may curb hunger, and several studies show that cannabis users have a lower body mass index (BMI). This makes cannabis great for obesity as well.

As for hypertension, the benefits of cannabis are a bit more complex. This is because, after inhaling cannabis, blood pressure and heart rate rise for about 30 minutes before tapering off and lowering, at least in older adults. This means that, although cannabis may potentially be used to treat hypertension, it needs to be dosed carefully, in the right way (ideally avoiding smoking cannabis), and in the right setting. Other studies show that a single dose of CBD reduces blood pressure.

Cannabinoids

THCV is a CB1 receptor antagonist in low doses, helping curb appetite. THCV also ameliorated insulin sensitivity in mouse models.
CBD may lower insulin resistance and boost gut hormone levels.
CBG may help destroy fat cells.
THC has analgesic (pain-killing), mood-boosting, and anti-inflammatory effects that can help manage some symptoms associated with metabolic syndrome, such as pain, anxiety, and insomnia.

Cannabinoid Ratios

THC:CBD 1:3
THC:CBD 1:2
THC:CBD 1:1
THC:CBD 2:1

Terpenes and Terpenoids

Humulene may suppress appetite.
Beta-caryophyllene can battle inflammation.
Pinene, which can potentially prevent heart disease.
Eucalyptol, which has bronchodilatory effects that could help ease breathing,

Flavonoids

Quercetin may boost the anti-inflammatory effects of aspirin on top of its potent anti-inflammatory effects.
Cannflavin A, B, and C
Apigenin
Catechin
Naringin

Effective Ways of Taking Medical Cannabis for Metabolic Syndrome and Cannabis

Routes of Administration

Sublingual
Ingestion
Topical

Special Formulations

A CBD-rich formulation or cannabis chemotype with some THCV, CBG, and THC may be ideal. Beta-caryophyllene, humulene, and pinene are some terpenes worth keeping an eye out for.

Dosing Methods

Tincture
Edible
Drinkable
Cannabis-infused topical cream or salve

What are the Pros and Cons of Taking Medical Cannabis for Metabolic Syndrome and Cannabis?

Potential Pros

CBD, CBG, and THCV could help regulate glucose levels and prevent insulin resistance.
Medical cannabis use may improve carbohydrate metabolism, helping control and maintain weight.
Bronchodilatory effects of THC, pinene and eucalyptol can help ease breathing, help keep blood vessels open, and improve circulation.
Medical cannabis can manage stress and anxiety associated with metabolic syndrome.
For some, cannabis may enhance the pleasure of exercise, meaning that they are more likely to carry on exercising.
CBD can lower blood pressure.
Cannabis users have lower odds of presenting with metabolic syndrome than those who have never used cannabis.

Potential Cons

Stimulating appetite may be helpful for people with diabetes but not so useful for controlling sugar intake.
Diabetes can negatively affect memory, perception, and coordination, and so can THC to some extent, exacerbating the problem.
Getting dry or cotton mouth and eyes is common for people with diabetes. Cannabis can make this aspect worse, which can harm oral health.
Some studies have noted that smoking cannabis can increase heart rate immediately after use, which can increase the likelihood of suffering from a stroke.
CBD may have a negative impact on the liver in those with metabolic syndrome.
One study shows an increase in the likelihood of metabolic syndrome in cannabis users.

Useful Anecdotal Information

Wilcox, Anna. “The Odd Science Behind Marijuana And Metabolism.” Herb, Oct. 03, 2019

Taking Control Of Your Diabetes, “Getting High without Getting High: Marijuana and Diabetes.” Mar. 24, 2021

Scientific Data Overview and Studies

Total Studies = 56
Positive Studies = 44
Inconclusive Studies = 9
Negative Studies = 3
34 Meta-Analyses (26 positive, 5 inconclusive, 3 negative); 15 Animal Studies (14 positive, 1 inconclusive); 3 Double-Blind Human Trials (2 positive, 1 inconclusive); 2 Human Trials (1 positive, 1 inconclusive); 2 Lab Studies (1 positive, 1 inconclusive)
11 studies include CBD (9 positive, 2 inconclusive); 11 studies include THC (9 positive, 2 inconclusive); 2 studies include CBG (both positive); 1 study includes CBC (positive); 1 study includes THCV (positive); 1 study includes THCA (positive); 7 studies include the endocannabinoid, anandamide (6 positive, 1 inconclusive); 9 studies include the endocannabinoid, 2-arachidonoylglycerol, aka 2-AG (7 positive, 2 inconclusive)
Possible Overall Efficacy: Moderate

Quotes from Studies

“Evidence shows that Cannabis sativa derivatives have therapeutic potential due to their anti-inflammatory properties. In addition, people who use cannabis have a lower body mass index than those who do not, making the plant an option to reduce and reverse inflammation and comorbidities in obesity.”

Cavalheiro EKFF, Costa AB, Salla DH, Silva MRD, Mendes TF, Silva LED, Turatti CDR, Bitencourt RM, Rezin GT. “Cannabis sativa as a Treatment for Obesity: From Anti-Inflammatory Indirect Support to a Promising Metabolic Re-Establishment Target.” Cannabis Cannabinoid Res. 2022 Apr;7(2):135-151. doi: 10.1089/can.2021.0016. Epub 2021 Jul 9. PMID: 34242511.

“Current marijuana users had lower odds of presenting with metabolic syndrome than never users (adjusted odds ratio [AOR] 0.69; 95% confidence interval [CI], 0.47-1.00; P = .05). Among emerging adults, current marijuana users were 54% less likely than never users to present with metabolic syndrome.”

Source: Vidot DC, Prado G, Hlaing WM, Florez HJ, Arheart KL, Messiah SE. “Metabolic Syndrome Among Marijuana Users in the United States: An Analysis of National Health and Nutrition Examination Survey Data.” Am J Med. 2016 Feb;129(2):173-9. doi: 10.1016/j.amjmed.2015.10.019. Epub 2015 Nov 5. PMID: 26548604; PMCID: PMC4718895.

“In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.”

Source: Farokhnia, M., McDiarmid, G.R., Newmeyer, M.N. et al. “Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study.” Transl Psychiatry 10, 71 (2020). https://doi.org/10.1038/s41398-020-0756-3

Conclusion

Although the evidence for medical cannabis’ therapeutic effects for metabolic syndrome is generally positive, the few human trials have shown positive and inconclusive results. There may be some aspects of metabolic syndrome that medical cannabis is excellent at controlling, but other elements may have some adverse effects, especially on the heart and liver. More in-depth research is needed.

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Medical Cannabis and Obesity

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Please note: the information in this article does not constitute medical advice