Does CBD Interact With Metformin?

  • Metformin is a U.S. Food and Drug Administration (FDA) approved medicine that is considered the first-line treatment for type 2 diabetes. Doctors prescribe the drug as monotherapy or together with other medications to manage high blood sugar levels in the body (1)
  • Using metformin has proven to be an effective solution in preventing diabetes in high-risk individuals. Some adverse reactions to the drug may be possible but are often trivial compared to the benefits that it offers (2)
  • Cannabidiol (CBD), the non-psychoactive phytocannabinoid present in Cannabis sativa, is said to have therapeutic benefits, especially for people with diabetes. Several clinical trials on mice and rats show positive improvements in the test subjects’ incidence of diabetes while reducing overall fat accumulation and high blood pressure related to the condition (3-4)
  • Since metformin is capable of effectively treating type 2 diabetes, it may be used together with CBD to improve the quality of life for people with the condition. However, no research exists to prove that these products are safe for use with each other.
  • The antihyperglycemic agent insulin may work well when used together with CBD oil. Research in 2016 on type 2 diabetes patients shows that a combination of tetrahydrocannabinol (THC) and CBD can lower insulin resistance while improving the effects of insulin in the body (5)

Can CBD Be Taken with Metformin?

Metformin is a U.S. Food and Drug Administration (FDA) approved medicine commonly used to treat type 2 diabetes. Doctors often prescribe this drug on its own or in combination with other diabetes medications to manage high glucose levels (6)

The medication has proven to be effective in preventing diabetes in high-risk individuals while also lowering the majority of its complications. Although there are some adverse reactions to metformin use, reports state that these effects are trivial when considering the benefits (7)

Cannabidiol (CBD), on the other hand, is a phytocannabinoid present in the Cannabis sativa plant. It is the non-euphoric component in cannabis that is said to contain therapeutic properties.

A study in 2016 on diabetic mice reveals that CBD treatment is capable of lowering the incidence of diabetes in the subjects. The mice were given a daily dose of 5 mg/kg CBD at least five times a week for ten weeks (8)

Additional research in 2018 investigates the mechanism of action of phytocannabinoids as anti-diabetic and anti-obesity agents. The study shows that cannabinoids can potentially support the treatment of insulin resistance caused by diabetes and obesity (9)

Seeing as metformin can effectively treat diabetes while CBD has possible healing properties, it is only natural to think of combining the two of them. However, there is no study proving that these products are compatible with each other.

There are enzymes in the liver that metabolize the number of active ingredients in medications taken by an individual. These are also the same proteins that the body uses to break down CBD.

In past research, CBD is seen as a potent inhibitor of cytochrome P450 enzymes. As an inhibitor, this means that taking it along with other medications may hinder liver enzymes from correctly processing other drugs (10-11)

Such a scenario could lead to increased or decreased levels of active medicines in the blood, causing problems related to toxicity or being subtherapeutic.

CBD interaction with CYP450 can alter how it affects the endocannabinoid system (ECS). The ECS is a complex system found in humans and animals that regulates the central nervous system, among others (12).

Metformin use comes with its side effects, and the more this medication enters the bloodstream, the higher the possibility of harmful reactions. Although its effects are not significant, it may cause a condition known as lactic acidosis. This condition brings with it symptoms such as muscle pain, drowsiness, dizziness, chills, and difficulty in breathing (13).

Since there is no clear indication of whether metformin users are at risk or not, if they use CBD, it is always better to err on the side of caution. People using metformin for diabetes should consult a doctor knowledgeable in cannabis before applying CBD in their regimen.

Only these professionals can provide a concept of the right dosage of these two products to avoid any adverse side effects.

Can Another Antihyperglycemic Be a Substitute for Metformin So CBD Oil Can Be Taken?

Insulin is an antihyperglycemic agent that is used to lower high blood sugar in people who have diabetes. Doctors often apply it by subcutaneous injection, but there are other forms that they can inject intravenously.

Research in 2016 on 62 subjects with type 2 diabetes reveals that a combination of tetrahydrocannabinol (THC) and CBD can decrease insulin resistance while stimulating the effect of insulin in the body. These same subjects were non-insulin-treated and were able to tolerate both CBD and THC well (14).

Another study in 2018 shows that low dosage CBD increases glucose uptake, lowers fat accumulation, and reverses insulin resistance in rats (15). This may be an additional indication that CBD can be used together with insulin to improve its effectiveness.

Although CBD and insulin intake in rodents may not be the same in humans, there is still a possibility that cannabidiol can enhance insulin efficacy. This is especially true since animal models are often used to understand how drugs work in human beings (16).

More research is needed to understand further the effectiveness and safety of using these two to treat diabetes.

Can CBD Replace Metformin?

As of this time, no research proves CBD to be a safe alternative to metformin use in humans who have diabetes. The majority of studies on how CBD can affect diabetes were carried out on rats and mice.

A study as early as 2006 on non-obese diabetic mice shows that CBD is capable of lowering the incidence of possible diabetes by changing the immune response system in rodents. The non-treated mice had a probability of 86% to develop diabetes, while CBD-treated subjects only had 30% (17).

The CBD treatment also significantly reduced plasma blood levels of the pro-inflammatory cytokines, while also lowering the possibility of pancreatic disease.

In 2016, research showed that cannabidiol could delay the onset of type 1 diabetes while remarkably reducing inflammation in the pancreas caused by the said condition. Female non-obese diabetic mice were administered daily intake of CBD for several weeks (18).

Another study in 2019 carried out on middle-aged diabetic rats wanted to test the beneficial effects of CBD on both ischemic diseases and diabetes. It revealed that CBD has effects on neuropathic pain, can improve memory performance, and lowers hippocampal levels of inflammation markers (19)

Experts suggest that perhaps medical marijuana and cannabinoids like CBD gummies can be used to treat the symptoms of diabetes. Since the studies on CBD as an antihyperglycemic are limited, it is always best to seek advice from a medical expert before considering replacing current anti-diabetic medication.

Drugs That Can Interact with Metformin

Metformin contains positively charged molecules (cationic) that can compete with similarly charged drugs for renal secretion via organic cation transporters found in the kidneys.

Quinidine, procainamide, trimethoprim, digoxin, and vancomycin are cationic medications that can interact with metformin. However, only cimetidine, which can be bought over-the-counter for heartburn, is linked to a case of metformin-associated lactic acidosis (MALA) (20).

The following are other medications that can have drug interactions with metformin:

  • Diuretics
  • Corticosteroids
  • Thyroid medications
  • Estrogen and oral contraceptives
  • Phenytoin
  • Calcium channel blockers

Mixing the drugs listed above, together with metformin, may affect blood sugar control in the body. Patients need to monitor their blood sugar levels frequently and notify their doctors of any sudden changes.

These drugs can reduce the ability of the kidneys to eliminate metformin from the blood and thus lead to lactic acidosis:

  • Cimetidine
  • Ranolazine
  • Vandetanib
  • Dolutegravir

Individuals should consult a doctor to see if these drug combinations are worth the risk. There may be safer options available that do not have the same probability of danger.

Below are medications that may increase the risk of lactic acidosis on metformin users:

  • Carbonic anhydrase inhibitors (CAIs) such as acetazolamide or topiramate

Regular monitoring of patients taking CAIs together with metformin may be necessary as this can aid in detecting early signs of lactic acidosis.

It is always best to consult a doctor to be aware of the possible side effects of metformin use. Physicians can change the dosage or even suggest a safer, alternate medication.

People switching from immediate-release to extended-release metformin tablets may experience fewer instances of diarrhea, as suggested by a study in 2004 (21).

Doctors continually monitor for signs of anemia and vitamin B-12 deficiency in individuals that have been taking metformin for at least a few months. Consuming iron and vitamin B-12 supplements may help prevent these issues if they arise in long-term metformin users.

Conclusion

Metformin is an FDA-approved medication that is prescribed to individuals who have type 2 diabetes. It is often given on its own or with other prescription drugs to manage high blood glucose levels in the body.

The said medication can effectively prevent diabetes in high-risk individuals, while also reducing most of its complications. There may be adverse reactions associated with metformin use, but most reports mention that these are only minor considering its benefits.

Cannabidiol, also known as CBD, is said to contain cannabinoid receptors that can benefit people with diabetes. Several clinical trials on mice and rats reveal the antihyperglycemic potential of the phytocannabinoid.

Since metformin can treat diabetes effectively, most people consider taking it together with the healing properties of CBD edibles. There are no studies, however, that prove these two products can be used together.

In fact, they may not work well with each other due to how the body processes both metformin and CBD products. Lactic acidosis is the most severe side effect that a person may experience with metformin overdose, which has symptoms such as dizziness, muscle pain, chills, and difficulty in breathing.

As no clear indication of whether metformin users are at risk or not when using CBD, it is best to avoid using them together for now. At the very least, seeking medical advice from a healthcare provider knowledgeable in the cannabis plant may be a possible option.

Insulin may be a potential antihyperglycemic agent that can work well in conjunction with CBD oil help. A placebo-controlled study in 2016 shows that CBD is capable of lowering insulin resistance while improving the effects of insulin in the body.

In 2018, a study on rats revealed that low tincture doses of CBD could enhance glucose uptake, improve weight loss, and reverse insulin resistance in the subjects. All these are potential indications that CBD can be used together with insulin to improve its effectiveness.


  1. Corcoran C, Jacobs TF. Metformin. [Updated 2020 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.
  2. Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658‐664.
  3. Lehmann C, Fisher NB, Tugwell B, Szczesniak A, Kelly M, Zhou J. Experimental cannabidiol treatment reduces early pancreatic inflammation in type 1 diabetes. Clin Hemorheol Microcirc. 2016;64(4):655‐662. doi:10.3233/CH-168021
  4. Ramlugon S, Levendal RA, Frost CL. Time-dependent effect of phytocannabinoid treatments in fat cells. Phytother Res. 2018;32(6):1080‐1089. doi:10.1002/ptr.6047
  5. Khalid A. Jadoon, Stuart H. Ratcliffe, David A. Barrett, E. Louise Thomas, Colin Stott, Jimmy D. Bell, Saoirse E. O’Sullivan, Garry D. Tan. Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care Oct 2016, 39 (10) 1777-1786; DOI: 10.2337/dc16-0650.
  6. Corcoran C. et al. op. cit.
  7. Nasri H. et al. op. cit.
  8. Lehmann C. et al. op. cit.
  9. Ramlugon S. et al. op. cit.
  10. Zendulka O, Dovrtělová G, Nosková K, et al. Cannabinoids and Cytochrome P450 Interactions. Curr Drug Metab. 2016;17(3):206‐226. doi:10.2174/1389200217666151210142051
  11. Grayson L, Vines B, Nichol K, Szaflarski JP; UAB CBD Program. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10‐11. Published 2017 Oct 12. doi:10.1016/j.ebcr.2017.10.001
  12. Lu HC, Mackie K. An Introduction to the Endogenous Cannabinoid System. Biol Psychiatry. 2016;79(7):516‐525. doi:10.1016/j.biopsych.2015.07.028
  13. Nasri H. et al. op. cit.
  14. Khalid A. et al. op. cit.
  15. Ramlugon S. et al. op. cit.
  16. Barré-Sinoussi F, Montagutelli X. Animal models are essential to biological research: issues and perspectives. Future Sci OA. 2015;1(4):FSO63. Published 2015 Nov 1. doi:10.4155/fso.15.63
  17. Weiss L, Zeira M, Reich S, et al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity. 2006;39(2):143‐151. doi:10.1080/08916930500356674
  18. Lehmann C. et al. op. cit.
  19. Santiago AN, Mori MA, Guimarães FS, Milani H, Weffort de Oliveira RM. Effects of Cannabidiol on Diabetes Outcomes and Chronic Cerebral Hypoperfusion Comorbidities in Middle-Aged Rats. Neurotox Res. 2019;35(2):463‐474. doi:10.1007/s12640-018-9972-5
  20. Dawson D., Conlon C. Case Study: Metformin-Associated Lactic Acidosis. Diabetes Care Aug 2003, 26 (8) 2471-2472; DOI: 10.2337/diacare.26.8.2471
  21. Blonde L., Dailey G., Jabbour S., Reasner C. Mills D. Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study. Accepted 23 Jan 2004, Published online: 05 Mar 2004. https://doi.org/10.1185/030079904125003278
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