The relationship between cannabis and diabetes is complex and not yet fully understood. On the occasion of World Diabetes Day, we dedicate this article to discover the potential benefits and risks of medical cannabis and CBD for diabetes management. This article is based on insights from the Handbook of Clinical Principles of Cannabinology, by Viola Brugnatelli and physician Fabio Turco.
What is diabetes?
Diabetes mellitus is a chronic condition in which the body has elevated levels of glucose (sugar) in the blood due to problems with insulin, a hormone essential for regulating sugar in the body.
There are two main types of diabetes: in type 1 diabetes, the body does not produce enough insulin due to autoimmune destruction of pancreatic cells, and sufferers need insulin for life. In type 2 diabetes mellitus, the body does not use insulin properly, which is called insulin resistance, and this form is closely related to obesity and is more common.
Symptoms of diabetes vary, but may include frequent urination, excessive thirst, extreme hunger, unexplained weight loss, fatigue, blurred vision, slow wound healing, numbness or tingling in hands and feet, and frequent infections. These symptoms tend to develop gradually in type 2 diabetes, which can make early detection difficult, while in type 1 diabetes they usually appear suddenly and severely.
Relationship between the Endocannabinoid System and Diabetes
The endocannabinoid system (ECS) is a network of receptors and molecules in our body that helps regulate important functions such as metabolism, appetite and inflammation. This system interacts with compounds we produce naturally, called endocannabinoids, and also with compounds present in cannabis, such as THC and CBD.
Through the endocannabinoid system, cannabinoids may influence the regulation of metabolism and inflammation, showing potential to improve insulin sensitivity and reduce some symptoms and complications associated with diabetes.
¿Cómo afecta el cannabis a la diabetes?
¿Puedo tomar o usar CBD si tengo diabetes?
¿El CBD puede tratar o mejorar la diabetes?
¿El cannabis afecta a los niveles de azúcar en sangre?
¿El CBD interactúa con otros medicamentos para la diabetes?
¿El cannabis puede empeorar la diabetes?
Potential of Cannabinoids in Diabetes Treatment
Studies link certain alterations in the endocannabinoid system to metabolic problems such as insulin resistance and chronic inflammation, which could indicate new treatment targets for diabetes and obesity.
Detail: CB2 receptors as an anti-obesity agent
Some studies suggest that people with obesity, common in type 2 diabetes, have reduced functionality of CB2 cannabinoid receptors, which are part of the endocannabinoid system. In research, it has been seen that in diabetic states, these receptors are less intensely activated. This indicates a possible link between the endocannabinoid system and metabolic problems such as insulin resistance and chronic inflammation.
This observation was supported by a study involving 501 children with obesity in Italy, where compromised CB2 receptor functionality was found. Children who received treatments with selective CB2 agonists showed a reversal of obesity-induced inflammatory states. These findings suggest that CB2 receptor modulation could be a potential strategy to treat inflammation and other metabolic problems related to obesity and diabetes.
Cannabis and CBD and Diabetes: Current Research
Arguably, there are currently two main perspectives on the use of medical cannabis in diabetes: one for and one against. Some studies suggest that it may improve insulin sensitivity and reduce inflammation, while others suggest that it may increase appetite and weight, which could worsen type 2 diabetes. In both cases, more research is needed to fully understand the effects of cannabis and individual cannabinoids in particular, and to determine their safety and efficacy.
Evidence Against the Use of Cannabis in Diabetes
The use of cannabis, particularly its psychoactive component THC, along with endogenous analogs such as anandamide that activate central CB1 receptors, has been linked to increased appetite and subsequent weight gain in animal studies. This effect is beneficial in situations such as cachexia or during chemotherapy, but is problematic for people with type 2 diabetes, where obesity can worsen insulin resistance.
On the other hand, hyperactivation of the CB1 receptor of the endocannabinoid system in peripheral tissues is linked to obesity and metabolic syndrome. Thus, cannabis administration could increase fat production and insulin resistance, complicating diabetes management. Inhibiting peripheral CB1 receptors could be a strategy to mitigate these effects, but more research is still needed.
The Case of the Drug Rimonabant and Precautionary Teaching
The drug Rimonabant, a CB1 receptor antagonist, showed benefits in weight reduction and improved metabolic markers, but was withdrawn from the market due to severe neuropsychiatric side effects, linked to suicide. This highlights the importance of targeting peripheral CB1 receptors to avoid risks. Current studies on compounds such as CBD, which modulate the endocannabinoid system without psychoactive effects, such as CBD or cannabidiol, show promise for treating diabetes-related metabolic syndrome.
Evidence Supporting the Use of Cannabinoids in Diabetes
Some studies have found that cannabis users are less likely to develop diabetes, despite the fact that cannabis can increase appetite. These findings suggest that cannabis may have a regulatory effect on metabolism, reducing the risk of diabetes.
Cannabinoids are also known to affect various metabolic pathways that influence blood sugar and insulin levels, which may explain why some studies have found that cannabis users have lower fasting insulin levels and lower insulin resistance, which may help prevent diabetes.
Research conducted at Harvard Medical School has found that cannabis can improve insulin sensitivity and lower blood glucose levels.
In particular, CBD, the non-psychoactive compound in cannabis, has shown potential in protecting insulin-producing pancreatic cells, suggesting potential benefits in the management and prevention of diabetes.
Despite these results, it should be noted that in all cases these are preliminary studies, more solid scientific evidence is lacking, and until more studies are done, it is not possible to affirm these properties. Patients are advised to consult their medical specialist before considering the use of CBD.
Cannabinoids for Diabetes: Current Research
Research on cannabinoids for diabetes is still at a preliminary stage. Some studies suggest that certain cannabinoids may improve glucose regulation and reduce inflammation, but more research is needed to fully understand their effects and determine their safety and efficacy in the treatment of diabetes. Here is a review of current research:
CBD and its Promising Role for Diabetes
CBD or cannabidiol shows potential in diabetes management by improving insulin sensitivity and reducing inflammation, although more research is needed to confirm its benefits and safety.
Detail: Studies on CBD for diabetes
In a 2006 animal study, it was shown that administration of CBD at a dose of 5 mg/kg daily significantly reduced the incidence of hereditary diabetes in a mouse model. In this study, 86% of the control group developed diabetes, compared to only 30% of the CBD-treated mice, indicating not only a lower incidence, but also a delayed onset of the disease.
Other studies corroborated these findings. Furthermore, in a mouse model of type 2 diabetes induced by a high-fat diet, control subjects developed diabetes by week 17, while the majority of CBD-treated mice remained diabetes-free until week 24.
Therapeutic Efficacy of Tetrahydrocannabivarin (THCV)
THCV is a cannabinoid found in small amounts in cannabis, with the ability to reduce appetite and alleviate inflammation and oxidative stress. On a more technical level, it acts as a CB1 receptor antagonist and CB2 receptor agonist. Preliminary studies have shown that THCV, even at low doses, can decrease food intake and body weight. In addition, research in 2013 found that THCV improves glucose tolerance and insulin sensitivity, suggesting its potential in the treatment of metabolic syndrome and type 2 diabetes. These benefits were confirmed in a subsequent clinical trial with diabetic patients, improving their blood sugar control.
THCA and its Potential for Diabetes
In 2020, a study in animal models on the effects of tetrahydrocannabinolic acid (THCA), the non-psychoactive precursor of THC, found that THCA significantly reduced obesity-induced fat mass and body weight gain. In addition, THCA improved glucose tolerance and insulin resistance, and prevented liver problems such as steatosis. Being a partial modulator of PPARγ receptors, THCA showed less activity on fat formation compared to other drugs such as rosiglitazone (oral antidiabetic), highlighting its potential in the treatment of diabetes. These results suggest the potential of THCA in the treatment of diabetes, although further research is warranted.
Ultimately, key cannabinoids, including CBD, THCV and THCA, as well as agents that inhibit peripheral CB1 receptors or activate CB2 receptors, and possibly GPR55 and GPR119 receptor agonists, are at the forefront of preclinical research. These compounds show significant therapeutic potential, highlighting the growing interest in harnessing their mechanisms for the management of diabetes.
Conclusions on the Use of Cannabis and CBD in Diabetes
Both cannabis and CBD are not currently approved medications for diabetes, and in case of diabetes, a specialist should be consulted before taking CBD or cannabis, in order to obtain professional advice and monitor dosages and possible interactions and effects.
What has been described here is that there are promising epidemiological findings and emerging clinical evidence on the potential of cannabis and its components for diabetes. Hopefully, in the coming years we will have more information and studies to deepen our understanding of the potential of cannabinoids to improve diabetes care.
The information in this article is adapted from Cannabiscentia’s Manual of Cannabinology Principles, by Viola Brugnatelli and Fabio Turco and Prohibition Partners. A guide on medical cannabis and cannabinoids for healthcare professionals where the European medical cannabis landscape is extensively covered. The second edition is now available.
Note: This is an informative article with no prescriptive character, it is not intended to prevent, diagnose or treat any disease. Its content can complement, but should never replace, the diagnosis or treatment of any disease or symptom. Cannactiva products are not medicines and are intended for external use. There may be new relevant scientific evidence since the date of publication. Consult with your physician before using CBD. The therapeutic approach must always be personalized and depends on the professional assessment.
References and further information
- Zhang J, Lin C, Jin S, Wang H, Wang Y, Du X, Hutchinson MR, Zhao H, Fang L, Wang X. The pharmacology and therapeutic role of cannabidiol in diabetes. Exploration (Beijing). 2023 Jul 12;3(5):20230047. doi: 10.1002/EXP.20230047. PMID: 37933286; PMCID: PMC10582612.
- Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G: Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001, 410:822- 825.
- Samson, Randy A., and Lori A. Samson. “Marijuana and body weight. Innovations in clinical neuroscience 11.7-8 (2014): 50. 3, 22 Strat and Foll. 2011. ʺObesity and Cannabis Use: Results From 2 Representative National Surveys.ʺ American Journal of Epidemiology 174: 929-933.
- Di Marzo V: The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008, 51:1356-1367.
- Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL. Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci. 1998;63(8):PL113-7
- Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity.
- Despres JP, Golay A, Sjostrom L: Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidaemia. N Engl J Med 2005, 353:2121-2134.
- Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Steg PG, Pearson TA, Cohen E, Gaudin C, Job B, Murphy JH, Bhatt DL: Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicen- tre, placebo-controlled trial. Lancet 2010, 376:517- 523.
- Weiss et al. 2006. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39:2
- Rodondi, Nicolas, et al. Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study). The American journal of cardiology 98.4 (2006): 478-484.
- Smit E, Crespo CJ Dietary intake and nutritional status of US adult marijuana users: results from the Third National Health and Nutrition Examination Survey. Public Health Nutr. 2001 Jun; 4(3):781-6.
- Penner et al. 2013. Marijuana use on glucose, insulin, and insulin resistance among US adults. American Journal of Medicine 126: 583-589.
- Alshaarawy, Omayma, and James C. Anthony. “Cannabis smoking and diabetes mellitus: results from meta-analysis with eight independent replication samples.” Epidemiology (Cambridge, Mass.) 26.4 (2015): 597.
- Levendal R, Schumann D, Donath M, Frost C. Cannabis exposure associated with weight reduction and b -cell protection in an obese rat model. Phytomedicine. 2012;19:575-582.
- Weiss, L. et al. (2008) Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology 54, 244-249.
- Riedel, G. et al. (2009) Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br. J. Pharmacol. 156, 1154-1166
- Rossi F, Bellini G, Luongo L, Manzo I, Tolone S, Tortora C, Bernardo ME, Grandone A, Conforti A, Docimo L, Nobili B, Perrone L, Locatelli F, Maione S, Del Giudice EM. Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation. J Clin Endocrinol Metab. 2016 Sep;101(9):3469-78. doi: 10.1210/jc.2015-4381. Epub 2016 Jun 13. PMID: 27294325.
- Zuardi, A.W. (2008) Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psychiatr. 30, 271- 280
- Wargent et al. 2013. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & Diabetes 3
- Jadoon, Khalid A., Stuart H. Ratcliffe, David A. Barrett, E. Louise Thomas, Colin Stott, Jimmy D. Bell, Saoirse E. O’Sullivan, and Garry D. Tan. O’Sullivan, and Garry D. Tan. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care 39, no. 10 (2016): 1777-1786.
- Palomares B, Ruiz-Pino F, Garrido-Rodriguez M, Eugenia Prados M, Sánchez-Garrido MA, Velasco I, Vazquez MJ, Nadal X, Ferreiro-Vera C, Morrugares R, Appendino G, Calzado MA, Tena-Sempere M, Muñoz E. Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochem Pharmacol. 2020 Jan;171:113693.
Evidence Supporting the Use of Cannabinoids in Diabetes
Some studies have found that cannabis users are less likely to develop diabetes, despite the fact that cannabis can increase appetite. These findings suggest that cannabis may have a regulatory effect on metabolism, reducing the risk of diabetes.
Cannabinoids are also known to affect various metabolic pathways that influence blood sugar and insulin levels, which may explain why some studies have found that cannabis users have lower fasting insulin levels and lower insulin resistance, which may help prevent diabetes.
Research conducted at Harvard Medical School has found that cannabis can improve insulin sensitivity and lower blood glucose levels.
In particular, CBD, the non-psychoactive compound in cannabis, has shown potential in protecting insulin-producing pancreatic cells, suggesting potential benefits in the management and prevention of diabetes.
Despite these results, it should be noted that in all cases these are preliminary studies, more solid scientific evidence is lacking, and until more studies are done, it is not possible to affirm these properties. Patients are advised to consult their medical specialist before considering the use of CBD.
Cannabinoids for Diabetes: Current Research
Research on cannabinoids for diabetes is still at a preliminary stage. Some studies suggest that certain cannabinoids may improve glucose regulation and reduce inflammation, but more research is needed to fully understand their effects and determine their safety and efficacy in the treatment of diabetes. Here is a review of current research:
CBD and its Promising Role for Diabetes
CBD or cannabidiol shows potential in diabetes management by improving insulin sensitivity and reducing inflammation, although more research is needed to confirm its benefits and safety.
Detail: Studies on CBD for diabetes
In a 2006 animal study, it was shown that administration of CBD at a dose of 5 mg/kg daily significantly reduced the incidence of hereditary diabetes in a mouse model. In this study, 86% of the control group developed diabetes, compared to only 30% of the CBD-treated mice, indicating not only a lower incidence, but also a delayed onset of the disease.
Other studies corroborated these findings. Furthermore, in a mouse model of type 2 diabetes induced by a high-fat diet, control subjects developed diabetes by week 17, while the majority of CBD-treated mice remained diabetes-free until week 24.
Therapeutic Efficacy of Tetrahydrocannabivarin (THCV)
THCV is a cannabinoid found in small amounts in cannabis, with the ability to reduce appetite and alleviate inflammation and oxidative stress. On a more technical level, it acts as a CB1 receptor antagonist and CB2 receptor agonist. Preliminary studies have shown that THCV, even at low doses, can decrease food intake and body weight. In addition, research in 2013 found that THCV improves glucose tolerance and insulin sensitivity, suggesting its potential in the treatment of metabolic syndrome and type 2 diabetes. These benefits were confirmed in a subsequent clinical trial with diabetic patients, improving their blood sugar control.
THCA and its Potential for Diabetes
In 2020, a study in animal models on the effects of tetrahydrocannabinolic acid (THCA), the non-psychoactive precursor of THC, found that THCA significantly reduced obesity-induced fat mass and body weight gain. In addition, THCA improved glucose tolerance and insulin resistance, and prevented liver problems such as steatosis. Being a partial modulator of PPARγ receptors, THCA showed less activity on fat formation compared to other drugs such as rosiglitazone (oral antidiabetic), highlighting its potential in the treatment of diabetes. These results suggest the potential of THCA in the treatment of diabetes, although further research is warranted.
Ultimately, key cannabinoids, including CBD, THCV and THCA, as well as agents that inhibit peripheral CB1 receptors or activate CB2 receptors, and possibly GPR55 and GPR119 receptor agonists, are at the forefront of preclinical research. These compounds show significant therapeutic potential, highlighting the growing interest in harnessing their mechanisms for the management of diabetes.
Conclusions on the Use of Cannabis and CBD in Diabetes
Both cannabis and CBD are not currently approved medications for diabetes, and in case of diabetes, a specialist should be consulted before taking CBD or cannabis, in order to obtain professional advice and monitor dosages and possible interactions and effects.
What has been described here is that there are promising epidemiological findings and emerging clinical evidence on the potential of cannabis and its components for diabetes. Hopefully, in the coming years we will have more information and studies to deepen our understanding of the potential of cannabinoids to improve diabetes care.
The information in this article is adapted from Cannabiscentia’s Manual of Cannabinology Principles, by Viola Brugnatelli and Fabio Turco and Prohibition Partners. A guide on medical cannabis and cannabinoids for healthcare professionals where the European medical cannabis landscape is extensively covered. The second edition is now available.
Note: This is an informative article with no prescriptive character, it is not intended to prevent, diagnose or treat any disease. Its content can complement, but should never replace, the diagnosis or treatment of any disease or symptom. Cannactiva products are not medicines and are intended for external use. There may be new relevant scientific evidence since the date of publication. Consult with your physician before using CBD. The therapeutic approach must always be personalized and depends on the professional assessment.
References
- Zhang J, Lin C, Jin S, Wang H, Wang Y, Du X, Hutchinson MR, Zhao H, Fang L, Wang X. The pharmacology and therapeutic role of cannabidiol in diabetes. Exploration (Beijing). 2023 Jul 12;3(5):20230047. doi: 10.1002/EXP.20230047. PMID: 37933286; PMCID: PMC10582612.
- Di Marzo V, Goparaju SK, Wang L, Liu J, Batkai S, Jarai Z, Fezza F, Miura GI, Palmiter RD, Sugiura T, Kunos G: Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature 2001, 410:822- 825.
- Samson, Randy A., and Lori A. Samson. “Marijuana and body weight. Innovations in clinical neuroscience 11.7-8 (2014): 50. 3, 22 Strat and Foll. 2011. ʺObesity and Cannabis Use: Results From 2 Representative National Surveys.ʺ American Journal of Epidemiology 174: 929-933.
- Di Marzo V: The endocannabinoid system in obesity and type 2 diabetes. Diabetologia 2008, 51:1356-1367.
- Colombo G, Agabio R, Diaz G, Lobina C, Reali R, Gessa GL. Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. Life Sci. 1998;63(8):PL113-7
- Osei-Hyiaman D, DePetrillo M, Pacher P, Liu J, Radaeva S, Bátkai S, Harvey-White J, Mackie K, Offertáler L, Wang L, Kunos G. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity.
- Despres JP, Golay A, Sjostrom L: Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidaemia. N Engl J Med 2005, 353:2121-2134.
- Topol EJ, Bousser MG, Fox KA, Creager MA, Despres JP, Easton JD, Hamm CW, Montalescot G, Steg PG, Pearson TA, Cohen E, Gaudin C, Job B, Murphy JH, Bhatt DL: Rimonabant for prevention of cardiovascular events (CRESCENDO): a randomised, multicen- tre, placebo-controlled trial. Lancet 2010, 376:517- 523.
- Weiss et al. 2006. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39:2
- Rodondi, Nicolas, et al. Marijuana use, diet, body mass index, and cardiovascular risk factors (from the CARDIA study). The American journal of cardiology 98.4 (2006): 478-484.
- Smit E, Crespo CJ Dietary intake and nutritional status of US adult marijuana users: results from the Third National Health and Nutrition Examination Survey. Public Health Nutr. 2001 Jun; 4(3):781-6.
- Penner et al. 2013. Marijuana use on glucose, insulin, and insulin resistance among US adults. American Journal of Medicine 126: 583-589.
- Alshaarawy, Omayma, and James C. Anthony. “Cannabis smoking and diabetes mellitus: results from meta-analysis with eight independent replication samples.” Epidemiology (Cambridge, Mass.) 26.4 (2015): 597.
- Levendal R, Schumann D, Donath M, Frost C. Cannabis exposure associated with weight reduction and b -cell protection in an obese rat model. Phytomedicine. 2012;19:575-582.
- Weiss, L. et al. (2008) Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology 54, 244-249.
- Riedel, G. et al. (2009) Synthetic and plant-derived cannabinoid receptor antagonists show hypophagic properties in fasted and non-fasted mice. Br. J. Pharmacol. 156, 1154-1166
- Rossi F, Bellini G, Luongo L, Manzo I, Tolone S, Tortora C, Bernardo ME, Grandone A, Conforti A, Docimo L, Nobili B, Perrone L, Locatelli F, Maione S, Del Giudice EM. Cannabinoid Receptor 2 as Antiobesity Target: Inflammation, Fat Storage, and Browning Modulation. J Clin Endocrinol Metab. 2016 Sep;101(9):3469-78. doi: 10.1210/jc.2015-4381. Epub 2016 Jun 13. PMID: 27294325.
- Zuardi, A.W. (2008) Cannabidiol: from an inactive cannabinoid to a drug with wide spectrum of action. Rev. Bras. Psychiatr. 30, 271- 280
- Wargent et al. 2013. The cannabinoid Δ9-tetrahydrocannabivarin (THCV) ameliorates insulin sensitivity in two mouse models of obesity. Nutrition & Diabetes 3
- Jadoon, Khalid A., Stuart H. Ratcliffe, David A. Barrett, E. Louise Thomas, Colin Stott, Jimmy D. Bell, Saoirse E. O’Sullivan, and Garry D. Tan. O’Sullivan, and Garry D. Tan. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, parallel group pilot study. Diabetes Care 39, no. 10 (2016): 1777-1786.
- Palomares B, Ruiz-Pino F, Garrido-Rodriguez M, Eugenia Prados M, Sánchez-Garrido MA, Velasco I, Vazquez MJ, Nadal X, Ferreiro-Vera C, Morrugares R, Appendino G, Calzado MA, Tena-Sempere M, Muñoz E. Tetrahydrocannabinolic acid A (THCA-A) reduces adiposity and prevents metabolic disease caused by diet-induced obesity. Biochem Pharmacol. 2020 Jan;171:113693.