Penner EA, Buettner H, Mittleman MA. The impact of marijuana use on glucose, insulin, and insulin resistance among US adults. Am J Med. 2013;126(7):583-589.
Data gathered by the National Health and Nutrition Examination Survey (NHANES) cross-sectional surveys from 2005 to 2010 were examined to calculate the relationship between regular marijuana use and measure of fasting glucose and insulin levels, insulin resistance, blood pressure, body mass index, waist circumference, and high-density lipoprotein cholesterol. Blood samples were drawn following a 9-hour fast. Marijuana use was self-reported in a private room.
The study included 4,657 men and women 20 to 59 years old; 578 were current marijuana users and 1,975 were past users.
Primary Outcome Measures
Fasting glucose and insulin levels, insulin resistance (HOMA-IR), blood pressure, body mass index (BMI), waist circumference, and high-density lipoprotein cholesterol
Study Parameters Assessed
From 2005 to 2010, 11,335 subjects aged 20 to 59 years completed the NHANES survey on illicit drug use. Data was self-reported in a private room. Of those, 4,657 also provided fasting blood samples, which were used to calculate these values.
Past and current marijuana use was associated with lower levels of fasting insulin, glucose, HOMA-IR, BMI, and waist circumference.
The medical use of marijuana nearly disappeared in the early part of the 20th century after the passage of the Marihuana [sic] Tax Act of 1937 and its consequent removal from the US Pharmacopoeia in 1942.1 Therapeutic applications were serendipitously rediscovered as social use of marijuana rapidly increased in the 1960s and 1970s.2,3 The Marihuana Tax Act was replaced by the Controlled Substances Act of 1970, which categorized marijuana as a substance having "no currently accepted medical use" with "a high potential for abuse" and "a lack of accepted safety for the use of the drug or substance under medical supervision." Marijuana was placed into the most restrictive category for prescriptive drugs, Schedule I. This designation made clinical research extremely difficult to conduct.
Marijuana's active molecules, the cannabinoids, were isolated in the early 1960s, and the first cannabinoid receptor (CB1) was identified in 1988.5 Another cannabinoid receptor (CB2) was soon located, and the discovery of endocannabinoids, endogenous substances that influence those receptors' activity, followed. These discoveries facilitated preclinical research into cannabinoids' activities within the varied range of diseases for which marijuana was being used therapeutically. Clinical research remained hampered by federal laws and regulations.
In part because of marijuana's association with appetite stimulation, researchers began to study the substance and its effects on calorie consumption and metabolism. Investigators uncovered a paradox: marijuana smokers ingest more calories than nonusers but have lower rates of obesity.6–8 Research with mouse models of diabetes revealed that the most common cannabinoids found in marijuana, delta-9 tetrahydrocannibinol (THC) and cannabidiol (CBD), inhibit the severity and onset of the disease respectively."9,10 Another study determined that a cannabis extract significantly protected rats' insulin-producing pancreatic cells from the damaging effects of obesity.11
Because of the unique barriers that exist with regard to researching cannabis' benefits in human subjects, another source of data must be consulted to confirm the trends seen in animal or in vitro models. Large epidemiological studies can provide evidence to strengthen or weaken preclinical observations. Data from the National Health and Nutrition Examination Survey (NHANES) of 4,657 participants found that "marijuana use was associated with a decreased prevalence of diabetes mellitus.12 The current study takes a closer look at the NHANES data to better understand the paradox of increased calorie intake resulting in lower weight and less incidence of diabetes.
The researchers used values for fasting serum insulin and fasting plasma glucose to calculate the homeostasis model assessment of insulin resistance (HOMA-IR), an indicator of insulin resistance. They found that regular, monthly marijuana users had significantly lower levels of fasting insulin, glucose, HOMA-IR values, and waist size than never users. The frequent marijuana smokers also had higher levels of high-density lipoprotein cholesterol (HDL-C), a marker of cardiac health. Yet we are unlikely to see widespread promotion marijuana smoking for its health benefits, due in part to the compromising effects of the harmful byproducts of combustion. Prior to the enactment of the Marihuana Tax Act, though, cannabis was frequently used as tinctures or pills. These modes of delivery could also allay concerns about undesired mind-altering effects. The cannabinoid CBD reduces the psychoactive effects of THC; therefore ingestion of a combined-cannabinoid remedy could provide health benefits without cognitive effects.13 The protective dose may also be much lower than the psychoactive doses. Investigators in Israel found that an ultra-low dose of THC, 3–4 magnitudes below a psychoactive dose, offered significant protection to the heart, brain, and liver against ischemic damage."15 It is possible that this could hold true for the pancreas.
The potential significant benefits of low-risk but illegal cannabis use puts the dedicated medical practitioner in an uncomfortable position, even in medical marijuana states. A physician's freedom to communicate the benefits of cannabis to patients was established by a Supreme Court case, but there is little education provided on the medical use of cannabis. Due to lack of knowledge and any published evidence base to turn to, many physicians are reluctant to recommend or even discuss cannabis as medicine with their patients. The difficulty in conducting clinical research to evaluate the potential medical benefits of cannabis has been mentioned and cannot be overstated.16 The number of regulatory hoops an investigator must jump through to get all the approvals required to study cannabis can be daunting.
What then are the clinical implications of this NHANES data analysis? Can cannabis use decrease diabetes, insulin resistance, and obesity? Can diabetics add cannabis as an adjunct to their hypoglycemic agents for synergistic benefits? Appreciating that the plural of anecdote is not evidence, we will share the impact of a cannabis extract on diabetes management of a personal friend. This 50-year-old woman is an insulin-dependent diabetic who was having difficulty with glucose control despite a normal body mass index. She added a daily dose of a cannabis extract to her insulin regimen. She reports that her glucose has been under much better control, dropping between 90 to 100 points after dosing.
This single anecdote in association with the strength of the NHANES findings would suggest that further research is warranted. We applaud Dr. Alpert, editor-in-chief of The American Journal of Medicine who calls for National Institutes of Health and Drug Enforcement Administration collaboration to facilitate the development of scientific investigations to provide physicians with the data they need to assist them in the "use and prescription of THC in its synthetic or herbal form.”16,17 Hopefully the increasing awareness of marijuana's chemistry and potential benefits will soon help to eliminate political barricades to scientific investigations.
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13. Stott CG, White L, Wright S, Wilbraham D, Guy GW. A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray. Eur J Clin Pharmacol. 2013;69(5):1135-1147.
14. Waldman M, Hochhauser E, Fishbein M, Aravot D, Shainberg A, Sarne Y. An ultra-low dose of tetrahydrocannabinol provides cardioprotection. Biochem Pharmacol. 2013;85(11):1626-1633.
15. Same Y, Fishbein M, Gafni M, et al. Long-term Protection of the Brain, the Heart, and the Liver by Ultra-low Doses of Tetrahydrocannabinol (THC). Presentation at the 23rd Annual Symposium of the International Cannabinoid Research Society. Vancouver, BC, Canada. June 2013.
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17. Alpert JS. Marijuana for diabetic control. Am J Med. 2013;126(7):557-558.