Does Cannabis Affect Insulin?
If you have ever consumed cannabis, you have probably experienced “the munchies.” Scientists consider THC and other CB1 receptor agonists to “reliably induce hyperphagia.”
But why does cannabis make you hungry? According to researchers who examined this topic, “cannabinoid receptors are expressed not only in the brain, but also in the gut and other peripheral organs involved in food intake, metabolism and energy homeostasis.”
Previous studies have shown that acute administration of cannabis “stimulates food craving, intake, reward, and promotes the storage of energy in adipose tissues.”
However, chronic daily administration of THC “suppresses weight gain, fat mass gain, and caloric intake of diet-induced obese rats, and epidemiological data indicate an association between chronic cannabis use and decreased prevalence of obesity and diabetes.”
While it is evident that cannabis affects metabolism and eating-related processes, there are contradictory findings in the scientific literature and “acute versus chronic cannabis use may lead to different, and even opposite, outcomes.”
In February of 2020, researchers conducted the first human laboratory investigation to explore how different routes of cannabis administration (smoked, vaporized, orally-ingested cannabis flower) affected “peripheral concentrations of appetitive and metabolic hormones in a sample of occasional and frequent cannabis users.”
They found that cannabis lowered insulin levels in all three routes of administration compared to a placebo condition, and that smoked cannabis produced higher concentrations of THC in the blood than either vaporized or orally consumed cannabis.
Why Study Different Ingestion Methods?
The researchers chose to investigate how different ingestion methods affect appetitive and metabolic hormones based on a previous study that found that the route of administration “alters THC pharmacokinetics, as well as cardiorespiratory and subjective effects.”
The researchers’ previous study into the pharmacokinetics of THC found that vaporizing cannabis “resulted in qualitatively stronger drug effects…and higher peak concentrations of THC in the blood” than smoking cannabis. 
Why Study Cannabis and Appetitive Hormones?
The researchers chose to examine peripheral concentrations of appetitive and metabolic hormones based on a previous study that indicated “a close link between cannabis use and energy homeostasis.”
The previous study examined appetitive and metabolic hormones in adult men living with HIV who smoked medical cannabis, and found that cannabis affected a variety of appetitive hormones, increasing blood concentrations of ghrelin (hormone that increases hunger) and leptin (hormone that decreases hunger) but had no significant effect on insulin.
Insulin is a hormone produced in the pancreas that “regulates the metabolism of carbohydrates, fats and proteins by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells.”
Due to a lack of research on cannabis and appetitive and metabolic hormones in humans, the goal of the study was both to explore how cannabis administration affected appetitive and metabolic hormones, and “potential differences in the effects of cannabis on endocrine outcomes when administered via different routes.”
How Did They Conduct The Study?
The study was randomized, double-blind and placebo-controlled with a double-dummy and crossover design. Participants were recruited through advertisements and word of mouth, and each underwent four dosing sessions in a random order: oral placebo followed by smoked or vaporized placebo; oral placebo followed by smoked cannabis; oral placebo followed by vaporized cannabis; oral cannabis follow by smoked or vaporized placebo. The oral dose was always administered as a brownie.
All sessions were completed within one year and the participants stayed in a secure in-patient facility the night before their dosing session to make sure they didn’t consume cannabis in the hours prior to the experiment.
During each dosing session, the participants’ blood was drawn at five different time intervals to measure blood THC and hormone levels. Specifically, the researchers looked at ghrelin, leptin, GLP-1, insulin, amylin and PYY.
What Did They Find?
The researchers found that cannabis affected insulin, GLP-1 and total ghrelin levels. Additionally, theyobserved that blood THC concentrations were significantly higher for smoked cannabis than orally ingested or vaporized cannabis. Vaporized cannabis resulted in higher blood THC concentrations than oral cannabis, but the difference “did not reach statistical significance.”
When the participants ate the oral placebo brownie, they experienced an expected spike of blood insulin concentrations due to the sugar in the brownie. But when they ate the THC brownie, “this acute insulin spike was blunted.”
At the fourth time interval, oral THC, smoked THC and vaporized THC all produced considerably lower insulin concentrations than the placebo condition. Cannabis seems to lower insulin levels.
According to the researchers, “the influence of cannabis on insulin observed in this study is in line with the established role of the endocannabinoid system in regulating glucose metabolism and, at large, energy balance.”
The researchers also observed that GLP-1 concentrations were lower when using cannabis. GLP-1 is a hormone that stimulates a decrease in blood glucose. The researchers state that there might not be a direct link between cannabis and suppressed GLP-1 levels, and that rather they might be observing a secondary effect of the suppressed insulin levels.
They also found that the route of administration affects total ghrelin levels, such that oral cannabis produced significantly higher “hunger hormone” levels than the smoked or vaporized cannabis sessions, as well as the placebo condition.
Cannabis exerts a variety of effects on eating-related systems, but the significance of these findings for cannabis users is not yet clear. For example, the precise relationship between cannabis and insulin may depend on a variety of factors like frequency of cannabis exposure or baseline metabolic state.
Limitations of the Study
While this study produced some interesting findings, the researchers note several significant limitations. They did not look at all the endocrine pathways related to appetite and metabolism, nor did they measure blood glucose or cholesterol levels. The study was conducted on twenty individuals, most of whom were male, so these results may not reflect the general population. And the laboratory setting may not have much relevance to real-life situations.
However, despite these limitations, the researchers uncovered that “cannabis administration, via oral, smoked and vaporized routes, modulated blood concentrations of some appetitive and metabolic hormones in cannabis users,” and provided further evidence that different administration methods have different pharmacokinetics. More studies are needed to determine the “mechanisms underpinning these effects.”
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 McCartney D, Benson MJ, Desbrow B, Irwin C, Suraev A, McGregor IS. Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research. Sports Med Open. 2020;6(1):27. Published 2020 Jul 6. doi:10.1186/s40798-020-00251-0
 Spindle TR, Cone EJ, Schlienz NJ, et al. Acute Effects of Smoked and Vaporized Cannabis in Healthy Adults Who Infrequently Use Cannabis: A Crossover Trial [published correction appears in JAMA Netw Open. 2018 Dec 7;1(8):e187241]. JAMA Netw Open. 2018;1(7):e184841. Published 2018 Nov 2. doi:10.1001/jamanetworkopen.2018.4841