Dr. David Pompei, PharmD, MS
Did you know that there is evidence that cannabis can affect insulin levels? How is it possible that cannabis could lower insulin levels? Before we get into the scientific research, we want to clarify that in no way is the following information meant to suggest that cannabis is a replacement for insulin treatment. Always consult with your doctor or licensed health care professional before making any changes to your lifestyle or routine.
In February 2020, researchers conducted the first human laboratory investigation to explore how three different ingestion methods - oral ingestion (e.g., eating weed edibles) smoking, and vaporizing cannabis flower - affect appetitive and metabolic hormones like insulin, ghrelin, and leptin "in a sample of occasional and frequent cannabis users.” We will explore the implications of this study in detail below, but here's a snapshot of what they found:
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.”
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.”
The scientists wanted to determine how three different routes of cannabis administration (smoking, vaporizing, oral ingestion) affected “peripheral concentrations of appetitive and metabolic hormones in a sample of occasional and frequent cannabis users.”
They designed these parameters based on a previous study that found that the route of administration “alters THC pharmacokinetics, as well as cardiorespiratory and subjective effects.”
Pharmacokinetics (PK) is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how a drug affects an organism.
The researchers’ previous study into the PK of THC found that vaporizing cannabis “resulted in qualitatively stronger drug effects…and higher peak concentrations of THC in the blood” than smoking cannabis. Given the wide-ranging effects of the human endocannabinoid system on processes from energy homeostasis to appetitive processes, they wanted to explore whether this difference in PK would lead to a difference in PD in insulin, ghrelin, leptin, and GLP-1 levels.
Here's a quick primer on what those terms mean:
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 had a medical marijuana card.
The researchers found that cannabis affected a variety of appetitive hormones, increasing blood concentrations of ghrelin (the hormone that increases hunger) and leptin (the 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.”
If cannabis does affect insulin, that would be an important area to research further. While there is not much research on how cannabis affects insulin levels, patients seeking a cannabis prescription at a medical marijuana clinic could ask a cannabis doctor about this topic.
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.”
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.
The researchers found that cannabis affected insulin, GLP-1, and total ghrelin levels. Additionally, they observed 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 in 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. As we discussed above, 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.
In conclusion, 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.
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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