The Sweet Taste of Science: Edibles’ Potency Increases with Dietary Fat

One of the barriers to cannabis’ complete absorption into the Western medical canon of pharmaceuticals has perhaps been its traditional method of ingestion. We have to wonder, for instance, if Advil needed to be smoked or vaporized, would it be as commonly used? Of course, cannabis and cannabis derivatives, can also be consumed as edibles. Until the creation of FDA-approved Dronabinol, pill form was not legally possible. However, cannabis has been baked into cakes, cookies, and tinctures for centuries. These preparations allow for discrete consumption with the added benefit of by-passing any lung irritation to the consumer. Even in the case of pill-based Dronabinol and its spray tincture cousin, Sativex, doctors recommend consuming medicine with some dietary fat.

Readers with a background in biology may quickly understand why. If a molecule is lipid-soluble, meaning it can chemically dissolve in a lipid (fat/oil), consuming the molecule with lipids therefore increases its “bio-availability”. We’ve written about bio-availability previously, but as a quick tune-up, this is the body’s ability to metabolize a molecule. Not all of the THC or CBD from a joint or edible can be processed. Depending on the method of administration, the human body has varying levels of efficiency. In other words, an edible and a joint with equal amounts of THC and CBD will not have equal effects. And likewise, an edible with 25 mg is not necessarily less potent than an edible with 50 mg, provided the 25 mg edible possesses a more bio-available composition.

However, despite a wealth of anecdotal and scientific evidence regarding increase in potency with fat or oil co-administration, few tests have measured the exact change in absorption of THC and CBD. Given that these are currently the two most popular therapeutic components of cannabis, having a knowledge of the influence of fats in patients’ diets could help both patients and doctors titrate the level of necessary oral cannabis intake (whether in pill form, cookie, etc.).

To rectify this lack of knowledge, researchers at The University of Nottingham School of Pharmacy employed rats and blood testing to achieve a basic idea of fat/oil influence on cannabinoid bio-availability. This study encompassed two major techniques. First, researchers gave rats an IV to effectively and directly administer cannabis solutions to the rats’ intestines, as a means for comparing direct administration of THC and CBD to the rodents’ blood.  These rats received either THC or CBD alone, at 4 mg/kg. Another group, on the other hand, received oral administration of THC or CBD alone, at 12 mg/kg in propylene glycol-ethanol-sterile water, which is a solution containing no fat or oil. Finally, the last group received a forced oral administration, at 12 mg/kg again but in sesame seed oil. After this feeding, either by IV or oral, researchers took blood samples at 5, 15, 30, 60, 120, 240, 360, 480, and 720 minutes after IV, and 30, 60, 120, 180, 240, 300, 360, 480, and 720 minutes after oral feeding. By using a centrifuge to separate the blood samples, researchers were able to measure the levels of THC and CBD in blood and thus readily available for use.

Secondly, researchers prepared a mock digestive system. Without getting too deeply into the chemistry, researchers prepared a bath of digestive fluid similar to the contents of mammalian stomach during fasting, then added 20 mg/mL solutions of THC or CBD to the bath and induced chemical digestion. Once again, researchers used a centrifuge to separate and measure solution composition after digestion.

As seen in the graph above, while IV administration of THC allowed a high level of cannabinoids to enter the bloodstream immediately, ultimately this THC concentration dipped as the body adjusted. On the other hand, edible preparations started slowly and tended to grow over time. Although the non-lipid oral administration started with a higher blood concentration, the lipid-based preparation ultimately surpassed the non-lipid concentration within 30 minutes and continued to grow. If readers notice, the plasma concentration graphed here is exponential, which means that lipid-based oral administration produced a plasma concentration of THC that was 2.5 times greater than the non-lipid plasma concentration. If these numbers are accurate, this could mean that a 20 mg THC edible with an oil source included might be as effective as a 50 mg dose of Dronabinol taken without any dietary fat.

Above, we notice the same pattern for CBD blood-plasma concentration, with a lipid-based preparation outperforming a non-lipid delivery by as much as three times the amount.

Finally, in the artificial digestion of THC and CBD with sesame seed oil, the results showed that approximately 1/3rd of THC and CBD were observed to be available in the microcellular layer, while the rest resided in the undigested lipid-fraction and sediment layer that had not dissolved in the lipid at all. In other words, edible THC and CBD’s basic bio-availabilities in fats is close to 30%.

In reality, almost every individual has a certain amount of dietary fat, so the gains seen in real life may not be as large as compared to a purely fat-free administration. However, the basic idea, that co-administration of THC or CBD with fats or oils increases potency significantly is completely true. Even in the case that fat administration could increase potency by only twice as much in practice, this is potentially cutting the cost of cannabis-based medicine by half. That does not mean that patients wanting the most from medical cannabis should increase overall fat consumption, which is obviously unhealthy. Instead, this means that patients may plan to consume the fatty parts of their diets at the time of cannabinoid administration. Likewise, doctors prescribing cannabis may also keep in mind the fat consumption of each patient when deciding how much to initially prescribe.


Works Cited

Atheer Zgair, Jonathan CM Wong, Jong Bong Lee, et al. “Dietary fats and pharmaceutical lipid excipients increase systemic exposure to orally administered cannabis and cannabis-based medicines.” American Journal of Translational Research (2016) 8:3448-3459.

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