Food Effects on Cannabinoids in the Body

• Effects Observed
• Delayed Maximum Concentration of THC
• Lower clearance (elimination) from the body
• Increased Exposure

Eating high-fat food before ingesting cannabis compounds can affect how our bodies process them. Examples of high-fat foods include fries, ice cream, fatty fish, or cheeses. On this page, we will explain what effects food can have on cannabis, the mechanisms behind them, and why this is important for the patients.

Effects Observed

Before being put on the market, an oral medicine undergoes numerous studies. Some of them focus on understanding the medicine’s interaction with food and how it can affect the absorption {call-out, text: Drugs entering the bloodstream from which they are distributed throughout the body} into the bloodstream. This and other pharmacokinetic {call-out, text: The effect that the body has on the drug, see insert relevant pharmacokinetic section} factors can determine the way in which the medicine eventually exerts its effects. Extensive studies on cannabis-food interactions are lacking. However, the few studies that have been done observe how the maximum concentration of active cannabinoid THC in the blood and the total THC exposure can be compared in a fed state {call-out, text: after a meal} vs. a fasted state {call-out, text: not having eaten for a certain period}. First, let’s define the important terms: Peak plasma concentration is the highest amount of a compound in plasma, the liquid part of the blood. After inhaling THC or CBD, the peak concentration in plasma happens much sooner than with oral intake, which includes the inevitable first-pass metabolism that breaks down cannabis compounds in the liver after they have gone through the gastro-intestinal tract. Peak effects of the compounds happen when the strength of an effect is at its highest, after which it typically gradually diminishes. One of the notable effects of THC is the “high” feeling. Peak plasma concentration does not happen at the same time as the peak THC effects because the effect induction mostly happens outside of the blood stream. An example of effect induction is THC binding to the endocannabinoid receptor CB₁ in the brain. The exact timing varies and depends on numerous factors. First, we are all different, as well as our physiology. Next, external factors often play a role. A major factor that influences what happens to orally ingested cannabinoids in our bodies is food, which is the focus of this Education Page. In the following sections, we will summarize the three ways in which high-fat food has shown to influence the body’s response to cannabis. They are: 1) delayed time to reach the maximum concentration of THC in the blood, 2) lower clearance or elimination from the body, and 3) larger cannabinoid exposure. All three are summarized in Figure 1 and Table 1 below.

Delayed Maximum Concentration of THC

When taking an oral THC product, such as a capsule, a pill, or an edible, after a high-fat meal, it is likely that the effects of THC reach their maximum later than they would if the THC product was taken on an empty stomach. Namely, the following three studies found that taking THC after food delays the peak plasma concentration, which is not a proof that peak effects of THC occur later as well, but it is likely to believe so. Study 1: oral capsules In a study by researcher Lunn and colleagues, THC was given as whole-plant extract capsules after a high-fat meal consisting of eggs, bacon, butter, along with other common breakfast foods. They found that in this case, the peak plasma concentration of THC occurred later than it did on an empty stomach.¹ Study 2: THC+CBD oromucosal spray Another study showed a similar outcome after administering a THC+CBD (cannabidiol) oromucosal spray in a fed state compared to a fasted state of 10 hours.² This was surprising, because food is not likely to influence compound absorption into the bloodstream via the oromucosal route as the absorption is supposed to happens directly through the mucosa in the mouth. This administration method should allow the compounds to skip the gastrointestinal system where food can interact with it. However, this finding indicates that the THC+CBD oromucosal spray most likely followed the oral path and may have been swallowed instead of directly absorbed from the tongue and the cheek. Study 3: liquid THC solution Researcher Oh and colleagues further examined the effect of food on dronabinol (synthetic THC) intake in a liquid form. Dronabinol is a pharmaceutical drug that is registered for treating anorexia in AIDS patients, and nausea and vomiting caused by chemotherapy.³ In this study, the researchers used a liquid dronabinol dissolved in alcohol for oral intake, termed “oral solution”. They found that in a fed state compared to a fasted state, just like with the capsule and the oromucosal spray, the oral solution had a delay in attaining its maximum concentration in the blood.² None of these three studies did decidedly prove that peak effects of THC occur later as well, but it is likely to think so, considering that peak effects generally happen after cannabis compounds have reached their maximum amount in the blood. Potential effects on the peak concentration and side effects Although food can affect the time needed for THC to reach its peak concentration in the plasma, the effects on the maximum plasma concentration itself so far have given mixed inconclusive results so far. After taking oral and oromucosal THC products, there were not any significant differences in the maximum concentration of THC or its metabolites between a fed and a fasted state, and mixed trends were found. For example, the studies with oral THC capsules and liquid THC found that a peak concentration of THC in the blood plasma is somewhat higher on an empty stomach than after a meal, which is similar to the results of a 2019 study on dogs. On the other hand, the THC+CBD oromucosal study found the opposite, with higher THC peak concentrations after eating, but with higher peak concentrations of active metabolites after fasting.^{1, 2, 4, 5} In the oral THC capsule study capsule, mild side effects, such as sleepiness, fatigue, and euphoria were reported in participants that fasted before taking the highest dose of THC, whereas these side effects were not seen in the fed volunteers.¹ This may imply that taking THC together with food instead of on an empty stomach could mitigate these side effects, but more studies need to further analyze how food influences THC’s effects.

Lower clearance (elimination) from the body

The research groups with Lunn and Stott independently observed that THC remains in the bloodstream longer when taken after food than when taken after fasting.^{1, 2} This is caused by changes in THC elimination: after food, the clearance of THC is decreased, which means that THC is cleared from the body at a slower rate.^{1, 2} Although not proven, this implies that THC effects last longer when used after food instead of on an empty stomach.

Consequently, Exposure is Increased

Clearance and overall exposure of a drug are inversely related, meaning that if the rate at which the drug is cleared from the blood is reduced, there is more drug that the body gets exposed to. In pharmacology, this exposure is typically expressed as the Area Under the Curve, or AUC, which you can see in Figure 1. The studies with the oral capsule, oral liquid THC, and with the oromucosal THC+CBD spray all reported this higher exposure after a fed state.^{1, 2, 4} The potential consequences of a higher exposure are manyfold. A higher exposure, also referred to as a higher bioavailability, can potentially lead to a higher chance of drug-drug interactions. Also, because there are more active compounds, the effects can be stronger in theory. We say in theory, because in practice, the oral administration of THC leads to the formation of its active metabolite, 11-oh-thc, whose quantity can vary greatly. The actual implications of a higher exposure after cannabinoid administration with food needs to be further explored, but professionals and patients should be aware of this phenomenon. Figure 1: The effect food has on the body after THC administration in capsule form is depicted in the graph below. On a fed stomach, shown in green, there was a later peak time of maximum concentration of THC in the bloodstream (1). The green area under the curve (AUC) (3) is bigger than the pink AUC (2), showing a greater exposure in fed versus fasted state. With food, the downward slope of the green graph (5) is also less steep than the pink one (4), indicating that THC stays in the blood longer.^{1, 2, 4} Although most data have been gathered for THC, it is likely that the effects are similar regarding oral CBD and potentially other cannabinoids. The differences that people anecdotally experience, such as feeling “high” considerably longer after consuming cannabis with high-fat food compared to on an empty stomach, are thought to be caused by the food-induced changes in cannabinoid plasma concentrations as shown in Figure 1. Table 1: Summary of the effects of food on cannabinoid intake

Parameter	Fed state	Fasted state	Potential effect change in fed state (speculative)
Time to maximum concentration	Increased🡑	Decreased🡓	Later effect
Maximum concentration	Inconclusive	Inconclusive	Inconclusive
Exposure	Increased🡑	Decreased🡓	More drug-drug interactions, potentially stronger effects
Clearance	Decreased🡓	Increased🡑	Increased duration of action

References:

1. Lunn, Stephanie; Diaz, Patrick; O'Hearn, Shannon; Cahill, Shaina P.; Blake, Alexia; Narine, Kelly; Dyck, Jason R. B. (2019). Human Pharmacokinetic Parameters of Orally Administered Δ 9 -Tetrahydrocannabinol Capsules Are Altered by Fed Versus Fasted Conditions and Sex Differences. Cannabis and Cannabinoid Research, 4(4), 255-264.
2. Stott, C. G.; White, L.; Wright, S.; Wilbraham, D.; Guy, G. W. (2013). A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray. European Journal of Clinical Pharmacology, 69(4), 825--834.
3. U. S. Food and Drug Administration FDA label Syndros (dronabinol). Food and Drug Administration.
4. Oh, D. Alexander; Parikh, Neha; Khurana, Varun; Cognata Smith, Christina; Vetticaden, Santosh (2017). Effect of food on the pharmacokinetics of dronabinol oral solution versus dronabinol capsules in healthy volunteers. Clinical Pharmacology: Advances and Applications, 9, 9-17.
5. Łebkowska-Wieruszewska, Beata; Stefanelli, Fabio; Chericoni, Silvio; Owen, Helen; Poapolathep, Amnart; Lisowski, Andrzej; Giorgi, Mario (2019). Pharmacokinetics of Bedrocan®, a cannabis oil extract, in fasting and fed dogs: An explorative study. Research in Veterinary Science, 123, 26-28.