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CBD may increase adverse effects of THC in edibles

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2 years ago

February 28, 2023

Antonio João Costa

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A study led by researchers from the Johns Hopkins Medicine found that relatively high doses of cannabidiol (CBD) can increase the adverse effects of delta-9-tetrahydrocannabinol (THC), the main active ingredient in cannabis that causes the euphoric effect attributed to cannabis. The results of this research demonstrate that, in edible cannabis products, CBD inhibits the metabolism or breakdown of THC, which can result in a stronger and longer-lasting psychotropic effect.

The results of the study, published on February 13th at the JAMA Network Open, found that the maximum amount of THC measured in participants' blood samples was almost twice as high after consuming a brownie containing THC with CBD than after eating a brownie with only THC, although the dose of THC in each brownie (20 mg) was the same. Furthermore, the peak amount of 11-OH-THC (a by-product of THC metabolism, which produces the psychotropic effect of cannabis when ingested) was 10 times higher after eating the brownie with the high CBD content, compared to the high-THC brownie.

The work examined the pharmacokinetics (absorption and elimination of a substance by the body) and pharmacodynamics (the body's response to a substance) between cannabis extracts whose concentrations of THC and CBD were variable.

"The fact that THC and CBD were administered orally was very important to the study and played a role in the behavioral effects and drug interactions we observed," said Austin Zamarripa, Ph.D., postdoctoral researcher. PhD from the Johns Hopkins University School of Medicine and lead author of the study.

The various human studies that have looked at these interactions were predominantly by inhalation or intravenously, or they were not administered simultaneously. For this reason, much of the existing data on interactions between THC and CBD may not apply to edible cannabis products, such as baked goods, candies and gummies, which are metabolized by the gut and liver.

“Overall, we observed stronger subjective effects, greater impairment of cognitive [thinking] and psychomotor [moving] ability, and greater increase in heart rate when the same dose of THC was administered in a high-CBD cannabis extract, compared to a high-THC extract without CBD,” says Zamarripa.

The study, which tested each type of cannabis extract and a placebo on the same subjects rather than using different people for each type of drug, was conducted from January 2021 to March 2022 at the Behavioral Pharmacology Research Unit at Johns Hopkins Bayview Medical Center. Investigators recruited 18 adult participants (11 men and 7 women) who had not used cannabis for at least 30 days prior to the start of the study.

Study volunteers participated in three sessions, each separated by at least a week. In each session, participants consumed a brownie containing either 20 mg of THC, 20 mg of THC, and 640 mg of CBD, or no THC or CBD (placebo). Neither the participants nor the researchers knew in advance which brownie the participants were eating in each session. Participants also received a drug cocktail, consisting of five cytochrome (CYP)-acting drugs, including: 100 mg of caffeine, 25 mg of losartan, 20 mg of omeprazole, 30 mg of dextromethorphan and 2 mg of midazolam. The cocktail was offered to participants about 30 minutes after eating each brownie. According to the release, this additional step will help researchers understand the interactions between THC and CBD in the metabolism of other drugs and dietary supplements regularly used by society.

To create a baseline for comparison, blood samples were taken from all participants before each session, along with their vital signs (heart rate and blood pressure) and measures of cognitive and psychomotor performance. Participants provided blood and urine samples at timed intervals for 12 hours and again approximately 24 hours after the administration was completed. Self-reported effects were measured using the Drug Effect Questionnaire (DEQ), a standardized tool used to assess aspects of subjective experiences after receiving a psychoactive substance such as THC.

“We have shown that with a relatively high oral dose of CBD [640 mg] there can be significant metabolic interactions between THC and CBD, so that the effects of THC are stronger, longer lasting and tend to reflect an increase in unwanted adverse effects. ,” says Ryan Vandrey, Ph.D., professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine and senior author of the study.

Vandrey noted that another of his team's recent studies found that CBD products are not always labeled correctly. “Our research suggests that it is important for people to be aware that if they are going to consume a CBD extract in high doses, they also need to be aware of interactions with other medications. Individuals should discuss with their physician whether to consider dose adjustments of THC and other medications if they are also consuming CBD,” says Vandrey.

The researchers say that future studies are needed to better understand the impact of CBD and THC dose, relative concentration, frequency of use, and individual health differences on how our body metabolizes.

In addition to Zamarripa and Vandrey, other investigators who contributed to the study include Tory Spindle, Renuka Surujunarain, and Elise Weerts of Johns Hopkins University; Sumit Bansal of the University of Washington; Jashvant D. Unadkat of the University of Washington and the Center of Excellence for Natural Product Drug Interaction Research; and Mary F. Paine of Washington State University and the Center of Excellence for Natural Product Drug Interaction Research.

Funding for this research was facilitated by the National Institutes of Health National Center for Complementary and Integrative Health, specifically the Center of Excellence for Natural Product Drug Interaction Research (U54 AT0008909) and the National Institute on Drug Abuse (T32 DA007209 and P01 DA032507) .

Vandrey has been paid as a consultant or scientific advisory board member for Canopy Health Innovations, MyMD Pharmaceuticals, Mira Pharmaceuticals, Syqe Medical, WebMD, Jazz Pharmaceuticals, and Radicle Science Inc. Spindle was a paid consultant for Canopy Health Innovations. Weerts has preclinical study funding agreements from MyMD Pharmaceuticals and Mira Pharmaceuticals. No other authors declared conflicts of interest.

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[Disclaimer: Please note that this text was originally written in Portuguese and is translated into English and other languages using an automatic translator. Some words may differ from the original and typos or errors may occur in other languages.]

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Antonio João Costa

I am one of the directors of CannaReporter, which I founded together with Laura Ramos. I am from the unique Island of Madeira, where I currently reside. While I was in Lisbon at FCUL studying Physical Engineering, I became involved in the national hemp and cannabis scene and participated in several associations, some of which I am still a member of. I follow the global industry and especially legislative advances regarding the different uses of cannabis.

I can be contacted by email at joao.costa@cannareporter.eu