A comprehensive meta-analysis of previously published studies has found that cannabidiol (CBD) – widely touted as a way to reduce the negative effects of cannabis – may actually be making products more potent by significantly increasing blood levels of delta-9-tetrahydrocannabinol (THC).
The review, published in Neuroscience and Biobehavioral Reviews, analysed data from 14 clinical trials involving 341 participants.
For years, health guidelines have nudged cannabis users towards products with more CBD and less THC, on the assumption that CBD softens THC’s effects. However, the researchers found that when CBD was taken alongside THC, it increased overall THC blood levels by an average of 31%.
More dramatically, high doses of CBD nearly doubled blood levels of 11-hydroxy-THC, an active metabolite which many scientists believe is equally or more potent than THC itself.
“Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC,” wrote lead researcher Lucy Chester and her team at the Research Centre, Centre Hospitalier de l’Université de Montréal.
The interaction appeared most significant with orally consumed cannabis products, such as edibles, capsules and oils, where CBD doses ranged from 105mg to 800mg. 11-hydroxy-THC (11-OH-THC) is a common metabolite produced when consuming edible cannabis products containing THC. The research suggests CBD may be blocking key liver enzymes (CYP2C9 and CYP2C19) responsible for breaking down both THC and 11-OH-THC. By inhibiting these enzymes, CBD essentially allows the psychoactive compounds to accumulate in the bloodstream.
The researchers found less dramatic but still significant effects with inhaled cannabis, where CBD doses were typically much lower (4mg to 30mg). One study using 400mg inhaled CBD had to be modified because participants couldn’t tolerate the throat irritation from such high doses.
The authors called for better-designed clinical trials to fully characterise this interaction, particularly studies using realistic doses and chronic CBD administration patterns that reflect real-world use. They noted that many people use CBD daily as a supplement or medication, which could lead to even more pronounced interactions.
“While it remains to be determined how CBD-related increases in THC and 11-OH-THC levels translate into behavioural or adverse effects, the findings from the meta-analysis highlight the need for caution and nuance when broadly encouraging high doses of CBD in combination with THC,” the study concluded.
