BackNew evidence reveals that CBD and THC don’t interact as we previously thought

For many years, it was believed that CBD and THC, the two most studied compounds of cannabis, worked in harmony, balancing their effects on the human body. However, recent research questions this premise, suggesting that instead of moderating each other, CBD could be the one enhancing the effects of THC in certain circumstances. What are the implications of this finding for the therapeutic and recreational use of cannabis?

 

Cannabis has gained attention in recent years not only as a recreational substance but also for its potential therapeutic benefits, especially in the treatment of pain. THC, the main psychoactive compound of cannabis, is known for its analgesic properties but also for causing a number of adverse effects such as cognitive impairment, anxiety, and psychomotor disorders. CBD, on the other hand, is non-psychoactive (though only on paper) and has been suggested to somehow counteract the negative effects of THC. This belief has led to the widespread use of CBD-rich cannabis products, or products with certain CBD/THC ratios, for both recreational and medicinal purposes. However, the scientific evidence supporting the idea that CBD can mitigate the adverse effects of THC is inconsistent. Some studies have shown that CBD can reduce THC-induced anxiety and psychosis, while others haven’t found such protective effects. In addition, it is also known that there is an 'entourage effect' involving other components that influences the experience of THC in cannabis, although scientific evidence is also very scarce in this field.

 

 

Now, a recent study published in Clinical Pharmacology & Therapeutics in September 2024, challenges the conventional belief about the interaction between cannabidiol (CBD) and tetrahydrocannabinol (THC), revealing that this attenuation of effects may not only be incorrect, but may actually be the opposite of what is commonly believed. The research was conducted at the Centre for Human Drug Research in the Netherlands using a five-way, cross-sectional, placebo-controlled, and double-blind study. This means that each participant received five different treatments in a random order, which included THC alone, THC combined with three different doses of CBD (10 mg, 30 mg, and 450 mg), and a placebo. Subjects received the treatments orally, with CBD being administered 30 minutes before THC to ensure that both substances reached their peak in the bloodstream simultaneously. Then, the researchers measured several effects at multiple times over six hours, using a combination of subjective self-reports (assessments of mood, anxiety, and the feeling of being "stoned"), objective tests (cognitive and psychomotor performance), and a series of pain tests which included heat, pressure, electrical stimulation, and exposure to cold. Instead of reducing the effects of THC, researchers found that the highest dose of CBD (450 mg) increased them significantly. These increased effects were probably due to CBD interfering with the metabolism of THC, causing higher levels of THC and its psychoactive metabolite in the bloodstream. Lower doses of CBD (10 mg and 30 mg) did not significantly alter the effects of THC, suggesting that CBD doesn’t counteract the effects of THC when they are taken together orally. "CBD does not in any way relieve the psychomimetic effects of THC or reduce anxiety", explained the researchers in their conclusions. "In any case, it will enhance the effects of THC at higher doses because CBD inhibits its breakdown in the liver".

 

This isn’t the first study to show that CBD inhibits the metabolism or breakdown of THC in edible cannabis products, which can result in stronger and longer-lasting effects. Another study led by researchers from the Johns Hopkins University School of Medicine previously found that relatively high doses of cannabidiol (CBD) can increase the adverse effects of delta-9-tetrahydrocannabinol (THC).  The results of this study, published in JAMA Network Open in February 2023, found that the maximum amount of THC measured in the participants' blood samples was almost twice as high after eating a brownie containing THC and CBD than after eating a brownie with only THC, even though the dose of THC in each brownie was exactly the same (20 mg). In addition, the maximum amount of 11-OH-THC (a metabolic by-product of THC that produces more intense effects than THC) was 10 times higher after eating the brownie with the high CBD extract compared to the one containing the high THC extract. Just like the Dutch research study, the American study examined pharmacokinetics (i.e., the absorption and elimination of a drug by the body) and pharmacodynamics (the response of the body to a drug) between cannabis extracts with different THC and CBD concentrations. Both studies were well designed and controlled, but they were limited to the oral administration route. Therefore, given that different methods of consumption (such as inhalation) give rise to different metabolic pathways and effects, these findings cannot be generalised to other common forms of cannabis use. Besides, a condition where only CBD was consumed was not included in either study, which would have provided clearer information about the specific effects of CBD without the influence of THC. Nevertheless, these findings coincide with another recent neuroimaging study published in Neuropsychopharmacology in July 2024, which found that CBD did not mitigate, and could actually worsen the disruptive effects of THC on brain connectivity. Researchers observed significant reductions in connectivity in key brain networks after cannabis use; and the addition of CBD caused even greater alterations in some cases. Similarly, a rodent study published in Neurobiology of Disease in August 2024 found that CBD did not protect against the harmful effects of prenatal cannabis exposure – in contrast, it appeared to exacerbate the impact of THC on brain development and the behaviour of offspring.

 

 

These studies suggest that it’s important for users to know that, if they’re going to take a high dose of a CBD extract, they should also consider its interactions with THC, just as they should also do with other medicines. The belief that CBD "domesticates" THC has greatly influenced the formulation of medicinal and recreational cannabis products; and many users choose THC and CBD products hoping for a more balanced, less psychoactive experience. However, new evidence suggests that this expectation may not be met in all cases. Scientists say more studies are needed in the future to better understand the impact of the CBD and THC dose, the relative concentration, the frequency of use, and individual health differences on how our bodies metabolise cannabinoids. And this type of research is necessary to correctly inform clinical and regulatory decisions regarding the therapeutic and recreational use of cannabis, which is currently the world’s most consumed recreational substance after alcohol. As science advances, it will be critical to rethink many things around these two compounds, always with the aim of ensuring a safe and effective experience for users.