A recent study published in Clinical Pharmacology & Therapeutics challenges conventional wisdom about the interaction between cannabidiol (CBD) and tetrahydrocannabinol (THC), revealing that it may be not only incorrect but actually the opposite of what is commonly believed. Contrary to popular belief that CBD can reduce the negative effects of THC, the study found that CBD did not mitigate these adverse effects. In fact, a high dose of CBD (450 mg) significantly enhanced the effects of THC, likely due to a pharmacokinetic interaction that increased THC levels in the bloodstream.
Cannabis has gained attention not only as a recreational drug but also for its potential therapeutic benefits, especially in pain management. THC, the main psychoactive compound in cannabis, is known for its analgesic properties but also for causing a range of adverse effects, such as cognitive impairment, anxiety, and psychomotor disturbances. CBD, on the other hand, is non-intoxicating and has been suggested to counteract some of THC’s negative effects. This belief has led to the widespread use of CBD-rich cannabis products, both for recreational and medicinal purposes.
However, the scientific evidence supporting the idea that CBD can mitigate THC’s adverse effects is inconsistent. Some studies have shown that CBD can reduce THC-induced anxiety and psychosis, while others have found no such protective effects. Scientists sought to clarify this issue by rigorously testing whether CBD could reduce the adverse effects of THC without compromising its analgesic benefits. By doing so, they aimed to provide clearer guidance on the safe and effective use of cannabis-based products.
“People active in the cannabis field always say that CBD takes off the edge from THC, anxiety can be less, there is an ‘entourage effect’ of other cannabinoids that plays a role in how THC in cannabis is experienced, but the scientific evidence was very thin. We are pharmacologists and know how to scientifically demonstrate interaction between drugs, which is why we performed a rigorous scientific experiment,” explained study author Geert Jan Groeneveld, a professor of clinical neuropharmacology at Leiden University Medical Center and CEO of the Centre for Human Drug Research.
The study involved 37 healthy volunteers, aged 18 to 45, who had experience with cannabis but used it infrequently. To participate, volunteers had to meet strict health criteria, including being free from any psychotic disorders or conditions that could affect their sensitivity to pain. Importantly, participants had to abstain from cannabis and other substances that could influence the study results for several weeks before the experiment.
The research was conducted at the Centre for Human Drug Research in the Netherlands using a double-blind, placebo-controlled, five-way crossover design. This means that each participant received five different treatments in a random order, with a sufficient washout period between sessions to ensure no carryover effects from previous treatments. The treatments included THC alone, THC combined with three different doses of CBD (10 mg, 30 mg, and 450 mg), and a placebo.
Participants received the treatments orally, with CBD administered 30 minutes before THC to ensure that both substances would peak in the bloodstream at the same time. The researchers then measured various effects at multiple time points over six hours, using a combination of subjective self-reports and objective tests.
The subjective measures included assessments of mood, anxiety, and the sensation of feeling “high,” while objective measures evaluated cognitive and psychomotor performance, such as reaction times and postural stability. Additionally, the researchers measured the analgesic effects using a series of pain tests that involved heat, pressure, electrical stimulation, and cold exposure.
Rather than reducing THC’s effects, the researchers found that the highest dose of CBD (450 mg) significantly increased them. Participants reported feeling more intoxicated, and their cognitive and psychomotor performance was more impaired compared to when they took THC alone. This increase in effects was likely due to CBD interfering with the metabolism of THC, leading to higher levels of THC and its psychoactive metabolite in the bloodstream.
The lower doses of CBD (10 mg and 30 mg) did not significantly alter the effects of THC. There was no reduction in THC-induced anxiety, cognitive impairment, or other adverse effects at these dose levels, suggesting that CBD does not counteract THC’s effects when taken together orally.
“CBD does not in any way alleviate psychomimetic effects of THC or reduce anxiety,” Groeneveld told PsyPost. “If anything, in higher dose levels it will enhance the effects of THC because the breakdown of THC in the liver is inhibited by CBD.”
Despite the increase in THC’s psychoactive effects with the highest dose of CBD, the pain-relieving effects did not significantly differ between the different treatment conditions. This finding suggests that while CBD may alter the overall experience of THC, it does not enhance its pain-relieving properties.
While the study was well-designed and controlled, it is not without its caveats. One limitation is the route of administration. The study only examined the effects of oral THC and CBD. Since different methods of consumption, such as inhalation, result in different metabolic pathways and effects, the findings may not generalize to other common ways of using cannabis.
Furthermore, the study did not include a CBD-only condition, which would have provided clearer insights into the specific effects of CBD without the influence of THC. However, the researchers have been conducting additional studies focused solely on high doses of CBD.
“We’ve continued to perform a study with CBD only, also very high dose levels, and to try to demonstrate effects on the central nervous system, on brain function,” Groeneveld said. “We haven’t published this yet, but we can tell you that there is no evidence whatsoever that CBD is active on the central nervous system. It does not cause sedation or lead to subjective drug effects that can be picked up by our very sensitive test battery that we also use to measure drug effects of drugs being developed by the pharmaceutical industry.”
The new findings are in line with a recent neuroimaging study published in Neuropsychopharmacology, which found that CBD did not mitigate and may even worsen the disruptive effects of THC on brain connectivity. Researchers observed significant reductions in connectivity across key brain networks after cannabis use, with the addition of CBD leading to even greater disruptions in some cases.
Similarly, a study on rodents published in Neurobiology of Disease found that CBD did not protect against the harmful effects of prenatal cannabis exposure; instead, it appeared to exacerbate the impact of THC on brain development and behavior in offspring.
The new study, “Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties,” was authored by Andriy A. Gorbenko, Jules A.A.C. Heuberger, Linda E. Klumpers, Marieke L. de Kam, Pamela K. Strugala, Saco J. de Visser, and Geert J. Groeneveld.
