A recent study published in Clinical Pharmacology & Therapeutics casts doubt on the conventional wisdom about the interaction between cannabidiol (CBD) and tetrahydrocannabinol (THC), proving that it's not only wrong, but actually commonly We revealed that it may be the opposite of what is believed. Contrary to the common belief that CBD can reduce the negative effects of THC, this study found that CBD does not reduce these negative effects. In fact, high doses of CBD (450 mg) significantly enhanced the effects of THC, likely due to pharmacokinetic interactions that increased THC levels in the bloodstream.
Cannabis is gaining attention not only as a recreational drug but also for its potential therapeutic effects, especially in pain management. THC, the main psychoactive compound found in cannabis, is known not only for its analgesic properties but also for causing a variety of adverse effects such as cognitive impairment, anxiety, and psychomotor disorders. On the other hand, CBD is non-addictive and has been suggested to counteract some of the negative effects of THC. This belief has led to CBD-rich cannabis products being widely used for both recreational and medical purposes.
However, the scientific evidence supporting the idea that CBD can alleviate the negative effects of THC is inconsistent. Some studies have shown that CBD can reduce THC-induced anxiety and psychosis, while other studies have found no such protective effects. Scientists sought to clarify this issue by rigorously testing whether CBD could reduce the negative effects of THC without compromising its analgesic effects. In doing so, they aimed to provide clearer guidance on the safe and effective use of cannabis-based products.
“People working in the cannabis field have always said that CBD takes the edge off THC, that anxiety may be reduced, and that other cannabinoids play a role in how THC in cannabis feels. They say there is an “entourage effect,” but the scientific evidence is very thin. We are pharmacologists and know how to scientifically prove interactions between drugs. That's why we carried out rigorous scientific experiments,'' explained study author Geert-Jan Groeneveld, professor of clinical neuropharmacology at Leiden University Medical Center and CEO of the Center for Human Drug Research. .
The study involved 37 healthy volunteers between the ages of 18 and 45 who had used cannabis but infrequently. To participate, volunteers had to meet strict health criteria, including not having any mental disorders or conditions that could affect their sensitivity to pain. Importantly, participants had to refrain from consuming cannabis or any other substances that could affect the study results for several weeks before the experiment.
The study was conducted at the Human Drug Research Center in the Netherlands using a double-blind, placebo-controlled, five-way crossover design. This means that each participant received five different treatments in random order, with sufficient washout periods between sessions to avoid carryover effects from previous treatments. Treatments included THC alone, THC combined with three different doses of CBD (10mg, 30mg, and 450mg), and a placebo.
Participants were treated orally, with CBD administered 30 minutes before THC to ensure both substances peaked in the bloodstream at the same time. The researchers then measured various effects at multiple time points over a 6-hour period using a combination of subjective self-reports and objective tests.
Subjective measures included ratings of mood, anxiety, and feeling “high,” while objective measures assessed cognitive and psychomotor abilities such as reaction time and postural stability. In addition, the researchers measured analgesic effects using a battery of pain tests, including heat, pressure, electrical stimulation, and cold exposure.
Researchers found that the highest dose of CBD (450mg) significantly increased the effects of THC, rather than reducing its effects. Participants reported feeling more intoxicated and having more impaired cognitive and psychomotor performance than when taking THC alone. This increased effect is likely because CBD interferes with the metabolism of THC, leading to increased levels of THC and its psychoactive metabolites in the bloodstream.
Lower doses of CBD (10 mg and 30 mg) did not significantly change the effects of THC. At these dose levels, there was no reduction in THC-induced anxiety, cognitive impairment, or other side effects, suggesting that CBD does not counteract the effects of THC when taken orally together.
“CBD in no way reduces the psychomimetic effects of THC or reduces anxiety,” Groeneveld told PsyPost. “Rather, CBD inhibits the breakdown of THC in the liver, thereby enhancing the effects of THC at higher dosage levels.”
Although the psychoactive effects of THC were increased at the highest doses of CBD, the analgesic effects were not significantly different between the different treatment conditions. This finding suggests that while CBD may alter the overall experience of THC, it does not enhance its analgesic properties.
Although this study was well designed and controlled, it is not without caveats. One limitation is the route of administration. This study only investigated the effects of oral THC and CBD. The results of this study may not be generalizable to other common ways of using cannabis, as different consumption methods, such as inhalation, have different metabolic pathways and effects.
Additionally, this study did not include a CBD-only condition, which would have provided clearer insight into the specific effects of CBD without the influence of THC. However, researchers are conducting additional studies focusing solely on high doses of CBD.
“We have continued our studies using only CBD and at very high dose levels to try to demonstrate its effects on the central nervous system and brain function,” Groeneveld said. “We haven't published this yet, but we can say that there is absolutely no evidence that CBD acts on the central nervous system. It does not cause sedation or is used to measure the medicinal efficacy of drugs being developed by the pharmaceutical industry. This does not lead to subjective drug effects that can be detected by the very sensitive test battery that we use.
This new finding is consistent with a recent neuroimaging study published in the journal Neuropsychopharmacology. The study found that CBD does not alleviate THC's destructive effects on brain connectivity and may even worsen them. Researchers observed that connectivity across major brain networks was significantly reduced after cannabis use, and the addition of CBD caused even greater disruption in some cases.
Similarly, a rodent study published in the journal Neurobiology of Disease found that CBD did not protect against the harmful effects of prenatal cannabis exposure. Rather, it appears to exacerbate THC's effects on offspring's brain development and behavior.
The new study “Cannabidiol increases the psychoactive effects and plasma concentrations of Δ9-tetrahydrocannabinol without improving its analgesic properties” was published by Andriy A. Gorbenko, Jules AAC Heuberger, Linda E. Klumpers, Marieke L. de Kam , written by Pamela K. Strugala. , Saco J. de Visser, Geert J. Groenefeld.
