Scientists reveal how CBD could help ease chronic pain, anxiety, and mood disorders.
Researchers have uncovered a potential way to harness the benefits of THC while minimizing its negative effects by using CBD. This research could revolutionize the way cannabis is used for pain management and anxiety relief, leading to more refined treatments.
CBD’s Role in Mitigating THC’s Effects
Researchers at the University of Mississippi have discovered how a compound in cannabis could help reduce the negative effects of THC, the plant’s primary psychoactive ingredient.
This finding paves the way for new applications of CBD, which may offer benefits for those dealing with anxiety, chronic pain, and other health conditions.
A New Avenue for Cannabis Research
Amar Chittiboyina, principal scientist and associate director of the National Center for Natural Products Research, led the study, which was recently published in ACS Neuroscience.
“This research will open a new avenue for anyone in the field of cannabis research,” Chittiboyina said. “It actually opens up new prospects or a new horizon in modulating cannabinoid receptors and harnessing THC’s beneficial effects for pain management.”
CBD’s Growing Popularity and the Farm Bill Effect
CBD is one of more than 200 natural cannabinoids in the cannabis plant, but unlike some of its counterparts, CBD is not psychoactive. Its popularity in the United States has grown since 2018, when the Agricultural Improvement Act decriminalized hemp.
“The 2018 Farm Bill passage effectively opened a Pandora’s box of research challenges,” Chittiboyina said. “CBD’s use proliferated across a wide spectrum from pain management, recreational purposes to seemingly endless other applications.
“However, the fundamental question lies in understanding how CBD works on various targets and exerts its perceived effects at the molecular level.”
Understanding the THC and CBD Connection
Cannabinoid receptor type 1 is a protein found throughout the body that regulates pain, mood, appetite, metabolism, and memory. Both CBD and THC bind to this protein.
When THC attaches to the receptor, the effect is like an off switch to a light bulb, effectively turning “off” the pain. But THC also has harmful side effects, including memory loss, nausea, and addiction.
When CBD binds to the receptor, however, it acts more like a dimmer switch, turning up or down the function of the protein.
A Breakthrough in CBD-THC Interaction
The researchers have discovered the locations on this protein molecule where CBD binds, meaning future research could “turn down” or minimize the side effects of THC use.
“Our primary objective is to harness the beneficial effects of THC while mitigating its undesirable side effects,” said Pankaj Pandey, a research scientist at the center.
Synthetic CBD and the Future of Pain Management
This research could help scientists develop a synthetic CBD that can alter receptor behavior more efficiently even than CBD, said Robert Laprairie, associate professor at the University of Saskatchewan and co-author of the study.
“When people talk about cannabis, they tend to focus on or think of it just as a drug, as the plant,” Laprairie said. “But we have a treasure chest of drug possibilities here and what we’re trying to do is pick out specific, very focused effects and refine those.
“We’re trying to pull out the benefits and leave the harms behind.”
CBD’s Potential Impact on Opioid Use
One example of new research that is made possible by the recent findings is that of William Neal, a postdoctoral researcher at the Ole Miss center. Neal’s upcoming research hopes to determine if CBD use would affect opioids like morphine in the body.
“In the event that CBD binds to an opioid receptor, you could have negative interplay with opiate drugs like morphine,” Neal said. “If you’re getting pain relief from opiates, and if CBD negatively interferes with the opioid receptor, it’s going to frustrate people who are prescribed opiates.
“As a result, CBD will reduce efficacy of opiates and could enhance the drug abuse liabilities.”
New Horizons in Cannabinoid Research
Neal’s research into the interaction of CBD and opioids is only one of many avenues that are opened due to this research, Chittiboyina said.
“That’s what I mean when I say this is a new horizon for cannabinoids research,” Chittiboyina said. “Often, to mitigate pain, patients combine opiates with cannabis, kratom, and other substances. Is this approach beneficial or detrimental?”
What’s Next? The Need for Further Study
More research is needed to confirm the team’s findings before they finalize their results.
“But if we can pinpoint how CBD interacts with multiple targets on molecular level, we will be in a stronger scientific position to develop solutions that are relevant to public health,” he said.
Reference: “Determination of the Negative Allosteric Binding Site of Cannabidiol at the CB1 Receptor: A Combined Computational and Site-Directed Mutagenesis Study” by Pankaj Pandey, Ayat Zagzoog, Robert B. Laprairie, William M. Neal, Robert J. Doerksen and Amar G. Chittiboyina, 15 January 2025, ACS Chemical Neuroscience.
DOI: 10.1021/acschemneuro.4c00343
This material is based on work supported by the National Institute of General Medical Sciences grant no. P30GM122733, the National Science Foundation XSEDE Bridges allocation no. CHE190092 and Mississippi State-sponsored National Center for Cannabis Research and Education.
