Summary: To lessen the negative effects of THC, the psychedelic part of cannabis, researchers have discovered how CBD and cannabinoid receptors interact. Unlike THC, which entirely activates the sensor and causes side effects like memory loss and habit, CBD acts as a converter, fine-tuning receptor activity.
This finding might lead to more precisely intended treatments that increase THC’s pain-relieving abilities while minimizing unintended side effects. Additionally, the study provides more precisely controlled command over sensor behavior, opening up new avenues for research on synthetic CBD.
Important Facts:
- CBD acts as a converter: unlike THC, CBD ties to cannabinoid receptor as a dim-light change, adjusting their work before thoroughly activating or deactivating them.
- Reducing THC Side Effects: This study suggests CBD could be used to reduce THC’s adverse consequences, such as memory loss and habit, while preserving its pain-relief components.
- Potential Software: Understanding CBD’s relationships could lead to artificial versions with increased medical benefits and fewer risks, especially for pain management.
Origin: University of Mississippi
Researchers at the University of Mississippi have discovered a method that can be employed to combat the harmful effects of THC, a psychoactive substances in hemp.
This discovery opens the door for novel ways that the CBD can be used to treat anxiety, chronic pain, and a variety of different conditions.
Amar Chittiboyina, main scholar and associate director of the , National Center for Natural Products Research, and a group of researchers recently , published their study in , ACS Neuroscience.
” This research may start a new street for anyone in the field of cannabis research,” Chittiboyina said. In terms of modulating cannabinoid receptor and utilizing THC’s beneficial results for pain management, it really opens up new perspectives or a new horizons.
CBD is , one of more than 200 normal cannabinoids , in the cannabis flower, but unlike some of its rivals, CBD is no psychedelic. Its popularity in the United States has grown since 2018, when the , Agricultural Improvement Act , decriminalized cannabis.
” The 2018 Farm Bill passing properly opened a Pandora’s box of study problems”, Chittiboyina said. “CBD’s employ proliferated across a broad spectrum from pain management, pleasure purposes to seemingly limitless different applications.
The key to understanding how CBD works on several goals and exerts its perceived results at the molecular level is, however, the basic problem is.
Cannabinoid sensor form 1 , is a proteins found throughout the body that regulates pain, temperament, appetite, digestion and storage. Both CBD and THC attach to this proteins.
When THC attaches to the sensor, the result is like an out switch to a mild light, properly turning” off” the problems. But THC even has harmful side effects, including , memory loss, nausea and , habit.
When CBD ties to the sensor, but, it acts more like a darker switch, turning up or down the performance of the proteins.
Future studies may “turn down” or lessen the negative effects of THC use because the researchers have discovered the locations where CBD binds to this protein molecule.
Our top priority is to funnel the useful effects of THC while minimizing its negative side effects, according to studies professor Pankaj Pandey at the center.
This research may help scientists develop a chemical CBD that may affect sensor behavior more effectively 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.
However, there are plenty of drug possibilities here, and what we’re trying to do is identify specific, precise effects and refine those.
” We’re trying to pull the benefits out and leave the negative effects behind.”
William Neal, a postdoctoral researcher at the Ole Miss center, is one of the recent discoveries that has made new research possible. In upcoming research, Neil hopes to find out whether CBD use would have an impact on how much of the body’s opioids, like morphine, are affected.
” 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.”
Neal’s investigation into the interactions between CBD and opioids is just one of many avenues that, according to Chittiboyina, have been made possible as a result of this investigation.
” 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?”
Before the team’s conclusions are finalized, more research is required to confirm their conclusions.
However, if we can understand how CBD interacts with various molecular targets, we will have a stronger scientific foundation to come up with solutions that are relevant to public health, he said.
Funding: This text is based on research that was supported by grant number 91 from the National Institute of General Medical Sciences. P30GM122733, the National Science Foundation XSEDE Bridges allocation no. CHE190092 and Mississippi State-sponsored National Center for Cannabis Research and Education.
About this research in neuropharmacology
Author: Clara Turnage
Source: University of Mississippi
Contact: Clara Turnage – University of Mississippi
Image: The image is credited to Neuroscience News
Original Research: Closed access.
Amar Chittiboyina and colleagues conducted a combined computational and site-directed mutagenesis study to determine the negative allosteric binding site of cannabidiol at the CB1 receptor. ACS Chemical Neuroscience
Abstract
A Combined Computational and Site-Directed Mutagenesis Study Determined the Negative Allosteric Binding Site of Cannabidiol at the CB1 Receptor.
Cannabinoid receptor 1 ( CB1R ) has been extensively studied as a potential therapeutic target for various conditions, including pain management, obesity, emesis, and metabolic syndrome.
Cannabidiol ( CBD ) has been identified as a negative allosteric modulator ( NAM ) of CB1R, among its other pharmacological targets, in contrast to orthosteric agonists like 9-tetrahydrocannabinol ( THC).
For CB1R NAMs, various binding sites have been identified in previous computational and structural studies. An extrahelical location within the membrane’s inner leaflet was revealed by an X-ray crystal structure analysis of the binding site for the NAM, ORG27569. In contrast, a number of computational studies have previously suggested that CBD might have several potential allosteric binding sites within the CB1R structure.
Given that a prior structural study suggested CBD might occupy the same site as ORG27569, we conducted a comprehensive investigation of potential CBD binding sites using molecular docking, molecular dynamics ( MD) simulations, metadynamics ( MTD ) simulations, binding free-energy calculations, and in vitro mutagenesis experiments.
Molecular docking, MD, and MTD simulations results, along with binding free-energy calculations, suggest that CBD may potentially bind to either the same extrahelical site as ORG27569 or a previously unidentified intracellular site located near TMHs 2, 6, and 7 and helix 8. This intracellular site is in line with the allosteric binding sites found in other G protein-coupled receptors ( GPRs ).
We conducted site-directed mutagenesis of key residues at each site to determine which allosteric site is the most conducive to CBD. Mutations at S4018.47ΔA and D4038.49ΔA augmented the binding of]3H] -SR141716A, suggesting these residues play critical roles in CBD binding.
As a result, the combined computational and mutagenesis results identified a binding site for CBD between TMHs 2, 6, and 7 and helix 8, involving residues Y1532.40, I1562.43, M3376.29, L3416.33, S4018.47, and D4038.49.
These findings help to inform the rational design of new, selective, and potent NAMs by providing valuable insights into how CBD binds to CB1R. Additionally, the identification of this previously undiscovered allosteric site may contribute to the polypharmacology of CBD caused by structural conservation in Class A GPCRs.
