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Cannabinoid CB2 receptors suppress neuropathic pain with no signs of physical dependence in study.

Medical marijuana is proliferating across the country due to the ability of cannabis ingestion to treat important clinical problems such as chronic pain. However, negative side effects and the development of tolerance limit the widespread therapeutic use of Δ9-tetrahydrocannabinol (Δ9-THC), the major neurological ingredient in cannabis.

THC’s side effects are produced via its actions at cannabinoid CB1 receptors in the brain. Thus, the medical community theorized that an agent with similar mechanistic actions, but that activate CB2 receptors instead, may eliminate the unwanted side effects while maintaining an equivalent level of efficacy.

Researchers at Indiana University tested this strategy and found that, unlike Δ9-THC, repeated dosing with the cannabinoid CB2 agonist AM1710 suppresses chemotherapy-induced pain in mice without producing tolerance, physical withdrawal, motor dysfunction, or hypothermia. Moreover, the therapeutic effects of AM1710 were preserved in mice lacking CB1 receptors but absent in mice lacking CB2 receptors.

The team state that the current study is important because it demonstrates beyond doubt that activation of cannabinoid CB2 receptors suppresses neuropathic pain without producing signs of physical dependence (i.e., a withdrawal syndrome) or other unwanted side effects associated with activation of CB1 receptors in the brain.

The team utilised animals that were treated with a chemotherapeutic agent (paclitaxel) to produce pain. When animals were given AM1710, a CB2 agonist, its pain-suppressive effects were fully preserved and its therapeutic effects were maintained even after repeated dosing.  Alternatively, and as expected, when animals were given Δ9-THC, they developed complete tolerance to the pain-suppressing effects of THC and with repeated dosing, THC was no longer effective in suppressing neuropathic pain.

When the THC-treated animals were challenged with a drug that blocks CB1 receptors in the brain, the animals showed a prominent withdrawal syndrome, indicating signs of physical dependence following removal of THC. Strikingly, this was not the case with the CB2 agonist; blocking either CB1 or CB2 receptors produced no signs of withdrawal in animals treated chronically with the CB2 agonist.

The team explain that the data suggests that CB2 receptors are an important target for suppressing chronic pain without unwanted side effects adding that it’s important to know whether the benefits of cannabis ingestion for pain could be attributed in large part to the stimulation of CB2 receptors.  CB2 agonists, in theory, would present less risk regarding addiction and intoxication than the ingestion of cannabis or THC.

The researchers summise that more work will be necessary before CB2 receptor agonists could be prescribed for use in humans, but for now, these data support the therapeutic potential of CB2 agonists for managing pain without the adverse effects associated with cannabis.

Source:   Indiana University

 

The Endocannabinoid System, Presented by Uberto Pagotto, MD, PhD.
The Endocannabinoid System, Presented by Uberto Pagotto, MD, PhD.

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Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.

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Most recently the Texas A&M University covered The Top 10 Healthinnovations series on their site with distinguished Professor Stephen Maren calling the inclusion of himself and his team on the list a reflection of “the hard work and dedication of my students and trainees”.

Michelle Petersen’s copy was used in the highly successful marketing campaign for the mega-hit film ‘Jumanji: The Next Level, starring Jack Black, Karen Gilian, Kevin Hart and Dwayne ‘The Rock’ Johnson. Michelle Petersen’s copywriting was part of the film’s coverage by the Republic TV network. Republic TV is the most-watched English language TV channel in India since its inception in 2017.

An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.

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