Lab-Designed Cannabis Compound Relieves Pain Without Side-Effects.

Researchers from Washington University School of Medicine and Stanford University have come up with a compound that mimics a molecule naturally found in cannabis.

In an animal study, published in the journal Nature, the compound was shown to have pain-relieving effects without causing drug dependence or any psychological side effects.

Researchers state that while more research is required, the compound shows a lot of promise as a form of nonaddictive pain relief that could help those living with chronic pain.

Opioids work by muting the feeling of pain in the brain commandeering the brain’s reward system and activating the discharge of dopamine and feelings of pleasure. 

Despite across-the-board public health warnings and media attention concentrated on the perils of opioid addiction, numerous overdose deaths still happen, with around 82,000 deaths in the U.S. being connected to opioids in 2022.

The cannabis plant produces endo-cannabinoids or natural cannabinoids naturally. These endo-cannabinoids attach to CB1 receptors on the surface of brain cells and pain-sensing nerve cells throughout the body.

This new research saw a cannabinoid molecule be produced with a positive charge. This positive charge prevented the molecule from crossing the blood-brain barrier but did allow it to engage with CB1 receptors elsewhere in the body. 

By engineering the molecule so that it was only able to bind with pain-sensing nerve cells located in areas of the body outside of the brain, the molecule was successful in achieving pain relief minus any risk of negative side effects.

They tested the modified synthetic cannabinoid compound in rodent models on nerve-injury pain and migraine headaches, gauging hypersensitivity to touch as a representative for pain. In both rodent models, injections were successful in reducing touch hypersensitivity.

“There is an urgent need to develop nonaddictive treatments for chronic pain, and that’s been a major focus of my lab for the past 15 years." -Vipin Rangari, PhD

Long-term pain relief

With long-term opioid use tolerance can develop limiting its effectiveness in the long term. This means that higher doses of opioids are required as time goes on to allow the patient to achieve the same level of pain relief. 

The modified compound used in the study presented prolonged pain relief with the rodent subjects showing no signs of developing tolerance after receiving twice-daily treatments over the course of nine days. 

“Clinical trials also have evaluated whether cannabis provides long-term pain relief. But inevitably the psychoactive side effects of cannabis have been problematic, preventing cannabis from being considered as a viable treatment option for pain. However, we were able to overcome that issue.”

The plan moving forward is to develop the compound into an orally taken drug that could then be evaluated for effectiveness in human clinical trials. -co-study author Robert W. Gereau, PhD, Dr Seymour and Rose T. Brown Professor

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