How we could harness medical marijuana for pain relief without the side effects

A new study demonstrates for the first time that the medically beneficial pain-relieving effects of THC can be separated from its undesirable cognitive side effects, argues Dr. Peter J. McCormick

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Experts and society are divided on the benefits and subsequent legalisation of medical marijuana.

In North America alone there is deep division with half the states and Canada legalising medical marijuana while the other half refuses. In the UK it is not legal to use medical marijuana, but ironically the UK is home to the most successful cannabis extract company in GW Pharmaceuticals, who have a product on the market that includes a mixture of cannabis extracts.  The success of the company and for the patients it treats strongly suggests the issue might need to be revisited, and at least more research performed on exploiting the possibilities.

Our own work in the area, including the most recent study, shows that there is a powerful argument for the potential of cannabis extracts.  We conducted a study which involved the testing of one of these extracts for the use of pain relief.  The impetus of our study was whether one compound contained in the marijuana plant could achieve therapeutic effects, while at the same time minimising or avoiding the undesirable side effects. Our results demonstrate for the first time that the medically beneficial pain-relieving effects of THC can be separated from its cognitive side effects.

There are multiple compounds contained within the marijuana plant that are of medical interest. The two major ones are cannabidiol and THC. Cannabidiol is in clinical trials to treat epilepsy and symptoms of Multiple Sclerosis, while THC has been linked for numerous treatments including pain relief and cancer.

 

Our work has revolved around THC, which is the main psychoactive compound in marijuana. THC is known to induce numerous undesirable effects, including memory impairments, anxiety, and drug dependence.  Importantly, THC also has numerous potentially therapeutic effects, including pain relief, muscle relaxation, and neuroprotection. THC acts in the body on a family of receptors, called cannabinoid receptors or docking stations, that go on to communicate that THC has ‘docked’ and will facilitate the above effects.

What we discovered was that not all of these cannabinoid docking stations were the same. We found that some were associated with another family of receptors, called serotonin receptors. When THC docks with cannabinoid-serotonin coupled receptors, the body responds with memory impairments. Using mice lacking this serotonin receptor, we revealed that the pain relief effects of THC were maintained while the memory problems caused by exposure to THC were lost in these mice.

In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and serotonin work together by physically interacting with each other. We were then able to interfere with this interaction and prevent the memory deficits induced by THC, but not its pain relieving properties.

Going forward, our study suggests that it would be possible to create a drug that can interfere with this cannabinoid-serotonin interaction and thus allow THC to provide side effect-free pain relief.

Importantly, our work was done in rodents, so it will important to first show that these same things can occur in humans. If they do, then this study will open doors to harnessing the potential of THC without the side effects.

Dr. Peter J. McCormick is a Lecturer in Cell Biology at the University of East Anglia

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