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Medical Cannabis Can Reduce Tremors, Finds Animal Study

Mar 23, 2021

Medical Cannabis Can Reduce Tremors, Finds Animal Study

A synthetic cannabinoid with similar properties to THC can effectively reduce essential tremor in mice, according to a new study from researchers at the University of Copenhagen, Denmark.

Published in Nature Neuroscience, the new study focused on the action of a cannabinoid analog on the body’s astrocytes – glial cells present in the central nervous system that facilitate neurotransmission – where previous research had traditionally only considered effects on the neurons in the spinal cord and brain, finding significant reductions in tremor.

The researchers behind the study say that this breakthrough could have important consequences on other areas of medical cannabis research, such as the use of cannabis in spinal cord injury and other conditions characterized by involuntary shaking, if future clinical trials can demonstrate the same mechanistic effect in humans.


Synthetic cannabinoid reduces tremor in mice model

Cannabis is already known to have beneficial therapeutic effects on motor disorders. Sativex, a cannabis-based medicine for treating multiple sclerosis-spasms, has already been approved for medicinal use in more than 25 countries, including Denmark.

The University of Copenhagen researchers wanted to look more closely at how cannabis, specifically THC, is able to mediate the symptoms of such motor disorders.

To do this, they injected the synthetic cannabinoid analog WIN55,212-2, which acts similarly to THC in the body, into the spinal cord of laboratory mice with essential tremor and looked for changes in their symptomatology.

After seeing a visible reduction in involuntary limb movements, the researchers repeated the WIN55,212-2 dosing experiment, but this time they actively knocked out the CB1 receptors in the astrocytes. With the CB1 receptors out of action, the anti-tremor effect of the cannabinoid was suppressed. To further verify the astrocytes’ role in the anti-tremor effect, researchers also analyzed slices of spinal cord from the mice using electrophysiological recordings.

“We discovered that an injection with the cannabinoid WIN55,212-2 into the spinal cord turns on the astrocytes in the spinal cord and prompts them to release the substance adenosine, which subsequently reduces nerve activity and thus the undesired shaking,” explained Associate Professor Jean-François Perrier, who led the research project, in a statement.


Targeted, safe treatment for tremor

The action of the spinal cord is responsible for the vast majority of movements in the body. Both voluntary movements and spontaneous ones are controlled by the activation of motor neurons within the spinal cord. In motor disorders such as essential tremor disorder, the motor neurons send conflicting signals to the muscles, which manifest as involuntary shaking.

With the new understanding that astrocytes play a part in cannabis’ effects, the researchers believe this could open up new avenues in exploring treatments for essential tremor that do not rely on modifying the motor neurons themselves. Instead, cannabis medicine could leverage the action of cannabinoids as a signaling molecule between the astrocytes and spinal neurons to lessen tremor.

“One might imagine a new approach to medical cannabis for shaking, where you – during the development of cannabis-based medicinal products – target the treatment either at the spinal cord or the astrocytes – or, at best, the astrocytes of the spinal cord”, commented Eva Carlsen, a postdoctoral researcher at the University of Copenhagen who worked on the astrocyte research as part of her PhD and postdoc projects.

“Using this approach will avoid affecting the neurons in the brain responsible for our memory and cognitive abilities, and we would be able to offer patients suffering from involuntary shaking effective treatment without exposing them to any of the most problematic side effects of medical cannabis.”

For the University of Copenhagen researchers, the next step is to develop clinical trials for patients with essential tremor that will enable the researchers to study whether this effect holds true for humans. But taking a broader view, they anticipate that this research could have the potential to bring about new innovations in tackling other movement disorders and spinal cord injuries.

“We have focused on the disease essential tremor. It causes involuntary shaking, which can be extremely inhibitory and seriously reduce the patient’s quality of life,” added Perrier. “However, the cannabinoid might also have a beneficial effect on sclerosis and spinal cord injuries, for example, which also cause involuntary shaking.”

 

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