Everybody has an opinion on medical cannabis. The fact is we do not know a lot about the effects of cannabis on bioprocesses.
A new study sheds light on how cannabinoids―compounds found in cannabis and the central nervous system―act on a specific type of star-shaped, supporting cells in the spinal cord, called spinal astrocytes, that display cannabinoid receptors on their surface, to reduce pathological tremors.
Although everyone experiences involuntary movements of body parts sometimes, pathological tremors are associated with motor disorders, brought about by traumatic injuries to the head or spine, or diseases such as multiple sclerosis, stroke, or neurodegenerative diseases. The authors show cannabinoids accomplish this by regulating the release of purines, metabolites and building blocks for nucleic acids, that regulate the transmission of electrical signals at synapses.
This new discovery published in the Nature Neuroscience article, “Spinal astroglial cannabinoid receptors control pathological tremor” by researchers at the Department of Neuroscience at the Faculty of Health and Medical Sciences at the University of Copenhagen, in Copenhagen, Denmark, that may prove vital to future research into mechanisms of cannabinoid action and the therapeutics potential of medical cannabis.
The team of scientists used a mouse model to demonstrate that a specific synthetic cannabinoid (cannabinoid WIN55,212-2) can reduce essential tremor―a common neurological disorder that causes rhythmic uncontrollable shaking of the head and limbs and affects more than 200,000 individuals per year in the U.S. The researchers show that WIN55,212-2 activates spinal astrocytes. Previous research into medical cannabis has focused on the nerve cells or neurons whereas astrocytes are a type of glial cells that provide nutrients to the nervous tissue, control ion balance, and play a role in the repair processes following infection and traumatic 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. However, the cannabinoid might also have a beneficial effect on sclerosis and spinal cord injuries, for example, which also cause involuntary shaking”, says Jean-François Perrier, PhD, associate professor at the Department of Neuroscience, who has headed the research project.
“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,” says Perrier. These findings may result in the development of targeted treatment with little or no side effects. In probing astrocytes to understand the biological effects of cannabis, the researchers take a novel approach as earlier studies have focused primarily on neurons.
“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,” says Eva Carlsen, PhD, postdoctoral researcher, who did most of the experiments during her PhD and postdoctoral 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,” says Carlsen.
Alternating limb movements initiate at the level of the spinal cord. Voluntary and spontaneous movements are triggered when the spinal cord’s motor neurons are activated. The motor neurons connect the spinal cord with the muscles. Each time a motor neuron sends electrical impulses to the muscles, it leads to muscle contraction and movement. Uncontrollable, involuntary shaking occurs when motor neurons in the spinal cord send out conflicting signals at the same time. Therefore, the team focused on investigating motor neurons in the spinal cord. In future studies, the team will carry out clinical tests on patients suffering from essential tremor.