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How can the medicinal properties of marijuana be improved to treat diverse neuropathologies?

The brain, being isolated from the rest of the body by the blood brain barrier, has its own specialized immune system consisting of the interplay between glial cells and small numbers of patrolling immune cells. This “brain immune system” is similar to the peripheral immune system in its ability to destroy foreign agents and repair injured tissue, though it does so with much less efficacy. Indeed, while the brain’s immune system can cope with minor insults and infections, its ability to mount effective responses against major disease processes is too weak, likely resulting in many of the devastating neuropathological conditions seen clinically. For example, the brain is unable to cope with:

  • Primary brain tumors and invading metastases,
  • Invading autoimmune cells, such as T-cells directed against oligodendrocytes inducing multiples sclerosis,
  • Many viruses, such as HIV that induce AIDS dementia,
  • ggregated proteins, such as beta-amyloid that induce Alzheimer’s disease,
  • And major injuries, such as spinal cord injury.

Remarkably, these disease processes often impair the functionality of glial cells, reducing their ability to clean and repair damaged cells while rendering them hostile against healthy cells. Thus, a novel and very promising therapeutic approach for the aforementioned diseases is to develop pharmacological agents that target glial cells to reinstate their reparative function while tempering their hostility.

My laboratory is interested in identifying the molecular machinery controlling pathology-induced changes in glial cell phenotype and developing pharmacological tools that will minimize their harmful phenotype and reinstate – or even boost – their native reparative function. Our current most promising target is the cannabinoid signaling system. Cannabinoids, the bioactive components produced by the marijuana plant Cannabis Sativa, have immunomodulatory properties that are quite different from currently available immunomodulatory drugs. In fact multiple sclerosis patients often exploit the medicinal properties of marijuana to relief their symptoms.

Cannabinoids act through specific receptors named CB1 and CB2. CB1 receptors are expressed by neurons and mediate the drug of abuse properties of marijuana, while CB2 receptors are expressed by glial and immune cells and mediate its immunomodulatory properties. This dichotomy has tremendous therapeutic potential for it allows the development of agents that specifically target CB2 receptors and thus regulate immune functions without inducing the drug of abuse adverse effects mediated through CB1 receptors.

We are currently testing whether agents acting through CB2 receptors can boost the brain’s immune system against brain tumors and/or temper the autoimmune response associated with multiple sclerosis. We chose to study these pathologies because they remain without cure and thus demand regimented scientific efforts to relieve these patients. Furthermore, these pathologies induce two extremely different brain immune responses – tumors inhibit the brain’s immune system, while multiple sclerosis exacerbates it – allowing for thorough testing of our novel therapeutic approach. Our goal is to identify cannabinoid agents devoid of drug of abuse properties that provide treatment of diverse neuropathologies.

 
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Updated 1/27/2005