Neuroinflammation is known to play a significant role in essentially all neurodegenerative processes. Diseases such as Alzheimer’s, Multiple Sclerosis (MS), Huntington’s Disease, and Parkinson’s Disease all involve hyperactive microglia, which are the live-in macrophages of the brain, spinal cord, and central nervous system. Macrophages are immune cells that capture and dissolve foreign substances, germs, and cancer cells within the body. The microglia in the brain and spinal cord form the first line of immune defense in the central nervous system. Unfortunately, in the case of aforementioned diseases, these cells have become overactive causing them to secrete excess substances, such as cytokines (cell signals that regulate cell group growth and response), glutamate, and harmful free radicals. This excessive production of chemicals causes inflammation, which leads to further cell death.

Cannabis and the family of chemicals it produces are known to act on two major cell receptor types named CB1 and CB2 respectively. The CB1 receptor is most commonly found in neurons throughout the brain. The psychedelic effects of cannabis come from this receptor’s function, which re-wires the way neurons signal each other. The CB2 receptor on the other hand, is found throughout the body, especially within the immune system cells. The effects of activating the CB2 receptor are more myriad, but within the immune system specifically four groups of effects have been identified:

1. induction of apoptosis or forced cell death

2. suppression of cell proliferation

3. induction of regulatory T cells

4. inhibition of pro-inflammatory cytokine/chemokine production and increase in anti-inflammatory cytokines

The last of these effects is the basis upon exploring using cannabinoids to halt the progress of neurodegenerative disorders. The idea is that if cannabinoids can prevent excess production of cytokine, inflammation will decrease, and the resultant cell death around that inflammation will not occur. This would go a long measure toward slowing progression of neuro-inflammatory diseases. However, it is important to note that tempering inflammation would still not allow the brain to recover to its pre-disease state and slow neural damage would inevitably continue to occur. Likewise, modern medicine currently utilizes a variety of treatments in these diseases as more or less palliative care.

Based on these observations, research groups worldwide have been testing specific cannabinoids and other CB2 agonists with various models of neuro-inflammatory disease, generally in rodents.

The following is a general review of effects noticed, grouped by disease:

  •  Alzheimer’s Disease – In Alzheimer’s cannabidiol has been shown to “reduce the transcription and expression of pro-inflammatory molecules in the hippocampus of an in-vivo model of induced neuroinflammation”. The hippocampus is the part of the brain that controls conversion of memory from short to long-term and controls spatial navigation. In Alzheimer’s, it’s one of the first areas of the brain to suffer damage and why patients have memory problems. Another agonist, which has the name SR141716A, also prevents amnesia induced by certain peptides, so these both promise a future in treating the disease.

 

  • Parkinson’s Disease – In this disease, the agonist WIN55,212-2 has been shown to protect mouse neurons from the neurotoxin MPTP, which is the chemical which leads to the death of dopaminergic neurons and causes Parkinson’s Disease.

 

  • Multiple Sclerosis (MS) – Although the cause of MS is unclear, researchers have determined that both genetic susceptibility and environmental trigger play a role. Some patients develop their symptoms of MS after contracting a virus. Likewise, testing rodents injected with a virus that intentionally lead to animal models of MS provided ground to investigate the effects that CB2 agonists might have on MS in humans. As is, cannabis concentrate is already prescribed under the name Sativex to alleviate neuropathic pain, spasticity, and overactive bladder symptoms associated with MS. Although some agonists did increase symptoms, several, including THC, delayed onset and reduced severity of symptoms. Three agonists, WIN55,212-2, ACEA, and JWH-015 were shown to improve motor function by attenuating microglia and immune cell infiltration into the spinal cord.

Exactly how these effects are achieved is still unknown. Although it is presumed that the effects of the CB2 agonists (any molecules that can activate CB2 receptors, including cannabinoids) stem from CB2 receptor activation, other theories have been proposed. One research group at the University of Bari has explored the extra-cannabinoid receptor binding activity of cannabidiol (CBD). Researchers there found that CBD can surprisingly communicate with the nucleus of the cell directly through interaction with nuclear hormone receptors. There are several possible chemical pathways through which cannabinoids can achieve their effects, beyond CB2 receptors. Further research will illuminate these pathways.

 

Works Cited

Slava Rom and Yuri Persidsky. (2013) Cannabinoid Receptor 2: Potential Role in Immunomodulation and Neuroinflammation. J Neuroimmune Pharmacol (2013) 8:608-620. DOI 10.1007/s11481-013-9445-9

Viviane Saito, Rafael Rezende, and Antonio Teixeira. (2012) Cannabinoid Modulation of Neuroinflammatory Disorders. Current Neuropharmacology (2012) 16:139.

Giuseppe Esposito, Caterina Scuderi, Marta Valenza, Guiseppina Togna, Valentina Latina, et. al. (2011) Cannabidiol Reduces Alpha-Beta Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPAR(gamma) Involvement. PLoS ONE 6(12): e28668. DOI: 10.1371/journal