NF-κb proteins (Sugamura et al. 2009). However, CB1 receptor blocking is a

requisite in order to modulate inflammation. CB1 blockade is associated with the

decreased expression of matrix metalloproteinase-9 (MMP-9) and inflammatory

cytokines (Han et al. 2009). All these studies indicate that cannabinoids have anti-

atherosclerotic activities. Therefore, they can be considered as potential treatment

options for atherosclerosis.

12.5.2 CNS Disorders

12.5.2.1 Multiple Sclerosis (MS)

Multiple sclerosis is an autoimmune inflammatory disease of the central nervous

system. Symptoms of MS include painful muscle spasms, tremor, paralysis, bladder

control loss, and difficulty in speaking. Due to loss of myelin, there is impairment in

conduction of impulse signals. MS is characterized by heightened Th1-mediated

immune response leading to increase in cytokines like tumor necrosis factor-α

(THF-α),

interferon-gamma

(IFN-γ),

interleukin-12,

lymphotoxin-α,

etc.

Upregulation of pro-inflammatory cytokines causes neurological disabilities like

MS. Thus, suppressing the pro-inflammatory cytokines might be the appropriate

target for the treatment of MS. First-line treatment for spasticity includes gamma

aminobutyric acid (GABA) B agonist like baclofen. They bind to the GABA

receptors and cause membrane hyperpolarization. This as a result modulates calcium

influx which further restricts the release of endogenous excitatory neurotransmitters.

Cannabinoids target the same as it has been observed that the expression of CB1

receptors is high in cerebellum. Administration cannabinoid agonist WIN55,212-22

can increase the effect of GABA signaling and inhibit the release of glutamate

(neurotransmitter) (Shen et al. 1996; Szabo et al. 2000; Garcia-Gil et al. 1999).

Cannabinoids also reduce the expression of Th1 cytokines by suppressing IFN-γ and

IL-12 (Klein et al. 1995, 1998, 2000). Some studies supported the beneficial effect of

dronabinol and cannador (THC+ CBD) in improving the spasticity (Petro and

Ellenberger 1981; Ungerleider et al. 1987; Vaney et al. 2004). Additionally,

cannabinoids are found to be effective against pain in MS (Consroe et al. 1997).

Another finding revealed that administration of Arvanil (capsaicin + anandamide)

can inhibit both spasticity and pain in animal model of experimental autoimmune

encephalomyelitis (EAE) (Brooks et al. 2002). In the study by Novotna et al.,

Sativex has been used as add-on therapy for patients who have failed to respond

adequately to the medication. Results in this study have favored the role of Sativex

as an effective anti-spasticity treatment (Novota et al. 2011). After this study in 2011

cannabis extract has received approval in Germany. Sativex has also secured FDA

approval for its analgesic effects.

12.5.2.2 Huntington’s Disease (HD)

Huntington’s disease is an autosomal dominant neurodegenerative disease. HD is

caused by mutation in htt encoding gene on chromosome number 4 leading to

excessive repeats of CAG triplet (>39 repeats) (Roos 2010; Myers 2004).

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