Huntington’s disease is characterized by choreatic movement, dementia, and pro-

gressive

motor

disturbance.

Low

expression

of

CB1

receptors

has

been

demonstrated in patients diagnosed with HD (Blázquez et al. 2011). Therefore,

activation of CB1 receptor can slow down the progression of this disease. It has

also been shown that CB2 receptors are overexpressed in striatal parenchyma in

diseased individuals of HD (Palazuelos et al. 2009). CB2 receptor activation can

ameliorate the inflammation. Nabilone, a synthetic cannabinoid similar to Δ⁹-THC

(FDA approved), has also showed the sign of improvement in the study by Curtis

and Rickards (2006) and Müller-Vahl et al. (1999). Along with THC, CBD is also

investigated to have positive effects in HD. To summarize all the studies,

cannabinoids may be useful strategies for HD treatment.

12.5.2.3 Alzheimer’s Disease (AD)

Alzheimer’s

disease

is

a

chronic

progressive

neurodegenerative

disorder

characterized by accumulation of neurotic plaques, which is rich in beta amyloid

(aβ) peptides and hyperphosphorylation of tau protein. During the last few years,

ECS has emerged as a potential therapeutic target to treat Alzheimer’s disease.

Several findings indicate the involvement of CB1 and CB2 receptors as there has

been an increase in production of endocannabinoids after neuronal damage. Interest-

ingly, three major observations after analysis of human post-mortem samples

revealed (1) overexpression of CB2 receptors in microglial activation (Ramírez

et al. 2005), (2) elevation in the 2-AG levels, and (3) reduction in CB1 receptors

found to be associated with the neuronal loss (Benito et al. 2003). A cannabinoid

agonist, WIN 55,212-2, and anandamide have been shown to prevent aβ-induced

neurotoxicity mediated via the CB1 receptors (Ramírez et al. 2005). Similar results

are observed in a study by Iuvone et al. on PC12 cells (Iuvone et al. 2004). It has also

been observed that administration of HU210 and JWH-133 blocked the aβ-induced

activation in cultured microglial cells. The studies conducted on mice also

demonstrated that treatment with CBD decreases the level of ROS, prevents

glutamate-induced toxicity, as well as inhibits the tau protein hyperphosphorylation

(Esposito et al. 2006, 2007). Thus, the available evidences from various findings

suggested that cannabinoids could be potential target in treatment for Alzheimer’s

disease due to its immunosuppressive, anti-inflammatory, and neuroprotective

properties.

12.5.2.4 Epilepsy

Epilepsy is a neurological disorder caused by an imbalance between inhibitory and

excitatory communication among neurons. The mechanism by which a normal brain

becomes epileptic is quite diverse, ranging from (1) neural circuit level (abnormal

synaptic connectivity) to (2) receptor level (abnormal GABA receptors) to (3) mem-

brane

level

(abnormal

ionic

channel

function).

Cannabinoids

protect

the

excitotoxicity of neuron by inhibiting the calcium channels and/or stimulating the

potassium channel. Cannabis has been used in treatment of epilepsy for centuries.

Researchers identified the role of THC and CBD as effective anticonvulsants in

epilepsy treatment (Consroe and Wolkin 1977a, b; Gordon and Devinsky 2001).

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