including R63Q, Q66R and H316Y. CNVs in Asian and Yoruba population have
been reported. Therefore, studying the CBR genomic structure, it’s polymorphic
nature, subtype specificity, their variants and associated regulatory elements that
confer vulnerabilities to a number neuropsychiatric disturbance may provide deeper
insight in unraveling the underlining mechanisms. Thus, understanding the eCB
system in the human body and brain will contribute to elucidating this natural
regulatory mechanism and provide potential therapeutic targets in health and
disease.
10.7 The Role of Endocannabinoids in Psychiatric,
Neuroinflammatory and Neurodegenerative
DisordersThe limited effectiveness of current therapies for most neurological and neurode-
generative disturbances including Alzheimer’s, Parkinson’s, and Huntington’s
diseases, multiple sclerosis, epilepsy and migraine underscores the need for
intensifying research efforts aimed at developing new medications for preventing or
retarding the disease process (Aso and Ferrer 2014 ). There is evidence that eCB
signaling modulate numerous concomitant pathological processes, including reg-
ulation of neuroinflammation, excitotoxicity, mitochondrial dysfunction and
oxidative stress (Aso and Ferrer 2014 ; Kong et al. 2014 ), and both CB1Rs and
CB2Rs are expressed in the immune system with higher CB2R expression in all
immune subtypes (Basu and Dittel 2011 ; Malfitano et al. 2014 ) and higher CB1Rs
expression in neurons. Extensive studies and reviews also in previous chapters have
demonstrated inin vitroandin vivothat CB2R is a potent regulator of immune
function and therefore a prime target in neuroinflammatory and neurodegenerative
disorders (Basu and Dittel 2011 ; Malfitano et al. 2014 ). While targeting the CB2Rs
in neuroinflammatory and neurodegenerative disorders may be clinically attractive,
CB2R gene structures differ in mice, rats and humans with different expression
patterns in the brain and periphery. CB2Rs are the main mediator of the
immunoregulatory effects of cannabinoids (Kong et al. 2014 ) and stroke or brain
injury upregulates the eCB system, including CBRs, thereby contributing to
immunosuppression that may limit neuroinflammation (Lehmann et al. 2014 ).
Medical marijuana and formulation of mixtures of cannabinoids are touted as
having positive effects in some neuroinflammatory and neurodegenerative disorders
including multiple sclerosis, epilepsy and migraine which together will encourage
progress towards clinical trials. Other lines of evidence have shown that elements of
the eCB neurosignaling system have neuroprotective capabilities and therefore are
potential targets for neurodegenerative disorders (Fagan and Campbell 2012 ).
However, more basic and clinical research is required for the development of
therapeutically effective cannabinoid compounds, and the complexity of CB2R
10 Cannabinoid CB2 Receptor Mechanism ofCannabis sativaL. 239