8.0 Conclusion and Future studies
The cannabinoid system has been shown in several preclinical and
clinical studies to be involved in the regulation of inflammatory and
immunomodulatory responses. Even though the exact role of the
endocannabinoid system in inflammation is not fully elucidated, a pool
of evidence points to the potential pharmacological modulation of this
system in the treatment or management of several inflammatory disease
conditions, including both central and peripheral inflammatory
disorders. Although individual variations in patient response to
cannabinoid-inclusive therapy have been reported, findings from these
studies have largely pointed to the potential successful translation of
pre-clinical research to the clinic. Additional well-controlled
randomized trials are however required to comprehensively evaluate the
true clinical efficacy and long-term risks associated with cannabinoid
therapy in inflammatory disorders.
CB2 receptors are primarily expressed on immune cells,
and pharmacological targeting of these receptors have been shown to
produce selective immunomodulation without profound immunosuppression.
Interestingly, CB2 receptor activation is without
psychotropic side effects, thus making it a suitable target for
pharmacotherapy. Since the psychotropic effects of cannabinoids pose
legal, social and therapeutic challenges, future studies may therefore
focus on the synthesis or identification of novel molecules with
increased affinities for the CB2 receptor for use in
inflammatory and autoimmune diseases. In addition, more studies are
required to investigate the exact biological effects of the
“not-so-popular” endocannabinoids virodhamine, 2-AG ether and
N-arachidonoyl dopamine and their possible effects on co-stimulatory
molecules, adhesion molecules, chemokines and cytokines, to ascertain
their roles in the inflammatory and immunomodulatory process.
Owing to the complexity of the pathophysiology of inflammatory
disorders, multi-target drug development and pharmacotherapy strategies
may be advantageous compared to single-target therapy as partly
evidenced by the effectiveness of OMDM198 over single-target small
molecules such as the FAAH inhibitor URB597 and the TRPV1 receptor
antagonist SB366791 in the management of osteoarthritis (Mlost et al.,
2018).
It has been demonstrated that gut inflammation alters the expression of
metabolizing enzymes of the endocannabinoid system, resulting in marked
changes in the levels of these enzymes in the local environment (Sharkey
and Wiley, 2016). Further studies aimed toward identifying genetic
and/or epigenetic alterations that affect functioning of the
endocannabinoid system, including the effect of glucocorticoid receptors
on the regulation of the expression of cannabinoid receptors andvice versa , are needed to shed more light on the relation
between inflammation and cannabinoid signaling. Notwithstanding,
pharmacological targeting of the cannabinoid system demonstrates
potential for safe and effective use in the treatment of inflammatory
diseases.
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