The therapeutic effects induced by cannabinoid drugs are well known since thousands of years. However, the recreational use of marijuana has indirectly limited a rigorous scientific evaluation of these pharmacological agents in the clinical practice.
In our laboratories, we have screened and selected several cannabinoid ligands in order to evaluate the therapeutic benefits that might be attributable to these drugs. Our pre-clinical analyses confirmed that cannabinoid compounds may have important clinical applications in the control of pain, glaucoma, gastro-intestinal transit, food intake and inflammation. Furthermore, we demonstrated that the potential abuse of these drugs can be significantly reduced by modifying their pharmacokinetic and/or pharmacodynamic profiles.
For instance, cannabinoid compounds showing a low propensity to cross the brain blood barrier may still bear important therapeutic properties in the control of acute and chronic pain, without inducing central effects or gratification and thus abuse liability. Similarly, drug delivery systems associated with cannabinoid compounds strongly improved the efficacy/tolerability profile of anti-glaucoma cannabinoids, without producing any evident behavioral alterations in laboratory animals.
Therapeutic opportunities may also come from a proper selection of cannabinoid drugs based on their pharmacodynamic profiles. The cannabinoidergic system is characterized by two receptors (CB1 and CB2 receptors), but only CB1 receptors are implicated in the reward mechanisms induced by cannabinoid drugs. We demonstrated that selective CB2 agonists possesses strong anti-inflammatory and analgesic properties that can be successfully employed in chronic inflammatory diseases, with no side effects related to drug abuse. Furthermore, pre-clinical results obtained from selective CB1 ligands showing a different intrinsic activity (agonism, antagonism and partial agonism) further remarked that the pharmacological properties of cannabinoid drugs can be largely modulated in order to obtain an optimal therapeutic effects and minimal side effects.
In conclusion, cannabinoid drugs seem to possess interesting therapeutic properties that can provide benefits in the clinical practice. Several strategies can be used in order to reduce the potential abuse of these drugs, while maintaining their therapeutic efficacy in controlling acute and chronic pain, glaucoma, gastro-intestinal transit, inflammation and food intake.
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