3 Endocannabinoid Receptor Genetics and Marijuana Use
CONCLUDING REMARKS AND FUTURE DIRECTIONS
The recent signicant progress in marijuana-cannabinoid research has led to a new understanding about the biological effects and the unique therapeutic possibilities of targeting the EPCS, which is activated by THC and marijuana use. In just a few years since the discovery of endocannabinoids that serve as cannabinoids in vivo, these lipid-signaling molecules and endolipids have been shown to participate in a broad array of physiological and pathological processes. However, the impact of “lipidomics” and these new lipid-signaling pathways in modulating behavioral neurobiology and aspects of drug addiction is of current interest. It is now clear that marijuana use is addicting in vulnerable populations. Just like most medications that are not benign, benzodiazepines, opiates, and marijuana have side effects that accompany their therapeutic use. Unlike opiates, the intensity of the craving and withdrawal reactions appear to be mild and vary from individual to individual.
Thus, we can look forward to a bright future of discoveries concerning the role of endocannabinoids in brain function, immune function, reproductive function, and emotional behavior, as well as the discovery of potential medicines to improve the health of many who suffer from various disorders.
One notable future direction is in brain injury and stroke for which there are currently no major drugs, and one cannabinoid based drug, HU211 (dexanabinol), has successfully completed phase II trials.
The success of rimonabant in clinical trials for obesity and cessation from smoking is heightening interest in the therapeutic potential of manipulating the endogenous marijuana system. Marijuana (cannabinoid) research appears to offer a solid scientic background as a signicant contribution in understanding human biology and in the development of cannabinoid based therapeutics. The only medical uses for which there has been rigorous scientic evidence are in the treatment of
sickness associated with cancer chemotherapy and to counter the loss of appetite and wasting syndrome in AIDS (Iversen, 2000). There is, however, scientic evidence for the potential thera-peutic use of cannabinoids for the treatment of psychomotor disorders, including spasticity, multiple sclerosis, epilepsy, disk prolapse, and attention decit hyperactivity disorder (ADHD), and its pain relief properties are no longer a matter of speculation. It is only a matter of time before new medications for the pharmacological manipulation of the link between endocannabinoid and other neurotransmitter systems will be developed as targets for the numerous indications of marijuana and endocannabinoid ligands. In the absence of clinical data on the abuse liability of endocannabinoids, the preclinical data indicate that as with marijuana, the endocannabinoids may have minimal abuse liability in humans. The safety prole of THC, the active ingredient of cannabis, is good. It has low toxicity in both the short and long term. As concluded by Iverson (2000), marijuana is not a completely benign substance. It is a powerful drug with a variety of effects. However, except for the harm associated with smoking, the adverse effects of marijuana use are within the range of the side effects tolerated for other medications. Unraveling the genetics of the EPCS that is a target for smoking marijuana is dependent on further understanding of the complex CB1, CB2, and CBn gene structure and the associated regulatory elements that are still poorly understood.
ACKNOWLEDGMENTS
G. R. Uhl’s laboratory is supported by NIDA/NIH intramural program. B. E. Akinshola acknowl-edges the support of grant AA13415 from NIAAA. E.S. Onaivi wishes to especially thank the Center for Research at William Paterson University for research and support of students working with him; he also acknowledges the continued Guest Scientist support by NIDA/NIH.
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