Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

Figure 1. (A) Structure of the most common cannabinoids found in Cannabis plants. All the compounds have been represented in their acidic, native form, and with a pentylic side chain; (B) the non-enzymatic decarboxylation of Δ9-tetrahydrocannabinolic acid (THCA) to THC.

Figure 2. Capitate-sessile (A) and bulbous (B) glandular trichomes. In (A), also some non-glandular trichomes (not secerning) are visible. (C), schematic representation of the current model of secretion of cannabinoids from the trichomes.

Figure 3. The biosynthesis of the main cannabinoids.

Figure 4. Cannabinoid-induced cellular signaling in neurologic disease.

Giacoppo, S.; Mandolino, G.; Galuppo, M.; Bramanti, P.; Mazzon, E. Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases.Molecules 2014, 19, 18781-18816.

Abstract

Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated.

Conclusions

In this review, we showed how the Cannabis plant, an ancient industrial crop, is drawing increasing attention as a pharmaceutical plant, and is today considered a true “bioreactor” source of botanical raw material from which high amounts of potentially valuable cannabinoids can be extracted. In the future, these molecules will be increasingly used in clinical trials necessary to assess the potential of each phytocannabinoid for the treatment of several diseases, among which CNS disorders.

Whereas, current treatments for CNS diseases are partially effective and have risks of side effects that are not easily tolerated by patients, the development of new synthetic cannabinoids or cannabinoid-derived drugs may represent an alternative strategy to pursue.

The observations from experimental models of neurological diseases, and now increasingly from clinical trials, underline the therapeutic usefulness of cannabinoids-based medicines for treatment of symptoms associated to these. In addition, there is growing evidence from experimental studies that Δ9-THC and other cannabinoids, notably CBD, have neuroprotective effects as a result of their antioxidant, anti-inflammatory and anticytotoxic properties which may prove disease modifying in CNS disorders.

Despite emerging evidence regarding putative therapeutic activities of cannabinoids, their effective introduction in the clinical use is still controversial and strongly limited by unavoidable psychotropic effects, exhibited by many of them.

The possibility of overcoming these side effects and developing novel approaches represents the main open question about the use of cannabinoids as new therapeutic drugs for the treatment of neurological disorders.

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