Possible therapeutic applications of cannabinoids

Marijuana and its preparations have been used in medicine for at least 50 centuries. Marijuana and its preparations have been used in medicine for at least 50 centuries. Recent discoveries in the knowledge of the endocannabinoid system summarized above have contributed to the revival of the study of the possible therapeutic applications of cannabinoids, which today constitutes a field of broad scientific, clinical and social debate. Based on the demonstration of the modulating function that endocannabinoids exert on numerous brain functions, the therapeutic potential that the pharmacological manipulation of their levels or the administration of cannabinoid agonists (either cannabinoids of the plant, or synthetic cannabinoids) has been suggested, could have on The treatment of diverse pathologies that affect the nervous system. In some of these diseases it has already been shown that there are changes in the expression of cannabinoid receptors and / or endocannabinoid levels in certain areas of the brain, which would justify the pharmacological study of this system. For example, and in general, cannabinoids exert analgesic effects that would make them useful in the treatment of pain. 

They could also be useful in the treatment of neuroinflammation processes, in which its administration would allow to alleviate some typical consequences of such disorders. Nowadays we also know that, under certain therapeutic windows, cannabinoids are able to protect neurons from various situations of damage, which may be of interest for the treatment of episodes of acute brain damage and perhaps neurodegenerative diseases. Their participation in the memory processes suggests that cannabinoids could be useful in disorders such as the extinction of aversive memories in situations of post-traumatic stress. Similarly, the presence of cannabinoid receptors in regions of the limbic system and the anterior hypothalamus would allow the manipulation of these receptors could be a pharmacologically relevant approach in the treatment of eating and metabolic disorders as well as of compulsive phenomena related to drug addiction.

The clinical use of cannabinoids and other compounds that affect cannabinergic signaling is nowadays quite restricted. Despite this, the clinical use of cannabinoids and other compounds that affect cannabinergic signaling is nowadays quite restricted. Prescription of THC (Marinol) and synthetic cannabinoid nabilone (Cesamet) capsules is now permitted in some countries, as well as the dispensing of standardized medical marijuana preparations to inhibit nausea and vomiting, stimulate appetite and attenuate Cachexia in cancer or AIDS patients. A new cannabinoid drug, Sativex, a gold-mucosal spray composed of cannabis extracts rich in THC and cannabidiol, has recently been approved for the treatment of cancer and neuropathic pain (so far only in Canada) and the spasticity associated with Multiple sclerosis (in several countries, including Spain). There are also other therapeutic possibilities of cannabinoids that are still in various stages of clinical trials.

Cannabinoids are fairly safe substances in the context of their clinical application, but their medical use is partly hampered by their unwanted psychoactive effects, including affective (euphoria), somatic (drowsiness, motor incoordination), Sensory (alterations in the temporal and spatial perception, disorientation) and cognitive (lapses of memory, confusion). Although such side effects may be transient and within acceptable margins for other drugs, it is clear that, at least for certain patients and diseases, it would be desirable to design cannabinoids lacking psychotropic actions. Since these depend on the central CB1 receptors, the most logical option would be to avoid the activation of these receptors (provided that the pathology in question makes it viable). Thus, for example, cannabinoids are being designed that selectively bind to the CB2 receptor and cannabinoids that do not cross the blood-brain barrier and therefore do not reach the central nervous system. On the other hand, the administration to experimental animals of inhibitors of the degradation (recapture or intracellular hydrolysis) of endocannabinoids has allowed to raise the levels of these compounds in restricted spatio-temporal contexts and, in this way, the induction of effects For example bradynexins, anxiolytics or analgesics with no known side effects. These types of compounds have not, however, been the subject of successful clinical trials.

It is necessary to carry out deeper basic research and more comprehensive clinical trials to better understand biological function and therapeutic potential. In this context of general field knowledge, our research group began to study the molecular mechanisms for some 15 years ago. Which cannabinoids, both endogenous and plant, act in the body. More specifically, our interest was focused on whether these compounds are capable of altering some central processes of cell biology such as proliferation, differentiation and survival, especially (but not exclusively) in the nervous system. The understanding of these events is essential for the precise knowledge of biological processes such as the development of the nervous system, as well as for the characterization of the etiology and progression of neurodegenerative diseases (characterized by dysfunction and loss of nerve cells) and processes Oncological (characterized by excessive cell proliferation and survival) and, therefore, for the design of rational therapies for its treatment. These three concrete paradigms form the basis of the main research projects carried out by our group today. For example, and very briefly, throughout this time we have observed that, after joining their receptors, cannabinoids modulate numerous intracellular signaling pathways in different types of neural cells, which translates into effects such as stimulation The proliferation of neural progenitor cells to generate neurons and cells of neuroglia, the protection and survival of neurons and cells of neuroglia, the inactivation of microglia cells and the induction of programmed death in tumor cells of glial origin. These cellular events have a clear physiological relevance in laboratory animals, in which cannabinoids, for example, control the development of the cerebral cortex, contribute to the regeneration and protection of nervous tissue in situations of damage, and inhibit Growth of malignant tumors.

The scientific community is now at a point where there has been a relatively good knowledge of how cannabinoids work in the body and what may be some of its more immediate therapeutic applications. However, it is necessary to carry out deeper basic research and more comprehensive clinical trials to better understand the biological function and therapeutic potential of these new chemical messengers of our organism.