The Contribution of Studies with Canabidiol and Synthetic Analogues in the Design of New Drug Candidates for Neuropsychiatric Disorders and Neurodegenerative Diseases

Abstract

Abstract:The first documented use of Cannabis for therapeutic purposes is dated from 2300 BC, with indications for the treatment of constipation, gout, beriberi, malaria, rheumatism and menstrual impairment. The search for therapeutic effects of Cannabis has already been pursued by scientists for over 50 years, and in the last 10 years, a new phase studies has started about marijuana constituents, such as Δ 9 -tetrahydrocannabinol (THC, 1) and cannabidiol (CBD, 2) for medicinal application. CBD is present in about 40% in the crude extract of Cannabis sativa, besides other 60 types of cannabinoids and a number of noncannabinoid constituents, accounting for approximately three hundred secondary metabolites. In spite of CBD being a constituent of Cannabis, it is deprived of the typical effects of the plant, differently from THC that induces anxiety and psychotic effects, being its main psychoactive component. Recent studies suggest that CBD could acts as a THC modulator in the brain, exhibiting anxiolytic and/or antipsychotic effects, antagonizing some undesirable effects of THC, as well as contributing with analgesic, antiemetic and antineoplastic, also affecting synapsis plasticity and facilitating neurogenesis. In this context, the scientific literature reinforces the need of advances and more investments in this research field, aiming a better knowledge about endocannabinoid system and the search for new natural and synthetic cannabinoids, supporting their use in the clinics and improving the available therapeutic arsenal for psychiatric and neurodegenerative diseases. Current data from studies dedicated to an improved understanding of its pharmacology and potential therapeutic applications, suggest that CBD and its analogues could play a singular role in the modulation of molecular targets related to central nervous system disorders, making possible the development of innovative, safer and efficient drugs for the treatment of non-responsive patients to the conventional clinics, with significant improvement in life quality and, perhaps, their cure.Keywords: Cannabidiol; cannabinoids; neuropsychiatric disorders; neurodegenerative diseases. ResumoO primeiro uso documentado da Cannabis para fins terapêuticos é datado de aproximadamente 2300 a.C., para o tratamento de constipação, gota, beribéri, malária, reumatismo e problemas menstruais. A busca por efeitos terapêuticos da Cannabis já recebe atenção de cientistas há mais de 50 anos, sendo que nos últimos 10 anos, tem-se observado uma nova fase de estudos acerca dos o po e tes da a o ha, a e e plo do Δ 9 -tetraidrocanabinol (THC, 1) e do canabidiol (CBD, 2) para uso medicinal. O CBD ocorre em cerca de 40% no extrato bruto de Cannabis sativa, além de outros 60 tipos de canabinoides e inúmeros constituintes não-canabinoides, totalizando cerca de 300 metabólitos secundários. O CBD, apesar de ser um constituinte da Cannabis, é desprovido dos efeitos típicos da planta, diferentemente do THC que induz a ansiedade e efeitos psicóticos, sendo o principal ingrediente psico...