: In the last few years research into Cannabis and its constituent phytocannabinoids has burgeoned, particularly in the potential application of novel cannabis phytochemicals for the treatment of diverse illnesses related to neurodegeneration and dementia, including Alzheimer’s (AD), Parkinson’s (PD) and Huntington’s disease (HD). To date, these neurological diseases have mostly relied on symptomatological management. However, with an aging population globally, the search for more efficient and disease-modifying treatments that could delay or mitigate disease progression is imperative. In this context, this review aims to present a state of art in the research with cannabinoids and novel cannabinoid-based drug candidates that have been emerged as novel promising alternatives for drug development and innovation in the therapeutics of a number of diseases, especially those related to CNS-disturbance and impairment.
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...
: Nowadays, neurodegenerative diseases (NDs), such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge for different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology, and medicine, once all these pathologies remain incurable, with high socio-economic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinics have not yet shown adequate effectiveness in disease-modifying effects, with very restricting options in the therapeutic arsenal, which highlight the permanent need for continued drug discovery efforts in Academia and Industry. In this context, natural products, such as curcumin (1), resveratrol (2), and cannabidiol (CBD, 3) have been recognized as important sources of inspiration, promising chemical entities, prototype models, and starting materials for medicinal organic chemistry. Once their molecular architecture, multifunctional properties and single chemical diversity could address the discovery, optimization, and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs, there may be a real chance of discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide, published in the scientific literature available in PubMed, SCOPUS, and Web of Sciences database, during the last 10 years of research devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs.
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