RESUMEN
INTRODUCTION: Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug-discovery campaigns. OBJECTIVE: This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America. METHODOLOGY: Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity. RESULTS: Our results reveal significant phytochemical diversity in Colombian-grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia's environments may have unique capabilities that allow the plant to express these compounds. Colombia's diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade. CONCLUSION: These findings underscore Colombia's capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.
RESUMEN
Endocannabinoid system, including endocannabinoid neurotransmitters (eCBs), has gained much attention over the last years due to its involvement with the pathophysiology of diseases and the potential use of Cannabis sativa (marijuana). The identification of eCBs and phytocannabinoids in biological samples for forensic, clinical, or therapeutic drug monitoring purposes constitutes a still significant challenge. In this scoping review, the recent advantages, and limitations of the eCBs and phytocannabinoids quantification in biological samples are described. Published studies from 2018-2023 were searched in 8 databases, and after screening and exclusions, the selected 38 articles had their data tabulated, summarized, and analyzed. The main characteristics of the eCBs and phytocannabinoids analyzed and the potential use of each biological sample were described, indicating gaps in the literature that still need to be explored. Well-established and innovative sample preparation protocols, and chromatographic separations, such as GC, HPLC, and UHPLC, are reviewed highlighting their respective advantages, drawbacks, and challenges. Lastly, future approaches, challenges, and tendencies in the quantification analysis of cannabinoids are discussed.
Asunto(s)
Cannabinoides , Cannabis , Endocannabinoides , Endocannabinoides/análisis , Endocannabinoides/metabolismo , Humanos , Cannabinoides/análisis , Cannabis/química , Cromatografía Líquida de Alta Presión/métodos , Cromatografía de Gases/métodos , AnimalesRESUMEN
The aim of this study was to evaluate the perioperative analgesic and sedative effects of oral CBD in cats undergoing ovariohysterectomy. Twenty-two cats were assigned to receive either oral cannabidiol oil (2 mg/kg, CBD group, n = 12) or placebo oil (0.1 mL/kg, Placebo group, n = 10) 60 min before the premedication. The anesthetic protocol included dexmedetomidine/meperidine, propofol, and isoflurane. Intravenous fentanyl was given to control cardiovascular responses to surgical stimulation. Pain was assessed at 0.5, 1, 2, 4, 6 and 8 h post-extubation using the UNESP-Botucatu multidimensional composite pain scale and the Glasgow feline composite-measure pain scale. Sedation scores were assessed at the same timepoints and at 15 min after the premedication. Morphine was administered as rescue analgesia. Higher sedation scores were recorded in the CBD group at 15 min after premedication (p = 0.041). Intraoperatively, more cats required fentanyl in the Placebo group than in CBD group (p = 0.028). The pain scores did not differ between groups, except at 0.5 h post-extubation when lower scores were detected in the CBD group (p = 0.003-0.005). Morphine was required in 100% of the animals in both groups. CBD increased preoperative sedation and decreased intraoperative analgesic requirements, with minimal evidence of postoperative analgesic benefits over the placebo.
RESUMEN
OBJECTIVE: Zombification, a magical and religious process in Haiti, has been scientifically studied and remains relevant. Originating from the convergence of African, Caribbean, and Christian rites, it involves a comatose trance, transforming individuals into living dead through Voodoo practices. Haitian zombies consistently exhibit a preserved expression marked by a nasal voice, a result of nasalization-using nasal cavities as resonators during phonation. The aim of this study was to ascertain the mechanisms through which zombification could impact the voices of the subjects. METHODS: A comprehensive investigation was conducted using both primary and secondary sources. Primary sources involved direct or reported testimonies of individuals undergoing zombification, with audio or video recordings available from the collections of the Laboratory of Anthropology, Archaeology, and Biology (UVSQ/Paris-Saclay University), as well as on the internet. Secondary sources encompassed the entirety of existing literature regarding zombification in Haiti on one hand, alterations in the voices of subjects when mentioned on the other hand, and toxicological hypotheses or evidence available on PubMed/Medline and Google Scholar. RESULTS: Few post-zombification observations exist, but 20th-century studies clarified the physio pathological process, confirming its reality. Wade Davis demonstrated in 1983 that zombification results from poisoning, with effects ranging from reversible to fatal, implicating substances like tetrodotoxin and datura. Nasalization can be natural or pathological, affecting various phonemes. No mutilating acts or surgery have been reported related to Haitian zombification. CONCLUSION: The pharmacological characteristics of tetrodotoxin, coupled with testimonials, present a medical hypothesis elucidating the biological mechanism underlying nasalization in this context. Given that tetrodotoxin induces flaccid paralysis as a neurotropic poison, its neurological impact could account for soft palate paralysis or spasms. Additionally, the severe hypotension induced by tetrodotoxin may elucidate oral and pharyngeal necrosis.
RESUMEN
OBJECTIVE: This study aims to investigate the neuroprotective effects of cannabidiol (CBD) on neurodevelopmental impairments in rats subjected to neonatal hypoxia, specifically examining its potential to mitigate motor and sensory deficits without the confounding effects of ischemia. METHODS: Neonatal Sprague-Dawley rats were allocated to one of four groups: Control, Control-CBD, Hypoxia, and Hypoxia-CBD. Hypoxia was induced on postnatal days 0 and 1. CBD (50 mg/kg) was administered orally for 14 days starting at postnatal day 0. Neurodevelopmental outcomes were assessed using the Neurodevelopmental Reflex Testing in Neonatal Rat Pups scale and the Revised Neurobehavioral Severity Scale for rodents. Statistical analyses were conducted using two-way and one-way ANOVA, with Tukey's post-hoc tests for group comparisons. RESULTS: Pup weights were recorded on specified postnatal days, with no significant differences observed across the groups (p = 0.1834). Significant neurological impairments due to hypoxia were noted in the Control group compared to the Hypoxia group, particularly in hindlimb grasping on postnatal day 3 (p = 0.0025), posture on postnatal day 12 (p = 0.0073), and in general balance and sound reflex on postnatal day 20 (p = 0.0016 and p = 0.0068, respectively). Additionally, a statistically significant improvement in posture was observed in the Hypoxia-CBD group compared to the Hypoxia group alone (p = 0.0024). CONCLUSION: Our findings indicate that CBD possesses neuroprotective properties that significantly counteract the neurodevelopmental impairments induced by neonatal hypoxia in rats. This study not only supports the therapeutic potential of CBD in managing conditions characterized by neurodevelopmental challenges due to hypoxia but also underscores the necessity for further investigation into the specific molecular mechanisms driving CBD's neuroprotective effects. Further research is essential to explore CBD's clinical applications and its potential role in treating human neurodevelopmental disorders.
Asunto(s)
Animales Recién Nacidos , Cannabidiol , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Animales , Cannabidiol/farmacología , Fármacos Neuroprotectores/farmacología , Ratas , Hipoxia/tratamiento farmacológico , Hipoxia/complicaciones , Masculino , Femenino , Trastornos del Neurodesarrollo/prevención & control , Trastornos del Neurodesarrollo/tratamiento farmacológico , Trastornos del Neurodesarrollo/etiología , Modelos Animales de EnfermedadRESUMEN
Background: Of the seventy million people who suffer from epilepsy, 40 percent of them become resistant to more than one antiepileptic medication and have a higher chance of death. While the classical definition of epilepsy was due to the imbalance between excitatory glutamatergic and inhibitory γ-aminobutyric acid (GABA)-ergic signalling, substantial evidence implicates muscarinic receptors in the regulation of neural excitability. Summary: Cannabinoids have shown to reduce seizure activity and neuronal excitability in several epileptic models through the activation of muscarinic receptors with drugs which modulate their activity. Cannabinoids also have been effective in reducing antiepileptic activity in pharmaco-resistant individuals; however, the mechanism of its effects in temporal lobe epilepsy is not clear. Key Messages: This review seeks to elucidate the relationship between muscarinic and cannabinoid receptors in epilepsy and neural excitability.
RESUMEN
Cannabidiol (CBD) has been investigated for several therapeutic applications, having reached the clinics for the treatment of certain types of epilepsies. This chapter reviews the potential of CBD for the treatment of substance use disorders (SUD). We will present a brief introduction on SUD and current treatments. In the second part, preclinical and clinical studies with CBD are discussed, focusing on its potential therapeutic application for SUD. Next, we will consider the potential molecular mechanism of action of CBD in SUD. Finally, we will summarize the main findings and perspectives in this field. There is a lack of studies on CBD and SUD in comparison to the extensive literature investigating the use of this phytocannabinoid for other neurological and psychiatric disorders, such as epilepsy. However, the few studies available do suggest a promising role of CBD in the pharmacotherapy of SUD, particularly related to cocaine and other psychostimulant drugs.
Asunto(s)
Cannabidiol , Trastornos Relacionados con Sustancias , Cannabidiol/uso terapéutico , Cannabidiol/farmacología , Humanos , Trastornos Relacionados con Sustancias/tratamiento farmacológico , AnimalesRESUMEN
This integrative review addresses the potential of the Endocannabinoid System (ES) and cannabinoids in the pathogenesis and treatment of periodontal disease (PD). Cannabinoid receptors are expressed in healthy and inflamed periodontal tissues, indicating a potential regulatory role for SEC in oral homeostasis. Healthy periodontal cells express more CB1 receptors, while inflamed sites show increased CB2 receptors. This suggests a dynamic involvement of the SEC in the inflammatory response associated with PD. Cannabinoids such as cannabidiol (CBD) and cannabinoid receptor agonists such as HU-308, anandamide (AEA), and methanamide (Meta-AEA) have demonstrated promising therapeutic potential in studies. CBD has been associated with the control of bone resorption, antibacterial activity, and increased production of gingival fibroblasts, indicating effects in mitigating the progression of PD. HU-308 demonstrated preventive effects against alveolar bone loss, and anti-inflammatory, osteoprotective, and pro-homeostatic properties in animal models of periodontitis. AEA and Meta-AEA have anti-inflammatory effects by reducing pro-inflammatory mediators such as IL-1, IL-6, and TNF-α. The activation of cannabinoid receptors attenuates inflammatory processes, inhibits alveolar bone loss, exerts antibacterial effects, and promotes tissue repair. However, clinical trials are especially needed to validate these results and explore the therapeutic potential of cannabinoids in the treatment of PD in humans.
RESUMEN
Endometriosis is a chronic proinflammatory pathology characterized by the growth of tissue similar to the endometrium outside the uterus, affecting approximately 5 to 15% of women worldwide. Suffering from endometriosis entails a complex pathophysiological process, significantly impacting the quality of life and reproductive function of affected women; therefore, it must be addressed in a personalized and comprehensive manner, as its management requires a multidisciplinary approach. This article aims to conduct a comprehensive literature review of endometriosis, not only as a pathophysiological condition but also as a significant factor impacting the social, nutritional, and mental well-being of those who experience it. Emphasis is placed on the importance of understanding and assessing the impact of the pathology to provide a better and more comprehensive approach, integrating various alternatives and strategic treatments for the factors involved in its development. The aim is to provide a complete overview of endometriosis, from its pathophysiology to its impact on the quality of life of patients, as well as a review of current treatment options, both pharmacological and alternative, in order to broaden the perspective on the pathology to improve the care of patients with this disease.
RESUMEN
Cyclic vomiting syndrome (CVS) is a disorder characterized by recurrent and unpredictable episodes of intense vomiting, interspersed with periods of apparent wellbeing. This disorder, which primarily affects children and adolescents but can persist into adulthood, has recently been the subject of extensive study and analysis in the medical literature. The aim of the present review is to examine the most important aspects of the epidemiology, pathophysiology, subtypes, diagnostic criteria, and current management of CVS. Even though the exact etiology remains unknown, genetic factors (polymorphisms), nervous system alterations and autonomic dysregulation, and environmental factors (use and abuse of cannabinoids) are postulated as possible triggers. CVS has significant diagnostic challenges, given that there is no specific test for confirming its presence. Thorough evaluation of symptoms and the ruling out of other possible causes of recurrent vomiting are required. Management of CVS typically involves a multidisciplinary approach. Pharmacologic options are explored, such as antiemetics and preventive medications, as well as behavioral and psychologic support therapies. Treatment personalization is essential, adapting it to the individual needs of each patient. Despite advances in the understanding of CVS, it remains a significant clinical challenge. This disorder impacts the quality of life of those affected and their families, underscoring the ongoing need for research and the development of more effective treatment strategies.
Asunto(s)
Vómitos , Humanos , Vómitos/terapia , Vómitos/etiología , Vómitos/fisiopatologíaRESUMEN
Cholesterol is crucial for the proper functioning of eukaryotic cells, especially neurons, which rely on cholesterol to maintain their complex structure and facilitate synaptic transmission. However, brain cells are isolated from peripheral cholesterol by the blood-brain barrier and mature neurons primarily uptake the cholesterol synthesized by astrocytes for proper function. This study aimed to investigate the effect of aging on cholesterol trafficking in astrocytes and its delivery to neurons. We found that aged astrocytes accumulated high levels of cholesterol in the lysosomal compartment, and this cholesterol buildup can be attributed to the simultaneous occurrence of two events: decreased levels of the ABCA1 transporter, which impairs ApoE-cholesterol export from astrocytes, and reduced expression of NPC1, which hinders cholesterol release from lysosomes. We show that these two events are accompanied by increased microR-33 in aged astrocytes, which targets ABCA1 and NPC1. In addition, we demonstrate that the microR-33 increase is triggered by oxidative stress, one of the hallmarks of aging. By coculture experiments, we show that cholesterol accumulation in astrocytes impairs the cholesterol delivery from astrocytes to neurons. Remarkably, we found that this altered transport of cholesterol could be alleviated through treatment with endocannabinoids as well as cannabidiol or CBD. Finally, according to data demonstrating that aged astrocytes develop an A1 phenotype, we found that cholesterol buildup is also observed in reactive C3+ astrocytes. Given that reduced neuronal cholesterol affects synaptic plasticity, the ability of cannabinoids to restore cholesterol transport from aged astrocytes to neurons holds significant implications in aging and inflammation.
Asunto(s)
Transportador 1 de Casete de Unión a ATP , Astrocitos , Cannabinoides , Colesterol , Lisosomas , Neuronas , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Animales , Colesterol/metabolismo , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Transportador 1 de Casete de Unión a ATP/metabolismo , Cannabinoides/farmacología , Cannabinoides/metabolismo , Células Cultivadas , Proteína Niemann-Pick C1 , Ratones , Envejecimiento/metabolismo , Técnicas de Cocultivo , Ratones Endogámicos C57BLRESUMEN
Chronic inflammation plays a crucial role in the onset and progression of pathologies like neurodegenerative and cardiovascular diseases, diabetes, and cancer, since tumor development and chronic inflammation are linked, sharing common signaling pathways. At least 20% of breast and colorectal cancers are associated with chronic inflammation triggered by infections, irritants, or autoimmune diseases. Obesity, chronic inflammation, and cancer interconnection underscore the importance of population-based interventions in maintaining healthy body weight, to disrupt this axis. Given that the dietary inflammatory index is correlated with an increased risk of cancer, adopting an anti-inflammatory diet supplemented with nutraceuticals may be useful for cancer prevention. Natural products and their derivatives offer promising antitumor activity with favorable adverse effect profiles; however, the development of natural bioactive drugs is challenging due to their variability and complexity, requiring rigorous research processes. It has been shown that combining anti-inflammatory products, such as non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and statins, with plant-derived products demonstrate clinical utility as accessible adjuvants to traditional therapeutic approaches, with known safety profiles. Pharmacological approaches targeting multiple proteins involved in inflammation and cancer pathogenesis emerge as a particularly promising option. Given the systemic and multifactorial nature of inflammation, comprehensive strategies are essential for long term success in cancer therapy. To gain insights into carcinogenic phenomena and discover diagnostic or clinically relevant biomarkers, is pivotal to understand genetic variability, environmental exposure, dietary habits, and TME composition, to establish therapeutic approaches based on molecular and genetic analysis. Furthermore, the use of endocannabinoid, cannabinoid, and prostamide-type compounds as potential therapeutic targets or biomarkers requires further investigation. This review aims to elucidate the role of specific etiological agents and mediators contributing to persistent inflammatory reactions in tumor development. It explores potential therapeutic strategies for cancer treatment, emphasizing the urgent need for cost-effective approaches to address cancer-associated inflammation.
RESUMEN
BACKGROUND: There is a need for novel treatments for neuroblastoma, despite the emergence of new biological and immune treatments, since refractory pediatric neuroblastoma is still a medical challenge. Phyto cannabinoids and their hemisynthetic derivatives have shown evidence supporting their anticancer potential. The aim of this research was to examine Phytocannabinoids or hemisynthetic cannabinoids, which reduce the SHSY-5Y, neuroblastoma cell line's viability. METHODS: Hexane and acetyl acetate extracts were produced starting with Cannabis sativa L. as raw material, then, 9-tetrahidrocannabinol, its acid counterpart and CBN were isolated. In addition, acetylated derivatives of THC and CBN were synthesized. The identification and purity of the chemicals was determined by High Performance Liquid Chromatography and 1H y 13C Magnetic Nuclear Resonance. Then, the capacity to affect the viability of SHSY-5Y, a neuroblastoma cell line, was examined using the resazurin method. Finally, to gain insight into the mechanism of action of the extracts, phytocannabinoids and acetylated derivatives on the examined cells, a caspase 3/7 determination was performed on cells exposed to these compounds. RESULTS: The structure and purity of the isolated compounds was demonstrated. The extracts, the phytocannabinoids and their acetylated counterparts inhibited the viability of the SHSY 5Y cells, being CBN the most potent of all the tested molecules with an inhibitory concentration of 50 percent of 9.5 µM. CONCLUSION: Each of the evaluated molecules exhibited the capacity to activate caspases 3/7, indicating that at least in part, the cytotoxicity of the tested phytocannabinoids and their hemi-synthetic derivatives is mediated by apoptosis.
Asunto(s)
Cannabinoides , Cannabis , Caspasa 3 , Supervivencia Celular , Neuroblastoma , Extractos Vegetales , Humanos , Cannabis/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Línea Celular Tumoral , Neuroblastoma/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 3/efectos de los fármacos , Cannabinoides/farmacología , Cannabinoides/química , Caspasa 7/metabolismo , Apoptosis/efectos de los fármacos , Acetilación/efectos de los fármacos , Cromatografía Líquida de Alta PresiónRESUMEN
There is growing interest in using cannabinoids across various clinical scenarios, including pain medicine, leading to the disregard of regulatory protocols in some countries. Legislation has been implemented in Brazil, specifically in the state of São Paulo, permitting the distribution of cannabinoid products by health authorities for clinical purposes, free of charge for patients, upon professional prescription. Thus, it is imperative to assess the existing evidence regarding the efficacy and safety of these products in pain management. In light of this, the São Paulo State Society of Anesthesiology (SAESP) established a task force to conduct a narrative review on the topic using the Delphi method, requiring a minimum agreement of 60% among panelists. The study concluded that cannabinoid products could potentially serve as adjuncts in pain management but stressed the importance of judicious prescription. Nevertheless, this review advises against their use for acute pain and cancer-related pain. In other clinical scenarios, established treatments should take precedence, particularly when clinical protocols are available, such as in neuropathic pain. Only patients exhibiting poor therapeutic responses to established protocols or demonstrating intolerance to recommended management may be considered as potential candidates for cannabinoids, which should be prescribed by physicians experienced in handling these substances. Special attention should be given to individual patient characteristics and the likelihood of drug interactions.
Asunto(s)
Cannabinoides , Manejo del Dolor , Humanos , Cannabinoides/efectos adversos , Cannabinoides/uso terapéutico , Brasil , Manejo del Dolor/métodos , Anestesiología , Sociedades Médicas , Técnica Delphi , Dolor Agudo/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate the in vitro antimicrobial and antibiofilm properties and the immune modulatory activity of cannabidiol (CBD) and cannabigerol (CBG) on oral bacteria and periodontal ligament fibroblasts (PLF). METHODS: Cytotoxicity was assessed by propidium iodide flow cytometry on fibroblasts derived from the periodontal ligament. The minimum inhibitory concentration (MIC) of CBD and CBG for S. mutans and C. albicans and the metabolic activity of a subgingival 33-species biofilm under CBD and CBG treatments were determined. The Quantification of cytokines was performed using the LEGENDplex kit (BioLegend, Ref 740930, San Diego, CA, USA). RESULTS: CBD-treated cell viability was greater than 95%, and for CBG, it was higher than 88%. MIC for S. mutans with CBD was 20 µM, and 10 µM for CBG. For C. albicans, no inhibitory effect was observed. Multispecies biofilm metabolic activity was reduced by 50.38% with CBD at 125 µg/mL (p = 0.03) and 39.9% with CBG at 62 µg/mL (p = 0.023). CBD exposure at 500 µg/mL reduced the metabolic activity of the formed biofilm by 15.41%, but CBG did not have an effect. CBG at 10 µM caused considerable production of anti-inflammatory mediators such as TGF-ß and IL-4 at 12 h. CBD at 10 µM to 20 µM produced the highest amount of IFN-γ. CONCLUSION: Both CBG and CBD inhibit S. mutans; they also moderately lower the metabolic activity of multispecies biofilms that form; however, CBD had an effect on biofilms that had already developed. This, together with the production of anti-inflammatory mediators and the maintenance of the viability of mammalian cells from the oral cavity, make these substances promising for clinical use and should be taken into account for future studies.
RESUMEN
Nowadays, the higher peak capacity achievable by comprehensive two-dimensional liquid chromatography (LC×LC) for the analysis of vegetal samples is well-recognized. In addition, numerous compounds may be present in very different amounts. Cannabinoids and terpenes represent the main components of Cannabis sativa inflorescence samples, whose quantities are relevant for many application purposes. The analyses of both families are performed by different methods, at least two different separation methodologies, mainly according to their chemical characteristics and concentration levels. In this work, concentration differences and sample complexity issues were addressed using an LC×LC method that incorporates an optimized modulation strategy, namely smart active modulation, for the simultaneous analysis of cannabinoids and terpenes. The system was built by interposing an active flow splitter pump between both dimensions. This set up aimed to exploit the known advantages of LC×LC. In addition, here we proposed to use the splitter pump for online control over the splitting ratio to facilitate the selective dilution of different eluted fractions containing compounds with highly different concentrations. This work represents the first application and demonstration of smart active modulation (SAM) in LC×LC to simultaneously determine analytes with significant differences in concentration levels present in complex samples. The proposed method was tested with eight different strains, from which fingerprints were taken, and numerous cannabinoids and terpenes were identified in these samples. With this strategy, between 49 and 54 peaks were obtained in the LC×LC chromatograms corresponding to different strains. THCA-A was the main component in six strains, while CBDA was the main component in the other two strains. The main terpenes found were myrcene (in five strains), limonene (in two strains), and humulene (in one strain). Additionally, numerous other cannabinoids and terpenes were identified in these samples, providing valuable compositional information for growers, as well as medical and recreational users. The SAM strategy here proposed is simple and it can be extended to other complex matrices.
Asunto(s)
Cannabinoides , Cannabis , Humanos , Cannabinoides/análisis , Cannabis/química , Terpenos/análisis , Inflorescencia/química , Cromatografía de Gases y Espectrometría de Masas , Cromatografía Líquida de Alta PresiónRESUMEN
Studies have demonstrated the neuroprotective effect of cannabidiol (CBD) and other Cannabis sativa L. derivatives on diseases of the central nervous system caused by their direct or indirect interaction with endocannabinoid system-related receptors and other molecular targets, such as the 5-HT1A receptor, which is a potential pharmacological target of CBD. Interestingly, CBD binding with the 5-HT1A receptor may be suitable for the treatment of epilepsies, parkinsonian syndromes and amyotrophic lateral sclerosis, in which the 5-HT1A serotonergic receptor plays a key role. The aim of this review was to provide an overview of cannabinoid effects on neurological disorders, such as epilepsy, multiple sclerosis and Parkinson's diseases, and discuss their possible mechanism of action, highlighting interactions with molecular targets and the potential neuroprotective effects of phytocannabinoids. CBD has been shown to have significant therapeutic effects on epilepsy and Parkinson's disease, while nabiximols contribute to a reduction in spasticity and are a frequent option for the treatment of multiple sclerosis. Although there are multiple theories on the therapeutic potential of cannabinoids for neurological disorders, substantially greater progress in the search for strong scientific evidence of their pharmacological effectiveness is needed.
Asunto(s)
Cannabidiol , Cannabinoides , Epilepsia , Trastornos Mentales , Esclerosis Múltiple , Enfermedad de Parkinson , Humanos , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Enfermedad de Parkinson/tratamiento farmacológico , Esclerosis Múltiple/tratamiento farmacológico , Receptor de Serotonina 5-HT1A/uso terapéutico , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Epilepsia/tratamiento farmacológico , Trastornos Mentales/tratamiento farmacológico , ComorbilidadRESUMEN
Trigeminal neuralgia (TN) is an intense and debilitating orofacial pain. The gold standard treatment for TN is carbamazepine. This antiepileptic drug provides pain relief with limited efficacy and side effects. To study the antinociceptive potential of cannabidiol (CBD) and its fluorinated analog PECS-101 (former HUF-101), we induced unilateral chronic constriction injury of the infraorbital nerve (IoN-CCI) in male Wistar rats. Seven days of treatment with CBD (30 mg/kg), PECS-101 (3, 10, and 30 mg/kg), or carbamazepine (10 and 30 mg/kg) reduced allodynia and hyperalgesia responses. Unlike carbamazepine, CBD and PECS-101 did not impair motor activity. The relief of the hypersensitive reactions has been associated with transient receptor potential vanilloid type 1 (TRPV1) modulation in the trigeminal spinal nucleus. CBD (30 mg/kg) and PECS-101 (10 and 30 mg/kg) reversed the increased expression of TRPV1 induced by IoN-CCI in this nucleus. Using a pharmacological strategy, the combination of the selective TRPV1 antagonist (capsazepine-CPZ - 5 mg/kg) with sub-effective doses of CBD (3 and 10 mg/kg) is also able to reverse the IoN-CCI-induced allodynia and hyperalgesia responses. This effect was accompanied by reduced TRPV1 protein expression in the trigeminal spinal nucleus. Our results suggest that CBD and PECS-101 may benefit trigeminal neuralgia without motor coordination impairments. PECS-101 is more potent against the hypernociceptive and motor impairment induced by TN compared to CBD and carbamazepine. The antinociceptive effect of these cannabinoids is partially mediated by TRPV1 receptors in the caudal part of the trigeminal spinal nucleus, the first central station of orofacial pain processing.
Asunto(s)
Cannabidiol , Neuralgia , Neuralgia del Trigémino , Animales , Masculino , Ratas , Analgésicos/farmacología , Analgésicos/uso terapéutico , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Carbamazepina/farmacología , Carbamazepina/uso terapéutico , Dolor Facial/metabolismo , Hiperalgesia/tratamiento farmacológico , Neuralgia/tratamiento farmacológico , Ratas Wistar , Neuralgia del Trigémino/complicaciones , Neuralgia del Trigémino/tratamiento farmacológicoRESUMEN
BACKGROUND: Natural and synthetic cannabinoids are being used worldwide to treat various symptoms in cancer patients. This study aims to map the therapeutic benefits and adverse effects associated with the use of cannabis-based drugs in these outcomes. METHODS: Following Joanna Briggs Institute guidelines a scoping review was conducted. The study protocol was available in the Open Science Framework public repository. An extensive search strategy involving databases like Cochrane Library, Embase, CINAHL, Medline/PubMed, Lilacs, Google Scholar, and Open Gray for gray literature analysis was executed by a skilled librarian. The inclusion criteria were primary studies (observational and randomized) that evaluated the efficacy and safety of cannabinoids in cancer patients. The review encompassed studies of diverse designs, publication years, and types, as long as they addressed cannabinoids' impact in oncology. RESULTS: Twenty-nine (82.86%) out of total of 35 were randomized and 6 (14.14%) were non-randomized. About 57.1% of studies utilized registered products as interventions, with THC being the most natural cannabinoid cited in variable doses and administration routes. Moreover, 62.85% of studies specified the cancer types (breast, lung, sarcomas, hematological and reproductive system), while only one study detailed cancer staging. The evaluated outcomes encompassed nausea and vomiting (77.14%), appetite (11.43%), pain (8.57%), and tumor regression (2.86%) across different proportions of studies. CONCLUSION: Cannabinoids show promise in managing pain, emesis, and anorexia/cachexia linked to cancer progression. New randomized clinical trials with a larger number of participants and observational studies on long-term safety are crucial to affirm their medicinal utility for cancer patients unresponsive to conventional drugs.
Asunto(s)
Cannabinoides , Marihuana Medicinal , Neoplasias , Humanos , Marihuana Medicinal/uso terapéutico , Marihuana Medicinal/efectos adversos , Neoplasias/tratamiento farmacológico , Cannabinoides/uso terapéutico , Cannabinoides/efectos adversos , Vómitos/inducido químicamente , Ensayos Clínicos Controlados Aleatorios como Asunto , Náusea/inducido químicamenteRESUMEN
Cisplatin is a platinum-based chemotherapy drug widely used to treat various solid tumours. Although it is effective in anti-cancer therapy, many patients develop peripheral neuropathy during and after cisplatin treatment. Peripheral neuropathy results from lesions or diseases in the peripheral somatosensory nervous system and is a significant cause of debilitation and suffering in patients. In recent years, preclinical studies have been conducted to elucidate the mechanisms involved in chemotherapy-induced peripheral neuropathic pain, as well as to promote new therapeutic targets since current treatments are ineffective and are associated with adverse effects. G-protein coupled receptors and ion channels play a significant role in pain processing and may represent promising targets for improving the management of cisplatin-induced neuropathic pain. This review describes the role of G protein-coupled receptors and ion channels in cisplatin-induced pain, analysing preclinical experimental studies that investigated the role of each receptor subtype in the modulation of cisplatin-induced pain.