Cannabis therapy in neurological disorders: Recent advances and perspectives (original) (raw)
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Cannabis Therapeutics and the Future of Neurology
Frontiers in Integrative Neuroscience
Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabisbased medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB 1 and CB 2 (tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptorgamma (PPARγ; THCA), 5-HT 1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment.
Therapeutic properties of cannabinoid drugs and marijuana in several disorders: A narrative review
Background. Anti-inflammatory, analgesic, anticonvulsant, and other effects have been attributed to cannabis , and so it has been widely used to treat several diseases. Objective. To assess the use and therapeutic effects of cannabinoid drugs and the cannabis plant in several diseases. Method. We carried out a narrative review of the literature that has reported the use of the cannabis plant (marijuana) and cannabinoid drugs (nabilone, cannabinol and dronabinol, among others). We conducted a search in Medline, Cochrane, SciELO and other web sites. Clinical, controlled, double-blind and randomized studies were included. The route of administration and the cannabinoid drugs used were assessed too. Results. Thirty-four studies were included. Nabilone was the cannabinoid drug more commonly used (12 studies), followed by delta-9-tetrahydrocannab-inol (THC) (11 studies). It was also found that the marijuana plant and cannabinoid drugs were used to treat many symptoms or diseases. Two studies were reported for Gilles de la Tourette's syndrome. Discussion and conclusion. Many scientific studies on the marijuana plant and cannabinoid drugs conclude that these are not as effective as conventional medications and thus their benefits should be taken with caution.
Revista de Pesquisa Cuidado é Fundamental Online
Objetivo: apresentar o estado da arte das publicações expressas na literatura cientifica mundial sobre a temática, bem como identificar os benefícios terapêuticos da Cannabis medicinal no tratamento dos sintomas das doenças neurodegenerativas especificamente doenças de Parkinson, esclerose múltipla e Alzheimer. Método: trata-se de uma revisão integrativa da literatura, cuja busca de dados foi realizada nas bibliotecas virtuais. Web of Science, Scopus, Medline, Lilacs, Cochrane Library e Scielo no período de agosto a outubro de 2021. Resultados: foram encontrados 158 artigos. Vinte e tres artigos foram selecionados para serem lidos na íntegra e 8 atenderam aos critérios desta revisão. Conclusão: as evidências mostram que embora cada vez mais prescritos ou autorizados, a cannabis medicinal ou os Canabinóides para a doenças neurodegenerativas continuam a ser controversos para muitos médicos.
Behavioural Neurology
Cannabidiol (CBD), derived from Cannabis sativa, has gained remarkable attention for its potential therapeutic applications. This thorough analysis explores the increasing significance of CBD in treating neurological conditions including epilepsy, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease, which present major healthcare concerns on a worldwide scale. Despite the lack of available therapies, CBD has been shown to possess a variety of pharmacological effects in preclinical and clinical studies, making it an intriguing competitor. This review brings together the most recent findings on the endocannabinoid and neurotransmitter systems, as well as anti-inflammatory pathways, that underlie CBD’s modes of action. Synthesized efficacy and safety assessments for a range of neurological illnesses are included, covering human trials, in vitro studies, and animal models. The investigation includes how CBD could protect neurons, control neuroinflammation, fend off oxidativ...
Neurology, 2014
Objective: To determine the efficacy of medical marijuana in several neurologic conditions. Methods: We performed a systematic review of medical marijuana (1948-November 2013) to address treatment of symptoms of multiple sclerosis (MS), epilepsy, and movement disorders. We graded the studies according to the American Academy of Neurology classification scheme for therapeutic articles. Results: Thirty-four studies met inclusion criteria; 8 were rated as Class I. Conclusions: The following were studied in patients with MS: (1) Spasticity: oral cannabis extract (OCE) is effective, and nabiximols and tetrahydrocannabinol (THC) are probably effective, for reducing patientcentered measures; it is possible both OCE and THC are effective for reducing both patient-centered and objective measures at 1 year. (2) Central pain or painful spasms (including spasticity-related pain, excluding neuropathic pain): OCE is effective; THC and nabiximols are probably effective. (3) Urinary dysfunction: nabiximols is probably effective for reducing bladder voids/day; THC and OCE are probably ineffective for reducing bladder complaints. (4) Tremor: THC and OCE are probably ineffective; nabiximols is possibly ineffective. (5) Other neurologic conditions: OCE is probably ineffective for treating levodopa-induced dyskinesias in patients with Parkinson disease. Oral cannabinoids are of unknown efficacy in non-chorea-related symptoms of Huntington disease, Tourette syndrome, cervical dystonia, and epilepsy. The risks and benefits of medical marijuana should be weighed carefully. Risk of serious adverse psychopathologic effects was nearly 1%. Comparative effectiveness of medical marijuana vs other therapies is unknown for these indications. Neurology ® 2014;82:1556-1563 GLOSSARY AAN 5 American Academy of Neurology; AE 5 adverse effect; CBD 5 cannabidiol; CI 5 confidence interval; CRS 5 category rating scale; HD 5 Huntington disease; ITT 5 intention-to-treat; MS 5 multiple sclerosis; NRS 5 numeric rating score; OCE 5 oral cannabis extract; THC 5 D-9-tetrahydrocannabinol; UHDRS 5 Unified Huntington's Disease Rating Scale; UPDRS 5 Unified Parkinson's Disease Rating Scale; VAS 5 visual analog scale.
Future of Cannabis and Cannabinoids in Therapeutics
Journal of Cannabis Therapeutics, 2004
This study reviews human clinical experience to date with several synthetic cannabinoids, including nabilone, levonantradol, ajulemic acid (CT3), dexanabinol (HU-211), HU-308, and SR141716 (Rimonabant ®). Additionally, the concept of "clinical endogenous cannabinoid deficiency" is explored as a possible factor in migraine, idiopathic bowel disease, fibromyalgia and other clinical pain states. The concept of analgesic synergy of cannabinoids and opioids is addressed. A cannabinoid-mediated improvement in night vision at the retinal level is discussed, as well as its potential application to treatment of retinitis pigmentosa and other conditions. Additionally noted is the role of cannabinoid treatment in neuroprotection and its application to closed head injury, cerebrovascular accidents, and CNS degenerative diseases including Alzheimer, Huntington, Parkinson diseases and ALS. Excellent clinical results employing cannabis based medicine extracts (CBME) in spasticity and spasms of MS suggests extension of such treatment to other spasmodic and dystonic conditions. Finally, controversial areas of cannabinoid treatment in obstetrics, gynecology and pediatrics are addressed along with a rationale for such interventions.
British Journal of …, 2012
Cannabidiol (CBD) is a phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with D 9 -tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like D 9 -tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB 2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
The therapeutic potential of cannabis
The Lancet Neurology, 2003
Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.
Review: Cannabinoids as Medicinals
Current Addiction Reports
Purpose of review There have been many debates, discussions, and published writings about the therapeutic value of cannabis plant and the hundreds of cannabinoids it contains. Many states and countries have attempted, are attempting, or have already passed bills to allow legal use of cannabinoids, especially cannabidiol (CBD), as medicines to treat a wide range of clinical conditions without having been approved by a regulatory body. Therefore, by using PubMed and Google Scholar databases, we have reviewed published papers during the past 30 years on cannabinoids as medicines and comment on whether there is sufficient clinical evidence from well-designed clinical studies and trials to support the use of CBD or any other cannabinoids as medicines. Recent findings Current research shows that CBD and other cannabinoids currently are not ready for formal indications as medicines to treat a wide range of clinical conditions as promoted except for several exceptions including limited use of CBD for treating two rare forms of epilepsy in young children and CBD in combination with THC for treating multiplesclerosis-associated spasticity. Summary Research indicates that CBD and several other cannabinoids have potential to treat multiple clinical conditions, but more preclinical, and clinical studies and clinical trials, which follow regulatory guidelines, are needed to formally recommend CBD and other cannabinoids as medicines.