Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

Devinsky, Orrin; Cilio, Maria Roberta; Cross, Helen; Fernández‐Ruiz, Javier; French, Jacqueline A.; Hill, Charlotte L; Katz, Russell; Marzo, Vincenzo Di; Jutras‐Aswad, Didier; Notcutt, William; Martı́nez-Orgado, José; Robson, Philip; Rohrback, Brian G.; Thiele, Elizabeth A.; Whalley, Benjamin J.; Friedman, Daniel J.

doi:10.1111/epi.12631

Cited by 852 publications

(704 citation statements)

References 68 publications

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“…The 2 major phyto-cannabinoid constituents with central nervous system activity are THC, responsible for the euphoric and mind-altering effects, and CBD, which lacks these psychoactive effects. Preclinical and clinical studies show CBD possesses a wide range of therapeutic properties, including antipsychotic, analgesic, neuroprotective, anticonvulsant, antiemetic, antioxidant, anti-inflammatory, antiarthritic, and antineoplastic properties (see [11,12,[16][17][18][19] for reviews). A review of potential side effects in humans found that CBD was well tolerated across a wide dose range, up to 1500 mg/day (orally), with no reported psychomotor slowing, negative mood effects, or vital sign abnormalities noted [20].…”

Section: Cbd Pharmacology Relevant To Anxiety General Pharmacology Anmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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Section: Cbd Pharmacology Relevant To Anxiety General Pharmacology Anmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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“…Cannabis has a long anecdotal history of use for the treatment of epilepsy, although, confusingly, significant reports of proconvulsant effects are also present in the literature (for a detailed review see [124]). CBD has a more consistent record and has been repeatedly shown to exert anticonvulsant effects in a variety of preclinical models and small, but flawed, clinical trials but the mechanism through which these effects are exerted remains to be determined [124]. Here, we consider the potential role that the pharmacological targets identified in part 1 can play in epilepsy and its symptoms.…”

Section: Epilepsymentioning

confidence: 99%

“…However, exploitation of adenosine agonists as epilepsy treatments has been unsuccessful owing to the very narrow therapeutic window that can result in significant adverse events. In particular, those affecting the cardiovascular system in humans and in animal models, which suggests that direct agonism of A 1 /A 2 receptors by CBD is unlikely and, as such, indirect elevation of local adenosine levels is not only more plausible but could represent a viable mechanism underlying CBD's anticonvulsant effects [124,155].…”

Section: Cbd Receptor Targets In Epilepsymentioning

confidence: 99%

Molecular Targets of Cannabidiol in Neurological Disorders

Bih

Chen

Nunn³

et al. 2015

Neurotherapeutics

447

323

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Cannabis has a long history of anecdotal medicinal use and limited licensed medicinal use. Until recently, alleged clinical effects from anecdotal reports and the use of licensed cannabinoid medicines are most likely mediated by tetrahydrocannabinol by virtue of: 1) this cannabinoid being present in the most significant quantities in these preparations; and b) the proportion:potency relationship between tetrahydrocannabinol and other plant cannabinoids derived from cannabis. However, there has recently been considerable interest in the therapeutic potential for the plant cannabinoid, cannabidiol (CBD), in neurological disorders but the current evidence suggests that CBD does not directly interact with the endocannabinoid system except in vitro at supraphysiological concentrations. Thus, as further evidence for CBD's beneficial effects in neurological disease emerges, there remains an urgent need to establish the molecular targets through which it exerts its therapeutic effects. Here, we conducted a systematic search of the extant literature for original articles describing the molecular pharmacology of CBD. We critically appraised the results for the validity of the molecular targets proposed. Thereafter, we considered whether the molecular targets of CBD identified hold therapeutic potential in relevant neurological diseases. The molecular targets identified include numerous classical ion channels, receptors, transporters, and enzymes. Some CBD effects at these targets in in vitro assays only manifest at high concentrations, which may be difficult to achieve in vivo, particularly given CBD's relatively poor bioavailability. Moreover, several targets were asserted through experimental designs that demonstrate only correlation with a given target rather than a causal proof. When the molecular targets of CBD that were physiologically plausible were considered for their potential for exploitation in neurological therapeutics, the results were variable. In some cases, the targets identified had little or no established link to the diseases considered. In others, molecular targets of CBD were entirely consistent with those already actively exploited in relevant, clinically used, neurological treatments. Finally, CBD was found to act upon a number of targets that are linked to neurological therapeutics but that its actions were not consistent withmodulation of such targets that would derive a therapeutically beneficial outcome. Overall, we find that while >65 discrete molecular targets have been reported in the literature for CBD, a relatively limited number represent plausible targets for the drug's action in neurological disorders when judged by the criteria we set. We conclude that CBD is very unlikely to exert effects in neurological diseases through modulation of the endocannabinoid system. Moreover, a number of other molecular targets of CBD reported in the literature are unlikely to be of relevance owing to effects only being observed at supraphysiological concentrations. Of interest and after excludin...

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“…Therefore, the preclinical evidence collected so far is highly suggestive of important benefits to be reached in newborns affected by HI encephalopathy with cannabinoid-based therapies, in particular with the nonpsychoactive phytocannabinoid CBD, which appears to be an adequate therapeutic option for the treatment of neonatal and infantile disorders. In fact, CBD has already been formulated as Epidiolex (GWPharma) and received the orphan designation from US and European regulatory agencies for the treatment infantile refractory epilepsies [76]. It may be a good choice for investigating the benefits of cannabinoid-based therapies in neonatal ischemia at the clinical level, alone or in combination with hypothermia, which is the only approved therapeutic strategy for this pathological condition.…”

Section: Cannabinoids and Brain Damage In The Immature Brain: Neonatamentioning

confidence: 99%

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

2015

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Cannabinoids form a singular family of plantderived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid targets) in key cellular substrates (e.g., neurons, glial cells, and neural progenitor cells). This potential is promising for acute and chronic neurodegenerative pathological conditions. In this review, we will collect all experimental evidence, mainly obtained at the preclinical level, supporting that different cannabinoid compounds may be neuroprotective in adult and neonatal ischemia, brain trauma, Alzheimer's disease, Parkinson's disease, Huntington's chorea, and amyotrophic lateral sclerosis. This increasing experimental evidence demands a prompt clinical validation of cannabinoid-based medicines for the treatment of all these disorders, which, at present, lack efficacious treatments for delaying/arresting disease progression, despite the fact that the few clinical trials conducted so far with these medicines have failed to demonstrate beneficial effects.

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Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders

Cited by 852 publications

References 68 publications

Cannabidiol as a Potential Treatment for Anxiety Disorders

Cannabidiol as a Potential Treatment for Anxiety Disorders

Molecular Targets of Cannabidiol in Neurological Disorders

Cannabinoids in Neurodegenerative Disorders and Stroke/Brain Trauma: From Preclinical Models to Clinical Applications

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