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Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

ABSTRACT: To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. ?(9) -Tetrahydrocannabinol (?(9) -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis. Cannabis and ?(9) -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of ?(9) -THC limit tolerability. CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models. The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the ?3 and ?1 glycine receptors. CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive. More recent anecdotal reports of high-ratio CBD:?(9) -THC medical marijuana have claimed efficacy, but studies were not controlled. CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy. However, we lack data from well-powered double-blind randomized, controlled studies on the efficacy of pure CBD for any disorder. Initial dose-tolerability and double-blind randomized, controlled studies focusing on target intractable epilepsy populations such as patients with Dravet and Lennox-Gastaut syndromes are being planned. Trials in other treatment-resistant epilepsies may also be warranted. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

SUBMITTER: Devinsky O

PROVIDER: S-EPMC4707667 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

Devinsky Orrin O Cilio Maria Roberta MR Cross Helen H Fernandez-Ruiz Javier J French Jacqueline J Hill Charlotte C Katz Russell R Di Marzo Vincenzo V Jutras-Aswad Didier D Notcutt William George WG Martinez-Orgado Jose J Robson Philip J PJ Rohrback Brian G BG Thiele Elizabeth E Whalley Benjamin B Friedman Daniel D

Epilepsia 20140522 6

To present a summary of current scientific evidence about the cannabinoid, cannabidiol (CBD) with regard to its relevance to epilepsy and other selected neuropsychiatric disorders. We summarize the presentations from a conference in which invited participants reviewed relevant aspects of the physiology, mechanisms of action, pharmacology, and data from studies with animal models and human subjects. Cannabis has been used to treat disease since ancient times. Δ(9) -Tetrahydrocannabinol (Δ(9) -THC ...[more]

PMID: 24854329

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Project description:Drug treatments available for the management of substance use disorders (SUD) present multiple limitations in efficacy, lack of approved treatments or alarming relapse rates. These facts hamper the clinical outcome and the quality of life of the patients supporting the importance to develop new pharmacological agents. Lately, several reports suggest that cannabidiol (CBD) presents beneficial effects relevant for the management of neurological disorders such as epilepsy, multiple sclerosis, Parkinson's, or Alzheimer's diseases. Furthermore, there is a large body of evidence pointing out that CBD improves cognition, neurogenesis and presents anxiolytic, antidepressant, antipsychotic, and neuroprotective effects suggesting potential usefulness for the treatment of neuropsychiatric diseases and SUD. Here we review preclinical and clinical reports regarding the effects of CBD on the regulation of the reinforcing, motivational and withdrawal-related effects of different drugs of abuse such as alcohol, opioids (morphine, heroin), cannabinoids, nicotine, and psychostimulants (cocaine, amphetamine). Furthermore, a special section of the review is focused on the neurobiological mechanisms that might be underlying the 'anti-addictive' action of CBD through the regulation of dopaminergic, opioidergic, serotonergic, and endocannabinoid systems as well as hippocampal neurogenesis. The multimodal pharmacological profile described for CBD and the specific regulation of addictive behavior-related targets explains, at least in part, its therapeutic effects on the regulation of the reinforcing and motivational properties of different drugs of abuse. Moreover, the remarkable safety profile of CBD, its lack of reinforcing properties and the existence of approved medications containing this compound (Sativex®, Epidiolex®) increased the number of studies suggesting the potential of CBD as a therapeutic intervention for SUD. The rising number of publications with substantial results on the valuable therapeutic innovation of CBD for treating SUD, the undeniable need of new therapeutic agents to improve the clinical outcome of patients with SUD, and the upcoming clinical trials involving CBD endorse the relevance of this review.

Project description:The use of cannabidiol (CBD) for therapeutic purposes is receiving considerable attention, with speculation that CBD can be useful in a wide range of conditions. Only one product, a purified form of plant-derived CBD in solution (Epidiolex), is approved for the treatment of seizures in patients with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex. Appraisal of the therapeutic evidence base for CBD is complicated by the fact that CBD products sometimes have additional phytochemicals (like tetrahydrocannabinol (THC)) present, which can make the identification of the active pharmaceutical ingredient (API) in positive studies difficult. The aim of the present review is to critically review clinical studies using purified CBD products only, in order to establish the upcoming indications for which purified CBD might be beneficial. The areas in which there is the most clinical evidence to support the use of CBD are in the treatment of anxiety (positive data in 7 uncontrolled studies and 17 randomised controlled trials (RCTs)), psychosis and schizophrenia (positive data in 1 uncontrolled study and 8 RCTs), PTSD (positive data in 2 uncontrolled studies and 4 RCTs) and substance abuse (positive data in 2 uncontrolled studies and 3 RCTs). Seven uncontrolled studies support the use of CBD to improve sleep quality, but this has only been verified in one small RCT. Limited evidence supports the use of CBD for the treatment of Parkinson's (3 positive uncontrolled studies and 2 positive RCTs), autism (3 positive RCTs), smoking cessation (2 positive RCTs), graft-versus-host disease and intestinal permeability (1 positive RCT each). Current RCT evidence does not support the use of purified oral CBD in pain (at least as an acute analgesic) or for the treatment of COVID symptoms, cancer, Huntington's or type 2 diabetes. In conclusion, published clinical evidence does support the use of purified CBD in multiple indications beyond epilepsy. However, the evidence base is limited by the number of trials only investigating the acute effects of CBD, testing CBD in healthy volunteers, or in very small patient numbers. Large confirmatory phase 3 trials are required in all indications.

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Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

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Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

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