The Biology and Potential Therapeutic Effects of Cannabidiol

Aug 23 2016 0 Comments Tags: Learn-More

“Cannabidiol: Barriers to Research and Potential Medical Benefits”

Mr. Chairman, Ms. Chairwoman, and Members of the Senate Drug Caucus, thank you for inviting the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), to participate in this hearing to share what we know about the biology and the potential therapeutic effects of cannabidiol (CBD), one of the main active chemical compounds found in marijuana. In light of the rapidly evolving interest in the potential use of marijuana and its derivative compounds for medical purposes, it is important to take stock of what we know and do not know about the therapeutic potential of CBD.


To date, 23 states and the District of Columbia have passed laws allowing marijuana to be used for a variety of medical conditions. Fifteen additional states have enacted laws intended to allow access to CBD oil and/or high-CBD strains of marijuana. Interest in the potential therapeutic effects of CBD has been growing rapidly, partially in response to media attention surrounding the use of CBD oil in young children with intractable seizure disorders including Dravet syndrome and Lennox-Gastaut syndrome. While there are promising preliminary data, the scientific literature is currently insufficient to either prove or disprove the efficacy and safety of CBD in patients with epilepsy.i and further clinical evaluation is warranted. In addition to epilepsy, the therapeutic potential of CBD is currently being explored for a number of indications including anxiety disorders, substance use disorders, schizophrenia, cancerpain, inflammatory diseases and others. My testimony will provide an overview of what the science tells us about the therapeutic potential of CBD and of the ongoing research supported by NIH in this area.

CBD Biology and Therapeutic Rationale

CBD is one of more than 80 active cannabinoid chemicals in the marijuana plant.ii Unlike the main psychoactive cannabinoid in marijuana, tetrahydrocannabinol (THC), CBD does not produce euphoria or intoxication.iii,iv,v Cannabinoids have their effect mainly by interacting with specific receptors on cells in the brain and body: the CB1 receptor, found on neurons and glial cells in various parts of the brain, and the CB2 receptor, found mainly in the body’s immune system. The euphoric effects of THC are caused by its activation of CB1 receptors. CBD has a very low affinity for these receptors (100 fold less than THC) and when it binds it produces little to no effect. There is also growing evidence that CBD acts on other brain signaling systems, and that these actions may be important contributors to its therapeutic effects.ii

Preclinical and Clinical Evidence

Rigorous clinical studies are still needed to evaluate the clinical potential of CBD for specific conditions.i However, pre-clinical research (including both cell culture and animal models) has shown CBD to have a range of effects that may be therapeutically useful, including anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties.

Anti-Seizure Effects

A number of studies over the last two decades or more have reported that CBD has anti-seizure activity, reducing the severity of seizures in animal,vii In addition, there have been a number of case studies and anecdotal reports suggesting that CBD may be effective in treating children with drug-resistant epilepsy.viii,ix,x However, there have only been a few small randomized clinical trials examining the efficacy of CBD as a treatment for epilepsy; the total number of subjects enrolled in these studies was 48. Three of the four studies reported positive results, including decreased frequency of seizures. However, the studies suffered from significant design flaws, including failure to fully quantify baseline seizure frequency, inadequate statistical analysis, and a lack of sufficient detail to adequately evaluate and interpret the findings.viii Therefore, the currently available information is insufficient to draw firm conclusions regarding the efficacy of CBD as a treatment for epilepsy; a recent Cochrane review concluded, there is a need for “a series of properly designed, high quality, and adequately powered trials.”xi

NIDA is currently collaborating with the National Institute on Neurological Disorders and Stroke to evaluate CBD in animal models of epilepsy in order to understand the underlying mechanisms and optimize the conditions under which CBD may treat seizure disorders, and determine whether it works synergistically with other anti-seizure medications. In addition, clinical trials are currently underway by GW Pharmaceuticals, testing the efficacy of Epidiolex, a purified CBD extract, for treatment of pediatric epilepsy.

Neuroprotective and Anti-Inflammatory Effects

CBD has also been shown to have neuroprotective properties in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s,xii,xiii,xiv stroke,xv glutamate toxicity,xvi multiple sclerosis (MS),xvii Parkinson’s disease,xviii and neurodegeneration caused by alcohol abuse.xix Nabiximols (trade name Sativex), which contains THC and CBD in roughly equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity associated with MS. It has not been approved in the United States, but clinical trials are ongoing, and two recent studies reported that nabiximols reduced the severity of spasticity in MS patients.xx,xxi There have been limited clinical trials to assess the potential efficacy of CBD for the other indications highlighted; however, a recent small double-blind trial in patients with Parkinson’s disease found the CBD improved quality-of-life scores.xxii

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