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.
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 models.vi,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.
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,xvglutamate 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
There have been multiple clinical trials demonstrating the efficacy of nabiximols on central and peripheral neuropathic pain, rheumatoid arthritis, and cancer pain.xxiii In addition, nabiximols is currently approved in Canada for the treatment of central neuropathic pain in MS and cancer pain unresponsive to opioid therapy. However, the current evidence suggests that the analgesia is mediated by THC and it is unclear whether CBD contributes to the therapeutic effects.xxiv THC alone has been shown to reduce pain;xxv,xxvi we are unaware of clinical studies that have explored the efficacy of CBD alone on pain. However, the anti-inflammatory properties of CBD (discussed above) could be predicted to play a role in the analgesic effects of nabiximols. Recent research has also suggested that cannabinoids and opioids have different mechanisms for reducing pain and that their effects may be additive, which suggests that combination therapies may be developed that may have reduced risks compared to current opioid therapies. However, this work is very preliminary.xxvii
In addition to the research on the use of cannabinoids in palliative treatments for cancer—reducing pain and nausea and in increasing appetite—there are also several pre-clinical reports showing anti-tumor effects of CBD in cell culture and in animal models.xxviii These studies have found reduced cell viability, increased cancer cell death, decreased tumor growth, and inhibition of metastasis (reviewed in McAllister et al, 2015).xxix These effects may be due to the antioxidant and anti-inflammatory effects of CBD;xxx however these findings have not yet been explored in human patients. There are multiple industry sponsored clinical trials underway to begin to test the efficacy of CBD in human cancer patients.
Marijuana can produce acute psychotic episodes at high doses, and several studies have linked marijuana use to increased risk for chronic psychosis in individuals with specific genetic risk factors. Research suggests that these effects are mediated by THC, and it has been suggested that CBD may mitigate these effects.xxxi There have been a few small-scale clinical trials in which patients with psychotic symptoms were treated with CBD, including case reports of patients with schizophrenia that reported conflicting results; a small case study in patients with Parkinson’s disease with psychosis, which reported positive results; and one small randomized clinical trial reporting clinical improvement in patients with schizophrenia treated with CBD.xxxiiLarge randomized clinical trials would be needed to fully evaluate the therapeutic potential of CBD for patients with schizophrenia and other forms of psychosis.
CBD has shown therapeutic efficacy in a range of animal models of anxiety and stress, reducing both behavioral and physiological (e.g., heart rate) measures of stress and anxiety.xxxiii,xxxiv In addition, CBD has shown efficacy in small human laboratory and clinical trials. CBD reduced anxiety in patients with social anxiety subjected to a stressful public speaking task.xxxv In a laboratory protocol designed to model post-traumatic stress disorders, CBD improved “consolidation of extinction learning”, in other words, forgetting of traumatic memories.xxxvi The anxiety-reducing effects of CBD appear to be mediated by alterations in serotonin receptor 1a signaling, although the precise mechanism remains to be elucidated and more research is needed.xxxvii
Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphinexxxviii and reduced cue-induced heroin seekingxxxix in animal models. A few small clinical trials have examined CBD and/or nabiximols (THC/CBD) for the treatment of substance use disorders; however, the available data are not sufficient to draw conclusions. NIDA is supporting multiple ongoing clinical trials in this area.