Major literature articles related to cannabidiol and cannabidiol-tetrahydrocannabinol combination for various indications.
Although clinical evidence is still needed to evaluate the potential of CBD as a drug for many specific conditions, 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 list of publications against each indication below reflects the work done to date and highlights the potential of CBD working alone, or in conjunction with THC at times, in treating and managing various illnesses.
CBD has anti-seizure activity, reducing the severity of seizures in animal models:
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:
Neuroprotective and Anti-Inflammatory Effects
CBD has been shown to have neuroprotective properties in cell cultures as well as in animal models of several neurodegenerative diseases, including Alzheimer’s:
Multiple Sclerosis (MS):
Neurodegeneration caused by alcohol abuse:
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, references below:
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 (Chagas et al. Effects of cannabidiol in the treatment of patients with Parkinson's disease: an exploratory double-blind trial. J Psychopharmacol. 28(11):1088-98, 2014).
There have been multiple clinical trials demonstrating the efficacy of nabiximols on central and peripheral neuropathic pain, rheumatoid arthritis, and cancer pain:
Russo EB. Cannabinoids in the management of difficult to treat pain. Therapeutics and Clinical Risk Management. 4(1):245-259, 2008.
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:
Although there are no controlled clinical studies that have explored the efficacy of CBD alone on pain, the anti-inflammatory properties of CBD 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:
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:
These studies have found reduced cell viability, increased cancer cell death, decreased tumor growth, and inhibition of metastasis:
These effects may be due to the antioxidant and anti-inflammatory effects of CBD:
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:
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:
Large 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:
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:
In a laboratory protocol designed to model post-traumatic stress disorders, CBD improved “consolidation of extinction learning”, in other words, forgetting of traumatic memories:
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:
Efficacy for Treating Substance Use Disorders
Early preclinical findings also suggest that CBD may have therapeutic value as a treatment of substance use disorders. CBD reduced the rewarding effects of morphine:
and reduced cue-induced heroin seeking 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.
Safety of CBD
For reasons discussed previously, despite its molecular similarity to THC, CBD only interacts with cannabinoid receptors weakly at very high doses (100 times that of THC):
and the alterations in thinking and perception caused by THC are not observed with CBD;
The different pharmacological properties of CBD give it a different safety profile from THC.
A review of 25 studies on the safety and efficacy of CBD did not identify significant side effects across a wide range of dosages, including acute and chronic dose regimens, using various modes of administration:
Bergamaschi et al. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49
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