COPENHAGEN, Denmark ― Currently there is not enough evidence to determine whether cannabidiol is beneficial in the treatment of psychiatric disorders, and more studies are needed to support the hype surrounding its potential benefits, experts say.
The researchers conducted a systematic review of all the available data regarding the use of cannabidiol for a range of psychiatric conditions, including schizophrenia, anxiety, and substance use disorder. They found no reliable evidence to back up the claims made for the drug.
The findings were presented here at the 13th World Congress of Biological Psychiatry and were recently published in the World Journal of Biological Psychiatry.
Study investigator Frederico Garcia, MD, PhD, Department of Psychiatry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, said, “Cannabidiol may be useful in psychiatry.”
However, he noted that it is currently not possible to definitively say one way or another whether it is beneficial and that “more evidence should be produced before we recommend its use in clinical practice.”
To examine the data supporting a role for cannabidiol in psychiatry, the researchers conducted a systematic literature review by searching the PubMed, Scielo, and ClinicalTrials.gov databases for English language articles published before August 2016.
From an initial 596 records identified from the PubMed and Scielo databases and 104 on the ClinicalTrials.gov database, 13 articles, including six case reports and seven randomized controlled trials (RCTs), and 21 registered clinical trials met the inclusion criteria.
The team categorized the standard of evidence in each trial and graded the recommendations on a scale of 1 to 5.
Table 1. Categorization of Standard of Evidence
| Category of Evidence | Description |
| A | Full evidence from controlled studies |
| B | Limited positive evidence from controlled studies |
| C1 | Evidence from uncontrolled studies |
| C2 | Evidence from case reports |
| C3 | Evidence based on the opinion of experts in the field or clinical experience |
| D | Inconsistent results; eg, positive RCTs are outweighed by an approximately equal number of negative studies |
| E | Negative evidence |
Dr Garcia noted that four oral formulations were used in the studies:
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Cannabidiol powder dissolved in oil, at doses of 200 mg, 400 mg, 600 mg and 800 mg
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Controlled-release cannabidiol (Arvisol, Echo Pharmaceuticals BV), at a dose of 320 mg
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Buccal spray with tetrahydrocannabinol (THC) and cannabidiol (Sativex, GW Pharmaceuticals), at a dose of 2.7 mg:2.5 mg per spray
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Buccal spray of cannabidiol diluted in alcohol
Schizophrenia, Anxiety Disorders
Dr Garcia said the rationale for using cannabis in the management of patients with schizophrenia is that its use is already highly prevalent among patients, that psychosis is related to cannabis with high THC content, and that in animal models, cannabidiol has been shown to have clozapinelike effects.
Moreover, anandamide, a natural cannabinoid produced in humans, is present in high levels in schizophrenia patients.
Of the available evidence, the team found three registered clinical trials, of which two were recruiting, and the results of the third had not been published. There were also two case reports, one with positive and one with negative results.
A cross-sectional study comparing cannabidiol with amisulpride in 42 patents found that the two compounds were comparable. However, Dr Garcia noted that the doses of amisulpride were “very low, so I don’t think they really used an active comparator in this study.”
Another cross-sectional study that compared cannabidiol with placebo in 29 schizophrenia patients found no difference between the two treatment arms.
In anxiety disorders, the rationale for using cannabidiol is that it modulates 5-HT1a and vanilloid type 1 receptors and that patients report relaxing and anxiogenic effects from the drug.
The team found three studies that examined the effect of cannabidiol on induced anxiety states and one study of the effect on social anxiety disorder. None of the studies yielded reliable evidence of a beneficial effect.
Dr Garcia explained that the rationale for cannabidiol use in affective disorders is the same as that for anxiety disorders, but no studies have been conducted to examine its impact.
Substance Use Disorders
In substance use disorders, the rationale is that cannabidiol antagonizes THC and is an agonist of 5-HT1a receptors. The team identified five trials that examined the impact of cannabidiol on cannabis dependence, three on opiate dependence, and one trial on cocaine cravings.
“Those trials are ongoing, so we don’t have the conclusions,” Dr Garcia said. “For tobacco, we have one double-blind RCT with 24 subjects. That reported a 40% decrease in the number of cigarettes smoked.”
For cannabis withdrawal, positive results have been seen in case reports. One open-label study suggested that cannabidiol was associated with good tolerability, but it did not include results on the impact on cannabis use.
Furthermore, one RCT, which included 51 patients treated with Sativex and psychosocial intervention, reported a reduction of withdrawal symptoms in 6 days.
“What is curious is that withdrawal symptoms normally appear after 15 days in cannabis addiction, so I consider this a main limitation of this study,” said Dr Garcia.
Two RCTs compared Sativex to placebo. They reported no difference between the groups, as well as no side effects.
Table 2. Evidence Level and Recommendation Grade
| Disorder | Evidence Level | Recommendation Grade |
| Schizophrenia (short term) | C1 | 4 |
| Generalized social anxiety disorder (acute) | C1 | 4 |
| Major depressive disorder | F | N/A |
| Bipolar disorder | F | N/A |
| Tobacco addiction | C1 | 4 |
| Cannabis withdrawal | B | 3 |
| Cannabis dependence | C2 | 4 |
Limited Evidence
“In summary, what we have is that the evidence available regarding the use of cannabidiol in psychiatry is very limited, and these studies are not well constructed. So, I think that we still have a lot of work to do to show if cannabidiol may be useful in psychiatry, and this is a need,” said Dr Garcia.
During the discussion following his presentation, Dr Garcia was asked his thoughts on the use of cannabidiol in the management of chronic pain. He replied that the use of cannabidiol for pain management had been examined by anesthesiologists and that such use did not fall under the domain of psychiatry. In that sense, he said, it is similar to the role of cannabidiol in epilepsy, which is being studied by neurologists.
However, Dr Garcia expects that, as with the use of cannabidiol for pain management and epilepsy, further and better studies could provide evidence for the use of cannabidiol in psychiatric conditions.
Fabricio Moreira, PhD, Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, co-chaired the session and also contributed to the study.
He told Medscape Medical News, “People have been talking too much about cannabidiol” and that there is little evidence that cannabidiol “works for any type of disorder.”
He said there is a strong need for clinical trials. He also said that scientists and clinicians need to make a concerted effort to deliver accurate information about cannabidiol to the public and not to overstate its effects.
“When we translate science to the lay person, to the public, most of the time we tend to increase the impact of the discovery of these drugs, and they create high expectations related to compounds, particularly when it comes to cannabinoids.
“I think there are interesting results on cannabidiol, but I agree it’s not enough to [use it] widely…. We should wait for more results and not do so much ‘advertising’ of it,” said Dr Moreira.
No funding for the study has been disclosed. Dr Garcia has numerous consulting, research, and speaking roles with Janssen, Daiichi-Sankyo, Pfizer, and Prefeitura de Belo Horizonte, among others.
13th World Congress of Biological Psychiatry. Abstract 1013, presented June 21, 2017.
World J Biol Psychiatry. Published online February 20, 2017. Abstract
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