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Cannabidiol shows promise in treating cognitive disorder



Background: Finding new strategies to treat cognitive disorders is a challenging task. Medication must defeat the blood–brain barrier.


Cannabidiol (CBD), a non-intoxicating compound of the cannabis plant, has gained recognition as a nutraceutical for its potential effectiveness in treating anxiety, oxidative stress, convulsions, and inflammation. However, the dose, tolerable upper intake, formulation, administration routes, comorbidities, diet, and demographic factors to reverse cognitive impairments have not been completely explored. Trials using CBD as a primary intervention have been conducted to alleviate cognitive issues.


This review evaluates the benefits of CBD supplementation, research design, formulations, and outcomes reported in randomized clinical trials.


Methods: An evidence-based systematic literature review was conducted using PUBMED and the Florida International University Research Library resources. Fourteen randomized trials were selected for review, and their designs and outcomes were compared conceptually and in the form of resume tables.


Results: CBD showed improvement in anxiety and cognitive impairments in 9 out of 16 analyzed trials. However, the variability could be justified due to the diversity of the trial designs, underpowered studies, assayed population, uncontrolled results for comorbidities, medications, severity of drug dependence, compliances, and adherences. Overall, oral single doses of 200 mg–1,500 mg or vaporized 13.75 mg of CBD were shown to be effective at treating anxiety and cognition with a good safety profile and no drug addiction behaviors.


Conversely, results that did not have a significant effect on treating cognitive impairments can be explained by various factors such as THC or other abuse drugs masking effect, low dose, and unknown purity of CBD. Furthermore, CBD shows potential properties that can be tested in the future for Alzheimer’s disease.


Conclusion: As medical cannabis becomes more accessible, it is essential to understand whether medication rich in CBD exerts a beneficial effect on cognitive disorders. Our study concludes that CBD is a promising candidate for treating neurocognitive disorders; however, more studies are required to define CBD as a therapeutic candidate for managing cognitive disorders.



Review process

The authors conducted a systematic literature screening using PUBMED and the Florida International University Research Library resources to identify high-quality randomized controlled trials that investigated the therapeutic effects of cannabidiol in neurocognitive disorders. Out of the 14 randomized trials analyzed, nine showed a positive impact of cannabidiol on treating anxiety and cognitive impairment.


Important observations

Among selected clinical trials, nine showed a positive impact of cannabidiol in treating anxiety and cognitive impairment. However, this variability in outcomes can be attributed to several factors, including the diversity in trial designs and trial populations, underpowered studies, small sample size, and the lack of control for comorbidities, medications, severity of drug dependence, participant compliance, and adherence.


Other factors that may explain such discrepancy include cannabidiol formulation, dose, route of administration, treatment duration, and participants' sociodemographic characteristics and lifestyle behaviors.  


Clinical trials with positive findings

A 12-week clinical trial was conducted to investigate the effects of high-purity cannabidiol on cognitive functions in anxiety disorder patients who were unresponsive to standard treatments.

The findings revealed that a dose escalation protocol from 200 milligrams per day to 800 milligrams per day of oral cannabidiol significantly reduced anxiety and depression severity and increased social and occupational functioning in participants at week 12. However, the positive effects were not sustained at the 6-month follow-up, suggesting that the benefits of CBD may be transient.


The trial also found an acceptable safety profile of cannabidiol with no clinical changes in blood parameters. Nonetheless, several limitations in the trial's design and data analysis, such as a small sample size and the lack of a control group, could have influenced the findings.


Another clinical trial investigating the effects of cannabidiol and tetrahydrocannabinol (THC) on cognitive functions revealed that inhalation of THC vapor but not cannabidiol vapor resulted in significant driving impairments in healthy participants with previous cannabis exposure.


Further analysis adjusting for alcohol levels in participants revealed that cannabidiol helped to significantly mitigate driving deficiencies associated with THC exposure. These findings underscore the importance of considering other variables, such as the presence of THC, which may confound the effects attributed to CBD alone.


Another trial investing driving performance in healthy participants revealed that 300 milligrams and 1500 milligrams of oral cannabidiol significantly improved attention levels after one month of treatment. However, it is important to note that these improvements were observed in a controlled, simulated environment, which may not fully replicate real-world conditions.


One trial investigating the mode of action of the most popular types of cannabinoids in healthy participants revealed that 600 milligrams of cannabidiol increased fronto-striatal connectivity more strongly than that caused by 10 milligrams of THC. This brain region is involved in learning, language, reward, motor, and addiction. Despite this increase in brain connectivity, no corresponding improvements in cognitive functioning were observed, highlighting the complex and not fully understood relationship between CBD's effects on brain connectivity and cognitive outcomes.


In patients with post-traumatic stress disorder, 300 milligrams of high-purity cannabidiol was found to reduce cognitive impairment associated with trauma recall. In a similar trial, the same dose of cannabidiol was


One trial investigating the kinetics of cannabidiol reported a higher plasma level of the compound when administered with a high-fat breakfast compared to that administered in the fasting stage with water.


One trial investigating addictive properties in healthy adults revealed that cannabidiol did not lead to drug addiction or adverse events. The trial also reported that cannabidiol had no significant effect on cognitive or motor assessments.


Two trials involving drug-addicted populations indicated that cannabidiol was effective in reducing cravings for illicit drugs. These trials also highlighted the effectiveness of cannabidiol in improving recall tasks and reducing anxiety.


Review summary 

The summary of findings reveals that oral single doses of 200 milligrams to 1,500 milligrams or vaporized doses of 13.75 milligrams of cannabidiol are effective in reducing anxiety and improving cognition. However, the effectiveness of CBD is not uniform across all studies, and these doses exhibit an acceptable safety profile and do not induce addictive behaviors.

With increasing accessibility and availability of medical cannabis, it has become essential to understand whether cannabidiol-containing medications exert a positive effect on cognitive disorders.


In this context, the review cautiously concludes that cannabidiol shows potential as a therapeutic candidate for treating neurocognitive disorders. Nevertheless, the authors emphasize that more comprehensive and well-powered studies are needed to definitively establish cannabidiol's efficacy in managing cognitive disorders.


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