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Adverse Effects of Oral Cannabidiol: An Updated Systematic Review of Randomized Controlled Trials (2020-2022)
José Diogo R Souza1, Julia Cozar Pacheco1, Giordano Novak Rossi1
1Department of Neurosciences and Behavior, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, Brazil.
Abstract:
(1) Background: With the massive demand for the use and commercialization of medicinal cannabidiol (CBD) products, new randomized clinical trials (RCTs) are being published worldwide, with a constant need for safety and efficacy evaluation. (2) Methods: We performed an update on a systematic review published in 2020 that focused on analyzing the serious adverse effects (SAEs) of CBD in RCTs and its possible association with drug interactions. We also updated the report of the most prevalent CBD adverse effects (AEs). We systematically searched EMBASE, MEDLINE/PubMed, and Web of Science without language restriction for RCTs that reported adverse effects after repeated oral CBD administration for at least one week in healthy volunteers or clinical samples published from January 2019 to May 2022. The included studies were assessed for methodological quality by the Quality Assessment of Controlled Intervention Studies tool. The present review is registered on PROSPERO, number CRD42022334399. (3) Results: Twelve studies involving 745 randomized subjects analyzed were included (range 1.1-56.8 y). A total of 454 participants used CBD in the trials. The most common AEs of CBD were mild or moderate and included gastrointestinal symptoms (59.5%), somnolence (16.7%), loss of appetite (16.5%), and hypertransaminasemia (ALT/AST) (12.8%). Serious adverse effects include mainly hypertransaminasemia with serum levels elevations greater than three times the upper limit of the normal (6.4%), seizures (1.3%), and rash (1.1%). All SAEs reported in the studies were observed on CBD as an add-on therapy to anticonvulsant medications, including clobazam and valproate. (4) Conclusion: Recent RCTs involving oral CBD administration for at least a week suggest that CBD has a good safety and tolerability profile, confirming previous data. However, it can potentially interact with other drugs and its use should be monitored, especially at the beginning of treatment.
Insights
This study found that medicinal cannabidiol (CBD) has a good safety profile in randomized clinical trials (RCTs), with mild side effects like gastrointestinal issues. However, potential drug interactions warrant monitoring, especially when using CBD with anticonvulsants.
Area of Science:
- Pharmacology and Toxicology
- Clinical Research
- Cannabinoid Science
Background:
- Growing demand for medicinal cannabidiol (CBD) necessitates ongoing safety and efficacy evaluations.
- Previous systematic reviews highlighted the need for updated safety data on CBD from randomized clinical trials (RCTs).
Purpose of the Study:
- To update the systematic review on serious adverse effects (SAEs) and drug interactions associated with CBD in RCTs.
- To report the most prevalent adverse effects (AEs) of repeated oral CBD administration.
Main Methods:
- Systematic search of EMBASE, MEDLINE/PubMed, and Web of Science for RCTs (Jan 2019-May 2022) reporting AEs of oral CBD.
- Inclusion of studies with at least one week of CBD administration in healthy volunteers or clinical populations.
- Quality assessment using the Quality Assessment of Controlled Intervention Studies tool; PROSPERO registration: CRD42022334399.
Main Results:
- Twelve RCTs with 745 subjects (454 using CBD) were analyzed.
- Common AEs: gastrointestinal symptoms (59.5%), somnolence (16.7%), loss of appetite (16.5%), and elevated liver enzymes (12.8%).
- Serious adverse effects included hypertransaminasemia (6.4%), seizures (1.3%), and rash (1.1%), primarily when CBD was an add-on to anticonvulsants like clobazam and valproate.
Conclusions:
- Recent RCTs confirm that oral CBD has a good safety and tolerability profile with prolonged use.
- Potential for drug interactions exists, necessitating careful monitoring during initial treatment phases.
- CBD's safety profile is generally favorable, but caution is advised when co-administered with other medications, particularly anticonvulsants.
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