Q&A: Too much CBD could be bad for the liver
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Key takeaways:
- Moderate- to high-dose CBD use was significantly associated with liver enzyme elevation and drug-induced liver injury.
- A researcher spoke with Healio about the implications of the findings.
A recent systematic review and meta-analysis revealed that moderate to high doses of cannabidiol were associated with liver enzyme elevation and drug-induced liver injury, meeting the criteria of common adverse drug events.
Specifically, Lindsay Lo, MSc, BSc, an MPH student at the University of Toronto’s Dalla Lana School of Public Health, and colleagues reported in the Journal of Internal Medicine that people who used cannabidiol (CBD) were nearly six times more likely to have elevated liver enzymes (OR = 5.85; 95% CI, 3.84-8.92) and nearly five times more likely to develop drug-induced liver injury, or DILI (OR = 4.82; 95% CI, 2.46-9.45), compared with people receiving placebo.
The CBD-associated liver enzyme elevations and DILI, they wrote, met the criteria of common adverse drug events. They also encouraged clinicians to screen for CBD use and monitor liver function among patients at increased risk.
Healio spoke with Lo to learn more about the findings, what primary care providers should know about them, if CBD should be considered safe and more.
Healio: Will you briefly describe your findings and what primary care physicians should know about them?
Lo: Our recent meta-analysis aimed to examine the association between CBD use, liver enzyme elevation and DILI. We found that moderate- to high-dose CBD use was significantly associated with liver enzyme elevation (OR = 5.85) and DILI (OR = 4.82). The risk of elevations was also significantly increased in individuals using anti-epileptic drugs, particularly valproic acid. However, there were still several cases of DILI in healthy adults that were not on any concomitant medications. Most cases of elevated liver enzymes and DILI resolved upon CBD discontinuation.
The frequency of liver enzyme elevations and DILI in individuals using CBD meets Council for International Organizations of Medical Sciences criteria as a common adverse drug event associated with CBD use. Clinicians are encouraged to actively inquire about CBD use and monitor for signs of elevated liver enzymes and liver dysfunction during CBD dose titration. At doses of less than 300 mg CBD per day, the risk of DILI is likely low.
Healio: What are the underlying mechanics at play?
Lo: The underlying pathophysiology of liver injury associated with CBD use remains unknown. Both high-dose CBD use and the use of concomitant medications, such as anti-epileptic drugs, appear to be risk factors but not sole determinants. Preclinical evidence has shown that high dose CBD impairs glutathione resynthesis, which may lead to liver injury. There also appears to be a genetic component. There is still limited research on this topic, especially for populations beyond seizure disorders. There is a great need for additional research and better reporting standards to determine the true proportion of elevated liver enzymes and DILI across a broad group of patients taking CBD, assess risk factors and outcomes, and determine optimal management.
Healio: You note that CBD-associated liver enzyme elevations and DILI meet the criteria for common adverse drug events. What is the risk for the general population?
Lo: Based on available data, if individuals are using less than 300 mg per day of CBD and not on any concomitant medications that are known to be potentially hepatotoxic, they are likely at a low risk for this adverse event. The risk adverse event is greatest when using doses greater than 1,000 mg per day of CBD. In a monitored medical cannabis program with a qualified health care provider, overall, it would be uncommon that CBD at these doses would be recommended. However, there were several cases of DILI noted around the 300 mg per day range, which some individuals may be reaching. Patients sometimes also use extra cannabis on the side to what is recommended. Additionally, there is much less research on this topic using lower doses, so we cannot say for sure that patients under this threshold have no risk.
Another important implication is for people who are self-treating or using CBD for adult use. While many edibles sold in shops may be within the 20 mg range, oils are a different story. You can purchase oils that contain 100 mg per mL of CBD (or even higher). It is not uncommon for people to then take multiple doses of this throughout the day, particularly if they are self-treating for medical purposes. Many people also order CBD from non-regulated sources online, which often have significantly higher concentrated CBD products. Since CBD is not seen as being harmful, people may have the mentality that more is better and may take very high amounts. Additionally, there have been increasing trends in cannabis potency, so it can only be expected that even more highly concentrated products will continue to hit the market. As such, this is important for primary care clinicians to be aware of or any clinician that commonly investigates potential liver injury. If there is a suspected liver injury, CBD should be included as one of the drugs screened for.
Healio: You also note that there is a common belief that CBD is safer than THC – would you agree? Should either be considered safe? For whom?
Lo: There is no doubt that in many ways CBD is safer than THC. A large portion of risk from cannabis use is due to the risk of adverse psychological or neurocognitive effects that are associated with THC consumption. However, just because CBD is generally safer than THC, it does not mean it has zero risk, as is the case with any drug. Since CBD is not seen as being harmful, people may have the mentality that more is better and may take very high amounts. This could put them at risk for CBD-associated liver injury. The safety of either CBD or THC comes down to how they are being used and individual circumstance. With proper use and monitoring for adverse events, both can be safe to use for the majority of individuals.
Healio: What are the clinical implications of your findings?
Lo: The results of this meta-analysis have important clinical implications, especially for primary care clinicians who may encounter patients with elevated liver enzymes to investigate the underlying etiology. Currently, the risk of CBD-associated liver injury is unknown to many. As trends in use and access to CBD increase, it will be important for clinicians to be aware of this potential adverse drug event. Based on the results of this meta-analysis, we recommend patients be screened for CBD use, especially those presenting with signs of liver injury. Additionally, clinicians are encouraged to monitor liver function in patients initiating CBD, particularly if they are titrating to higher doses (>300 mg/day) or using CBD with antiepileptic medications.
Healio: Is there anything else you’d like to add?
Lo: We are working on a follow-up paper we expect to be published later this year that will provide clinical guidance in detecting, managing and mitigating the risk of CBD-associated hepatotoxicity.