CBD is generally well tolerated, but it does cause side effects, especially at higher doses. The most common ones are drowsiness, diarrhea, reduced appetite, and fatigue. At higher doses, CBD can also stress the liver. Because most CBD products on the market are unregulated, some side effects may come not from CBD itself but from contaminants or unlabeled THC in the product.
The Most Common Side Effects
Clinical trials of pharmaceutical-grade CBD give us the clearest picture of what to expect. In controlled studies, these were the side effects reported most often:
- Drowsiness and sedation: The single most frequent complaint. Roughly 23 to 25% of people taking CBD in clinical trials experienced sleepiness, compared to 8% on a placebo. For some, this progressed to noticeable lethargy or sedation.
- Decreased appetite: Reported by 16 to 22% of CBD users in trials, versus 5% on placebo. Some people also lost weight.
- Diarrhea: Occurred in 9 to 20% of trial participants depending on the dose, sometimes accompanied by abdominal discomfort.
- Fatigue and general weakness: About 11 to 12% of participants felt unusually tired or run down.
- Dry mouth: A commonly reported nuisance effect.
- Sleep disruption: Paradoxically, while CBD makes many people sleepy, about 5 to 11% of participants in trials reported insomnia or poor sleep quality.
- Irritability: Between 5 and 9% of people experienced agitation or irritability.
- Rash: Skin reactions affected 7 to 13% of participants at different doses.
Most of these side effects are mild and resolve after stopping CBD or lowering the dose. In clinical trials, only about 3 to 12% of people dropped out because of side effects, with higher doses causing more dropouts.
Liver Stress at Higher Doses
One of the more serious concerns with CBD is its effect on the liver. In clinical trials, 8 to 16% of people taking CBD showed elevated liver enzymes, markers that indicate the liver is working harder than normal or sustaining mild damage. Only 3% of people on a placebo had similar elevations. In a smaller study of 200 healthy adults taking a moderate dose for four weeks, 6% developed liver enzyme levels three times the upper limit of normal, while nobody in the placebo group did. Those elevations first appeared around day 21 and normalized within one to two weeks after stopping CBD.
This liver effect follows a clear dose pattern. At daily totals under about 60 mg (roughly 1 mg per kilogram of body weight), studies have not found liver enzyme abnormalities. The risk appears at doses in the range of 150 to 600 mg per day and above, which researchers classify as “high dose.” In trials, the 20 mg/kg/day group had double the rate of liver enzyme elevations compared to the 10 mg/kg/day group. Liver stress was also the most common reason people had to stop taking CBD in clinical studies.
How CBD Interferes With Other Medications
CBD is processed through the same liver pathways that break down a long list of common medications. It competes for and slows down several of these pathways, which means other drugs can build up to higher levels in your bloodstream than expected. This is the same general mechanism behind grapefruit warnings on medication labels, but CBD affects a broader set of enzymes.
The medications most likely to be affected include blood thinners, certain antidepressants, anti-seizure drugs, some heart medications, and immunosuppressants. One example from published research: people using an antidepressant and smoking cannabis simultaneously experienced increased irritability, restlessness, and insomnia, likely because cannabinoids slowed the drug’s breakdown. If you take any prescription medication, this interaction risk is worth discussing with a pharmacist or prescriber before adding CBD.
Side Effects Depend on Dose
Nearly every CBD side effect gets worse as the dose goes up. Researchers describe this as a “dose-response relationship,” though it’s not always proportional, meaning doubling the dose doesn’t necessarily double the risk. Still, the trend is consistent across studies. At the lower end of consumer CBD use (around 10 to 50 mg per day), serious side effects are uncommon. Once doses climb into the hundreds of milligrams per day, the rates of drowsiness, diarrhea, appetite changes, and liver strain all increase meaningfully.
This matters because over-the-counter CBD products vary wildly in their actual CBD content, and many people escalate their dose over time without clear guidance. What feels like a new side effect may simply reflect a higher dose than you realize.
Contamination and Mislabeling in CBD Products
Because most CBD products are not regulated the way pharmaceuticals are, some side effects people attribute to CBD may actually come from what else is in the bottle. Research funded by the National Institutes of Health found that hemp-derived CBD products contained heavy metals like lead and mercury. Hemp plants naturally absorb contaminants from soil, so products made from plants grown in polluted ground can concentrate those toxins.
Mislabeling is also widespread. A study published in JAMA found that 21% of CBD products sold online contained THC that wasn’t listed on the label. Even small amounts of THC can cause unexpected psychoactive effects and trigger positive drug tests. In one study, two out of six participants who vaped a product containing just 0.39% THC tested positive on standard employment-style urine drug screens. For people subject to drug testing, this is a real and underappreciated risk.
Pregnancy and Breastfeeding
The FDA strongly advises against using CBD during pregnancy or while breastfeeding. There is no comprehensive research on how CBD affects a developing fetus or a nursing infant. In animal studies, high doses of CBD caused problems with the reproductive systems of developing male fetuses. CBD also transfers into breast milk, exposing infants to the compound and potentially to any contaminants in the product, including unlabeled THC, pesticides, or heavy metals.
What We Don’t Know Yet
Most clinical data on CBD covers study periods of a few weeks to a few months. The long-term effects of daily CBD use beyond 12 months remain largely unknown. Federal health agencies have specifically flagged this gap, noting that the effects on the developing brain (relevant for adolescents and young adults), proper dosing for various conditions, and chronic safety profiles all lack solid evidence. The side effects documented in shorter trials are well established, but whether new concerns emerge with years of daily use is still an open question.