Cannabidiol (CBD): Side Effects and Possible Interactions

The safety profile of cannabidiol (CBD) has been acknowledged by major health agencies, such as the World Health Organization (WHO), as being well-tolerated by animals and humans, and rarely producing any side effects.

However, CBD has a profound impact on a doens of pathways and systems, which explains its therapeutic versatility. That being said, this versatility is also the reason why CBD interacts with so many prescription meds and over-the-counter (OTC) products.

This article reviews some of the most common side effects and medications that CBD has the potential to interact with, along with an explanation of why. It also includes a few medications that CBD does not interact with, but we are frequently asked about.

How CBD and drugs interact: Understanding drug metabolism.

Metabolism can refer to how your body uses energy for weight management, or the way drugs are metabolized in your body.

The former is known as the basal metabolic rate, or in simple terms, the number of calories a person needs to maintain healthy body functions while at rest.

The latter is very different from the basal metabolic rate. Drug metabolism refers to how a substance is processed and used by the body — with the majority of this processing happening in the liver.

Scientists call it the ‘first-pass effect’ or ‘first-pass metabolism.’

Using straightforward terms, when you take a medication, it is broken down in the liver into its active compounds so that the body can use them. Just like carbohydrates are broken down into sugars, fats into triglycerides, and proteins into amino acids — drugs break down into their individual ingredients.

From there, they are controlled by specific enzymes, which transform these compounds into metabolites. These metabolites then influence different processes in your body and are flushed with urine once used up.

How is CBD metabolized?

Drug metabolism determines the rate at which the body processes medications and other therapeutic compounds into their individual metabolites and how long they can stay in your system.

When you take CBD in the form of an oils, capsules, or gummies, it has to pass through your gut, where it is released into the bloodstream. From there, they travel through the bloodstream to the liver, where it absorbs through the hepatic portal. The liver breaks CBD down into its metabolites using enzymes, after which it can circulate throughout the body in the bloodstream again.

CBD's side effects.

CBD is safe to take in appropriate doses. Doses of up to 1,000mg daily have been used safely.

CBD can cause some side effects, such as dry mouth, low blood pressure, lightheadedness, and drowsiness. Signs of liver injury have also been reported with high doses of the prescription form of CBD, called Epidiolex.

CBD's potential interactions with common drugs.

This section covers the most common interactions between CBD and medications. Speak to your healthcare professional if you're unsure about these combinations:

CBD and Ibuprofen Interaction

Ibuprofen is one of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), meaning it can produce similar benefits to CBD in terms of inflammation and pain relief. Previously we’ve mentioned that NSAIDs interact with CBD, which may raise concerns about potential negative interactions between CBD oil and Ibuprofen.

According to a study from the Journal of Neurology Research, there have been no reported interactions between CBD and ibuprofen, although it doesn’t mean they do not exist. Health experts suggest that potential interactions may be dosage-dependent. If a certain dosage threshold is breached, CBD and NSAIDs like Ibuprofen can lead to unforeseen and potentially severe nervous system pathology.

CBD and Adderall Interaction

A 2020 study found that higher doses of medical cannabis led to a decreased use of ADHD medication in adults. Products containing a higher concentration of CBD were linked to lower ADHD scores. This means that CBD can interact with ADHD meds, decreasing their efficacy, while still providing more pronounced neurological benefits. The potential side effects of interactions between CBD and Adderall may lead to decreased appetite.

CBD and Lamictal Interaction

Using medical cannabis and Lamictal may increase side effects such as dizziness, confusion, drowsiness, and difficulty concentrating. Elderly consumers may also experience impairment in judgment. That being said, none of these side effects were proven to result from CBD use per se. When it comes to interactions between CBD and Lamictal, it can make the medication more or less effective, depending on the dosage.

CBD and Antibiotics Interaction

There is no known interaction between CBD and antibiotics, although these interactions may occur if an antibiotic is metabolized through the cytochrome P450 enzyme system. Some studies indicate that taking CBD and antibiotics together may amplify the effects of one another without any negative side effects. However, more research is needed to confirm these findings on a larger scale.

CBD and Omeprazole Interaction

CBD can inhibit the enzymes that are targeted by omeprazole and other Proton Pump Inhibitors (PPIs). Taking CBD with certain heartburn medications can increase the risk of diarrhea.

CBD and Thyroid Medications

Some people report mild nausea when taking CBD oil together with their thyroid medications. Since both substances are processed by the CYP450 enzyme system, taking CBD with a thyroid medication may cause hyperthyroidism because more thyroxine would be secreted than the body could metabolize.

CBD and Lisinopril Interaction

CBD can temporarily lower blood pressure, so taking it alongside medications like Lisinopril might reduce it even more, making you feel lethargic and weak. Always consult your doctor before adding CBD to your routine if you use anti-hypertension meds.

CBD and Prednisone Interaction

Since both CBD and corticosteroids are potent inhibitors of the CYP450 enzyme system, concomitant use may increase the risk of systemic side effects from corticosteroid use due to decreased glucocorticoid clearance. Corticosteroids like prednisolone and hydrocortisone should never be taken with CBD.

CBD's potential interactions with other drugs.

CBD displays moderate interaction with some medications.

Speak to your healthcare professional if you're unsure about these combinations:

Medications changed by the liver may interact with CBD.

Some medications are changed and broken down by the liver. CBD might change how quickly the liver breaks down these medications. This could change the effects and side effects of these medications. These include the following substrates:

• Cytochrome P450 1A1 (CYP1A1)
• Cytochrome P450 1A2 (CYP1A2)
• Cytochrome P450 1B1 (CYP1B1)
• Cytochrome P450 2A6 (CYP2A6)
• Cytochrome P450 2B6 (CYP2B6)
• Cytochrome P450 2C19 (CYP2C19)
• Cytochrome P450 2C9 (CYP2C9)
• Cytochrome P450 2D6 (CYP2D6)
• Cytochrome P450 3A4 (CYP3A4)
• Cytochrome P450 2C8 (CYP2C8)
• Glucuronidated drugs

Sedative medications (CNS depressants) may interact with CBD.

CBD might cause sleepiness and slowed breathing. Some medications, called sedatives, can also cause sleepiness and slowed breathing. In some cases, taking CBD with sedative medications might cause breathing problems and/or too much sleepiness.

Clobazam (Onfi) may interact with CBD.

Clobazam is changed and broken down by the liver. CBD might decrease how quickly the liver breaks down clobazam. This might increase the effects and side effects of clobazam.

Eslicarbazepine (Aptiom) may interact with CBD.

Eslicarbazepine is changed and broken down by the body. CBD might decrease how quickly the body breaks down eslicarbazepine. This might increase levels of eslicarbazepine in the body by a small amount.

Rufinamide (Banzel) may interact with CBD.

Rufinamide is changed and broken down by the body. CBD might decrease how quickly the body breaks down rufinamide. This might increase levels of rufinamide in the body by a small amount.

Valproate may interact with CBD.

Valproic acid can cause liver injury. Taking cannabidiol with valproic acid might increase the chance of liver injury. CBD and/or valproic acid might need to be stopped, or the dose might need to be reduced.

Zonisamide may interact with CBD.

Zonisamide is changed and broken down by the body. CBD might decrease how quickly the body breaks down zonisamide. This might increase levels of zonisamide in the body by a small amount.

Brivaracetam (Briviact) may interact with CBD.

Brivaracetam is changed and broken down by the body. CBD might decrease how quickly the body breaks down brivaracetam. This might increase levels of brivaracetam in the body.

Everolimus (Zostress) may interact with CBD.

Everolimus is changed and broken down by the body. CBD might decrease how quickly the body breaks down everolimus. This might increase levels of everolimus in the body.

Tacrolimus (Prograf) may interact with CBD.

Tacrolimus is changed and broken down by the body. CBD might decrease how quickly the body breaks down tacrolimus. This might increase levels of tacrolimus in the body.

Methadone (Dolophine) may interact with CBD.

Methadone is broken down by the liver. CBD might decrease how quickly the liver breaks down methadone. Taking cannabidiol along with methadone might increase the effects and side effects of methadone.

Carbamazepine (Tegretol) may interact with CBD.

Carbamazepine is changed and broken down by the body. CBD might decrease how quickly the body breaks down carbamazepine. This might increase levels of carbamazepine in the body and increase its side effects.

Sirolimus (Rapamune) may interact with CBD.

Sirolimus is changed and broken down by the body. CBD might decrease how quickly the body breaks down sirolimus. This might increase levels of sirolimus in the body.

Stiripentol (Diacomit) may interact with CBD.

Stiripentol is changed and broken down by the body. CBD might decrease how quickly the body breaks down stiripentol. This might increase levels of stiripentol in the body and increase its side effects.

Lithium may interact with CBD.

Taking higher doses of CBD might increase levels of lithium. This can increase the risk of lithium toxicity.

Warfarin may interact with CBD.

CBD might increase levels of warfarin, which can increase the risk for bleeding. CBD and/or warfarin might need to be stopped, or the dose might need to be reduced.

Tamoxifen (Soltamox) may interact with CBD.

Tamoxifen is changed and broken down by the body. CBD might affect how quickly the body breaks down tamoxifen. This might affect levels of tamoxifen in the body.

Citalopram (Celexa) may interact with CBD.

Citalopram is changed and broken down by the body. CBD might decrease how quickly the body breaks down citalopram. This might increase levels of citalopram in the body and increase its side effects.

How much CBD should you take?

On average, clinical studies show that 150mg - 300mg of CBD are ideal for managing stress and its manifestations (anxiety, depression, burnout, and PTSD). However, clinical literally also demonstrates that there's a difference between the efficacy and effects of CBD isolate and full-spectrum CBD. This section examines the clinical literature for the most effective doses of each and their intended purpose.

Preclinical research by Gallily and colleagues observed a bell-shaped dose-response curve for the anti-inflammatory and anti-nociceptive (pain from inflammation and injury) effects of CBD isolate, while a linear dose-response was noted for a full-spectrum high-CBD product.

That's because full-spectrum CBD contains other therapeutic compounds, whereas CBD isolate contains nothing but the isolated single-compound CBD extract. For example, full-spectrum CBD contains trace amounts of CBN, which promotes sleep and balances inflammation, and CBG, which reduces pain. Full-spectrum CBD also contains terpenes and flavonoids, compounds that give different cannabis strains their unique scents, flavours, and even the highs themselves.

CBD dosages in clinical studies.

In a 2021 study on CBD for stress and burnout, 300mg of CBD was sufficient for reducing emotional exhaustion and burnout symptoms among frontline health care professionals.

In 2022, researchers published results from a clinical trial indicating that a 4-week treatment with a high-CBD (full-spectrum) sublingual product effectively reduces moderate-to-severe anxiety. Patients experienced significant anxiety reduction within a week, with all achieving and maintaining treatment response by week 3; this is notably faster than conventional pharmacotherapy which can take up to 12 weeks. These findings confirm and expand on prior research.

Notably, treatment response was achieved with a much lower dose (~30 mg/day) in this trial compared to a previous one using a single CBD isolate (~300 mg/day). This difference might be linked to the "entourage effect," where the combined action of various compounds, including cannabinoids, terpenoids, and flavonoids, can enhance the overall effects of cannabinoids when they work together synergistically.

A 2022 case study showed that pure CBD worked well for treating autism spectrum disorder (ASD) in childhood but stopped being effective during puberty, leading to increased hyperactivity and aggression. The solution was enriching pure CBD with a specific blend of calming terpenes, which significantly reduced aggressive behavior. Importantly, this improvement was achieved with significantly less CBD, less than half the amount used in pure CBD treatment (0.19 mg/bw vs. 0.48 mg/bw, respectively).

A meta-analysis published in the peer-reviewed journal Frontiers in Psychology revealed that patients with refractory epilepsy needed lower average doses when treated with full-spectrum, high-CBD products compared to single extracted CBD isolates. Patients using CBD-rich extracts had a lower average dose (6.0 mg/kg/day) compared to those using purified CBD (25.3 mg/kg/day). For somebody weighing 70kg, that's 420mg of full-spectrum CBD vs. 1,771mg of CBD isolate.

Furthermore, single extracted CBD products were linked to more frequent reports of mild and severe side effects than full-spectrum, high-CBD products.

Final verdict on the best CBD dosage.

The short of it is that research still isn't quite sure what the perfect dose is, or if the dose even depends on factors like weight.

Based on the available data, it appears that benefits for daily stress, anxiety, burnout, and depression are within the 150 - 300mg of full-spectrum CBD taken daily, although in some cases it can be as low as 30mg. For sleep and pain, you'll likely need higher doses.

As a rule of thumb, we recommend starting with 50mg per dose and gradually increasing your dose on a day-by-day basis until you achieve the desired benefits.

Takeaways.

The list of drugs that we’ve mentioned above is by no means definite and doesn’t include all the pharmaceutical substances that may interact with CBD. Similarly, not all the medication from these categories will necessarily cause an interaction — as is the case for antibiotics and Ibuprofen.

A consultation with a doctor experienced in CBD and cannabis use can help you establish the right routine for your medications and supplements to avoid potentially negative interactions. Some compounds work synergistically with CBD, so asking your doctor can help you maximize the effect of your treatment.

You can also use our CBD Dosage Calculator to guide you in finding the optimal dosage for yourself.

Again, if you’re not sure if CBD will interact with the medication that you might be taking, a consultation with a health professional will not harm — unlike trying to figure out these interactions on your own.

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