Interaction of CBD with medications: is it safe to take CBD products with your medications?
CBD (cannabidiol) is one of the most popular dietary supplements over the last decade. Every year, more and more people are turning to CBD to support their battle with chronic health conditions such as anxiety, chronic pain, epilepsy, insomnia, depression, and more.
Various medications are used to treat all of these ailments. It is common for people to take CBD alongside other medications to treat the same or other health ailments.
While CBD alone has been shown to be safe in rigorous clinical trials, there is always a chance of negative interaction with other medications. Some are more likely to interact than others. In this guide, we'll look at what medications are most likely to interact with CBD, how severe the interaction is, and offer some tips to minimize your chances of experiencing side effects.
CBD and drug interaction table
|
Class of drug |
Amplification of the effect |
Weakening of the effect |
Hepatic metabolism |
Severity of interaction |
|
✅ |
✅ |
Medium |
||
|
Alcohol |
✅ |
Moderate |
||
|
✅ |
✅ |
Medium |
||
|
✅ |
Moderate |
|||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Medium |
||
|
✅ |
✅ |
Medium |
||
|
✅ |
Medium |
|||
|
✅ |
✅ |
High |
||
|
✅ |
✅ |
High |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
High |
|||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
Moderate |
|||
|
✅ |
✅ |
Moderate |
||
|
✅ |
Moderate |
|||
|
✅ |
Moderate |
|||
|
✅ |
Medium |
|||
|
✅ |
Moderate |
|||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
✅ |
Moderate |
||
|
✅ |
Moderate |
|||
|
✅ |
✅ |
Medium |
||
|
✅ |
Moderate |
|||
|
✅ |
Moderate |
|||
|
✅ |
Moderate |
|||
|
✅ |
Medium |
|||
|
✅ |
Medium |
|||
|
✅ |
Moderate |
|||
|
✅ |
✅ |
Moderate |
||
|
✅ |
Medium |
|||
|
✅ |
Moderate |
There are three ways CBD can interact with other drugs
1. Agonistic interaction (↑↑↑)
An agonistic interaction between two substances occurs when both substances have the same effect on the body. Both substances together act on the same receptors or force an effect in the same direction.
A good example of this is CBD and blood pressure lowering drugs. Both substances exert a force on the vascular system to lower the pressure in the arteries. When both substances are taken together, the force can be too high - leading to low blood pressure, which can cause side effects such as dizziness or fainting.
2. Antagonistic interaction (↓↓↓)
An antagonistic interaction is the opposite of an agonistic interaction. It occurs when two substances have opposite effects on each other. One may exert a positive force on a bodily function, while the other weakens that effect by acting in the opposite direction.
Most of the negative effects of this interaction result from the absence of effects. You may be taking something to treat an ailment, but the effects of CBD cancel out those effects and reduce the effectiveness of the drug. The symptoms you experience as a result come from the fact that the treatment is no longer working and your ailments are returning. An example of this is the interaction between CBD and stimulants.
3. Metabolic competition
This is the most common interaction that CBD has with other drugs. Virtually every substance you take is eventually metabolized in the liver. The compounds are absorbed into the bloodstream where they travel through the body to exert their effects. Eventually, they are filtered by the liver. A specialized set of enzymes is tasked with breaking down the compound into a smaller form.
The resulting metabolites are then filtered out of the body by the kidneys. There are dozens of enzymes in the liver, each designed to break down a specific type of molecule. Most drugs require some of these enzymes to break down completely - including CBD.
If two or more compounds require the same enzymes to break down, they may end up competing for them. This can slow down the rate of metabolism of the compounds - leading to longer lasting effects and a build-up of compounds in the body.
Think of it this way. When you go to the cafeteria at your local grocery store, there are many different places to order food. But maybe you prefer a certain type of food. If many other people in the store prefer the same food, a line will form at that booth, even though all the other nearby restaurants have no lines.
CBD is metabolized by the following liver enzymes: CYP1A1 / CYP1A2 / CYP1A22 / CYP1B1 / CYP2B6 / CYP2C19 / CYP2D6 (potent) / CYP3A4 (potent) / CYP3A5
CBD & blood pressure medication
CBD is unlikely to have any major negative interactions with this class of drugs in general, but there is always a chance of an interaction due to the similarity of their effects. CBD has blood pressure lowering effects on its own, which may cause further blood pressure lowering when used in combination with prescription antihypertensives.
The goal is for blood pressure to drop until it is in the healthy range (120/80). If it drops too low, it may not be sufficient to pump blood against gravity to the brain. When we are unable to effectively push blood to the brain, we may feel dizzy or lightheaded. In severe cases, this can cause us to faint.
ACE & CBD inhibitors
Type of interaction: ↑↑↑↑ Increased effect (agonistic)
Severity: Medium
ACE stands for angiotensin-converting enzyme. It is responsible for converting angiotensin I to angiotensin II - a potent vasoconstrictor (tightens arteries and increases blood pressure). ACE inhibitors block this enzyme to prevent narrowing of the arteries. They are used to fight high blood pressure.
CBD is unlikely to interact directly with ACE inhibitors, but may enhance its effects. In some cases, blood pressure can drop too low - causing side effects such as dizziness or fainting.
ACE inhibitors with possible interactions with CBD:
Benazepril Hydrochloride (Lotensin)
Captopril (Tensiomin)
Enalapril (Vasotec)
Fosinopril (Monopril)
Lisinopril (Lispril)
Moexipril (Univasc)
Perindopril (Aceon)
Quinapril (Accupril)
Ramipril (Altace)
Trandolapril (Mavik)
Alphablockers & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Medium
Alpha-adrenergic receptors are found throughout the arterial system. When these receptors are activated, the smooth muscles in the arteries contract - by narrowing the arteries, blood pressure increases. This is one of the body's main responses when we are under stress.
Alphablockers inhibit adrenergic receptors in the arteries and prevent high blood pressure caused by these receptors. CBD can further lower blood pressure and lead to hypotension - especially in the evening or when the user feels particularly relaxed. Interactions are rare, but it may be necessary to reduce the dose of CBD when taking alphablockers.
Alphablockers with possible interactions with CBD:
Carvedilol (Coreg)
Doxazosin (Cardura)
Prazosin (Minipress)
Terazosin (Hytrin)
Angiotensin II & CBD receptor blockers
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Angiotensin II is made by an enzyme called ACE. In most cases, drugs with ACE inhibitors are used first, but if they do not work, an angiotensin II receptor blocker may be used instead.
CBD can interact with these drugs by enhancing their effects. CBD is a known antihypertensive agent that can make the blood pressure too low and cause side effects mimicking hypotension.
Angiotensin II receptor blockers with possible interaction with CBD:
Candesartan (Atacand)
Eprosartan (Teveten)
Irbesartan (Avapro)
Losartan (Cozaar)
Telmisartan (Micardis)
Valsartan (Diovan)
Beta-blockers & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Betablockers target the heart directly. They reduce heart rate and the force of each contraction. This puts less pressure on the arteries and thus lowers blood pressure overall.
CBD is unlikely to interact directly with betablockers, but may compete for metabolism in the liver and cause blood pressure to be too low due to the similarity of effects.
Beta-blockers with possible interaction with CBD:
Acebutolol (Sectral)
Atenolol (Tenormin)
Betaxolol (Kerlone)
Bisoprolol (Zebeta)
Carteolol (Cartrol)
Metoprolol tartrate (Lopressor)
Metoprolol succinate (Toprol-XL)
Nadolol (Corgard)
Penbutolol (Levatol)
Pindolol (Visken)
Propranolol hydrochloride (Inderal, InnoPran & Pronol)
Sotalol hydrochloride (Betapace)
Timolol (Blocadren)
Calcium channel blockers & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Calcium channel blockers work by reducing the amount of calcium that enters the muscle cells of the heart. Calcium is needed for muscle contraction, so by reducing calcium concentrations in heart cells, these drugs may reduce the contractile force of the heart muscle.
Reducing the contractile force of the heart lowers systolic blood pressure in a similar way to beta-blocker drugs. CBD does not interact directly with calcium channel blockers, but may cause blood pressure to drop too low (in theory). It is not common for people taking calcium channel blockers to have negative interactions with CBD.
Calcium channel blockers that can interact with CBD:
Amlodipine (Norvasc, Lotrel)
Bepridil (Vasocor)
Diltiazem hydrochloride (Cardizem CD, Cardizem SR, Dilacor XR, Tiazac)
Felodipine (Plendil)
Isradipine (DynaCirc, DynaCirc CR)
Nicardipine (Cardene SR)
Nifedipine (Adalat CC, Procardia XL)
Nisoldipine (Solar)
Verapamil hydrochloride (Calan SR, Covera HS, Isoptin SR, Verelan)
Central Antihypertensives & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Central agonists do the same job as alpha-blockers - they prevent or reduce arterial contractility and lower blood pressure. They use a completely different mechanism and are usually prescribed when alphablockers do not work.
CBD can interact with these drugs because of the similarity of effects. However, side effects from taking these two classes of drugs are uncommon.
Central antihypertensives with possible interaction with CBD:
Methyldopa (Aldomet)
Clonidine hydrochloride (Catapres)
Guanabenz cetate (Wytensin)
Guanfacine hydrochloride (Tenex)
Diuretics & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Diuretics are a group of drugs used to lower blood pressure by promoting the removal of electrolytes and fluids from the vascular system. If the volume of fluid in the blood decreases, blood pressure will drop along with it.
CBD is unlikely to interact directly with these drugs. However, CBD and diuretics produce the same results - reduced blood pressure. This means that taking these two substances can cause blood pressure to drop too much - resulting in dizziness and fainting.
Diuretics with possible interaction with CBD:
Chlorthalidone (Hygroton)
Chlorothiazide (Diuril)
Hydrochlorothiazide (Esidrix, Hydrodiuril & Microzide)
Indapamide (Lozol)
Metolazone (Mycrox, Zaroxolyn)
Amiloride hydrochloride (Midamor)
Spironolactone (Aldactone)
Triamterene (Dyrenium)
Furosemide (Lasix)
Bumetanide (Bumex)
α-blockers & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Medium
These drugs were some of the first blood pressure medications ever invented. Reserpine has been around since the 1950s. These drugs have many negative side effects and are nowadays only used as a last resort (when other antihypertensives don't work).
CBD can interact with these drugs by causing blood pressure to get too low. It can also interfere with the metabolism of these drugs, increasing the likelihood of side effects. Negative interactions between α-blockers and CBD are more common than with many other blood pressure medications and should be avoided or used with caution.
α-blockers with possible interaction with CBD:
Guanadrel (Hylorel)
Guanethidine (Ismelin)
Reserpine (Serpasil)
CBD & blood thinners
Type of interaction: Metabolic competitor
Severity: High
Blood thinners are a class of drugs used to treat heart disease and stroke. They work by blocking clotting factors or fibrinogen to prevent or break up blood clots that could get stuck in the arteries and cause a heart attack or stroke.
CBD does not directly interact with blood-thinning drugs or have similar effects. However, some blood thinners, such as Warfarin (the most commonly prescribed blood thinner), have negative interactions with CBD.
Warfarin is particularly difficult for the body to metabolize and requires the combined efforts of many different CYP450 enzymes in the liver - primarily CYP3A4 and CYP2C19. Others include CYP1A1, CYP1A22, CYP2C19, CYP2D6 and CYP3A5.
CBD has been shown to struggle for metabolism with all seven of these enzyme pathways and can lead to slow metabolism of warfarin. Within days or weeks, warfarin blood concentrations can rise, leading to a much higher risk of negative side effects caused by the drug itself. These side effects can be life-threatening.
As a result, CBD should not be taken along with any blood-thinning medication unless recommended by the prescribing physician.
Blood thinners that may interact with CBD:
Apixaban (Eliquis)
Dabigatran (Pradaxa)
Enoxaparin sodium (Lovenox)
Heparins
Rivaroxaban (Xarelto)
Warfarin (Coumadin, Jantoven)
Clopidogrel (Plavix)
CBD & Painkillers
CBD is a powerful painkiller in its own right, but it works through completely separate mechanisms than most other painkillers. This means that it is not as likely to interact directly with conventional painkillers. That said, there are several ways that CBD can interfere with different types of painkillers.
The most common is through competitive hepatic metabolism. CBD will interfere with the liver's ability to metabolize painkillers, which could increase the likelihood of treatment side effects - especially with regularly taken medications.
CBD also shares a similar set of side effects as these drugs - such as sedation, dehydration, loss of appetite, diarrhea, and low blood pressure.
You should only take CBD at the same time as painkillers after consulting your doctor. It is also likely that you will need to reduce your dose of CBD
when combined with pain medication.
Opioid analgesics & CBD
Interaction type: Metabolic competitor
Severity: Mild
Opioid painkillers are very common. There are many different types of opioid medications prescribed to treat pain of various origins. They work by activating opioid pain receptors located in the spinal cord and brain. These receptors act as a gateway for pain signals traveling from the body to the brain. When they are activated, either by opioid drugs or by naturally occurring opioids in our bodies (called endorphins), the gates close and reduce the pain signal before it reaches the brain.
Opioids are extremely effective painkillers, but they have a dark side. The opioid system is also closely linked to our dopamine reward system. Activation of opioid receptors causes feelings of euphoria and pleasure that we can easily become addicted to.
CBD is often used as an alternative to opioid medications to prevent addiction - especially for long-term pain that requires regular treatment over weeks, months or years. Taking opioid medications for long periods of time dramatically increases the chances of addiction.
Most opioids do not interact strongly with CBD, but there is potential for negative interaction. CBD can increase the side effects of opioids by competing with metabolism in the liver and can therefore increase the likelihood of overdose.
If you are taking opioid painkillers, you should always talk to your doctor before taking CBD. Your doctor may recommend an adjusted dose of both substances to reduce the risk of side effects.
Opioid analgesics with possible interactions with CBD:
Buprenorphine
Codeine
Pethidine (Meperidine, Demerol)
Fentanyl
Hydrocodone
Hydromorphone (Dilaudid)
Methadone
Morphine
Oxycodone
Tramadol
NSAIDs & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
NSAID stands for "non-steroidal anti-inflammatory drug". They are the most common painkillers. Some of the most well-known examples include Tylenol, Advil, Aleve, and Aspirin.
These drugs work by blocking the enzymes COX-1 or COX-2, which are responsible for the production of pro-inflammatory molecules. Blocking this enzyme stops the inflammation that causes various forms of pain - for example, in an injury, headache or stomach pain.
Several studies have shown that CBD and NSAIDs work synergistically - meaning they mutually enhance the benefits of reducing both pain and inflammation. Many people take NSAID medications and CBD together, but caution is necessary. Because of the synergy between the two substances, it is important to use a smaller dose to avoid side effects.
NSAID medications and CBD are metabolized through the same liver enzymes. The competition for liver enzymes will cause both compounds to remain unmetabolized in the bloodstream for longer periods of time. This is only likely to cause problems if you are taking repeated doses. Since NSAIDs are usually only used regularly or for short periods of time, it is unlikely that the amount of substances from these drugs will rise to toxic levels in the blood. Daily aspirin is an exception, but the dose is much lower and is unlikely to cause problems.
If you take NSAIDs daily, you should consult your doctor before taking CBD. If NSAID concentrations are too high, it can lead to serious liver damage.
NSAIDs with possible interactions with CBD:
Ibuprofen
Celecoxib
Paracetamol (Paralen, Panadol)
Naproxen (Nalgesin)
Ketorolac (Toradol)
Etodolac
Meloxicam
CBD & anti-anxiety medication
One of the most important benefits of CBD is its ability to manage anxiety symptoms. It works by regulating the endocannabinoid system and a neurotransmitter known as GABA. Prescription drugs used to treat anxiety also work through GABA - which can be thought of as a "brake pedal for the neurological system." It is responsible for slowing down neurological activity when it becomes too hyperactive (as is the case with anxiety).
Since CBD and anxiety medications share a similar mechanism of action, there is a particularly high chance that they will interact. It's common for people to combine the two drugs to achieve a lower dose of prescription medication and prevent addiction.
However, these substances should only be combined in consultation with a physician. It may be necessary to reduce the dose of anxiety medication to avoid the risk of side effects.
Benzodiazepines & CBD
Type of interaction: ↑↑↑↑ Increased effect (agonistic)
Severity: high
Benzodiazepines are the most commonly prescribed group of medications for anxiety management. They work by increasing the binding capacity of GABA to inhibit electrical activity in the brain. They are highly effective in preventing or warding off anxiety attacks and also promote sleep in people suffering from insomnia or reduce the frequency and severity of attacks.
Unfortunately, these drugs are also highly addictive. Some drugs, such as Xanax, can lead to addiction in as little as two weeks. Always check with your doctor before combining these medications for any reason.
CBD is very likely to interact with benzodiazepines. The interaction enhances the effects of both substances, which can make them stronger. People who take benzodiazepines and CBD report feeling more sedated and sleepy than usual. Some people use CBD to wean themselves off benzodiazepines by gradually increasing the dose of CBD and decreasing the dose of benzodiazepines.
Benzodiazepines with possible interactions with CBD:
Alprazolam (Xanax)
Chlordiazepoxide (Elenium)
Clonazepam (Rivotril)
Clorazepate (Tranxene)
Diazepam (Valium)
Estazolam (Prosom)
Flurazepam (Dalmane)
Lorazepam (Ativan)
Midazolam (Dormicum)
Oxazepam (Alepam)
Temazepam (Restoril)
Triazolam (Halcion)
Quazepam (Doral)
Barbiturates & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: High
Barbiturates are an older class of anxiety and insomnia medications and anticonvulsants. They have mostly been replaced by benzodiazepines, which are both more effective and less dangerous.
This class of drugs has a similar effect on the body to both CBD and benzodiazepines. Combining CBD with barbiturates is not a good idea, whatever the reason. The combination is very likely to lead to serious side effects.
Barbiturates with possible interactions with CBD:
Amobarbital
Butabarbital (Butisol)
Methylphenobarbital (Mebaral)
Pentobarbital (Nembutal)
Phenobarbital (Luminal)
Secobarbital (Seconal)
CBD & antidepressants
CBD is an excellent antidepressant - but only when used long-term. The benefits of CBD for depression become apparent after a prolonged period of time. CBD promotes hormonal and neurochemical balance and reduces inflammation in the brain that could be contributing to depressive symptoms.
Most prescription antidepressants work through completely separate mechanisms and are unlikely to interact directly with CBD. Instead, most of the dangers associated with the combination of these substances come from the struggle of liver metabolism.
Antidepressants are used daily, so any changes in the metabolic rate of these drugs could lead to a gradual increase in blood concentrations. If left unchecked, drug concentrations can reach toxic levels - leading to serious side effects such as serotonin syndrome.
Selective Serotonin Reuptake Inhibitors & CBD
Interaction type: Metabolic competitor
Severity: Medium
Serotonin is one of the key regulators of mood, so these drugs are used to increase the concentration of serotonin at synapses to improve mood. Whenever serotonin is released, it is reabsorbed at synapses where it is broken down. SSRIs work by blocking the reabsorption of serotonin - allowing it to stay at the synapses for longer periods of time.
Selective serotonin reuptake inhibitors (SSRI) - are the most common class of antidepressants used today.
In general, CBD can be taken with antidepressants, but with caution. Most of the dangers of this combination come with long-term joint use. CBD can slow the metabolism of SSRI and cause them to accumulate in the blood. If the dose is too high, it can cause something called serotonin syndrome - which happens when serotonin levels are too high.
The side effects of this condition can be serious and should be avoided at all costs. If you're going to combine CBD with an SSRI, be sure to stick to lower doses, take a break every few days, and talk to your doctor if you experience any side effects.
SSRIs with possible interactions with CBD:
Citalopram (Citalec)
Dapoxetine (Priligy)
Escitalopram (Cipralex)
Fluoxetine (Prozac, Deprex)
Fluvoxamine (Faverin)
Paroxetine (Seroxat)
Sertraline (Zoloft)
Vortioxetine (Brintellix)
Serotonin and norepinephrine reuptake inhibitors & CBD
Interaction Type: Metabolic Competitor
Severity: Mild to moderate
Serotonin and norepinephrine reuptake inhibitors (SNRI) are a secondary treatment option for depression when SSRIs do not work. SNRIsare also a good choice for people who have both depression and anxiety.
These medications work by the same mechanism as SSRI, but with one difference. These drugs increase concentrations of serotonin and the related neurotransmitter norepinephrine. CBD may interact with SNRI drugs in two main ways - it competes for drug metabolism in the liver (primarily with the CYP3A4 enzyme) and may negate some of the benefits of SNRIs (in theory).
SNRI follow a very specific dosing schedule, just like SSRI. The dose is administered carefully to achieve consistent levels of the drug in the body. The dose is calculated based on weight and titrated to ensure consistent levels of the individual patient's metabolism.
When CBD is added to the mixture, it can alter the rate of drug metabolism. Over time, the concentration of drugs can increase, eventually leading to symptoms of toxicity or overdose.
SNRIs with possible interaction with CBD:
Atomoxetine (Strattera)
Desvenlafaxine (Pristiq)
Duloxetine (Cymbalta, Dulsevia)
Levomilnacipran (Fetzima)
Milnacipran (Toledomin)
Venlafaxine (Effexor)
Tricyclic Antidepressants & CBD
Interaction Type: Metabolic Competitor
Severity: Medium
Tricyclic antidepressants are an older class of medications for depression. They are still used today, but only when other treatments do not produce the desired results. They block the reuptake of serotonin and norepinephrine, but also interact with other neurotransmitters. They are considered a "dirty drug" because they interact with receptors we don't want to target. This gives them a lot of other side effects that other drugs like SSRIs or SNRIs don't have.
CBD and tricyclic antidepressants can be combined, but always check with your doctor first. Compared to other antidepressant medications, there is a greater chance of serious side effects with higher doses of CBD.
Tricyclic antidepressants with possible interactions with CBD:
Amitriptyline (Elavil)
Amoxapine (Asendin)
Desipramine (Norpramin)
Doxepin
Imipramine (Melipramine, Tofranil)
Nortriptyline (Notrilen, Pamelor)
Protriptyline (Vivactil)
Trimipramine (Surmontil)
Monoamine oxidase inhibitors & CBD
Type of interaction: Metabolic competitor
Severity: Mild
Monoamine oxidase (MAO) is the primary enzyme responsible for the breakdown of the monoamine class of neurotransmitters. This includes serotonin, dopamine, and noradrenaline - all of which are involved in mood regulation. MAO inhibitors are used to increase the concentration of neurotransmitters in the brain to improve mood.
This class of antidepressants is not as popular as SSRI or SNRI. They are considered less effective and lead to side effects more often than other classes of drugs. Some people find this class of drugs more effective for mood regulation than other antidepressants. Everyone is different, so it is common for a doctor to try several medications to see what works in treating a new patient with depression.
CBD does not directly interact with MAO, but may compete for metabolism in the liver. Many MAO inhibitors are metabolized by the enzymes CYP2D6, CYP1A2, and CYP2C19 - all of which are also affected by CBD.
Like all antidepressants, MAO inhibitors are used consistently every day. If metabolism is slowed enough for these drugs to accumulate in the blood, side effects or toxicity may result. It is wise to take lower doses of CBD and take regular breaks if you are combining these two substances together.
If you have been prescribed MAO inhibitors, you should consult your doctor before taking any other substances.
MAO inhibitors with possible interaction with CBD:
Isocarboxazid (Marplan)
Phenelzine (Nardil)
Selegiline (Selegos)
Tranylcypromine (Parnate)
Serotonin molecule.
Serotonin antagonists and serotonin reuptake inhibitors & CBD
Interaction type: Metabolic competitor (CYP3A4)
Severity: Mild
Serotonin antagonists and serotonin reuptake inhibitors (SARI) are a type of antidepressant, anxiolytic, and insomnia medication. They are rarely used as a first line of defense against depression, but are commonly prescribed to patients with depression, anxiety, and insomnia.
These drugs block the serotonin 5-HT2A receptor and block serotonin transporters - leading to increased serotonin activity in the brain.
These drugs are heavily dependent on CYP3A4 enzymes in the liver. When taken together with CBD, concentrations of this drug can increase, leading to a higher risk of side effects from the treatment and a higher likelihood of developing dependence on the drug.
The most common side effects of SARI drugs include headaches, nausea, indigestion, confusion, restlessness and sedation.
SARI drugs with possible interactions with CBD:
Trazodone (Trittico)
Nefazodone (Serzone, Nefadar)
Norepinephrine & Dopamine Reuptake Inhibitor & CBD
Type of interaction: ↓↓ ↓ Reduced effect (antagonistic)
Severity: Mild
Noradrenaline-dopamine reuptake inhibitors (NDRIs) are used to treat depression as well as a number of other medical conditions - including ADHD, narcolepsy, and Parkinson's disease. They work by increasing the concentration of dopamine and norepinephrine in the brain by blocking the reuptake channels that work to destroy them.
CBD is unlikely to have any significant interactions with these drugs - but with consistent use it can cause an increase in NDRI concentrations. CBD may interfere with the metabolism of these drugs, which require CYP2B6 enzymes. CBD competes for these enzymes, but as much as other enzymes.
Many of the effects of NDRI drugs are naturally stimulatory. CBD has a greater inhibitory effect on the brain, which could negate many of the benefits of these drugs and reduce their effectiveness. Some findings suggest that this effect is beneficial in mitigating common side effects of these drugs. More research is needed to fully understand whether it is safe to combine CBD with NDRIs.
If you are taking any psychiatric medications, you should talk to your doctor before trying CBD.
NDRIs with possible interactions with CBD:
Bupropion (Budeprion, Elontril)
Amineptine (Survector)
Desoxypipradrol
Dexmethylphenidate (Focalin)
Difemetorex (Cleofil)
Diphenylprolinol
Ethylphenidate (Centedrine)
Fencamfamin (Glucoenergan, Reactivan)
Fencamine (Altimina, Sicoclor)
Lefetamine (Santenol)
Methylenedioxypyrovalerone
Methylphenidate (Ritalin)
Nomifensine (Merital)
O-217
Phenylpiracetam (Phenotropil)
Pipradrol (Meratran)
Prolintane (Catovit)
Pyrovalerone (Centroton)
Solriamfetol (Sunosi)
Tametraline
WY-46824
CBD & stimulants/eugeroics
Type of interaction: ↓↓↓ Reduced effect (antagonistic)
Severity: Mild
Stimulant medications are used to treat conditions such as ADHD, narcolepsy, or chronic fatigue syndrome. They are often used to increase attention and concentration at work or university. They work by increasing the secretion of neurotransmitters such as dopamine and noradrenaline.
Many people take CBD along with stimulant medications as a way to counteract some of the side effects of these drugs - which often include muscle tension and anxiety. Caution is always necessary when using substances together that have opposing effects - one pushes the nervous system into a higher gear (stimulants), the other suppresses nervous system activity (CBD).
Serious interactions are unlikely when stimulants and CBD are combined, but it is wise to be cautious with dosage. Check with your doctor first and start with only a very small dose of CBD. You can gradually increase the dose by adding 2 mg of CBD to each of your daily doses until you find the right balance for your body.
It's possible that CBD will reduce the effectiveness of stimulant medications, which may prevent them from working. Some of the other cannabinoids in cannabis plants can also interfere with stimulants - primarily THC.
Stimulants and THC are a bad combination and often lead to side effects. Always make sure that the cannabis products you use contain almost no THC or related cannabinoids such as CBN or THCV.
Stimulants & eugeroics with possible interaction with CBD:
Amphetamine
Lisdexamfetamine
Dextroamphetamine sulphate
Methylphenidate (Ritalin)
Atomoxetine (Strattera)
Modafinil (Vigil)
CBD & immunomodulators
Immunomodulators are drugs that interact with the immune system. Some increase immune activity, others suppress it. They are used to block inflammation, treat allergic reactions, treat autoimmune disorders, or stimulate immune activity during infections or cancer treatment.
CBD has a strong correlation with the immune system but does not interact with most immune system drugs. A few exceptions include antihistamines and immunosuppressants.
Antihistamines & CBD
Type of interaction: ↑↑↑ Increased effect (antagonistic)
Severity: Medium
Antihistamines are mainly used to treat allergic reactions. Histamine is a compound released by a special type of immune cell called mast cells (mast cells). These cells remain dormant until something activates them (the allergen).
When they become active, mast cells burst and release large amounts of histamine and other pro-inflammatory compounds. These compounds cause the symptoms we experience as an allergic reaction (runny nose, watery eyes, swelling, itching and sneezing or coughing).
One of the main side effects of antihistamines is sedation. Histamine also plays a role in regulating mental alertness and stimulation, so blocking this compound can cause sedation and fatigue. The sedative and relaxing properties of CBD can further amplify the side effects of antihistamines.
If you are already suffering side effects from taking antihistamines, it is wise not to take CBD. While this substance is unlikely to result in any serious interactions, it is likely to exacerbate the side effects you are already experiencing.
Antihistamines with possible interactions with CBD:
Carbinoxamine (Rotoxamine)
Desloratadine (Clarinex)
Hydroxyzine (Atarax)
Levocetirizine
Brompheniramine (Dimetapp)
Cetirizine (Zyrtec)
Chlorpheniramine
Clemastine (Mescaline, Tavegyl)
Diphenhydramine (Benadryl)
Fexofenadine
Loratadine (Claritin)
Immunosuppressants & CBD
Type of interaction: ↓↓↓ Reduced effect (antagonistic)
Severity: Severe
CBD should never be taken with immunosuppressants unless on the direct recommendation of your physician.
CBD has immune stimulating properties, especially in people with suppressed immune function. Taking CBD along with immunosuppressants may suppress or negate the effects of immunosuppressants. This can render the drugs ineffective, leading to a worsening of the underlying condition.
Since immunosuppressive drugs are used to treat serious medical conditions or to prevent organ rejection after an organ transplant, it can be very dangerous if the drugs do not work effectively.
Immunosuppressive drugs with possible interactions with CBD:
Azathioprine (Imasup)
Mycophenolate mofetil
Cyclosporine (Equoral)
Methotrexate (Injexate)
Leflunomide (Leflon)
Prednisone
Cyclophosphamide (Endoxan)
Chlorambucil (Leukeran)
Nitrogen yperite
CBD & diabetes medication
About 1 in 10 Czechs have been diagnosed with diabetes (2020). This makes diabetes medication one of the most common concerns for people who want to use CBD.
There are dozens of medications that doctors can prescribe to manage diabetes, depending on the severity of the condition. Most of these medications will not interact with CBD directly - however, it is wise to start with a low dose of CBD to reduce the risk of negative interactions.
CBD has some regulatory effects on blood sugar levels, which can cause blood pressure to become too low when taking medications such as metformin or DPP-4 inhibitors. If blood pressure drops too low, it can lead to hypoglycemia and fainting - which can be dangerous.
If you are taking anti-diabetic medication, always talk to your doctor before using CBD.
Alpha-glucosidase inhibitors
Interaction type: No significant interaction expected (possible mild agonist effect)
Severity: Mild
Alpha-glucosidase is an enzyme in the digestive system responsible for breaking down sugars so they can be absorbed. These drugs are used to block the effects of this enzyme and to reduce the amount of sugar that can enter the blood.
CBD is unlikely to have a strong reaction with these drugs. There is a small risk of interaction, causing blood sugar levels to drop too low due to similar effects on blood sugar levels. It is also possible that when alpha-glucosidase inhibitors are taken at the same time, CBD absorption is affected, leading to reduced CBD effectiveness.
Alpha-glucosidase inhibitors with possible interaction with CBD:
Biguanides & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
There is only one biguanide on the market today - called metformin - which is not only the most common treatment for type II diabetes, but also one of the most commonly prescribed drugs in the world. Metformin works by blocking the liver's production of glucose, thereby lowering blood sugar levels and increasing the sensitivity (effectiveness) of insulin in the body.
There are two potential interactions between CBD and metformin. Both compete for the same liver enzymes (primarily CYP3A4), which could lead to increased concentrations of both substances.
The second interaction involves the effects of both substances on blood sugar levels. Both metformin and CBD lead to an overall reduction in blood glucose levels - although they achieve this by completely different mechanisms. It is possible that CBD and metformin may lead to hypoglycaemia when used together.
Consequently, many people take CBD together with metformin without any side effects. Some reports even suggest that CBD and Metformin have a positive interaction - leading to even better results.
The risk of this interaction is low, but not zero. If you are taking Metformin to treat diabetes, you should always ask your doctor about CBD before taking it.
Biguanides with possible interactions with CBD:
Metformin (Diareg, Metformin, Siofor, Stadamet, Nosmaglyc)
DPP-4 inhibitors
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Dipeptidyl peptidase-4 (DPP-4) is an enzyme whose function is to break down a class of digestive enzymes called incretins. Incretins stimulate insulin production after a meal and block the production of glucagon (which counteracts insulin). DPP-4 inhibitors block this enzyme, leading to an increase in incretin concentration. This is thought to promote higher insulin levels and lower glucagon levels.
Many of these drugs, especially saxagliptin and sitagliptin, require a large involvement of liver enzymes such as CYP3A4 and CYP3A5 enzymes [7]. They also have a very long half-life.
This increases the risk of adverse effects when used in combination with other substances that require metabolism from these enzymes - including CBD. DPP-4 inhibitors other than sacagliptin and sitagliptin do not have a strong dependence on these enzymes and are much less likely to interfere with CBD.
DPP-4 inhibitors are used on a daily basis, so it is possible that over time, if used in conjunction with CBD, blood concentrations of the drug may increase to toxic levels. This would lead to higher rates of side effects caused by the treatment itself - these include nausea, flu-like symptoms or painful skin reactions.
Second, the main effect of DPP-4 inhibitors is to lower blood glucose levels. This could amplify the hypoglycemic effects of CBD and lead to symptoms associated with low blood sugar.
DPP-4 inhibitors with possible interaction with CBD:
Alogliptin (Vipidia)
Linagliptin (Trajenta)
Saxagliptin (Onglyza)
Sitagliptin (Januvia, Tesavel)
GLP-1 & CBD agonists
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
GLP-1 is a glucagon-like peptide-1 - which is an incretin-based drug. These drugs are similar to DPP-4 inhibitors, but instead of blocking the enzyme that destroys incretin, they stimulate incretin receptors with synthetic versions of these important hormones.
The effects are increased feelings of satiety and increased insulin secretion. They are used in weight loss and blood sugar control. GLP-1 agonists do not have a strong effect on CYP450 enzymes and are unlikely to have a significant interaction with CBD.
The main concern about potential interactions between CBD and GLP-1 receptor agonists is the anti-appetite effect. Both CBD and GLP-1 agonists reduce appetite.
GLP-1 agonists with possible interaction with CBD:
Albiglutide
Dulaglutide (Trulicity)
Exenatide (Byetta, Bydureon)
Liraglutide (Victoza, Saxenda)
Semaglutide (Ozempic)
Glinides & CBD
Type of interaction: ↑↑↑↑ Increased effect (agonistic)
Severity: Mild
Glinides act by stimulating insulin release in diabetic patients. They stimulate the beta cells of the pancreas directly where insulin is produced.
The chances of interactions between CBD and meglitinides are very low - but not nil. The combined effect of these substances on lowering blood sugar can lead to hypoglycemia (low blood sugar).
Glinides are primarily metabolized by CYP2C8 and CYP3A4. CBD has only been shown to compete with the former, but this is unlikely to lead to significant competitive hepatic metabolism issues with this class of drugs.
Glinides with possible interaction with CBD:
Nateglinide (Starlix)
Repaglinide (Prandin)
SGLT-2 inhibitors & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
SGLT-2 is a sodium and glucose transporter involved in the reabsorption of sugar by the kidney. Blood is first filtered by the kidneys, which removes various metabolites and sugar. Much of the removed sugar is then reabsorbed later by SGLT-2 transporters.
Medications block this transporter to prevent sugar from re-entering the system - leading to an overall reduction in blood sugar levels. CBD is unlikely to interact negatively with these drugs, but could theoretically cause blood sugar levels to drop too much - leading to hypoglycemia (low blood sugar).
SGLT-2 inhibitors with possible interaction with CBD:
Dapagliflozin (Farxiga)
Canagliflozin (Prominad)
Empagliflozin (Jardiance)
Ertugliflozin (Steglatro)
Sulfonylurea & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Sulfonylureas work similarly to glinides by stimulating insulin secretion from the pancreas.
CBD is unlikely to interact directly with these drugs, but it is possible that the combination will lead to a stronger effect on blood sugar control, which could cause blood sugar levels to become too low. Hypoglycaemia can cause dizziness, poor coordination, mood changes and fainting.
Sulfonylurea with possible interaction with CBD:
Glimepiride (Amaryl, Glimepiride)
Glipizide (Glucotrol, Minidiab)
Glibenclamide (Glyburide)
Chlorpropamide (Diabinese)
Tolazamide
Tolbutamide (Orinase)
Thiazolidinediones & CBD
Interaction type: Unknown interaction (not recommended)
Severity: Mild
Thiazolidinediones are a class of drugs that bind and activate the gamma receptor activated peroxisome proliferator located in fat cells. This drug increases the maturation of fat cells and increases the conversion of sugar to stored fat - thereby lowering systemic blood sugar levels. The main side effect of these drugs is weight gain.
There are no known interactions between CBD and thiazolidinediones, but theoretically the combination could lead to an excessive drop in blood sugar.
In addition, CBD has been shown to interact with fat storage, which could interfere with the ability of these drugs to exert their effects. This could negate the effectiveness of these drugs. Until further research is done, it is not recommended to combine CBD and thiazolidinediones unless recommended by a physician.
Thiazolidinediones with possible interaction with CBD:
Rosiglitazone (Avandia)
Pioglitazone (Actos, Novapio)
Insulin & CBD
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
Insulin is the primary treatment for patients with type I diabetes (juvenile-onset diabetes). People with this type of diabetes cannot make insulin on their own.
Studies have shown that CBD can affect insulin resistance and blood sugar levels - but there is no indication that CBD blocks the effects of insulin or causes an unnatural drop in blood sugar.
That said, most experts are cautious about taking CBD and insulin together because they fear it may cause problems with hypoglycemia.
Insulin Aspart (NovoLog, NovoRapid, Fiasp)
Insulin Glulisine (Apidra, Apidra, SoloStar)
Insulin Lispro (Humalog, Liprolog, Admelog)
Insulin Isophane (Novolin N, Humulin N, Insulatard)
Insulin Degludec (Tresiba)
Insulin Detemir (Levemir)
Insulin Glargine (Lantus, Toujeo, Abasaglar)
CBD & erectile dysfunction (ED) drugs
Most erectile dysfunction medications work the same way. They promote dilation of the small blood vessels that supply blood flow to the penis. By dilating the arteries, it is easier for men to achieve an erection.
CBD is unlikely to interact with these drugs, but it could interfere with metabolism in the form of competition for CYP3A4. This would lead to stronger effects of both CBD and ED medications, which could increase the risk of side effects from these drugs, which include headaches, indigestion, diarrhea, or priapism.
If you are taking either of these medications, take a more moderate dose of CBD than you might otherwise take.
Erectile dysfunction medications with possible interactions with CBD:
Sildenafil (Viagra)
Tadalafil (Cialis)
Vardenafil (Levitra, Staxyn, Vivanza)
Avanafil (Stendra)
Mirodenafil (Mvix)
Udenafil (Zydena)
CBD & 5α-Reductase Inhibitors
5α-Reductase inhibitors are a class of drugs that block the conversion of testosterone to dihydrotestosterone (DHT) by blocking the enzyme that performs the conversion.
When testosterone is converted to DHT by an enzyme called 5-alpha-reductase, it is thought to alter the life cycle of the hair follicle - causing the hair to become shorter, thinner and eventually stop growing altogether. In the prostate, this is associated with a condition called benign prostatic hyperplasia (BPH) - which is an increase in tissue leading to a larger organ size.
5-alpha-reductase inhibitors are common drugs to treat both male pattern baldness and BPH. CBD can interfere with the metabolism of these drugs on CYP3A4 enzymes - although the likelihood of negative side effects with this combination is rare, it is not zero. Interactions may include an increased risk of side effects from the drugs, such as breast enlargement, skin rashes, and decreased libido.
5α-reductase inhibitors with possible interaction with CBD:
Alfatradiol (Avicis, Avixis,Pantostin)
Dutasteride (Avodart)
Epristeride (Aipuliete, Chuanliu)
Finasteride (Gefin, Finpros, Adafin, Proscar)
Serenoa creeper extract (Permixon, Serenoa)
CBD & statins
Interaction type: Metabolic competitor (CYP3A4)
Severity: Moderate
Statin drugs are used to reduce cholesterol production in the liver. They work by blocking an enzyme called HMG-CoA reductase.
While CBD is unlikely to interact with statin drugs directly and has a completely separate set of effects, there is a strong potential for CBD to interfere with the metabolism of statins - most of which rely heavily on CYP3A4 enzymes in the liver.
Taking CBD and statins together could lead to increased serum concentrations of the drug over time. Always talk to your doctor before using CBD with statins.
Statins with possible interactions with CBD:
Atorvastatin (Atoris, Atorstad, Torvacard)
Lovastatin (Mevacor, Altocor)
Pitavastatin (Livalo, Livazo)
Pravastatin (Pravachol, Selektine)
Rosuvastatin (Crestor, Rosulip, Zuvamor)
Simvastatin (Zocor)
Proton Pump Inhibitors & CBD
Interaction type: Metabolic Competitor (CYP2C19)
Severity: Mild
Proton pump inhibitors (PPIs) are the most commonly prescribed group of medications for the management of heartburn, gastroesophageal reflux disease (GERD), and other stomach acid-related conditions. They work by blocking the parietal cells in the stomach that secrete stomach acid.
PPI drugs are largely metabolized by the liver enzyme CYP2C19, which is also one of the tools used to metabolize CBD, albeit to a lesser extent. This could be a source of negative interaction with CBD.
The most likely negative interaction is a stronger impact of CBD due to slower metabolism. If you are taking proton pump inhibitors, you should take a smaller dose of CBD.
Proton pump inhibitors with possible interaction with CBD:
Pantoprazole (Apo-panto, Nolpaza, Controloc)
Ranitidine (Zantac)
Omeprazole (Omeprazole, Ortanol)
Lansoprazole (Lanzul, Prevacid)
Rabeprazole (Rapoxol, Aciphex)
Esomeprazole (Emanera, Nexium)
Dexlansoprazole (Kapidex, Dexilant)
CBD & asthma medication
Type of interaction: ↓↓↓ Reduced effect (antagonistic)
Severity: Mild
Asthma is a chronic immune disorder affecting the lungs. When the immune system is exposed to an allergen, it causes the airways to close and secrete thick mucus that makes breathing difficult. Asthma medications focus on blocking the immune response and forcing the airways open to allow more air to flow into the lungs.
CBD interacts strongly with one asthma drug in particular known as theophylline. CBD can speed up the elimination of theophylline from the body, leading to reduced effectiveness.
Other interactions can occur with steroid-type drugs such as albuterol and ipratropium bromide. CBD relaxes the sympathetic nervous system, which can counteract the effects of these drugs - which rely on sympathetic nervous system activation to dilate the airways and treat symptoms.
Anyone with a history of asthma should avoid inhaled forms of CBD use, including the use of a vaporizer.
Asthma medications with possible interactions with CBD
Salbutamol (Ventolin)
Fluticasone (Flixotide, Nasofan)
Montelukast (Montelar, Montelukast)
Ipratropium bromide (Atrovent, Apovent, Aerovent)
Theophylline (Theoplus, Afonilum, Euphyllin)
CBD & antimicrobials
Interaction type: Mixed (increased or decreased effect)
Severity: Mild
There are four main types of antimicrobials - antibacterials, antifungals, antivirals and antiparasitics (include anthelmintics, antiamoebics and antiprotozoics).
There are so many different compounds that act as antimicrobials, it is difficult to group them all into one. Each compound works differently, is metabolized differently and produces different side effects.
Some studies suggest that CBD may increase the effectiveness of some antibiotics and may offer a promising solution to the problem of antibiotic resistance.
However, this is not the case for all antimicrobials. Some antimicrobials compete for the same enzymes in the liver. Antimicrobials are different, so check with your doctor about whether or not CBD is safe to take with your prescription medication.
CBD & alcohol
Type of interaction: ↑↑↑ Increased effect (agonistic)
Severity: Mild
CBD has little interaction with alcohol. Both substances have a sedative and hypotensive effect. When taken together, these side effects can be accentuated.
It's rare that people experience anything more than a mild interaction between the two substances, but in some cases the impact can be severe, leading to dizziness, loss of coordination, fainting, or lethargy and malaise.
Summary: Will CBD interact with my medications?
CBD is a very safe health supplement overall. It rarely produces more than mild side effects and has a low potential to interact with most medications or other dietary supplements. However, negative drug interactions are still possible.
There are three ways CBD can interact with other drugs - it can enhance the primary or side effects of other drugs by having the same effect. It can stop the effects of a drug or substance by producing opposite effects. Or it can interfere with the metabolism of certain drugs in the liver - causing an increase in blood concentrations of the drug.
The greatest caution is needed when taking CBD with benzodiazepines, barbiturates, immunosuppressants or drugs used to lower blood pressure.
If you are taking prescription medications, it is a good idea to talk to your doctor about taking CBD first. If you use CBD, start with a very low dose at first and increase it only after you know how your body reacts. If you're taking medication long-term, it's also a good idea to take regular breaks from taking CBD every few days.
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