CBD Drug interactions

CBD Oil Drug Interactions – The CYP450 Pathway

Research has begun to demonstrate that cannabidiol (CBD) has the potential to effectively help a large number of people. CBD interacts with the endocannabinoid system in a way that produces very few unintended side-effects.

While the majority of the vast majority of the science indicates CBD is safe for use and consumption, it does pose a few risks that, if not properly understood, could be dangerous.

One of these risks is the inhibition of the cytochrome P450 enzyme system.

Competing with cytochrome 

The basic mechanism of the CBD-drugs interaction is their effect on cytochrome P450. This sofisticated moniker relates to a family of liver enzymes which plays the crucial role in metabolizing drugs. This key enzyme group metabolizes most of the drugs we consume, including more than 60 percent of marketed meds. It is therefore extremely versatile compound, especially considering that the majority of liver enzymes metabolize only one substance – or a group of substances.

Enters CBD. In short, cannabidiol acts as a competitive inhibitor of cytochrome P450.Great, but what does it mean? This means that while being itself metabolised by P450 CBD largely “draws all his attention” – thus halting its action on other substances it would normally metabolise  (another potent inhibitor of P450 is bergapten, commonly found in grapefruit). Of course, it is not that easy – the  course and effects of inhibition of the process will depend on the dose and form of CBD intake… and also on whether we use isolate or the whole plant extract (which is the advisable way in most cases, due to the hauled entourage effect). Especially the last factor should be considered, bearing in mind that the majority of pre-clinical trials and clinical trials have been carried out on pure CBD or on drugs based on its isolate (eg. Sativex).

Will CBD will make the drugs stop working?

Without delving deeper into the nature of the complex CBD-cytochrome interaction one thing is known for sure: starting from a certain threshold dose, cannabidiol will gradually slow down metabolising of certain drugs. To make things more complex, neither the threshold dose (GW Pharmaceuticals, studies have shown no interactions below the 40mg dose, although others estimated the limit already at 25mg), nor whether the slowing down of the drug metabolism would weaken… or strengthen their effect cannot be clearly defined!

To explain this apparent paradox we have to realize how complex the process of metabolising any substance is. The key ingredient of a drug may sometimes have a completely different effects than its metabolites. Take, for example, ethanol – it makes us feel great – at the beginning, but its metabolites … well, we’ll see on the first of January. Sometimes the difference is just the potency of the drug – for instance, much stronger than the psychoactive effects of THC (the major psychoactive compound of cannabis) are those of its main metabolite – 11-OH-THC. The ability of limiting the amount of this derivative explains the antipsychotic effect of CBD when administrated together with THC, an interesting property analyse in depth here. The same happens with medicines – there are some drugs that combined with a large dose of CBD will produce a much weaker effect – because the main active substance are their metabolites, but there are also those – and they are many of them – that work primarily in their “basic version”; and to metabolize them means  effectively discarding them from the body, thus halting their effect. And it is this latter group of drugs that is related to the potentially dangerous side effects of taking large doses of pure CBD.

The most serious interactions

As it is often – far too often! – the case with cannabidiol, studies on its interactions with other medicines are still quite scarce. The researcher who explained the CBD interaction with cytochrome P450 was Lester Bornheim to whom we owe discovering the potential of CBD in the treatment of refractory epilepsy.. Bornheim drew scientists’ attention to the interesting property, which was confirmed by number of further studies: although CBD could potentially alleviate epilepsy, at the same time it interacts with cytochrome P450 – and it does it more effectively than conventional antiepileptic drugs. This, in turn,  causes those drugs to remain longer in the body in a non-metabolized form. Given the toxicity of substances such as clobazam, admissionning CBD together with the more conventional measures should be carefully monitored, as it may likely effect with the need to reduce the dose of the latter. The matter is even more complex, as it has been proven that the dose of CBD able to disturb the effect of the traditional medicines can still be too low to allow the trigger the antiepileptic effect of CBD itself – so that the patient will only experience negative side effects, without any therapeutic ones! These, and other, problematic interactions with medicines are being dicussed it the Project CBD report we have recently published.

Other equally serious potential side can be caused by mixing CBD with chemotherapy drugs. The very principle of this group of drugs is based on the fact that their daily dosage lays just below the toxicity threshold. The consequences of their prolonged presence in the bloodstream – something that can be, indeed, caused by CBD – are grave: the toxicity level may be exceeded, and the medicine will effectively become a poison!

More common, but potentially just as dangerous, is the troublesome interaction  of CBD and anticoagulants, such as warfarin. Again, we are dealing here with a prolonged effect of the drug – which could be potentially dangerous. At this point it is essential to tell your doctor before you start to take large doses of CBD.

There are also reports of potentially problematic interactions of cannabidiol and: rifampicin, alcohol, griseofulvin, phenobarbital and sulfonylurea.

Should I quit my therapy or dump CBD?

There is no need to panic, though. Most likely you do not need to quit taking anything, still – it is always a wise idea to consult a doctor. Stay calm, and let us remind you the following:

  • quoted data relates to CBD as a drug – that is, in the form it is not used in Switzerland,
  • the CBD is available in Switzerland in the form of CBD hemp oil – organic plant products with the status of dietary supplements
  • Interactions of CBD and certain other medicines are often connected to the cannabidiol’s impact on the very same diseases the drug had been prescribed to heal in the first place – the dose reduction won’t necessarily not change the effectiveness of the treatment, as CB will simply replace the medicine
  • so far, all scientific data indicates that the CBD brings more benefits than the potential harm , and the latter can be avoided through better understanding of the mechanism of interaction Once again – further research is needed here.

All the above do not change the fact that even with CBD’s  being “just” a dietary supplements,  any sign – or fear – of its potential interactions with any medication (not prescription drugs) calls for the consultation with the physician. In the interner we can come across  an advice like “do grapefruit test” – if a drug can be taken with the fruits, the CBD will make no harm neither. Although there is some logic in to this madness (the large amounts of bergapten contained in these fruits would interact with cytochrome P450 in a similar way as CBD does), this is not a wise idea: medicinal grade CBD works stronger  than a biggest grapefruit, long gone are also the days when doctors condemned anything that had anything to do with cannabis.

What is the Cytochrome P-450 System?

Found within the liver, the cytochrome P450 enzyme system is responsible for metabolizing potentially toxic compounds, including over 60% percent of any drugs you have consumed.

According to Davis’s Drug Guide, this system contains more than 50 enzymes that process and eliminate toxins.

Why Does CYP450 Matter?

In order to determine the appropriate dosages of medications, doctors make calculations using the average amount of time it takes for various drugs and medications to be processed through the cytochrome P450 system.

If only one drug is being processed, and the system is generally healthy, these averages provide accurate dosage information.

However, certain substances have the ability to affect processing times within this system, making drugs metabolize faster or slower than they would on their own.

Similarly, if the cytochrome P450 system is unhealthy due to problems with the liver or other pre-existing conditions, drugs may not metabolize as they should.

Cannabidiol in the Cytochrome P-450 System

Cannabidiol can inhibit the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times.

Interestingly, CBD is not alone in its effect on drug metabolism. Grapefruit, watercress, St. John’s Wort, and goldenseal all have a similar impact in terms of CYP450 inhibition.

When the CYP450 system is impacted in this way, it leads to higher levels of certain drugs in your system at one time. This can cause unwanted side effects, and sometimes, an overdose.

If you are taking a medication affected by cannabidiol, you should consult your doctor to make sure that it is safe for you to supplement your personal care routine with CBD. From there, the two of you may consider adjusting the dosage on your medications so that you can use both products safely.  

Drugs that Interact with Cannabidiol

Any drug metabolized by CYP450 enzymes could potentially interact with cannabidiol. According to the Indiana University Department of Medicine, drugs known to use the CYP450 system include:

  • Steroids
  • HMG CoA reductase inhibitors
  • Calcium channel blockers
  • Antihistamines
  • Prokinetics
  • HIV antivirals
  • Immune modulators
  • Benzodiazepines
  • Antiarrythmics
  • Antibiotics
  • Anesthetics
  • Antipsychotics
  • Antidepressants
  • Anti-epileptics
  • Beta blockers
  • PPIs
  • NSAIDs
  • Angiotension II blockers
  • Oral hypoglycemic agents
  • Sulfonylureas

This list does not include all of the potential medications impacted by cannabidiol. Nor will every medication in the categories contained on this list will cause an interaction. For these reasons, you should consult with a medical professional before supplementing with CBD.

There are certain medications, known as “prodrugs,” that need to be metabolized to produce the therapeutic compound. In other words, you ingest an inactive compound and once in the body, it is processed into the active drug. If this processing is dependent on CYP3A4 (part of the larger CYP450 system), then inhibitors can result in too little active drug in the body for the desired therapeutic effect.

Codeine, for example, is a prodrug that is metabolized into morphine which provides the effect.

Vyvanse and Concerta are two other popular pharmaceutical medications for ADHD that fall into this category.

If you are worried that your CYP450 pathway may not be functioning properly, physicians can test the system to ensure that the medications you take are metabolizing as expected.

Combining Alcohol and CBD Oil

Alcohol and cannabis are both widely consumed in our society and the effects of combining the two are well known.

What is less understood by the general public, is the effects of combining alcohol and the cannabinoid compound CBD.

Alcohol depends on a few different metabolic pathways in the human body, with the primary enzymes involved being:

In people who only drink socially or occasionally, ADH and ALDH handle the entire workload of metabolizing ethanol. However, when binge drinking (or during chronic consumption of alcohol) CYP450 gets involved to assist the overloaded ADH and ALDH pathways.

Here are some interesting tidbits about alcohol and CBD:

  • The CB1 receptor is a significant player in the reinforcing and motivating attributes of alcohol. [S]
  • Combining alcohol and CBD results in significantly lower blood levels of alcohol. [S]
  • CBD reduces the reinforcement, motivation and relapse for alcohol. [S]
  • CBD protects the liver from damage done by binge-drinking alcohol. [S]
  • CBD prevents against alcohol-induced neurodegeneration. [S]
  • CBD attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury. [S]
  • Cannabinoids have an effect on nearly all enzymes responsible for metabolizing alcohol. [S]
  • CB1 receptor agonists (THC) encourage alcohol consumption, while CB1 receptor antagonists (CBD) decrease it. [S]

Although the pharmacokinetics of alcohol and CBD are not yet well-understood, what we do know is CBD inhibits the CYP450 enzyme system, and this system plays a significant role in alcohol metabolism.

Additionally, as found in mice, CBD alters levels of ADH and ALDH to varying degrees.

It is important to be mindful and cautious when mixing CBD and alcohol.

Caffeine and CBD – Better than a PB&J

Caffeine is the world’s most famous and commonly consumed psychoactive drug. Who doesn’t ingest even a little from time to time?

CBD is rapidly gaining ground on coffee in terms of popularity and so it only makes sense that people would start combining the two.

As it turns out, the two substances go very well together!

Caffeine is molecularly very similar to adenosine, a compound produced in our bodies that activates the A2a receptor. Caffeine binds to the A2a receptors, inhibiting the reuptake of adenosine.

When adenosine binds to the A2a receptor, the result is what is commonly known as the ‘rest and digest’ effect. Consequently, blocking adenosine from binding results in vasodilation, which increases clarity and alertness.

CBD is also a partial agonist of the A2a receptor; so the theory goes that by combining caffeine and CBD, adenosine is blocked across the board, resulting in not only more stimulation, but reduced anxiety (due to CBD’s effects on other neurotransmitters systems).

It is worth noting that these effects depend on the serving size of the CBD. High amounts of CBD are more likely to cause drowsiness and sedation.

Additionally, caffeine is metabolized by a CYP450 enzyme, specifically CYP1A2. As CBD inhibits the CYP450 enzyme system, a slowed excretion rate of caffeine will occur. This can mean the effects of the caffeine will be more prolonged and drawn out. The can be both good and bad!

On the bright side, CBD and caffeine together will cause the boost from your morning cup of coffee to last all day instead of just a few hours. On the downside, it’s easy to overdo it and end up wide-eyed in bed when you are trying to go to sleep.

Considering this information, again, it is best to be mindful and cautious when mixing caffeine and CBD.

Can CBD Oil Be Addictive?

One of the most common questions we get is: Can I get addicted to CBD oil? The answer depends on what you mean by “addicted.”

When looking at the chemical impacts of CBD, the answer is no. Cannabidiol is not physically addictive in the same way opiates, cocaine, alcohol, and other drugs can be. Also, CBD does not produce any physical withdrawal symptoms when you stop using it. In fact, CBD is currently being researched as a potential tool for minimizing the severe withdrawal from drugs like opiates.

But, having said that, human beings can get addicted to just about anything including exercise, music, sex, and food.

Because CBD can alter essential liver enzymes, it is crucial to do your research, talk to your physician, and figure out how to best consume CBD for your specific situation.

Information and education will be your most powerful weapons going forward.

How To Use CBD Oil

When taking cannabidiol, it is important to consume only the recommended serving size.  

Raising or lowering this amount may produce the opposite of the desired effect.

Keep in mind that some people may metabolize cannabidiol differently because of anomalies within the cytochrome P45O (CYP450) enzyme system. And depending on when you take your medications, you may find an unintended increase or decrease in CBD concentrations in your blood.

If you suspect that you are not metabolizing CBD as expected, ask your doctor to test your cytochrome P450 enzyme system before adjusting your dosage.

Common medications checked in combination with cannabis

 

 

Finally, let us remind you once again: dietary supplements produced by PharmotechSA are safe and tested so as they should not induce any undesirable side effects.Our extracts contain only cannabinoids from legally grown hemp. At the same time,they are not medicinal products whatsoever, and the manufacturer does not make any health claims regarding their use.