CBD – Drugs Interactions

Today we are about to address a quite sensitive issue - the interaction of pharmaceutical drugs and cannabidiol (CBD).

Although the CBD oils available without prescription do not possess the status of medicine, many people would use them for general health purposes – as they do with any other dietary supplement of plant origin. Used in this way, the CBD hemp oil should not produce any side effects, but what about taking it with pharmaceutical drugs at the same time?

Ask your doctor!

Before moving on to discuss the potential interactions, we would like to remind you of two things. First of – most of the studies discussed here applies to medicine-grade CBD preparations – in which both the composition and the doses differ significantly to the food grade CBD oils products. The doses of CBD provided by food supplements are typically much lower. You can draw the conclusion that the potential negative (or positive) side interaction between the drugs and cannabidiol applied in medical doses does not necessarily relate to CBD as a dietary supplement – and this might be true.

But there is also a second – and way more important! – caveat that you should keep in mind. In the case of use of any medication, not only a prescription drug, and not just those listed in the article, if you have any doubt as to their interaction with the CBD (or anything else) the first thing you should do is to consult your doctor. Do not believe uncritically in everything you read on the Internet (including this article) – they may draw your attention to the potential properties of plant products, but in case of any doubt, the doctor has the last word. Long gone are the times in which the cannabis scene was associated with altmed, and conflicted with the doctors – and this is a good thing.

Bearing in mind all the above, let’s move on and consider the mechanism of the CBD-drugs interaction.

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. P450s are considered to be the most versatile biocatalysts in nature.

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 inhibitors of P450 are for example flavonoid naringin and furanocoumarins like 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. Especially the last factor should be considered, bearing in mind that some pre-clinical and clinical trials looking at CBD-drugs interaction have been carried out on pure CBD and others on drugs based on extract containing both, THC and CBD (eg. Sativex).

Will CBD 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 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. Nevertheless, considerable progress has been made in recent years. The researcher who first 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 some antiepileptic 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 antiepileptic medicines can still be too low to allow the trigger the antiepileptic effect of CBD itself – so that the patient would only experience negative side effects, without any therapeutic ones. These, and other, problematic interactions with medicines are being discussed it the Project CBD report.

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 administered in large doses.
  • Food grade CBD might be different to medical grade products due to differences in composition .
  • Interactions of CBD and certain other medicines can be sometimes 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 change the effectiveness of the treatment, as CBD will simply “substitute” the medicine.
  • So far, 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 supplement, any sign – or fear – of its potential interactions with any medication (not only prescription drugs) calls for the consultation with the physician. In the internet we can come across “grapefruit test” – if a drug can be taken with the fruits, the CBD should make no harm neither. Although there is some logic in this (the large amounts of furanocoumarins contained in these fruits would interact with cytochrome P450 in a similar way as CBD does) it is always better to ask your doctor.

 

Finally, let us remind you once again: dietary supplements with CBD are not medicinal products and are not intended to diagnose, treat, cure, or prevent any disease. Consult your physician before use if you have a medical condition or are taking any medication.

 

Sources:

Chesney E, Oliver D, Green A, et al. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials [published online ahead of print, 2020 Apr 8]. Neuropsychopharmacology. 2020;10.1038/s41386-020-0667-2. doi:10.1038/s41386-020-0667-2

Devitt-Lee A, Primer on Cannabinoid-Drug Interactions available: https://www.projectcbd.org/how-to/cbd-drug-interactions

Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58(9):1586-1592. doi:10.1111/epi.13852

Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56(8):1246-1251. doi:10.1111/epi.13060

Kossen J: How Does Cannabis Interact With Other Drugs?

Landmark CJ, Brandl U. Pharmacology and drug interactions of cannabinoids. Epileptic Disord. 2020;22(S1):16-22. doi:10.1684/epd.2019.1123

Qian Y, Gurley BJ, Markowitz JS. The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. J Clin Psychopharmacol. 2019;39(5):462-471. doi:10.1097/JCP.0000000000001089

Zendulka O, Dovrtělová G, Nosková K, et al. Cannabinoids and Cytochrome P450 Interactions. Curr Drug Metab. 2016;17(3):206-226. doi:10.2174/1389200217666151210142051

 

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