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cbd oil and plavix

Plavix

Generic Name(s) : clopidogrel

Clopidogrel/Cannabidiol Interactions

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Serious. These medicines may interact and cause very harmful effects. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Cannabidiol may slow down how quickly your liver process clopidogrel to its active form.

What might happen:

Your clopidogrel may not work as well or at all.

What you should do about this interaction:

Make sure your healthcare professionals (e.g. doctor or pharmacist) know that you are taking these medicines together. Your doctor may want to change your medicine.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

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CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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RE: No need for alarm. Just watch your dosing!

This is a very thorough article and is a good reminder of several significant drug interactions such as those seen with dabigatran, warfarin and clopidogrel.

However, though the data is biochemically accurate, it leaves the reader with an alarmist impression of many possible drug interactions with cannabinoids found in the cannabis plant. It is important to remember that most of these events occur very rarely in clinical practice, and I suggest taking a more pragmatic approach to address this problem. The following explanation should reassure the readers, and hopefully the authors!

THC and CBD have completely different mechanisms and effects, but THC clearly has the most serious unwanted adverse effects that we wish to avoid. These can occur even with small doses of THC and clinicians do require a basic knowledge of clinically relevant interactions. However, we need to put this in perspective and consider the most likely scenarios which will be relevant in our practice. There are in fact two situations which warrant further inquiry when considering drug interactions with THC in particular:

1) Patients on a steady dose of THC who will be starting strong CYP 3A4 and 2C9 inhibitors, and
2) Patients on a steady dose of strong CYP 3A4 and 2C9 inhibitors who will be starting THC.

Both these situations present specific challenges.

For patients who are taking a steady dose of THC, adding a strong CYP 3A4 and 2C9 inhibitors is known to increase plasma levels of THC which can lead to significant adverse events. Of these, clarithromycin, non-dihydropyridine CCBs, antiretrovirals, ketoconazole, fluconazole and amiodarone are the most frequently used in medical practice. Luckily there are often alternatives to using these drugs, but if they cannot be avoided, gradually reducing the dose of THC should be advised over the course of several days in order to reach a new steady state.

Conversely, for patients already taking a strong CYP3A4 or 2C9 inhibitor, the addition of THC should also be approached with caution. In these patients, starting with a smaller, sub-psychoactive dose should prevent accidental intoxications from occurring. The literature often suggests a starting dose of approximately 2.5 mg of THC, often considered to be the “psychoactive threshold”.[1] However, I start all my patients with a smaller dose of THC, in the 1 mg range, thus avoiding not only the possible drug interactions, but also the possible genetic CYP3A4 and 2C9 polymorphisms which can also increase THC levels in certain individuals.

As for the effects of strong CYP 3A4 and 2C9 inhibitors on CBD levels, there are several reasons why this should not be a cause for concern. The therapeutic range of CBD has yet to be determined but is probably very wide. Furthermore, serious adverse events are negligible even with very high doses of CBD, so an interaction which increases CBD levels is not likely to cause any serious adverse effect.

The article also mentions the effects which THC and CBD may have on the metabolism of other drugs. THC and CBD are both substrates of several CYPs and they may alter the levels of several medications, such as warfarin and tacrolimus. These interactions, may sound alarming, but they are rarely seen in clinical practice. The reason is very simple: they are dose-related effects of THC and CBD. When low recommended therapeutic doses are used in most conditions such as chronic pain, this should not be an issue.

The therapeutic range of cannabinoids such as THC and CBD has been the focus of much debate and a growing consensus has emerged in the last few years, thanks in part to the clinical studies using nabiximols and small RCTs using inhaled cannabis.[2-5] The dosages of THC and CBD required for most medical conditions have been shown to be far below the doses necessary for many of the drug interactions mentioned in this article, with one particular exception being high-dose CBD regimens used in childhood epilepsy or GVHD for example.[6] Articles that review the interactions and adverse effects of cannabis too often omit this crucial bit of medical cannabis knowledge, and therefore imply that high dose CBD or THC is the norm for most conditions. This is not the case.

One only needs to remember that the drug interactions caused by THC and CBD are directly related to the dose at which these cannabinoids are used. As a result, significant interactions are rarely encountered at “therapeutic doses” of THC and CBD in most clinical settings such as in chronic pain management in older patients taking multiple medications.

As for the topic of interactions with smoked cannabis (CYP 1A2), this too should not be a concern if we properly counsel our patients to avoid this route of administration. Vapourizers are just as effective and do not produce the compounds responsible for these interactions.

In addition, I think it would have been useful to mention a recently published article which looked at possible interactions between cannabis and check-point inhibitors.[7] This is of particular concern, given the interest patients are showing for cannabis and its role in cancer care.

1. Russo Ethan B. “Taming THC: Potential Cannabis Synergy and Phytocannabinoid‐terpenoid Entourage Effects.” British Journal of Pharmacology, vol. 163, no. 7, July 2011, pp. 1344–64, doi:10.1111/j.1476-5381.2011.01238.x.

2. Collin, C., et al. “A Double-Blind, Randomized, Placebo-Controlled, Parallel-Group Study of Sativex, in Subjects with Symptoms of Spasticity Due to Multiple Sclerosis.” Neurological Research, vol. 32, no. 5, June 2010, pp. 451–59, doi:10.1179/016164109X12590518685660.

3. Lichtman, Aron H., et al. “Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as an Adjunctive Therapy in Advanced Cancer Patients with Chronic Uncontrolled Pain.” Journal of Pain and Symptom Management, vol. 55, no. 2, Feb. 2018, pp. 179-188.e1, doi:10.1016/j.jpainsymman.2017.09.001.

4. Wilsey, Barth, et al. “Low Dose Vaporized Cannabis Significantly Improves Neuropathic Pain.” The Journal of Pain : Official Journal of the American Pain Society, vol. 14, no. 2, Feb. 2013, pp. 136–48, doi:10.1016/j.jpain.2012.10.009.

5. Ware, Mark A., et al. “Smoked Cannabis for Chronic Neuropathic Pain: A Randomized Controlled Trial.” CMAJ: Canadian Medical Association Journal = Journal de l’Association Medicale Canadienne, vol. 182, no. 14, Oct. 2010, pp. E694-701, doi:10.1503/cmaj.091414.

RE: No need for alarm. Just watch your dosing! This is a very thorough article and is a good reminder of several significant drug interactions such as those seen with dabigatran, warfarin and