CBD and interaction with medications

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they are not medicines;
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Our blog articles are for informational purposes only and are not intended to qualify our products as medicines or to attribute therapeutic properties to them.

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Over the past few years, thanks to the publication of a considerable number of studies demonstrating how Cannabidiol (CBD), the non-psychoactive cannabinoid of Cannabis, can potentially play a supportive role for many conditions, the number of people using CBD alongside various types of medications has increasingly grown.

Hence the need to shed light on what can currently be scientifically asserted regarding the interaction of CBD with commercially available drugs.

Can CBD and medications be taken together?

CBD and medications can only be taken together under the supervision of a doctor because CBD is processed by cytochrome P450 enzymes, which are responsible for the metabolism of various drugs and could therefore interact with their metabolism.

CBD and interaction with drugs: preclinical evidence

The interaction of CBD with other drugs, it is linked to its hepatic metabolism by the enzymes of the CytP450 family, involved in the metabolism of numerous drugs. CBD acts as a inhibitor of some of the enzymes of this family, as a result, there could be an increase in the effect of CBD or the medications taken.

Let's understand a little better:

Increase in the effect of CBD when taken concurrently with drugs that inhibit CytP450 and therefore slow down the metabolism of CBD. Among these, it is important to remember antiviral drugs, antifungals, amiodarone (antiarrhythmic), calcium channel blockers (antihypertensives), isoniazid (antitubercular), and macrolide antibiotics such as clarithromycin and erythromycin).

Reduction of CBD effects when taken concurrently with drugs that induce CytP450 and therefore increase the metabolism of CBD (among these some antibiotics like rifampicin and rifabutin and many antiepileptics such as carbamazepine, phenobarbital, phenytoin, and primidone; similar effects could also occur with troglitazone, which is an antidiabetic, and with St. John's wort, which is an antidepressant)

Increase in the effect of drugs metabolized by isoenzymes of the CytP450 family, which are inhibited by CBD, such as omeprazole (gastroprotective), risperidone (antipsychotic), warfarin (anticoagulant), and diclofenac (anti-inflammatory), just to name a few.

These are the potential effects related to the interaction of CBD with other drugs, deduced solely from what is currently known about its pharmacokinetics and those of other drugs. These are potential effects to be confirmed in clinical practice and to be further investigated in terms of dosages and magnitude.

What drug interactions occur with CBD?

At the moment the greater evidence concerns the interaction with antiepileptic drugs. The concurrent use with antiepileptic drugs appears to result in increased concentrations of rufinamide, topiramate, zonisamide, eslicarbazepine, and a metabolite of clobazam (N-desmethylclobazam), which among other possible effects, has a stronger sedative effect.
Another significant finding that emerged from the studies concerns theincrease in liver function indices such as ALT and AST in case of simultaneous administration with valproate.

The studies have focused on this aspect because epilepsy (particularly drug-resistant epilepsy) is the condition for which research has been most thorough, with the recent market introduction of Epidiolex; a CBD-based drug for the treatment of these rare forms of epilepsy.

Always in clinical practice, it is important to emphasize how a recent case report has demonstrated how the simultaneous intake of CBD (with a starting dosage of 5/mg/kg/day) with warfarin (the most widely used anticoagulant in the world) alter the trend of INR in a non-linear way (value that expresses our coagulation status), with potentially significant side effects from a clinical perspective, such as possible bleeding (related to an increase in INR).

This effect is generally linked to the ability of CBD to inhibit the isoenzyme CYP2C9, responsible for the metabolism of the most active isomer of warfarin.

For the moment it can be stated with reasonable certainty that CBD may interfere with the metabolism of numerous drugs; it remains to be understood, however, with which of them and at what dosages.

CBD and psychotropic drugs

If CBD and psychotropic drugs are used simultaneously, CBD could inhibit the activity of CYP2D6, an enzyme specific to the metabolism of certain psychotropic medications. This could lead to an increase in the levels of psychotropic drugs in the body and, in some cases, raise the risk of side effects.

Several psychotropic drugs are indeed subject to metabolism by a specific enzyme within the cytochrome P450 family, known as CYP2D6. This group includes substances such as fluoxetine (Prozac), paroxetine (Paxil), and some antipsychotics like haloperidol.

Another enzyme of the same family is CYP3A4, responsible for the metabolism of various psychotropic drugs, including some anxiolytics such as diazepam (Valium) and antidepressants such as sertraline (Zoloft).

The CBD can also inhibit the activity of the enzyme CYP3A4, with potential effects similar to those previously described.

However, the interference of CBD on cytochrome P450 is not permanent; by stopping the use of CBD, the enzymes will return to their normal function over time. The required period may vary between individuals, depending on the amount of CBD used and the duration of use.

The interaction between CBD and psychotropic drugs, for example between CBD and Xanax, it essentially depends on the type of drug and the enzymes involved in its metabolism, which is why it is important to consult a doctor before using CBD and psychotropic drugs together.

CBD and benzodiazepines

As we have seen, cannabidiol (CBD) has the ability to inhibit the activity of the enzyme P450, which plays a crucial role in the metabolism of numerous drugs, including antidepressants, which fall into the category of psychotropic drugs. This is why careful and informed evaluation remains fundamentally important in the case of co-use of CBD and benzodiazepines.

Cannabidiol and medications: conclusions

In summary, the most plausible interactions that may occur in the case of co-administration of Cannabis with other drugs are the following:

Increase in the effects of Cannabis when used simultaneously with drugs that inhibit some of the isoenzymes responsible for the metabolism of the main phytocannabinoids, such as clarithromycin, erythromycin, macrolides, isoniazid, antivirals, antifungals, amiodarone, calcium channel blockers, antidepressants, and proton pump inhibitors

Reduction of the effects of Cannabis in relation to the use of drugs that induce the enzymes involved in Cannabis metabolism, such as carbamazepine, phenobarbital, phenytoin, troglitazone, St. John's wort, rifampicin, and rifabutin

Inhibition of some isoenzymes (for example CyP2D6 and CyP2C9) by Cannabis and the consequent increase in the effects of drugs metabolized by these enzymes, such as omeprazole, risperidone, warfarin, and diclofenac.

These are just some of the potential issues related to the interaction of CBD with medications; we say potential issues because they are derived almost exclusively from preclinical studies, mainly in vitro, and there is not yet solid clinical data to support them.

However, when we move into the field of clinical practice, it is certainly necessary to consider the evidence related to the simultaneous use of Cannabis (or products derived from it) with certain antiepileptic drugs and anticoagulants/antiplatelet agents, as well as the reported additive sedative effects when used concurrently with alcohol, opioids, and benzodiazepines.

Regarding the interaction with antiepileptic drugs, it has been shown that the co-administration of a CBD-based medication (recently marketed) used for the treatment of drug-resistant forms of epilepsy can cause:

An increased plasma concentration of topiramate, rufinamide, zonisamide, eslicarbazepine, and N-desmethyl clobazam (a metabolite of clobazam), with, in the latter case, a possible consequent greater sedative effect

An increase in some liver function indices, such as ALT and AST transaminases, in case of concurrent use with valproate.

Taking into consideration the interaction of CM with anticoagulant and antiplatelet drugs, a recent review has reported the following possible conditions:

In case of simultaneous use of Cannabis and warfarin, there could be an increase in the plasma concentration of the latter and in the INR, with a consequent increased risk of bleeding events

In case of simultaneous intake of CBD and clopidogrel, the latter may have a reduced effect, resulting in an increased risk of ischemic events

We also remind you that CBD cannot be used during pregnancy or breastfeeding.

If you are undergoing drug therapy and want to use CBD, talk to your doctor first and always make sure to purchase a safe product made from certified and controlled hemp plants.

We have been cultivating our plants in Abruzzo since 2013 and monitor every step of the production chain internally to offer quality products top. In addition, we collaborate with Universities and Research Institutes to promote studies and scientific dissemination on the world of hemp.

Bibliography

Yamaori, S., Ebisawa, J., Okushima, Y., Yamamoto, I., Watanabe, K. Potent inhibition of human cytochrome P450 3A isoforms by cannabidiol: Role of phenolic hydroxyl groups in the resorcinol moiety. Life Sci. 2011, 88, 730–736.

Yamaori, S., Okamoto, Y., Yamamoto, I., Watanabe, K. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab. Dispos. 2011, 39, 2049–2056
3-Interactions between cannabidiol and commonly used antiepileptic drugs Tyler E. Gaston, E. Martina Bebin, Gary R. Cutter, Yuliang Liu, and Jerzy P. Szaflarski for the UAB CBD Program Epilepsia, 58 (9):1586–1592, 2017.

Tyler E. Gaston E. Martina Bebin, Gary R. Cutter, Yuliang Liu, and Jerzy P. Szaﬂarski for the UAB CBD Program; Interactions between cannabidiol and commonly used antiepileptic drugs; Epilepsia, 58(9):1586–1592, 2017.

Orrin Devinsky, MD, Anup D. Patel, MD, Elizabeth A. Thiele, MD, Matthew H. Wong, MD, Richard Appleton, MD, Cynthia L. Harden, MD, Sam Greenwood, PhD, Gilmour Morrison, Kenneth Sommerville, MD, and On behalf of the GWPCARE1 Part A Study Group; Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome; Neurology 2018 Apr 3; 90(14): e1204–e1211.

Leslie Grayson, Brannon Vines, Kate Nichol, Jerzy P. Szaflarski, for the UAB CBD program; An interaction between warfarin and cannabidiol, a case report; Epilepsy & Behavior Case Reports 9 (2018) 10-11.