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 Cannabis is a sophisticated plant that contains more than a thousand different phyto or plant-based cannabinoids. Cannabidiol aka CBD is the second most prevalent Phyto cannabinoids present in cannabis Sativa plants. Do cannabis and CBD interact with other drugs? Which patient groups should you be careful with when prescribing cannabis or using CBD? Based on the guidelines from Health Canada Dr Julie Moltke tries to answer some of the main questions about cannabis and its interactions.
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”. 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. 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. 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.
6. MacCallum, Caroline A., and Ethan B. Russo. “Practical Considerations in Medical Cannabis Administration and Dosing.” European Journal of Internal Medicine, vol. 49, 2018, pp. 12–19, doi:10.1016/j.ejim.2018.01.004.
7. Taha T, Talhamy S, Wollner M, Peer A, Bar-Sela G. 1545PDThe effect of cannabis use on tumor response to nivolumab in patients with advanced malignancies. Ann Oncol [Internet]. 2017 Sep 1 [cited 2018 Mar 9];28(suppl_5). Available from: https://academic.oup.com/annonc/article/28/suppl_5/mdx388.005/4109591
Competing Interests: Presenter (CME): Aurora, Spectrum Therapeutics, Tilray Ad board: Inventive/Shoppers Drug Mart, Spectrum Therapeutics
CBD Vs Other Drugs Interactions: What Drugs Should Not be Taken with CBD?
Cannabis is a sophisticated plant that contains more than a thousand different phyto or plant-based cannabinoids. Cannabidiol aka CBD is the second most prevalent Phyto cannabinoids present in cannabis Sativa plants. Some sparse study suggests that CBD might have therapeutic advantages for a variety of ailments. However, as CBD becomes more widely available, questions like: “What drugs should not be taken with CBD?”, “How will CBD interact with my existing medications?” often arise in consumers’ minds.
CBD may cause harmful interactions with several other existing prescribed drugs, according to somewhat limited studies. The conclusions aren’t definitive, and further study into CBD’s interactions with various medicines is required.
Most physicians and healthcare practitioners advise people who use CBD for medicinal or pleasurable purposes to avoid combining it with other prescribed regular medications. Most importantly, talk to your doctors first about potential CBD drug interactions and side effects before introducing any CBD products for trial use.
In this post, we will try our best to answer all the questions mentioned above. Especially What drugs should not be taken with CBD, plus the CBD effects & interactions with conventionally prescribed medications.
What Effects & Interaction will CBD Have with Drugs and Medications?
Do you know or hear something about the grapefruit tests? Several pharmaceutical medicines will have grapefruit warning signs on it’s packaging label to recommend the ingestion of citrus fruits before treatment. A set of proteins called cytochrome P450 (CYPs) enzymes break down several medicines in the liver and small intestines. This technique offers the advantage of a drug to the desired objective.
Grapefruit interrupts CYP activities and slows down the typical breakdown of the drug by these proteins. The fruits further enhance the negative impacts and effectiveness of the medication. A 2013 research released in the Journal of the Canadian Medical Association entitled “Grapefruit Medication Interactions: Forbidden Fruit or Avoidable Consequences?” found that grapefruit can raise blood pressures by combining with around 85 medicines. The documented effects included irregular beating of heart, major organ failures, internal bleedings and fatality.
Further, in 1993 research carried out at the University of California, San Francisco, by pharmacology experts and published in the ‘Biochemical Pharmacology’ magazine CBD found that the normal function of cytochrome P450 enzymes in mice is disrupted like the grapefruit tests. The study suggested that while obstruction can enable patients to absorb lesser prescribed dosages, it might also trigger a lethal chemical compounds formation on the body. Following the release of this report, numerous medical and scientific publications have provided proof of the effects of CBD on people like grapefruit tests on human beings.
The category types, grade and pureness of CBD significantly influence how it reacts to our body as well as prescribed common drugs. You may also detect how the two can interact in your body by taking CBD and any other prescription medicine. But CBD vs drugs interactions on any person, based on gender, age, weight & several variables naturally responds uniquely.
Now let’s explore the existing CBD drug interactions studies with a range of everyday prescription and pharmaceutical medicines.
Should I take ibuprofen with CBD?
The NSAID is a medication that lowers bodily pain and inflammation and is an anti-inflammatory nonsteroidal medication. Ibuprofen is susceptible to blood thinning and may induce vertigo, breathlessness, and vomiting.
The danger of undesirable negative effects may possibly extend the duration and force of ibuprofen. Thus far, no research on the human subject has explicitly examined the interactions of CBD and NSAIDs. However, two experiments of the animal models of 2006 and 2008 published in Pain and Pharmacology respectively show the use of NSAIDs such as ibuprofen in the reduction of pain in other cannabinoids can synergize.
Before using ibuprofen with CBD, patients should visit their health care practitioner.
Should I take warfarin with CBD?
Warfarin, sometimes called Coumadin under the brand name, is a blood thinning (anticoagulant) drug that is used to prevent the development of dangerous blood clots that may induce heart attacks as well as strokes. Serious hemorrhages, several headaches, edema or abrupt ending pains are among the dangers posed by Warfarin.
A 2017 study published in Epilepsy & Behavior Case Reports at the University of Alabama, Birmingham, demonstrated that CBC boosts the effectiveness of medicines prescribed for thinning blood by decreasing the way the body decomposes warfarin and prolongs it’s stay inside the body system. CBD may worsen certain associated risks by extending the duration of warfarin’s presence on the body.
Patients who use standard warfarin and coumadin should check for customized information from their healthcare practitioner and take blood testing prior to starting any CBD program.
Should I take thyroid medication with CBD?
Thyroid medicine is used for the treatment of thyroid disorders. Mainly an underactive thyroid (hypothyroidism) by replacing thyroid hormones and an overactive thyroid (hyperthyroidism) with antithyroid drugs as well. Various drugs accomplish such goals via alternative routes inside the human body. Thyroid hormone substitution treatments have side effects such thoracic discomfort, anxiousness, hypertension, and nausea. Although rashes, irritation, temperature, pains and headache may involve negative impacts of anti-thyroid drugs.
There’s currently limited information on CBD oil and thyroid medication interactions, especially with standard thyroid hormone substitution and thyroid medicines. Thyroid patients should be consulted with their doctor first, if they wish to try a CBD solution.
Should I take Eliquis with CBD?
Eliquis often termed apixaban is a blood thinning drug used in veins, heart, lungs and limbs after any hip and knee replacement surgery. Apixaban is a blood thinner used to reduce the risk of stroke or blood clots. Eliquis raises the threat of serious hemorrhage. So doctors usually prescribe specific doses of Eliquis for the general patients.
The Eliquis process in the liver, the same proteins on which CBD works to slow down metabolization, is processed by CYP proteins. It might lead to a significant risk of serious bleeding, an overdose of the body’s substances.
Before utilizing CBD and Eliquis patients should contact their doctor first.
Should I take Plavix with CBD?
The brand name Plavix is a clopidogrel medicine that is often recommended for people who have had or may have had a cardiac disease. The medicine acts by inhibiting the formation of blood platelets in the arteries close to the heart.
A 2011 research published in Life Sciences shows CBD might have inhibiting effects on the CYP2C19 enzyme that metabolizes Plavix. This may lead to Plavix staying in the body longer and weakening its total effects. Further, more deep study is needed in order to establish whether the effectiveness of Plavix in reducing heart attack might be determined.
Patients who use Plavix or clopidogrel should check with their doctors about CBD.
Should I take Tylenol with CBD?
Acetaminophen is a popular medication for pain and fever relaxation, generic name for Tylenol. Acetaminophen is susceptible to liver and illness, causing nausea, various headaches and sleeplessness.
The CYP450 enzyme metabolizes both the acetaminophen and CBD, which reduces the efficacy of both drugs while they are digested inside the body. A disputed 2019 research published on mice by the University of Arkansas in ‘Molecules magazine’ said that higher doses of CBD lead to liver damage that can exacerbate the liver toxicity probability of acetaminophen compounds. But the authors of the study were criticized for cherry-picking and of constructing research to indicate possible toxicity of CBDs. The one and only research they tested with live human subjects where CBD liver damage was not demonstrated.
Further study is needed to determine possible interactions of CBD and acetaminophen. Patients who want to receive both should counsel their doctor at the same time.
Should I take metoprolol with CBD?
Metoprolol is a beta-blocker that is meant to cure high blood pressure by lowering the pace of the heart and altering epinephrine, a hormone associated with stress and other mechanisms. Beta blockers reduce blood pressure and can cause unwanted symptoms like: vertigo, lightheadedness, breathlessness, heartburn, and chilly arms and legs.
There was no study showing possible CBD interactions with metoprolol. Some placebo-controlled study in 2017 published on JCI Insight, from the University of Nottingham, England has connected CBD to reduced blood pressure when taken independently. Nonetheless, the people using metoprolol might have negatively affected CBD blood pressure levels.
A 2011 research on rats presented in the British Journal of Pharmacology also reveals that CBD has possible nausea-reduction characteristics that might help calm down metoprolol related negative effects.
Patients using the CBD should visit their doctor to find out whether they are taking metoprolol or other beta-blockers.
Should I take metformin with CBD?
Metformin is a grownup medicine for the management of blood sugar levels with Type-2 diabetes patients. Hypoglycemia, vomiting, diarrhea, nausea, and muscular discomfort are negative effects of metformin.
A 2006 research published in the Autoimmunity journal indicated that CBD decreased diabetes in animal test subjects. Although till date, CBD potentials for therapy with human diabetes or interactions with metformin have been particularly explored in limited study. Only one 2016 research carried out in Diabetes Care by the American Diabetes Association, investigated CBD effectiveness and did not find any significant glucose effects in patients with Type-2 diabetes.
CBD interactions with diabetes require additional investigation. Patients who use metformin must discuss if CBD is appropriate for them with their doctor.
Should I take Xanax with CBD?
‘Xanax’ also known by generic name ‘Alprazolam’ is a panic disorder, anxiety and depression treated benzodiazepine drug. Xanax common side effects include dizziness, lack of balance, loss of memory and anxiousness highly in the morning hours.
A CYP3A4 enzyme suppressed by CBD dissolves Xanax into the liver. If CBD is taken, Xanax might possibly extend the duration in the system and raise or prolong the chance of undesirable adverse reactions. Different studies including a 2011 study published in the journal called ‘Neuropsychopharmacology’ have revealed possible antidepressant effects of cannabinoids. One day, CBD may be considered a substitute for drugs similar to Xanax.
No studies have clearly reported Xanax vs. CBD interactions. Patients interested in CBD who use Xanax must seek additional information with their healthcare professionals.
Should I take statins with CBD?
Statins are a subclass of cholesterol-lowering and protective medicines for cardio-vascular or heart related attack and stroke. The common adverse effects of statins include muscular pain, increased sugar levels, nausea and headaches.
The CYP activity in the liver which inhibits CBD processes statins. Although no study has investigated special encounters between CBD and statins. The strength, duration of statins in the system and the risk of adverse effects might possibly be increased by CBD.
Prior to utilizing CBD, those who take statins should contact their medical practitioner.
What drugs should not be taken with CBD?
When evaluating whether CBD is taken with certain drugs or not, CBD’s known effects on liver function and enzymes which decompose specific pharmaceutical drugs are significant. The effect of CBD works on the same metabolites as grapefruit is consequently identical to the risk of many pharmaceutical drugs including grapefruit warning signs should not be taken with CBD.
These classes of drugs include a substantial percentage of contemporary prescription medicines, such as benzodiazepines, antihistamines, haloperidol, anti-retroviral, statins, cyclosporine, sildenafil, warfarin, and other CYP3A4 and CYP2D6 metabolized medicines.
Another kind of medication which is not recommended to use in combination with CBD is clobazam, mainly used to treat epileptic seizure. But Epidiolex is a CBD based medication authorized by the FDA which may be prescribed for epilepsy by doctors. There is substantial information from medical test trials on Epidiolex. However, a 2019 study released in the journal F1000Research done by Columbia University researchers suggests that the medicine Epidiolex might produce negative side effects.
No studies have demonstrated that grapefruit and medication interactions might cause severe consequences, involving irregular heartbeat and sudden cardiac death, kidney failure and muscle damage. While the 2013 survey previously referenced in Canadian Medical Association Journals showed that it can lead to severe effects. Each patient’s condition is distinct, and if they contemplate using CBD along with special prescription medicines, they should talk to their medical practitioners first.
Does CBD oil have effects on blood pressure?
An already mentioned 2017 research titled, “A single dosage of cannabidiol in a randomized crossover study, lowers blood pressure in healthy volunteers” released in the JCI Insight newspaper confirms the CBD’s possibility to decrease blood pressure levels. Experts also show that the angst and stress-reduction characteristics of CBD oil might help reduce blood pressure level altogether. However, taking CBD oil with prescribed medicine for blood pressure or beta-blockers could lead to both medications doubling and lead to critically lower blood pressure levels.
Does CBD oil help with blood thinning?
There are no studies showing that the blood can be diluted by CBD oil itself. As previously referenced in a 2017 study published in Case Epilepsy & Behavior Reports, CBD oil does boost the effects of bloods diluting or thinning meds like warfarin. Also might potentially push the presence of warfarin above appropriate limits.
So, before using CBD and blood thinner together patients should contact their doctor first.
Does caffeine work against CBD?
Caffeine and CBD are becoming two highly popular consumer products, especially when combined together. Caffeine may revive and alert people who are falling asleep. In addition, a 2007 study on rats published in Pharmacology Reports demonstrated that caffeines is processed by CYP enzymes which are inhibited by CBD. This might prolong the duration of caffeine presence on the body and the stimulant effects of caffeine might increase.
Consult Your Doctor First
You must consult your doctor before using any cannabidiol for the first time. If you are unclear whether CBD interacts with a medicine that you are already taking. Substantial mild benefits of such non-intoxicating, non addictive cannabinoid especially apply to CBD’s possible medication contraindications.
In all cases, it is not CBD that is responsible for the hazardous consequences that occur when you are using other medicines with this cannabinoid. It is only the fact that many prescription drugs on the market are safe only when they are metabolized at a particular pace and CBD might accidentally intoxicate such medicines by allowing them to last longer than they should in your system.
Legal: The detailed information on this informative article is founded on existing research and must not be interpreted as clinical counsel. If you have any queries regarding any prescription drugs and CBD, definitely discuss it with your physician or medical practitioner first.
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Cannabis Medicine and Its Interactions – How does CBD and Cannabis Interact with Other Drugs?
Cannabis Drug Interactions – How Does THC and CBD Interact with Other Medicines?
As a doctor who considers prescribing cannabis or a patient wishing to try CBD or medicinal cannabis, you need to be aware of how the cannabinoids might interact with other medications in the body.
Cannabis can interfere with the metabolism of blood thinners
Since some cannabinoids can inhibit enzymes like cytochrome P450 liver enzymes (CYP) as well as P-glycoprotein and UDP-glucuronosyltransferases it has the potential to interact with medications that are metabolised by these enzymes. One of the major patient groups to consider is the one with cardiovascular disease using blood thinners, so-called anticoagulant or antiplatelet treatment.
THC can increase the risk of bleeding in patients in Warfarin treatment
Delta-9-tetrahydrocannabinol, also known as THC, may inhibit cytochrome P450 enzyme CYP2C9, which is responsible for metabolising Warfarin, a blood thinner used for people who receive new heart valves, among others. This can cause the INR (elevated international normalisation ratio), a measurement of the time it takes the blood to clot to go up, which in turn can cause internal bleeding(1).
Cannabidiol can increase the risk of stroke by inhibiting CYP2C19 in people using clopidogrel
Cannabidiol (CBD) has been shown to inhibit the CYP2C19, which is responsible for converting clopidogrel to its active thiol metabolite. Clopidogrel is often given to people who had a heart attack (myocardial infarction) or a cerebral stroke. Since CBD can block the activity of CYP2C19, it has the potential to lead to sub-therapeutic levels of the active metabolite and consequently an elevated risk of stroke(2).
Be careful when treating people with cardiovascular disease
It is essential always to think carefully before initiating cannabis treatment and to monitor patients closely who have a history of unstable cardiovascular disease, myocardial infarction or stroke. If you are a doctor who has a patient on anticoagulant medications whom you know, or suspect uses cannabis, it might be worth bringing up this risk.
Caution is also advised when prescribing cannabis to people who are in therapy with sedative-hypnotics like barbiturates or benzodiazepines. This also includes other psychoactive drugs with an effect on the central nervous system. Cannabis has the potential to have an additive or synergistic effect with these drugs which can cause severe drowsiness, dizziness and other unwanted side-effects(3).
Lastly, cannabis might add to the depressive effects of alcohol on the central nervous system and you should advice patients to be careful when using these substances together.