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Meds Drug Interactions with Cannabis


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Twenty-six states and the District of Columbia currently have laws broadly legalizing marijuana in some form.But, regardless of legal status, recreational and medicinal use of marijuana is common across the United States. With this increasing availability and also the increasing potency of marijuana, it is important for both users and healthcare professionals to be aware of the potential drug interactions associated with marijuana use.

Tetrahydrocannabinol (THC) is the primary psychoactive cannabinoid found in marijuana. Cannabidiol (CBD) is also found in high concentrations in marijuana but is not psychoactive; it has an antagonistic effect at the cannabinoid receptors and appears to block some of the effects of THC. Cannabinol (CBN) is a relatively weak psychoactive cannabinoid existing in very small quantities within the marijuana plant but is one of the primary metabolites of THC.The marijuana plant contains more than 50 other cannabinoids, but synthetic medications approved by the US Food and Drug Administration (eg, dronabinol and nabilone) contain only THC without any CBD. The pharmacologic effect of these products may differ from that of natural cannabis.

Data are limited regarding the potential drug interactions associated with marijuana use; however, unstudied interactions can be theorized based on the metabolism of the primary cannabinoids in marijuana.

CYP450 Enzymes
Cytochrome P450 (CYP450) enzymes are responsible for the metabolism of most chemicals and medications that enter the human body. Humans have roughly 60 CYP genes. CYP450 enzymes occur primarily in liver cells where drug metabolism occurs.

Chemicals or drugs may be substrates, inhibitors, or inducers of CYP450 enzymes. Substrates are substances that are metabolized by the enzyme. Inhibitors reduce the activity of the enzyme, preventing the metabolism of its substrates and thus increasing the substrate concentration and effect. Inducers, on the other hand, increase the activity of the enzyme, enhancing the metabolism of its substrates and thus decreasing the substrate concentration and effect.

The CYP1A2, CYP3A4, CYP2C9, and CYP2C19 enzymes are known to be affected by marijuana use.

Smoking marijuana regularly is believed to cause induction of the CYP1A2 enzyme, which may decrease serum concentrations of 1A2 substrates.One study reported that theophylline clearance was 48% greater in individuals who smoked more than 2 joints weekly. Marijuana would be expected to have a similar effect on other 1A2 substrates.

Other 1A2 substrates. Aminophylline, caffeine, clozapine, duloxetine, estradiol, estrogens, flutamide, fluvoxamine, frovatriptan, lidocaine, melatonin, mexiletine, mirtazapine, olanzapine, propranolol, ramelteon, rasagiline, ropinirole, tizanidine, triamterene, zolmitriptan.

The CYP3A4 enzyme is involved in the metabolism of both THC and CBD. Therefore, 3A4 inhibitors may increase serum concentrations of these cannabinoids, while 3A4 inducers may decrease the serum concentrations. In one study performed in the United Kingdom, rifampin (3A4 inducer) reduced the concentration of THC by 40% and CBD by 20%. In the same study, ketoconazole (3A4 inhibitor) was found to increase the concentration of THC by 20%. It would be expected that other 3A4 inhibitors and inducers would produce a similar effect.

Strong 3A4 inducers. Carbamazepine, enzalutamide, fosphenytoin, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's wort.

Strong 3A4 inhibitors. Clarithromycin, darunavir, grapefruit juice, itraconazole, ketoconazole, lopinavir, mifepristone, nefazodone, nelfinavir, ombitasvir, paritaprevir, ritonavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil, voriconazole.

In addition to CYP3A4, CYP2C9 is the other known enzyme responsible for metabolism of THC. In a study of patients who were poor metabolizers of 2C9, THC concentrations were found to be threefold higher than in those with normal 2C9 function.While no known studies have looked specifically at the effects of 2C9 inhibitors and inducers on THC concentrations, they would be expected to have similar effects as the 3A4 inhibitors and inducers.

Strong 2C9 inducers. Barbiturates, carbamazepine, phenytoin, rifabutin, rifampin, rifapentine, St. John's wort.

Strong 2C9 inhibitors. Amiodarone, cimetidine, clopidogrel, delavirdine, disulfiram, fluconazole, fluorouracil, gemfibrozil, metronidazole, phenytoin, sulfadiazine, sulfamethoxazole, tolbutamide, valproic acid, voriconazole.

In addition to CYP3A4, CYP2C19 is the other known enzyme responsible for metabolism of CBD.In one study, omeprazole (2C19 inhibitor) did not increase serum concentrations of CBD. Even with these unexpected results, 2C19 inhibitors and inducers should be assumed to have similar effects on CBD concentrations as the 3A4 inhibitors and inducers until further studies provide a better understanding.

Strong 2C19 inducers. Barbiturates, carbamazepine, phenytoin, primidone, rifampin, rifapentine, St. John's wort.

Strong 2C19 inhibitors. Chloramphenicol, cimetidine, clopidogrel, delavirdine, efavirenz, esomeprazole, felbamate, fluconazole, fluoxetine, fluvoxamine, isoniazid, modafinil, omeprazole, oxcarbazepine, ticlopidine, voriconazole.

Other Potential Drug Interactions With Marijuana
Central nervous system (CNS) depressants. Clear evidence exists that THC can enhance sedative, psychomotor, respiratory, and other effects of CNS depressant drugs and alcohol.

Anticholinergic agents, cocaine, sympathomimetics. Cannabinoids are known to cause tachycardia. Several drug monographs and clinical studies have been published indicating that concomitant use of marijuana with anticholinergics, cocaine, or sympathomimetic agents can further enhance tachycardic and hypertensive effects of cannabinoids.

Disulfiram and fluoxetine. At least two case reports of individuals taking disulfiram and at least one case report of an individual taking fluoxetine while also using marijuana indicate a possible interaction causing symptoms of hypomania. Prescribing information for nabilone and dronabinol also includes this drug interaction to warn prescribers of the potential risk.

Warfarin. A single published case report describes an interaction with a patient taking warfarin who also regularly smoked tobacco and marijuana. The patient had multiple comorbidities and was taking at least 10 other medications. On at least two occasions, the patient's international normalized ratio (INR) increased to values over 10 with episodes of bleeding. The only change reported for both occasions was an increase in the amount and frequency of marijuana smoking. Patients who take warfarin and use marijuana regularly should receive close INR monitoring for any potential interaction.

Antiepileptic drugs (AEDs). A recent study examined baseline serum AED levels to identify drug-drug interactions between CBD and 19 AEDs during an open-label safety study in 81 patients (39 adults, 42 children) with refractory epilepsy. As doses of CBD were increased, the researchers noted an increase in the serum levels of topiramate (P<.01), rufinamide (P<.01), and desmethylclobazam (P<.01) and a decrease in the levels of clobazam (P<.01) in both adult and pediatric patients. In adult patients, a significant increase in the serum levels of zonisamide (P=.02) and eslicarbazepine (P=.04) was observed with increasing CBD dose. No other drug interactions among the 19 AEDs were noted. The authors recommended monitoring serum AED levels in patients receiving CBD, as drug-drug interactions may be correlated with adverse events and laboratory abnormalities.

Be Aware and Educate Patients
Patients using marijuana should be educated to avoid drugs that affect associated CYP450 enzymes. When these drugs cannot be avoided, and marijuana use is expected to continue, the patient should be monitored closely for potential drug interactions.

Smoking more than two joints weekly is likely to increase the risk for drug-related interactions. No data exist monitoring large-scale marijuana use in the United States. However, in Washington, a state in which marijuana use is legal, the average user is estimated to smoke two to three joints per week.

With growing legalization and use throughout the nation, healthcare professionals must exercise heightened caution in the situation of concomitant use of medications and marijuana.
Mixing the Pot? 7 Ways Marijuana Interacts with Medicines


Marijuana interactions
Marijuana is currently not approved by the U.S. Food and Drug Administration as a treatment for any medical condition, but a number of states do allow people to use the drug for medical or recreational purposes. Still, users should be aware that marijuana may interact with other prescription medications.

Although there's been limited research on marijuana's potential drug interactions, here's what doctors know about how marijuana interacts with other medications:


Marijuana may interact with drugs, including Viagra, that are broken down by chemicals in the liver known as cytochrome P450 enzymes, according to the Mayo Clinic. That's because compounds in marijuana can inhibit these enzymes. Therefore, marijuana may prevent other drugs from being broken down properly.

As a result, people who smoke marijuana and take these drugs may have increased levels of these other drugs in their blood, which "may cause increased effects or potentially serious adverse reactions," the Mayo Clinic said.

In one case, reported in 2002 by researchers in the United Kingdom, a 41-year-old man had a heart attack after taking marijuana and Viagra together. The researchers said they could not prove that the marijuana-Viagra combination was definitely the cause of the man's heart attack; however, they did say that doctors "should be aware" of the effects of inhibiting cytochrome P450 enzymes when prescribing Viagra.


Another commonly prescribed drug that's broken down by the cytochrome P450 enzymes is the blood thinner warfarin, which is prescribed to treat and prevent blood clots. In 2009, doctors at the Cheyenne Veterans Affairs Medical Center in Wyoming reported the caseof a 56-year-old man who was admitted to the hospital with stomach bleeding after smoking marijuana frequently while taking warfarin. He went home after a week in the hospital, but then was readmitted just 15 days later with a nosebleed and bruising. He told his doctors that he smoked marijuana, and he was counseled on the potential interactions of marijuana and warfarin.

Because marijuana affects the cytochrome P450 enzymes, it may inhibit the breakdown of warfarin, leading to an increase in warfarin's effects, the report said. The man stopped smoking marijuana and did not experience further bleeding complications over the next nine months during which the researchers followed up with him.


When people take benzodiazepines — which include muscle relaxants as well as drugs that treat anxiety, such as Valium — in combination with marijuana, the result can be "central nervous system depression," according to according to a 2007 review paper in the American Journal of Health-System Pharmacy. This means that people can experience decreased breathing and heart rates, and loss of consciousness.

According to the Mayo Clinic, marijuana can increase the drowsiness caused by benzodiazepines and some other drugs (such as barbiturates and codeine). Therefore, people need to be cautious if they drive or operate machinery after using these drugs with marijuana, the Mayo Clinic said.

The antifungal medication ketoconazole also inhibitscytochrome P450 enzymes. When this medication is taken with marijuana, it slows the breakdown of tetrahydrocannabinol, or THC, the active ingredient in marijuana, in the body. So, taking the two drugs together may increase the concentration of THC in the body, according to a 2014 article in the trade journal Pharmacy Times.

The antidepressant fluoxetine, commonly called by its brand name Prozac, can inhibit cytochrome P450 enzymes. This means that, like ketoconazole, fluoxetine mayslow down the metabolism of THC and therefore increase the concentration of THC in the body.

In 1991, researchers reported a case of a 21-year-old who experienced severe mania and psychosis after taking fluoxetine and using marijuana. The researchers hypothesized that marijuana might also increase levels of the chemical serotonin in the brain, which would enhance the effects of fluoxetine, but this is not proven.

The antibiotic medication rifampin, which is used to treat tuberculosis and Legionnaires' disease,can boost the activity of cytochrome P450 enzymes. This means that rifampinmay speed up the breakdown of THC, reducing the levels of that substance in the body, according to the Pharmacy Times.


Diabetes medications
Marijuana may affect people's blood-sugar levels, according to the Mayo Clinic. Indeed, some studies have found that marijuana users are less resistant to the effects of insulin, the hormone that helps blood sugar get inside cells, which could mean that their systems are better able to control their blood sugar levels.

But on the flip side, other studies have found that marijuana users are at increased risk of developing prediabetes, a condition in which people have elevated blood sugar levels.

People who take marijuana with drugs for diabetes should be monitored closely, and adjustments to their medications may be necessary, the Mayo Clinic said.

Unsurprisingly, this is an increasingly popular Google search as more and more individuals turn to medical cannabis for their day-to-day form of therapy. However, very little reliable information is accessible on this topic. Generally speaking, it is recommended not to combine other drugs with an antibiotic prescription. Marijuana is a natural plant though, so doesn’t that mean it’s ok?

Yes, but it could be problematic. Using marijuana at the same time with antibiotics isn’t advisable. However, it might not be as dangerous as some would expect. With that said, while you should not take any of the information you find here as medical advice, this article should give a better idea of what to expect if you decide to use marijuana while taking medicine.

How Marijuana Interacts with Medication?

As you probably knew, cannabis has a reputation as a safe drug – at least in terms of overdose potential and toxicity. It is also vital to remember that everything your body ingests has either a chemical or a psychological response. As for instance, using cannabis while on antidepressants can increase any or all side effects. We’ve also learned that smoking marijuana can be associated with symptoms of bronchitis. But in terms of precise information on the use of antibiotics and marijuana, little research is available.

Possible Adverse Reactions When Mixing Cannabis and Antibiotics

Though there is a very low risk, there’s always a likelihood of unfavourable reactions when you mix medications. Why? Drugs can act upon organs, systems and functions within the body. When one medication activates a particular system, it can very easily influence how the second medication is metabolized. For instance, cannabis that’s also been shown to possess antibiotic potential is known to inhibit the cytochrome p450 enzymes produced in our liver.

These enzymes are accountable for the biosynthesis of certain macrolide antibiotics such as erythromycin, troleandomycin, and miocamycin. Suppose cannabis use is inhibiting these enzymes. In that case, you are more susceptible to any side effects caused by the antibiotic – meaning that an erythromycin user may be more susceptible to the known side effects like nausea, vomiting and diarrhea.

If you observe any side effects following antibiotic use, consider reducing your cannabis usage by half until you have finalized your antibiotic therapy. In case of severe side effects, it is advisable to stop using marijuana entirely until the bacterial infection has been addressed.

When to Not to Use Antibiotics with Medical Cannabis

As we’ve previously mentioned, antibiotics can interact negatively with certain other medications and drugs. As a result, many of us are left wondering about the interaction between antibiotics and marijuana. So, can you smoke marijuana on antibiotics or not? If none of the side effects have made their appearance and your doctor even advised you to continue so, it means you can. However, if your doctor warns you against mixing medical cannabis with your current antibiotic, always follow their instructions. There are certain instances in which cannabis may actually worsen your problem. It may sound counterintuitive, but you want to avoid smoking weed or vaping it if you’re taking antibiotics to cure a lung or respiratory infection. As you know, the chemical and smoke can irritate the organs that prescription drugs are trying to repair.

Final Verdict

Marijuana use does not appear to have adverse effects when consumed along with antibiotics. Of course, be sure you check in with your doctor before continuing medical cannabis use along with your antibiotic drugs.

Lastly, it never hurts to take your time, do your own research and consider all the facts. We repeat the fact that the information in this article is entirely informative and should not be taken as medical advice.

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