Can cannabis be dangerous when used with other medication?

Can cannabis be dangerous when used with other medication?


DISCLOSURE: Patients should always talk to their physicians about their use of cannabis with other substances or drugs. If your physician isn’t in possession of modern information about cannabis use, there are plenty of physicians who ARE current on the use of cannabis for medicine and are always in search of patients in need of education.

The cannabis industry takes a lot of criticism from what we’ll call “traditional” news outlets and media for claiming the medicinal benefits of the plant. This has been going on for decades, since it was prohibited first in 1937 via the Marijuana Tax Act and then with fervor in 1970 with the Controlled Substance Act. Several things happened as a result of these regulations – people had to purchase cannabis via the black market, and social and moral stigma was born – asserting that hippies and criminals used “the devil’s lettuce.” Most significantly, research and the ability to conduct clinical trials about the efficacy of cannabis as medication were stymied in the United States.

Fortunately, we’ve evolved somewhat since then, not only in public policy but as a result of so many of us who used our votes to legalize the medicine and no longer hide our usage behind closed doors and whispers.  But the lack of sanctioned published academic research has left many new potential patients cautious about its use alone or alongside other medications.

What IS the right answer to the question about whether or not cannabis interacts with conventional pharma? Well, that really depends on the source of your information. A Google search can bring you 68k results when you ask the question, and some of the answers provided cite small studies, while others don’t cite studies at all. Here’s what we found – and vetted with pharmacists and physicians.

It’s important to understand the difference between “additive” and “synergistic” effects. Additive means the interaction between two substances equals the sum of their parts (e.g. 1+1 = 2). Synergistic implies that when two substances are used simultaneously, the effect is greater than the sum of their parts (e.g. 1+1 = 3.). It’s important to remember that THC/CBD ratios and different strains (varied cannabinoid and terpene profiles) can influence side effects.

Blood Thinners

Warfarin has a narrow therapeutic window, so even minor changes to the anticoagulant’s effect can increase the risk of bleeding and thrombosis. Because THC and CBD can inhibit the metabolic activity of the CYP2C9 enzyme, they can increase warfarin levels and thereby increase the risk of bleeding.

Epilepsy Drugs

CBD increases the effects and the side effects of clobazam, a benzodiazepine often prescribed for treating seizures associated with Lennox-Gastaut syndrome in children and adults. Instead of being contraindicated, CBD was also FDA-approved for treating seizures associated with Lennox-Gastaut syndrome, as well as Dravet syndrome. Marketed as Epidolex, this prescription CBD was the first-ever marijuana-derived drug approved by the FDA.

However, CBD is a potent CYP2C19 inhibitor. When these two drugs are used together, the CBD interaction contributes to clobazam’s efficacy, resulting in a three-fold increase in the plasma concentration of clobazam’s active metabolite. The downside is that this interaction also increases clobazam’s side effect of sedation. As a result, clinicians are advised to lower the dose of clobazam when used in conjunction with CBD.

Taking CBD with valproate can raise liver enzyme levels and may cause liver injury. The prescribing information for Epidolex recommends discontinuing or adjusting the dose of Epidolex and/or valproate if liver enzyme elevations occur.


Many sedatives– alcohol, benzodiazepines, barbiturates such as phenobarbital, and narcotics, such as codeine, influence GABA neurotransmitters in the central nervous system, producing a calming effect. Likewise, cannabinoids can produce sedative effects. When combined with sedatives, cannabis produces an additive effect. Users should exercise extreme caution, or better yet, avoid the combination altogether.

Sedatives are not technically antidepressants. Nonetheless, many patients experiencing depression are also prescribed sedatives. Both cannabis and sedatives can cause people to feel sleepy or drowsy, an effect commonly reported in prescribed sedative medications such as clonazepam (Klonopin), lorazepam (Ativan), phenobarbital (Donnatal), and zolpidem (Ambien). Mixing cannabis and these medications can amplify these effects.



SSRIs—such as Prozac, Paxil, Zoloft, Celexa, and Lexapro—are the most commonly prescribed drugs to treat depression. Patients report fewer side effects and drug interactions with SSRIs than many other types of antidepressants.

Adverse interactions with cannabis appear rare. However, there has been some speculation fueled by isolated case reports that combining cannabis and SSRIs could increase the risk of hypomania–a mild form of mania–in vulnerable populations (e.g. persons with bipolar disorder). Generally, physicians favor SSRIs because the occurrence of adverse interactions with other drugs is relatively rare.

SNRIs – such as Cymbalta and Effexor XR.

A newer class of antidepressants, adverse interactions between SNRIs and cannabis or other drugs are rare.

NDRIs – examples include bupropion (Wellbutrin, Aplenzin, Forfivo XL). NDRIs are also sometimes prescribed for ADHD and smoking cessation. There have been very few adverse cannabis interactions reported.

Pain Medication

Most studies suggest there is a significant relationship between the body’s own opioid system and the body’s own endocannabinoid system. However, characterizing the specific mechanisms by which they interact proves challenging. Nonetheless, the pain-relieving properties of cannabis are well-established. Numerous medical professionals have come forward to suggest cannabis (as an alternative pain medication) could play a role in stemming the overuse of prescription (and illicit) opioids. These opioids could include oxycodone, fentanyl, morphine, and others.


According to research on chemical compounds as a whole, virtually all of them interact with other compounds. There are, for example, 82 identified drug interactions with caffeine (Does Starbucks know this?). Even “benign” substances are known to interact with many prescription drugs – Xanax users are warned to avoid grapefruit, for instance. In terms of cannabis, most potential interactions that have been identified are relatively mild. Some drugs seem to work together with cannabis favorably. When was the last time you saw an ad for a pharmaceutical “miracle” that didn’t have at least 20 seconds of “potential side effects” airtime? 

As a result of its therapeutic versatility, one of the most compelling arguments for cannabis is that it can actually reduce the need to combine multiple medications several of which have a high risk potential of producing adverse interactions. Dr. Donald Abrams, chief of hematology-oncology at San Francisco General Hospital and a professor of clinical medicine at the University of California, San Francisco, echoes this important but often overlooked point: “Why would I write six different prescriptions, all of which may interact with each other, when I could just recommend one medicine?” Why indeed?

Note: In some cases, cannabis may actually increase the effectiveness or potency of other drugs. But, even if the interaction is potentially beneficial, close monitoring by a medical professional, along with regular blood work, is important as a patient may need adjust their dosing accordingly.