Does Cannabis (Marijuana) Interact With Benzodiazepines?

In our latest question and answer, the pharmacist discusses whether or not marijuana interacts with the benzodiazepine class of medications.

Jan 17, 2018

joe asked

My doctor has told me that she would discontinue my RX for temazepam because I also use medical marijuana for chronic insomnia. She told me that it's a dangerous pharmacological combination. I wanted to get a pharmacist's opinion. Is there a specific contraindication to using temazepam and medical marijuana concurrently? Thank you.


Drug interaction studies with cannabis (i.e. marijuana) are lacking to the point where making conclusive statements regarding an interaction with one drug or another isn't justifiable in most cases. In studies that have evaluated the topic, it appears the likelihood of any significant drug interaction would be rare

Unfortunately, we don't fully understand the complete effects of cannabis when used medicinally or recreationally, and this includes how cannabis could affect concomitant medications, such as temazepam, a benzodiazepine.

However, when drug interactions with cannabis have been evaluated in studies, caution is typically advised when combining with benzodiazepine medications due to the potential of additive side effects and theoretical interactions, which we discuss in more detail below.

Benzodiazepine - Cannabis (Marijuana) Drug Interaction

The most commonly listed drug interaction with cannabis is with medications that are CNS (central nervous system) depressants, such as barbiturates and benzodiazepines. This interaction however, is more based on theory than observing the interaction clinically. In fact, it is exceedingly rare to see a reported cannabis drug interaction in clinical trials.

There are thought to be two main, potential mechanisms of cannabis drug interactions:

  • Cannabis is extensively metabolized by cytochrome P450 (i.e. CYP P450) enzymes. Most studies indicate that cannabis has an inhibitory effect on some of those enzymes (specifically CYP 2C9, 2C19 and 3A4), potentially increasing levels of other medications that are metabolized through that system (due to inhibition of metabolism). However, other studies note a potential for the opposite as well (induced metabolism).
  • Additive potential of adverse reactions (e.g. increased likelihood of sedation etc...).

Theoretically, there should be an extensive list of medications that cannabis interacts with due the inhibition of the certain CYP P450 enzymes, as mentioned. The majority of prescription medications we take are metabolized by CYP P450 enzymes. Interestingly enough, when cannabis was tested with medications known to be metabolized through that system (e.g. ketoconazole), no significant changes in drug levels were recorded. 

In fact, cannabis has been extensively tested with a variety of medications (e.g. tricyclic antidepressants) and no drug-drug interactions have been observed that would contraindicate the use of other drugs.

Now, there have been a few studies that provided an exception to the lack of drug interaction findings. One example is with the drug clobazam, a benzodiazepines derivative medication. A study noted that levels of the clobazam active metabolite (N-desmethylclobazam) significantly increased when used alongside cannabidiol (CBD) only. This is potentially due to metabolizing enzyme induction from CBD intake. It is possible that a dose reduction may be needed with this specific medication.

The study referenced above also noted slightly increased levels of other anti-epileptic drugs, but no change was considered clinically significant. News outlets have raised the question of whether or not cannabis negatively interacts with anti-epileptic drugs, of which benzodiazepines would be included. What can be said now is that evidence is very preliminary and if interactions exist, small dosage adjustments may be needed for certain medications.

What most studies conclude in terms of drug interactions however, is that there is no medicine that cannot be used with cannabis if monitored appropriately. There have been no findings of any serious drug interaction outside of certain medications needing a potential dosage adjustment, and even these appear to be exceedingly rare.

Lastly, caution is advised with any CNS depressant medications due to the potential of additive sedation. Cannabis is theorized to affect GABA, an inhibitory neurotransmitter in the body which can cause sedation and drowsiness. Sedation and fatigue are commonly reported side effects of cannabis use (depending on the plant species used).

Due to the potential of additive sedation, caution is advised when combining benzodiazepines (CNS depressant) and cannabis. There are however, no reported interactions with them (with the exception of clobazam). In addition, there have been no reported deaths or hospitalizations due to interactions with cannabis and benzodiazepines.

For reference, commonly used benzodiazepines include:

  • Alprazolam (Xanax)
  • Clobazam (Onfi)
  • Clonazepam (Klonopin)
  • Ativan (Lorazepam)
  • Diazepam (Valium)
  • Temazepam (Restoril)
  • Triazolam (Halcion)

To summarize, there are no reported interaction between cannabis and benzodiazepine medications (with the possible exception of clobazam). Data is lacking but based on studies that have been conducted, interactions are theoretical based on:

  • Cannabis alterations of metabolizing enzymes
  • Additive side effects

When cannabis is used with CNS depressant drugs, such as benzodiazepines, there is a concern of additive side effects such as sedation and fatigue. There are also potential drug interactions based on how a drug is metabolized (even though many studies show no clinical significance when these potential interactions were tested).

Nevertheless, as data is lacking, caution and monitoring is advised when using a new combination of medications. The general recommendation when using cannabis, is to start your dose low, and increase dose to effect while tolerable.

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