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Does cannabis interact with antidepressants?

October 3, 2016

Cannabis can make people feel more relaxed, less stressed, and, of course, happier. So predictably, people experiencing depression or anxiety are much more likely to use cannabis — and more of it — than people not suffering from these conditions.

Of course, many people with these conditions also take prescription antidepressants. Consequently, it’s important for medical professionals and patients to be educated on potential interactions that could arise by combining the two.

Remarkably, despite years of research investigating links between cannabis use and psychiatric disorders, few rigorous studies have been published that closely examine how cannabis and antidepressants may interact. Robust searches of Google Scholar and the National Institutes of Health PubMed website produced few relevant studies. Even the National Institute on Drug Abuse (NIDA) website carries very little information on this topic.

Researchers from the Division of Child and Adolescent Psychiatry at the University of Connecticut Health Center conducted an extensive review of the limited scientific literature and published a report, Psychotropic Medications and Substances of Abuse Interactions in Youth. They noted — and I’m paraphrasing — that while one might presume combining psychoactive drugs and psychotropic medications would increase the chances of patients experiencing adverse effects, there have been (astonishingly) few reports documenting adverse effects arising from interactions between the two.


What Are the Side Effects of High-THC Cannabis?

The University of Connecticut researchers explain why there may be so few reports: it’s possible adverse events are “relatively rare” or “do not happen.” Moreover, “newer psychotropic medications have a relatively high therapeutic index” — as a class of drugs, they are less likely to produce adverse interactions. However, they also noted that lack of recognition or awareness could be to blame, and patients experiencing adverse effects may resist disclosing their cannabis use for fear of stigmatization.

Nonetheless, it’s likely that newer antidepressants carry a low to moderate risk for interactions, while older antidepressants carry a higher risk. Characterizing the risk as “moderate,” RxList, an online index of drugs published by WebMD, advises patients who use cannabis to “be cautious” and “talk with [their] health provider.”

Risks of drug interactions

risks of cannabis and antidepressant interactions

One of the challenges facing physicians prescribing antidepressants to patients who also use cannabis (or any other substance, for that matter) is that it makes it more difficult to prescribe the most appropriate drug at the right dose, and co-occurring cannabis use can impede their ability to accurately assess efficacy of prescribed drugs.

Physicians note that one of the most significant variables when patients combine any sort of drug — over-the-counter, prescription, or illicit — is the ability to measure to what degree each produces side effects and how they affect behavior and mood. Obviously, the more substances a patient is using, the more difficult it is to isolate the effects of each. This is why physicians will often start a patient on one drug and add other drugs later.

Cannabis users who are considering a new prescription drug to treat depression or anxiety may want to consider — at least temporarily — abstaining from use and allowing the antidepressants to take effect. Allan Schwartz, LCSW, Ph.D. a psychotherapist and licensed clinical social worker in Colorado and New York, has found that (particularly in severe cases) patients should abstain from cannabis and other substances during treatment. “I was, at times, able to get patients to agree to stop their marijuana use for a few weeks just so they could determine whether there was or was not an improvement in mood,” says Schwartz. “These individuals were surprised, but were willing to admit that they felt real improvement in mood and functioning.”

There’s also evidence to suggest patients are more likely to misuse cannabis or transition from occasional to chronic use when they’re depressed. In fact, those suffering from anxiety or depression use cannabis at rates between two and eight times greater than those without these conditions.

Anecdotally, many physicians report that some patients who use cannabis, alcohol, or other drugs during treatment — particularly those with severe depression or bipolar disorder — are less likely to adhere to their treatment protocols, including prescription drugs and behavioral interventions (e.g. cognitive behavioral therapy, psychotherapy, etc.).

Schwartz says he has seen patients go on and off their medications, often with disastrous results. “I have directly witnessed the tragedy of patients going off of their medications for bipolar disorder, using marijuana and ending up re-hospitalized in worse shape than any time prior to the relapse,” claims Schwartz. “In fact, it has been my experience that many of these unfortunate patients experienced multiple relapses and were caught in an endless cycle of hospitalizations marked by periods of instability in between.”

Beyond these generalized risks, each class of antidepressants is unique and associated with varying side effects and potential interactions. Based on a review of scientific literature, below is a summary of the most common classes of antidepressants and associated risks:

Selective serotonin reuptake inhibitors (SSRIs)

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.

Potential cannabis interaction risk: Low to moderate

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, however, many physicians favor SSRIs because the occurrence of adverse interactions with other drugs is relatively rare.

Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Examples include duloxetine (Cymbalta) and venlafaxine (Effexor XR).

Potential cannabis interaction risk: Low to moderate

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

Norepinephrine and dopamine reuptake inhibitors (NDRIs)

Examples include bupropion (Wellbutrin, Aplenzin, Forfivo XL). Notably, NDRIs are one of the few antidepressants largely absent of sexual side effects. They’re also sometimes prescribed for ADHD and smoking cessation.

Potential cannabis interaction risk: Low to moderate

There have been very few adverse interactions reported.

Monoamine oxidase inhibitors (MAOIs)

Examples include tranylcypromine (Parnate), phenelzine (Nardil), and isocarboxazid (Marplan). MAOIs have fallen out of favor for treatment due to reported side effects and dangerous interactions (which can be fatal) with numerous foods and medications.

Potential cannabis interaction risk: High

A search for case reports on PubMed documenting adverse interactions between cannabis and MAOIs did not produce any results. However, given the high-risk profile of MAOIs to produce significant side effects and induce adverse interactions with numerous foods and medications, the use of cannabis is not recommended.

Tricyclic antidepressants

Examples include imipramine (Tofranil), amitriptyline, doxepin, trimipramine (Surmontil). While reported side effects and interactions are less common with tricyclics than MAOIs, more people report undesirables side effects with tricyclics than newer antidepressants. Consequently, they’re usually only prescribed to patients who’ve been unresponsive to other treatments.

Potential cannabis interaction risk: High

One case report documented a 17-year-old boy with depression and insomnia who was prescribed 25mg of amitriptyline. After speaking with the teen’s friends and doing a search of his bedroom, parents confirmed the only other substance he’d been using was cannabis. He was checked into the ER for a racing heartbeat (tachycardia). The attending physician reported that without intervention, adverse interactions could potentially be “life-threatening” and cautioned physicians against prescribing tricyclics to treat depression or insomnia in patients who use cannabis or other drugs. Other case reports have been filed citing similar concerns.


Sedatives are not technically considered antidepressants. However, 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.

Potential cannabis interaction risk: High

From a pharmacological perspective, the potential for adverse interactions to arise from combining cannabis and antidepressants (with a few notable exceptions) appears fairly low. However, there are other risks to consider: most notably, antidepressants could be less effective or take longer to work; patients may be at higher risk to go on and off treatment protocols, thereby prolonging recovery; and, finally, the risk of transitioning from moderate use to problematic use is significantly higher in individuals experiencing depression.

For patients experiencing severe depression (or bipolar), the risks are even greater. Individuals should carefully consider these risks and moderate their use of cannabis accordingly.

High-CBD cannabis for anxiety

blooming outdoor medical marijuana plant

Finally, patients should keep in mind that while there is evidence that low doses of THC can produce desirable effects (such as euphoria and relaxation), high doses can do the opposite — too much THC can increase anxiety (or even induce a panic attack). The second most prominent cannabinoid in cannabis, CBD, counteracts many of the adverse effects of THC, and significant preliminary evidence suggests CBD may be useful to combat anxiety, depression, and other psychiatric disorders. Therefore, if you’re experiencing anxiety or depression and choose to use cannabis, seek out strains that are high in CBD.

Jeremy Kossen's Bio Image

Jeremy Kossen

Jeremy is a contributing writer at Leafly. He is a best-selling author, podcaster, and entrepreneur.

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  • mrd28s

    One thing this article doesn’t address is that marijuana and these pharmaceuticals do have one thing in common. There are many different strains which give many slightly different reactions, just like their are different types of antidepressants that do the same. There is also some differences of how marijuana effects different people in general, pharmaceuticals the same.
    This makes up for a lot of different combinations, which can be a little harder to dose, but I think in the future when TRUE and REAL testing and analysis IS finally allowed, it will benefit by using both drugs to “fine tuning” it for the individual. I think combining marijuana has the possibility to counter some of the bad side effects of using the anti depressants AND interject it’s own qualities of stress, muscle, and pain relief that normally go along with depression.
    I think that it would be a dream, for big pharma to actually come together side by side with the medical marijuana community though… Just a dream!
    Great article though!

    • Joe

      I think only by legalization and strict regulation to enforce strength testing and high punishment for fraudulent claims, this can be achieve.

      • Jeremy Kossen

        Although I’m instinctively anti-regulation, I’ve evolved on this issue greatly (having seen too many horror stories when you let the chickens in the coop run wild — not just in this industry but real estate, banking, other businesses, etc.) and I think the industry needs to be proactive and put forth sensible regulatory frameoworks that can be adopted state-by-state that protect the consumer without stifling creativity.

      • mrd28s

        This did NOT work for the pharmaceutical industry, why would you think it would work here?
        Oh wait, WE actually care about the patients more than the money!!

        • F1ahughes798

          Sure you do. Why not give it away, then?

    • Jeremy Kossen

      You’re 100% right. Cannabis contains hundreds of compounds — cannabinoids and terpenoids — that variously influence outcomes. I would have loved to address the mechanistic actions of every cannabinoid and terpenoid in this article, but unfortunately, that would require an entire book! But, to your point, different strains produce different effects. Point well taken. Thank you for your comment!

    • NaughtayMonkay

      I take SSRI medications for anxiety and depression but I intentionally don’t take them on regular basis but rather occasionally because I get it’s effects when I start and my stress is less intense for couple days. Well, in my experience, when I had taken an antidepressant about 8 hours or so before smoking the effects of marijuana are better. I feel greater change of thought which without an antidepressant I can either not get at all or need to use more greater amount of marijuana, which I don’t enjoy. I tried to get a feel for this interaction a number of times and so far it seems to happen each time. It’s probably because more serotonin from the antidepressant complementing anandamide and dopamine resulting from marijuana.

    • Donna Novi

      Excellent points and comments. I am more than excited for the future studies that can now be conducted. I have studied Cannabis for several years and although I don’t work in a dispensary, I am qualified to do so. I 100% agree with the ‘strain’ part of your comment. I have seen some amazing, almost unbelievable turnarounds for friends and family. However, we are currently in the throes of what appears to be a psychotic break (my Mother’s 61 year old husband) and we aren’t sure if it’s the sheer quantity of cannabis he is consuming (he tends to be a glutton) or is it the combo of his anti-depressant, high doses of thc and large quantities with alcohol thrown in in or did something trigger a dormant manic depressive gene (family history)? Watching this person over the last 2 1/2 weeks has been surreal. He is having delusions of grandeur; yelling, spending their savings like water, not sleeping. You would swear there is an amphetamine at play here, nothing like one expects from cannabis use. Have you or anyone here ever seen such a thing? We are trying to get him help but he hasn’t threatened our lives yet or tried to harm himself. This is what scares me about thc w/out cbd, you can get way too much of it in your body by eating it and via concentrates and the natural plant has both components. I am NOT saying that both thc and cbd isolated aren’t useful, I am only wondering about studies that can help us understand the effects on a person who grossly abuses substances and combines multiple substances. I am also searching for answers. With legalization I believe we will get some answers!

  • MG Deegan

    It my broken disc

    • MG Deegan

      I love medical marijuana flower it works for me

  • Joe

    Excellent article, a must read.

  • Thanks for all the research on this. Cannabis has so many potential uses, but in the rush to end prohibition, I worry that some of the potential risks are being overlooked.

    I’m glad that people are taking an objective look at all aspects of cannabis.

    • Joel Munson

      Know what? In the rush to create prohibition, all of the benefits were overlooked and the risks were overstated.

  • lovingc

    One thing the writer of this story needs education on is bipolar disorder, there are many shades of affect on daily life. Not all bipolar sufferers are the same, not all of us swing from manic to depressive. Mine shows up as a lower sense of happiness. Some are maniac all the time. So blanket statements about bipolar are meaningless .

  • One

    Jeremy wonderfully written. Trying to find information on “chunky crimson” a strain developed to help with hepatitis c. Researchers from wit showed 98.8% total cure 0.02 % unchanged. Trying to locate it or something comparable. 0ne-

  • Joe

    Good information, will like to see the new administration open research on drugs interaction base on real consumer of the pharmaceutical drugs and marijuana users of various consumption level of THC. That will be real research and no fix research to support the DEA position.

  • Indica Ape

    Question my doctor prescribed me fluoxetine for nervousness (I tend to worry a lot). I told him I smoked cannabis and have been smoking cannabis for over around 2 years. He never told me not to smoke while on this medication. This is my second day on the medication and I have not smoked cannabis out of concern. Anyone here smoke cannabis and take fluoxetine any bad experiences?

  • Geoff Jacobs

    Here’s my problem and I really hope someone can help me… I take 10mg of Lexapro everyday. I was taking 20, but, I weened myself off and discovered that I was a tear-gushing crybaby over every silly issue that came up and every heartwarming video I saw, and I felt like Hell. So, I went back on the Lexi’s but now I’m only taking 10mg.
    The problem is, I vape Cannabis because of another issue and when I do, I only vape ONE SINGLE toke?! This ONE toke gets me high as a kite, BUT, it always makes me paranoid and super anxious!! So far, I have used only a Sativa oil.
    WHAT is my problem??? Do I need an Indica? A Hybrid? Or, do I ween off of the Lexapro and stay on the Cannabis??
    PLEASE let me know your opinions!!

    • Jeffrey Blechman

      Perhaps stop smoking Pot?

    • Wayne Bristol

      Get a strain with a higher CBD content to counteract the negative effects of the THC.

  • MG Deegan

    I am a medical marijuana patient card holder I smoke 24 7 medical license I have pain triple mine grane knees callerbone twisted Nick gamco instead gocmo

  • Gwen Burkett

    I would like to see more testing/information relating to use of marijuana by a person who is bipolar.

  • Katelyn Lockwood

    How to sensibly buy LEGAL cbd oil? Because I got a letter saying customs has confiscated my package two times already and I’m pissed.

  • Tanya

    i am currently taking 12.5 mg amitriptyline after 8 months weaning from 25mg by taking melatonin or natural sleepaid every night. i am having problems with insomia, headache, anxiety. Has anyone tried CBD oil with thc for depression and cdbalive thca for insomia while on amitriptyline? any side effects and have you tried spacing out the antidepression meds and the cbd? Any comments or suggestions would be highly appreciated!

  • Deborah Coleman

    Antidepressants cause suicidal thoughts. I’ll stick with CANNABIS. It’s a neuroprotectant and does no harm. I replaced all Pharma in September 2014 with cannabis. I’ll never take another pharmaceutical drug. Ever. It’s PHARMAKEIA . wakey wakey

  • Jim

    I completely agree with this article. I have been issues with my depression for over 10 years. I was on citalopram and other meds that gave me a ton of side effects. I was then on Lexapro and then came across CBD. I wasn’t sure about side effects, but I found your article, as well as which helped me weigh the pros and cons of adding CBD to my prescription medications.

    Thank you for your content, you have really helped me improve my quality of life.

  • Lisa

    Can taking an antidepressant tame your high on cannabis?

  • Prince Sol

    Someone needs to start making cannabis tablets with different strains for different effects.