What to Know About Antidepressants and Cannabis

cannabis-leaf-brain-By Shidlovski
Photo: Shidlovski/shutterstock

Depression is more rampant than ever before. Whether you want to blame it on your least favorite politician, doctors over-diagnosing their patients, or the crisis of work-life balance brought on by smartphones, the numbers confirm that the problem is growing out of control. With more people suffering from depression, it stands to reason that more people are taking antidepressants to combat the ruinous symptoms that come with it.

From 1999 to 2014, use of antidepressants by Americans 12 and up increased by 65%. Right now, almost 13% of Americans are taking an antidepressant, and a quarter of those people have been taking the medications for over 10 years. As medical and recreational marijuana become more available to the public, the overlap between those who are on medication and those who use marijuana keeps growing.

The question then becomes: How do antidepressants and cannabis interact? Are they dangerous to take together? Does cannabis cancel out the positive effects of an antidepressant?

An Intro to Understanding Antidepressants

doctor holding anti-depressant bottle

It's difficult to evaluate the relationship between antidepressants and cannabis because of one peculiar fact: We don't actually know how antidepressants work; we just know that they're effective in treating depression.


The most common types of antidepressant are SSRIs, or selective serotonin reuptake inhibitors. The fancy name is a nod to the drugs' function, which is to increase the circulating levels of serotonin in the brain. Serotonin helps regulate multiple functions, such as mood, appetite, libido, socialization behaviors, sleep, and memory.

In other words, this key neurotransmitter (or the lack of it) has a direct impact on depressive symptoms. But there are other common antidepressants that focus on other compounds in the brain with the goal of balancing everything out.

Using the drug interaction checker at RXlist.com, it becomes clear that many of the most popular antidepressants run little risk of producing negative interactions.

You've almost certainly heard of the SSRIs Prozac, Celexa, Zoloft, or Lexapro. They are some of the most commonly used drugs for depression, and they have the lowest reported number of interactions with other drugs.


Serotonin and norepinephrine reuptake inhibitors (SNRIs) like Cymbalta and Effexor are a newer category of antidepressants, and they carry little risk of interaction with cannabis and other drugs, too.

Norepinephrine and dopamine reuptake inhibitors (NDRIs) are low-risk for interactions, and they have the lowest rate of sexual side effects as a bonus. If you're taking one of these antidepressant types, your risk of encountering an adverse interaction with cannabis are slim to none. Other types of drug, however, are much more dangerous.

MAOIs &Tricyclics

Monoamine oxidase inhibitors (MAOIs) are fairly rare nowadays, and they’re usually prescribed only if other antidepressants haven't worked. If you're taking an MAOI for depression, you shouldn't even think about throwing cannabis into the mix. MAOIs are notorious for producing terrible interactions with other drugs.

You've probably seen at least one drug commercial with a laundry list of side effects starting with "don't use this medication if you take MAOIs." These drugs are so reactive, even foods can set them off.

Things as innocuous as aged cheddar and soy sauce can cause a hypertensive crisis and hemorrhagic stroke! This is an antidepressant that shouldn't mix with anything, let alone cannabis.

As some of the first antidepressants developed, tricyclics have mostly been dropped in favor of newer drugs with fewer side effects. But, like MAOIs, they're still a good option when other medications have been ineffective. Unfortunately, the laundry list of symptoms attached is extensive—and we do have evidence of at least one severe interaction with marijuana.

A Concerning Case Report

The evidence comes in the form of a case report of a 17-year-old boy who experienced severe adverse effects from a tricyclic. To cope with a "chaotic household," reduce his depression symptoms, and help him sleep, he took 25 mg of amitriptyline. After just a week of taking this tricyclic, he was rushed to the emergency room with tachycardia.

The poor kid's heart was racing at 300 beats a minute and had been doing so for 24 hours.

brain neuron_A_riakhin
Photo: _A_riakhin/ shutterstock
He reported no drug or alcohol use, other than occasional use of marijuana. His friends and family confirmed this, making it increasingly clear that the culprit was likely an interaction between the two substances. The boy had been taking his amitriptyline the week before and had smoked very heavily the night before he went to the emergency room.

The conclusion of the case study makes it clear that "A life-threatening sustained supraventricular arrhythmia is a possible consequence of taking tricyclic antidepressants and smoking marijuana." But other than this report, cases of marijuana interacting with antidepressants are all but impossible to find.

Sussing Out Side Effects

It's very possible that the lack of reporting on antidepressants and cannabis is due to the ongoing stigma surrounding the drug. Although marijuana is becoming more accepted, most people are still uncomfortable discussing it with their doctors.

This may have created a huge gray area, where people are actually experiencing side effects or diminished efficacy of their antidepressants due to cannabis use, and they just don't know it.

There's a chance that taking antidepressants and cannabis concurrently dulls the effect of the depression medications. A 2007 study confirmed that the CB1 receptors, the primary site of action for THC, have a direct impact on serotonin levels in the brain.

They actually influence the cells that manufacture the serotonin, like SSRIs do. However, while SSRIs uniformly work to increase the available serotonin in the brain, it seems THC can have a variable effect.

Dr. Gabriella Gobbi led the research team conducting this study at McGill University. The team utilized a synthetic form of THC to test its antidepressant properties in rats. They found that at low doses, the THC "had a potent anti-depressant effect." But at high doses, the serotonin levels in the rats' brains precipitously dropped.

They actually dropped below the serotonin levels of the rats in the control group. All positive effects were totally reversed once the rats received higher THC doses.

Concurrent Antidepressant and Cannabis Use

If your depression is being treated with an SSRI, chronic cannabis use will at least partially cancel out the drug's efficacy. While the SSRI works to keep serotonin levels up, large amounts of THC may deplete it as fast as it's produced.

The good news here is that an occasional, moderate smoke likely won't have the same effect. Consuming cannabis mindfully and responsibly is possible, even though antidepressants and cannabis should not mix in the long term.

Watching your THC intake is the best way to ensure no interactions occur, and one way to do that is by using CBD-rich strains. Some of these low-THC strains can actually help treat some of the symptoms of depression without interfering unduly with your antidepressant.

Microdosing CBD is another safe option for those on antidepressants. CBD behaves similarly to the THC observed in the McGill study, in that lower doses have a higher efficacy than larger doses. CBD also produces beneficial effects through its binding to the CB2 receptors, which have significantly less sway over serotonin production.

Caution is Key

The bottom line is that antidepressants and cannabis don't go hand in hand, but the occasional smoke session won't kill you. As with all medical questions, remember: It really is crucial to talk to your doctor about your cannabis use before starting or stopp