Is it Safe to Mix Magic Mushrooms With Antidepressants?

“If the results are confirmed in subsequent studies … antidepressants may no longer need to be stopped for psilocybin treatment,” says Dr. Miri Halperin Wernli.

Highlights.

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We get asked a lot of questions about whether or not it’s safe to mix magic mushrooms with antidepressants.

It's a valid question because those with depression often seek out alternative therapy through psychedelics. But because there’s more than one kind of antidepressant, and because many are known to have numerous interactions, the answer can be convoluted.

For example, SSRIs — the most common class of antidepressants — work through the human body’s serotonergic system.

Because many psychedelics and recreational drugs work on the very same system, there is some controversy around whether or not this would generate excessive levels of serotonin — which are associated with severe and sometimes fatal events.

When we first wrote this article in 2020, there were no human clinical trials investigating the use of psilocybin therapy and antidepressants.

However, recent evidence from a clinical trial demonstrates that a common SSRI, escitalopram, may be safe to use alongside psilocybin therapy. Supported by the University Hospital Basel and Mind Medicine, Inc. (MindMed), the aim of the study was to investigate the subjects' response to psilocybin after pretreatment with escitalopram or placebo.

That isn't to say that all antidepressants react with magic mushrooms the same way, or that all SSRIs are compatible with magic mushrooms.

In this article, we're covering the available data on magic mushrooms and SSRIs, SNRIs, Lithium, and MAOIs.

If you’re taking antidepressants, but want to experiment with magic mushrooms, the most important thing to do is talk to the doctor who prescribes your antidepressants. If they aren’t friendly to the concept of alternatives, find one who is. You may be required to wean off antidepressants before using psychedelics, but this should only be under the supervision of the professional who prescribes them to you.

Mixing magic mushrooms with SSRIs.

SSRIs are one of the most commonly prescribed antidepressants because, as a class of antidepressants, they are considered to have the fewest drug interactions and side effects. SSRI stands for selective serotonin reuptake inhibitor, and as we mentioned, it works on the nervous system’s usage and production of serotonin. 

The most common ones include:

• Citalopram (Celexa, Cipramil)
• Escitalopram (Lexapro, Cipralex)
• Fluoxetine (Prozac, Sarafem)
• Fluvoxamine (Luvox, Faverin)
• Paroxetine (Paxil, Seroxat)
• Sertraline (Zoloft, Lustral)

There is currently one clinical trial that specifically addresses the interaction between magic mushrooms and antidepressants.

Biotechnology company MindMed has released new data showing how a selective serotonin reuptake inhibitor (SSRI) interacts with psilocybin in humans, providing preliminary evidence these drugs could be safely used together without impacting psilocybin’s effectiveness to tackle depression and anxiety.

SSRI drugs are the most commonly prescribed antidepressant that can relieve the symptoms of depression by increasing the level of serotonin — often referred to as the “feel-good hormone” because it is responsible for stabilizing our mood, feelings of wellbeing, and happiness — within a person’s brain.

Because psilocybin is being investigated as a treatment for depression and anxiety, it is vital to understand how this drug interacts with current antidepressant treatments. Before this study, it was unclear if antidepressant medicines would interact with psilocybin, with some case reports indicating that antidepressants may reduce a person’s response to psychedelics.

The MindMed-sponsored study, carried out by the University Hospital Basel Liechti Lab, showed that pre-treatment with the SSRI escitalopram had no relevant impact on the positive mood effects of psilocybin. However, it significantly reduced negative effects such as anxiety and adverse cardiovascular reactions when compared with a placebo pre-treatment in healthy human participants.

For the study, participants either received 10mg of escitalopram daily for seven days followed by 20mg daily for the next seven days, including the day of psilocybin administration, or 14 days of placebo pre-treatment before psilocybin administration.

“These results indicate that psilocybin may be dosed during escitalopram treatment without apparent impact on the effect of psilocybin,” explains the study’s Principal Investigator, Dr. Matthias Liechti.

Some researchers theorize that because psilocybin and SSRIs work on the serotonergic system in different ways, magic mushrooms and SSRIs might be complementary.

In a 2020 study, researchers discovered that, in addition to psilocybin and psilocin, magic mushrooms contain an alkaloid called b-carboline. This alkaloid falls into a category of compounds called MAOIs (monoamine oxidase inhibitors), which are known to adversely interact with SSRIs. However, in this study, researchers concluded that MAOIs can be safely co-administered with SSRIs, as long as they aren't MAO-B inhibitors.

But for this to be safe, the SSRI dose has to be at the lower end of the therapeutic index and has to be monitored closely. 

So what does this mean for SSRI takers?

It means — it's likely safe, but you should always talk to your doctor. It seems as though there is a safe way to co-administer magic mushrooms and SSRI but it should be done under supervision to ensure that your SSRI dose is safe with your psilocybin dose. 

Mixing magic mushrooms with SNRIs.

SNRIs are similar to SSRIs except that they also work on norepinephrine as well as serotonin. They are typically prescribed when SSRIs aren’t tolerated and might also be beneficial for people with anxiety.

SNRI drugs include:

• Desvenlafaxine (Pristiq, Khedezla)
• Duloxetine (Cymbalta)
• Levomilnacipran (Fetzima)
• Venlafaxine (Effexor XR)

Given that SNRIs work in a very similar way to SSRIs, the same assumptions can be made about SNRIs. There’s a possibility that magic mushrooms are safe to use with SNRIs depending on the dose of both, but again this should be supervised by the professional who prescribes the SNRI.

Mixing magic mushrooms with Lithium, MAOIs, and other antidepressants.

Though there are no clinical trials on the co-administration of lithium with magic mushrooms, this is not recommended. There are reports of people mixing lithium with LSD and psilocybin mushrooms and experiencing seizures and heart attacks.

Because MAOI-type antidepressants are, in fact, MAOIs, it's not recommended to use them with psilocybin. Psilocybin mushrooms also contain an MAOI and so it might sound counterintuitive to avoid mixing, but it's not known to what degree MAOI antidepressants potentiate the effects of magic mushrooms or even dampen them.

For all other antidepressants, there is next to no information about interactions. For this reason, we recommend avoiding concomitant use unless you have been given the OK from your doctor, or until you can wean off them.

It is possible antidepressants might dampen the effects of magic mushroom treatment.

Tryptamines, such as psilocybin, are lovers of serotonin receptors, and like we just talked about, so are pharmaceutical antidepressants. Antidepressants like SSRIs don’t just affect serotonin levels but they also modulate and affect serotonin receptors.

Benjamin Malcolm, the owner of Spirit Pharmacist, hypothesizes that because of the way that SSRIs and SNRIs modulate serotonin receptors, antidepressants may actually dampen magic mushrooms' therapeutic potential.

He offers this chart for interactions between different kinds of antidepressants and psychedelic drugs.

You can find his full compilation of possible drug interactions here.

When you look through the chart, you’ll notice that most of the time Benjamin Malcolm recommends weaning off antidepressants and discontinuing their use at least two weeks before using magic mushrooms. He also says that prolonged, chronic antidepressant use can lead to an overall dampened effect of magic mushrooms.

Don’t try this at home, folks.

The overwhelming advice, in light of how little we know, is to wean off antidepressants before you take magic mushrooms in any kind of therapeutic fashion. Although it’s unlikely to walk yourself into any kind of fatal event, not knowing at which correct doses to co-administer the two is unsafe. Plus, you don’t know how much of a disservice you’re doing to your antidepressant treatment or your magic mushroom experience.

If you’re one of the many people who is seeking an alternative treatment for depression and wants to try psilocybin, we recommend talking to your doctor to wean off before you try magic mushrooms. It’s the safest way to dip your foot in this ocean and your overall treatment might be much better off not mixing the two.

Have you ever weaned off antidepressants to use magic mushrooms? We’d love to hear your story — drop it in the comments.

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