Shrooms and SSRI: Comparing Psychedelics

The Controlled Substances Act lists psychedelics as a Class 1 Substance. This act hinders the use of natural psychedelics into their potential antidepressant effects.

But, scientists carried out extensive research on psilocybin and other psychedelics. They focused on its use and safety.

In these clinical trials, scientists used psilocybin with over 40,000 patients. The patients received the drug without serious adverse events.

Imperial College London’s Centre for Psychedelic Research focuses on two research themes:

  • the use of psychedelic therapies for mental health care
  • tools used to probe the brain’s basis of consciousness

They were the first to conduct Clinical Trials on psychedelics. These trials kick-started global efforts to develop psilocybin therapy. Their human hallucinogen research show psilocybin’s potential for future depression treatment.

The Centre for Psychedelic Research at Imperial College London tested their theory. They compared a placebo group with a psilocybin group.

Secondary outcomes showed reductions in depressive symptoms. This was after the administration of one or two doses of psilocybin.

These results were also observed in trials across several patient populations.

A new study suggests using SSRI drugs with psilocybin to treat depression.

To confirm this, they carried out a clinical trial to get results. They also tested using psilocybin with other psychedelics.

To do this, they had to get confirmation of a diagnosis of depression and medical history. These were all gathered from each patient’s general physician.

The results say that you can use psilocybin during escitalopram treatment. Escitalopram is a type of SSRI. Results show that using it with psilocybin has no clear impact.

Other secondary outcomes generally favored psilocybin over escitalopram. But the analyses were not corrected for many comparisons.

So, it is possible that external factors affected the outcome. Psychological support could have helped those in the escitalopram group.

Evidence from various trials showed the positive effect of a psychedelic experience.

Magic Mushrooms and SSRI

Psilocybe semilanceata magic mushrooms

How does psilocybin work? Many psychedelics and antidepressants work by modifying the body’s serotonin system.

Now, we know that psilocybin alters the body’s serotonin system. What are the possible risks? Is it all right to have a psilocybin experience while on antidepressants? In layman’s terms, is it safe to take magic mushrooms and SSRI together? Or can I use it with other medicines?

But before we move forward, let’s first lay down the foundations.

What is SSRI (Selective Serotonin Reuptake Inhibitor)?

SSRI selective serotonin reuptake inhibitors (SSRI) are prescribed antidepressants by physicians. These are often given to those with symptoms:

  • Major Depressive Disorder
  • OCD
  • PTSD
  • other anxiety disorders

Examples of Selective Serotonin Reuptake Inhibitors

The most commonly prescribed antidepressants, Selective Serotonin Reuptake Inhibitors SSRI antidepressants include:

  • citalopram
  • escitalopram
  • fluoxetine
  • fluvoxamine
  • paroxetine
  • sertraline

Serotonin Modulators and Stimulators and Serotonin Antagonists and Reuptake Inhibitors are like SSRIs. They boost serotonin levels in the brain and activate more serotonin receptors.


The therapeutic effects of combining psilocybin and SSRI medication are still unknown. But, using SSRIs or SNRIs can have acute and chronic side effects. This includes headaches, diarrhea, and sexual dysfunction.

Also, SSRIs (selective serotonin reuptake inhibitors) can reduce the effect of psilocybin. This can lessen the experience of a trip or a retreat.

The chronic use of SSRIs and MAOIs shows a decreased sensitivity to psychedelics. MAOIs, also known as monoamine oxidase inhibitors, include ibogaine.

Taking certain psychedelics with lithium or tricyclic antidepressants has serious side effects. One of these includes seizures.

Ketamine has antidepressant effects. But it works more as a classic psychedelic rather than an SSRI or SNRI. This is because it affects one or more of the monoamine neurotransmitters.

The nasal spray Spravato (esketamine) is the only FDA-approved option for treating depression.

Several clinical studies all suggest reduced effects of MDMA with antidepressants. But, they have not resulted in adverse effects. Adverse events in the psilocybin group occurred 24 hours after the dosing day. Headache is the most common adverse event.

Chronic use of tricyclic antidepressants and lithium potentiate the psychedelic effects. Thus, creating a safety concern. TCAs and TeCAs have a less sophisticated impact on physiology. They can cause death by their effects on the heart. So, it is not recommended to mix these with psilocybin.

Meanwhile, ibogaine is toxic and dangerous to consume alongside other drugs.


The poison will always depend on the dose. When using SSRIs, the risk is high of developing serotonin syndrome. This is a condition where your body becomes overstimulated due to certain medications. It can cause insomnia, restlessness, confusion, high blood pressure, and more.

The occurrence of serotonin syndrome is rare.

But, it is not recommended to take Monoamine Oxidase Inhibitors (MAOIs) with psilocybin. One example of MAOI is ayahuasca.

The symptoms of mild serotonin syndrome overlap with ordinary ayahuasca experiences. This includes diarrhea, dilated pupils, sweating, or changes in body temperature.


There is more research into the working mechanisms of psilocybin. This includes other psychedelic substances.

capsules lined up on a metallic surface

Recent research suggests psychedelics could benefit a lot of people. Especially those living with mood disorders, including anxiety and depression.

Magic mushrooms have a “liberating effect” on the depressed mind.

Also, psilocybin causes delayed transient headaches in healthy volunteers.

In some trials, the beneficial effects of psilocybin lasted until the study ended. Some experienced positive effects three weeks after their second psilocybin dose.

So the list of health problems psilocybin can help address continues to grow. Now, we know that psychedelic therapy works not only for depression. But it can also address other mental illnesses, such as anorexia or addiction.

Final Thoughts

Serotonergic psychedelics should all be safe to use while on antidepressants. These psychedelics include psilocybin mushrooms, LSD, and DMT (without MAOIs)

But if you are unsure, you may want to discuss psychedelic therapies with them. Have you tried several antidepressants without getting adequate relief? If not, it’s best to seek professional medical help.

Do not use any substance, illegal or otherwise, without medical supervision.

With more time, we will see more places that will legalize psilocybin therapy. Especially for the treatment of a range of mental health issues.

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