Psychedelic science is in its infancy stage, so there is a lot that is still unknown. One of these unknowns is the safety and efficacy of taking a psychedelic medicine while on a Selective Serotonin Reuptake Inhibitor (SSRI).

This is a question that is often discussed. There has always been concern and interest about the interaction between these two drug classes, but little is known about it. The answer to this question has major implications in the psychedelic drug development space because a lot of the people who could benefit from psychedelic-assisted therapy are currently taking an SSRI.

Since they both affect the same receptors in the brain, it is reasonable to assume that one will influence the effects of the other. However, scientists are not sure exactly how they interact.

A recent study from COMPASS Pathways begins to shed light on this question. This is the first study of its kind, and the results are preliminary. However, it does give scientists and psychedelic therapists a first look at how the drug classes interact. 

Up until now, common practices regarding the use of SSRIs and psychedelics have been based on educated guesses. These beliefs and common practices have been used for decades. The goal of these practices is to err on the side of caution until more research is available. 

Psychedelic therapists have been more concerned with safety than efficacy concerning this issue. Many psilocybin and ayahuasca retreat centers will not treat anyone who is currently taking SSRIs for fear of adverse effects. 

Though there is a hypothesis that SSRIs blunt the effects of psychedelics, most practitioners are more concerned with the potential harm that could come to patients by mixing the two. However, this is all speculation.

There really hasn’t been any data on the interaction between psychedelics and antidepressants until now. In July, psychedelic mega-company COMPASS Pathways released results from a phase 2 study testing its synthetic psilocybin drug (COMP360) alongside an SSRI. 

Some patients in the study reported a headache. This was the most commonly reported adverse effect of the treatment. Other than that, there were no major issues reported. 

As for efficacy, the data is promising. The study showed similar results to the company’s phase 2 study testing COMP360 for treatment-resistant depression without the use of SSRIs. In fact, the remission rates were slightly higher compared to the study where patients were forced to go off their SSRIs before receiving psychedelic-assisted therapy. The data suggests that allowing patients to continue taking their medication is beneficial to the outcome of psychedelic treatment. 

“Dr. Guy Goodwin, Chief Medical Officer at COMPASS Pathways, said, ‘It has long been thought that SSRIs could interfere with the potential therapeutic effect of psilocybin. This data is exciting because it provides a preliminary signal that this is not the case and that patients could remain on their SSRI antidepressant medication and experience the same effect from COMP360 psilocybin treatment as people who are not on SSRIs.’”

It has long been believed that antidepressants blunt the effects of psychedelics. This belief is based on several self-reported studies from back in the 90s. These studies are the only real evidence that this belief is true, and it certainly isn’t reliable scientific data. 

The COMPASS study shows no evidence that SSRIs blunt the effects of psychedelics. In fact, there may be some benefits in not forcing patients to withdraw from their medication before taking psychedelics. 

Allowing patients to stay on their medication while receiving this novel treatment could make it more accessible. SSRIs are a habit-forming drug, and coming off them can be challenging; it can even be dangerous when done improperly. Withdrawal symptoms include anxiety, insomnia, dizziness, and a return of depression— to name just a few. 

COMPASS said, “This could have important clinical implications for patient choice, if COMP360 psilocybin treatment receives regulatory approval for treatment-resistant depression. Withdrawing from antidepressants can be unwelcome for some patients, so the possibility of having the choice to remain on their antidepressant could eventually make COMP360 psilocybin treatment more accessible.”

Ultimately, this is about patient choice and discovering which options they have for their treatment. There is some speculation that when compared to patients who have never been on SSRIs, those who are on them get less benefit from psychedelics. However, regardless of the potential blunting of effects, this data shows that psilocybin is likely still effective when taken in tandem with SSRIs.

It is important to note that this study cannot be applied to all psychedelics. Other psychedelic compounds may have different interactions with SSRIs. It is believed that mixing MDMA or the south american psychedelic brew Ayahuasca with antidepressants can cause Serotonin Syndrome. Although there needs to be more data to confirm the hypothesis, this issue can be very dangerous and should be taken seriously. Symptoms can include shivering, fever, and even seizures.

Ultimately, more research is needed to fully understand the interactions between these two drug classes. COMPASS’S clinical trial only included 19 patients. Larger, controlled trials will likely be done in the future to confirm the result of this study and further explore the subject. 

There is also more data needed on how antidepressants interact with other psychedelic compounds. MDMA will be the first psychedelic to enter the medical space in the US, and one report suggests that SSRIs dampen the psychedelic experience. Once again, the data supporting this hypothesis is limited. However, it is important to gather more data on this issue that will affect many people seeking out psychedelic-assisted therapy. 

More comprehensive studies exploring the interactions between SSRIs and various psychedelic compounds are needed. However, these trials cost a significant amount of money, and most companies are focusing their resources on clinical trials that will help them turn a profit as quickly as possible. Some for-profit companies, such as COMPASS Pathways, will put resources toward this kind of research. However, it will largely depend on research institutions to continue this research.