Are Selective Serotonin Reuptake Inhibitors (SSRIs) safe to use with psilocybin-containing psychedelics, such as psilocybin mushrooms?

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Last updated: April 7, 2025View editorial policy

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From the Guidelines

Combining SSRIs with psychedelics like magic mushrooms is not recommended due to potential safety concerns, and individuals should consult with a knowledgeable healthcare provider before use. SSRIs (such as fluoxetine/Prozac, sertraline/Zoloft, escitalopram/Lexapro, and paroxetine/Paxil) can interact with psilocybin (the active compound in magic mushrooms) in unpredictable ways, as both substances affect serotonin systems in the brain 1. Some key considerations include:

  • The potential for SSRIs to diminish or block the effects of psychedelics, leading some users to take higher doses, which can be dangerous
  • The theoretical risk of serotonin syndrome, although this appears rare in practice with this specific combination 1
  • The importance of not abruptly stopping SSRIs to use psychedelics, as this can cause withdrawal symptoms or worsening mental health
  • The need for individualized guidance from a healthcare provider, taking into account specific medications, dosages, and personal health history 1. When prescribing SSRIs, it is essential to consider their potential interactions with other substances, including illicit drugs like LSD, and to start with a low dose, increasing slowly and monitoring for symptoms, especially in the first 24 to 48 hours after dosage changes 1.

From the Research

Safety of SSRIs with Psychedelics

  • The combination of selective serotonin reuptake inhibitors (SSRIs) and psychedelics like magic mushrooms may pose a risk of serotonin toxicity (ST) 2.
  • However, serotonergic psychotropics that do not contain monoamine oxidase inhibitors (MAOIs) are considered low risk in combination with psychedelics that also do not contain MAOIs 2.
  • Signs and symptoms of ST that warrant immediate medical attention include myoclonus, extreme and fluctuating vital signs, agitation or comatose mental state, muscle rigidity, pronounced hyperthermia, and/or seizure activity 2.

Interaction between SSRIs and Psychedelics

  • Studies suggest that SSRIs may attenuate the effects of psilocybin mushrooms, both during and after SSRI use 3.
  • The probability of weaker than expected drug effects was higher for participants taking SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs) with psilocybin mushrooms 3.
  • The dampening effect of SSRIs on psilocybin drug effects may last as long as 3-6 months following antidepressant discontinuation 3.
  • Another study found that individuals on serotonergic antidepressants during psychedelic use displayed reduced subjective effects but similar antidepressant effects compared to those not undergoing SSRI treatment 4.

Clinical Experience and Guidelines

  • Clinical experience and guidelines suggest that combining different antidepressants, including SSRIs, may be beneficial for some patients, but more rigorous clinical trials are needed to develop rational treatment guidelines 5.
  • An overview of SSRI and SNRI therapies for depression highlights their widespread use and importance in treating mood and anxiety disorders, but does not specifically address interactions with psychedelics 6.

References

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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