When exploring the use of psilocybin magic mushrooms, many people wonder how antidepressants may influence its effects. This is an important question, especially because both substances interact with serotonin systems in the brain. Understanding how these substances interact is crucial for safety and for setting accurate expectations about the experience.
Our large-scale study at Unlimited Sciences found that 4.6% of participants reported using psilocybin while also taking an antidepressant. Among these individuals, the acute effects of psilocybin were noticeably weaker, with lower scores for mystical experiences and challenging experiences. This suggests that antidepressants may dampen the intensity of psilocybin’s effects.
What Research Says About Antidepressants and Psychedelics
Although research is still limited, some studies offer valuable insights. Evidence shows that chronic use of serotonergic antidepressants (such as SSRIs) can reduce the subjective effects of classic psychedelics like LSD and psilocybin. For example, this study found that individuals taking serotonin-selective antidepressants experienced decreased or abolished responses to psychedelics.
Other medications, such as buspirone (BuSpar, a common anxiolytic / anti-anxiety medication acting as a serotonin receptor agonist), have also been studied. In this controlled study, they reported that buspirone reduced psilocybin-induced visual perceptual changes. This aligns with user experiences indicating that certain psychiatric medications may blunt the psychedelic experience.
Anecdotal user reports from Erowid, a non-profit educational organization that provides information about psychoactive plants and chemicals, frequently report a reduction or absence of effects of psychedelics while using common SSRIs.
Safety Concerns: Serotonin Syndrome and Toxicity
One primary safety concern when mixing serotonergic drugs is serotonin syndrome, a rare but potentially life-threatening condition caused by excessive serotonin. However, evidence suggests this risk is low with psilocybin.
However, in a 2022 talk, Dr. Erica Zelfand reviewed data from over 400 participants and found no strong evidence suggesting toxic interactions between antidepressants (SSRIs or otherwise) and classic psychedelics like psilocybin or LSD. While caution is always advised, toxicity appears to be extremely rare in these combinations.
Escitalopram (Lexapro) and Psilocybin: A Closer Look
More recent research provides additional nuance. This study examined the interaction between psilocybin and escitalopram, a commonly prescribed SSRI. In this study, participants took escitalopram daily for two weeks (gradually increasing from 10 mg to 20 mg) before receiving psilocybin. Results showed that pre-treatment with escitalopram:
- Did not reduce psilocybin’s positive mood effects
- Significantly reduced negative effects, such as anxiety and adverse cardiovascular reactions
- Did not alter the pharmacokinetics of psilocin, the active compound formed when psilocybin is converted into in humans by the process of dephosphorylation
These findings suggest that escitalopram and psilocybin may be safely administered together under controlled conditions, although subjective intensity may still be affected.
The Bottom Line
Current evidence suggests that while the risk of serotonin toxicity when combining SSRIs with psilocybin is low, the subjective effects of psilocybin may be reduced. Research is ongoing, and individual responses can vary widely. Anyone considering psilocybin while taking antidepressants should approach this decision with caution, seek medical advice, and consider the potential for diminished effects.
If you’re looking for personalized guidance and support before or after a psychedelic experience, the Unlimited Sciences Psychedelic Info Line offers free, 1:1 support for answering questions about psychedelic safety, integration, and emotional processing.
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