Can You Safely Take Psychedelics While on Antidepressants? What Science Says

Is it safe to take classic psychedelics like psilocybin or LSD while on antidepressant medication, or do you need to stop your medication first? 

Synopsis 

For years, the standard advice has been to stop taking antidepressants before psychedelic therapy to avoid dangerous interactions like serotonin syndrome and to ensure the psychedelic experience isn't blunted. However, a growing body of recent research, including a major 2025 scoping review, challenges this long-held belief. These studies suggest that combining antidepressants with classic psychedelics, particularly psilocybin, is generally safe and does not increase the risk of serotonin syndrome. While some evidence indicates that antidepressants might slightly reduce the intensity of the psychedelic experience, this effect is not consistent across all studies. This article explores the latest scientific evidence on combining antidepressants and psychedelics, helping you understand the real risks and benefits so you can make a more informed decision about your mental health journey.

The Long-Held Fear: Serotonin Syndrome and Blunted Effects

For many people considering psychedelic-assisted therapy for conditions like depression, a major roadblock often appears right at the start: the need to stop taking their antidepressant medication. This recommendation has been a standard part of most clinical trial protocols and a common piece of advice in psychedelic communities. The reasoning behind it is twofold. First, there's the fear of a dangerous drug interaction called serotonin syndrome. Since both traditional antidepressants (like SSRIs) and classic psychedelics (like psilocybin and LSD) affect the brain's serotonin system, the concern has been that combining them could overwhelm the system, leading to a potentially life-threatening condition. Symptoms of serotonin syndrome can range from mild (shivering, diarrhea) to severe (seizures, high fever, unconsciousness). Second, there's the belief that antidepressants, particularly SSRIs, can blunt or even completely block the subjective effects of psychedelics. Since many believe the mystical or insightful experience is key to the therapy's effectiveness, anything that diminishes it is seen as a problem.

This has created a difficult dilemma for patients. Tapering off antidepressants can be a challenging process, sometimes leading to withdrawal symptoms or a worsening of their depression, right at a time when they are preparing for a powerful and potentially emotionally intense psychedelic experience. For many, the risk of stopping their medication feels greater than the potential benefits of the therapy. But what if this long-held belief is wrong? What if you didn't have to choose between your current medication and the potential of psychedelic therapy? Recent scientific research is beginning to paint a very different picture, one that could change the landscape of psychedelic medicine.

New Research Challenges Old Assumptions

A groundbreaking 2025 scoping review published in the Journal of Psychopharmacology has provided the most comprehensive look at this issue to date. The researchers analyzed 18 studies on the concomitant use of antidepressants and classic psychedelics and came to a startling conclusion: the combination is generally safe and tolerable, with no increased risk of serotonin syndrome, especially when using psilocybin [1]. This is a major departure from the cautious approach that has dominated the field for decades. The review suggests that the theoretical risk of serotonin syndrome may have been overstated. While both types of drugs act on the serotonin system, they do so in different ways. Classic psychedelics are partial agonists of the 5-HT2A receptor, meaning they only partially activate it. This is different from other drugs that can cause serotonin syndrome by massively increasing the amount of serotonin in the synapse. In fact, some researchers now believe that psychedelics may even compete with serotonin for the same receptors, which could theoretically reduce the risk of overstimulation [2].

But what about the blunted effects? The 2025 review did find some evidence that antidepressants might attenuate the acute subjective effects of psychedelics, but this was not a consistent finding across all studies. Some studies reported no significant difference in the intensity of the experience for those on antidepressants. This suggests that while some people might have a milder experience, it's not a universal outcome. It also raises the question of whether a full-blown mystical experience is always necessary for therapeutic benefits. Some studies included in the review reported significant improvements in depression and other mental health symptoms even in patients who continued their antidepressant medication. This hints at the possibility that the neurobiological effects of psychedelics, such as increased neuroplasticity, may be just as important as the subjective experience itself.

Another important study from 2022 by Malcolm and Thomas specifically investigated the serotonin toxicity of serotonergic psychedelics. They concluded that serotonin agonists like psilocybin have a lower risk of causing serotonin toxicity, both on their own and when combined with other serotonergic drugs like SSRIs [3]. They also noted that when serotonin-releasing agents like MDMA are combined with SSRIs, the effect is usually a blunting of the drug's effects, not an increase in toxicity. This further supports the idea that the risk of serotonin syndrome from combining SSRIs and classic psychedelics is low.

The Antidepressant Discontinuation Dilemma

The requirement to stop antidepressants before psychedelic therapy isn't just an inconvenience; it can be a serious health risk. Antidepressant discontinuation syndrome is a well-documented phenomenon that can cause a range of distressing physical and psychological symptoms, from dizziness and nausea to anxiety and a return of depressive symptoms. For someone already struggling with their mental health, this can be a major barrier to accessing psychedelic therapy. A 2024 study by Marwood and colleagues highlighted the potential for antidepressant discontinuation to compromise the effects of psilocybin, not because of a direct drug interaction, but because of the negative impact of withdrawal on the patient's mental state [4]. Another 2024 study by Erritzoe and colleagues found that discontinuing serotonergic antidepressants before psilocybin therapy did not appear to compromise the psychedelic experience, but it did create a significant burden for patients [5].

These findings, taken together, suggest that the long-held practice of requiring patients to stop their antidepressants before psychedelic therapy may be not only unnecessary but also potentially harmful. By allowing patients to continue their medication, we can increase access to these promising therapies and avoid the risks associated with antidepressant withdrawal. This could be a game-changer for the millions of people who are currently taking antidepressants and are interested in exploring psychedelic therapy.

A New Path Forward: Making an Informed Decision

The latest research is clear: the old rules about combining antidepressants and psychedelics may no longer apply. While it's still important to approach this with caution and under the guidance of a qualified medical professional, the evidence suggests that for many people, it may be safe to continue taking their antidepressant medication while undergoing psychedelic therapy. This is a significant shift in our understanding and one that could open the door to healing for many more people.If you are considering psychedelic therapy and are currently taking an antidepressant, it's crucial to have an open and honest conversation with your doctor. They can help you weigh the potential risks and benefits based on your individual health history and the specific medications you are taking. While the risk of serotonin syndrome appears to be low, it's not zero, and your doctor can help you monitor for any potential side effects. It's also important to remember that everyone's experience is different. While some people may find that their antidepressant doesn't affect their psychedelic experience at all, others may notice a blunting of the effects. The key is to go into the experience with realistic expectations and a focus on your own healing journey.

References

[1] Tap, S. C., Thomas, K., Páleníček, T., Stenbæk, D. S., Oliveira-Maia, A. J., van Dalfsen, J., & Schoevers, R. (2025). Concomitant use of antidepressants and classic psychedelics: A scoping review. Journal of Psychopharmacology. https://doi.org/10.1177/02698811251368360

[2] Malcolm, B., & Thomas, K. (2022). Serotonin toxicity of serotonergic psychedelics. Psychopharmacology, 239(6), 1881–1891. https://doi.org/10.1007/s00213-021-05876-x

[3] Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., ... & Malievskaia, E. (2023). Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology, 48(1), 1-8. https://doi.org/10.1038/s41386-023-01648-7

[4] Marwood, L., et al. (2024). The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression. Journal of Psychiatric Research, 173, 104-111. https://doi.org/10.1016/j.jpsychires.2024.03.018

[5] Erritzoe, D., et al. (2024). Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression. eClinicalMedicine, 70, 102518. #https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00097-X/fulltext

  Disclaimer: Psychedelic Assisted Psychotherapy has not been approved by any regulatory agencies in the United States, and the safety and efficacy are still not formally established at the time of this writing.