Could Microdosing Psychedelics Help Schizophrenia? Emerging Research

Could microdosing psychedelics, a practice that has been historically contraindicated for schizophrenia, actually have a therapeutic role in treating the negative and cognitive symptoms of the disorder? 

Synopsis 

The relationship between psychedelics and schizophrenia has always been a complex and cautious one. For decades, the prevailing wisdom has been that psychedelics are dangerous for people with schizophrenia, as they could trigger or worsen psychosis. However, a new wave of research is challenging this long-held belief, exploring the possibility that low, non-hallucinogenic doses of psychedelics—a practice known as microdosing—could actually be a safe and effective treatment for some of the most challenging symptoms of schizophrenia. A 2025 study in the International Journal of Molecular Sciences proposes that a specific subtype of schizophrenia, characterized by deficits in serotonin signaling, might benefit from low-dose psychedelic therapy. This article will delve into the groundbreaking research that is reconsidering the connection between psychedelics and schizophrenia, exploring the scientific rationale, the potential benefits, and the crucial safety considerations of this emerging and controversial field.

A Controversial Idea: Rethinking Psychedelics and Schizophrenia

For as long as there has been research into psychedelics, there has been a strong and consistent warning: these powerful substances should be avoided by people with schizophrenia. The fear has always been that psychedelics, which can induce psychosis-like states in healthy individuals, could trigger a full-blown psychotic episode or worsen existing symptoms in those with a predisposition to the disorder. This has led to the exclusion of people with a personal or family history of schizophrenia from almost all modern psychedelic clinical trials. But what if this long-held belief is not the full story? What if, under the right conditions and at the right dose, psychedelics could actually be a part of the solution for some of the most debilitating symptoms of schizophrenia?

This is the controversial but increasingly compelling idea that a new wave of researchers is beginning to explore. They are not suggesting that people with schizophrenia should take high, hallucinogenic doses of psychedelics. Instead, they are investigating the potential of microdosing—taking a sub-perceptual dose of a psychedelic, such as psilocybin or LSD, on a regular basis. The theory is that these low doses could have a therapeutic effect on the brain without inducing a full-blown psychedelic experience. This could be particularly beneficial for the so-called “negative” and cognitive symptoms of schizophrenia, such as apathy, lack of motivation, and difficulty with memory and attention. These symptoms are often the most difficult to treat with traditional antipsychotic medications and can have a profound impact on a person's ability to function in daily life.

The Serotonin Connection: A New Hypothesis

A 2025 study published in the International Journal of Molecular Sciences by Cassetta and colleagues has put forth a fascinating new hypothesis that could change the way we think about psychedelics and schizophrenia [1]. The researchers propose that there may be a specific subtype of schizophrenia, which they call “deficit schizophrenia,” that is characterized by a deficiency in serotonin signaling in the prefrontal cortex. This is the part of the brain that is responsible for executive functions like planning, decision-making, and social behavior. The authors suggest that for people with this specific subtype of schizophrenia, low doses of psychedelics could help to restore normal serotonin signaling, leading to an improvement in negative and cognitive symptoms.

This is a radical departure from the traditional view of schizophrenia as a disorder of dopamine excess. While dopamine undoubtedly plays a role in the positive symptoms of schizophrenia, such as hallucinations and delusions, it has been less successful in explaining the negative and cognitive symptoms. The serotonin hypothesis opens up a new avenue for research and treatment, one that could be particularly well-suited to the unique properties of psychedelic drugs. Classic psychedelics like psilocybin and LSD are known to be potent agonists of the serotonin 2A (5-HT2A) receptor, which is highly expressed in the prefrontal cortex. By stimulating these receptors, low doses of psychedelics could help to boost serotonin signaling in this crucial brain region, potentially leading to a reduction in negative and cognitive symptoms.

A Rationale for Safe Implementation

Of course, the idea of giving a psychedelic to someone with schizophrenia is not without its risks. The potential for triggering psychosis is a serious concern that cannot be ignored. However, a 2023 paper by Wolf and colleagues in Molecular Psychiatry provides a thoughtful and comprehensive rationale for the safe implementation of psychedelic therapy in schizophrenia [2]. The authors acknowledge the risks but argue that they can be mitigated through a careful and cautious approach. They suggest a number of strategies for minimizing the risk of psychosis, including starting with very low doses, carefully screening patients to identify those who are most likely to benefit and least likely to have an adverse reaction, and providing a supportive and structured therapeutic environment.

Another important consideration is the potential for psychedelic-induced psychosis. A 2025 systematic review and meta-analysis by Sabé and colleagues re-examined the evidence for this phenomenon and found that while it can occur, it is rare and often associated with pre-existing risk factors [3]. This suggests that with careful screening and monitoring, it may be possible to safely administer psychedelics to some people with schizophrenia. A 2023 review by Maćkowiak also explored the potential of subpsychedelic dosing and microdosing in schizophrenia, highlighting the need for more research in this area [4].

The Path Forward: A New Frontier in Psychiatry

The research into the use of microdosing for schizophrenia is still in its very early stages, and there are many unanswered questions. We need more research to understand the long-term effects of this treatment, the optimal dosages and treatment protocols, and the specific subtypes of schizophrenia that are most likely to benefit. It is also crucial that this research is conducted in a safe and ethical manner, with the well-being of patients as the top priority.

Despite the challenges, the potential of microdosing to treat the negative and cognitive symptoms of schizophrenia is a tantalizing prospect. For the millions of people who are struggling with these debilitating symptoms, it offers a glimmer of hope for a new and more effective treatment. As we continue to unravel the complex relationship between psychedelics and schizophrenia, we may find that these powerful compounds, when used carefully and responsibly, have a valuable role to play in the future of psychiatry.

A New Paradigm for a Complex Disorder

The idea of using psychedelics to treat schizophrenia is a paradigm shift, one that challenges long-held beliefs and opens up new avenues for research and treatment. While the road ahead is long and requires a great deal of caution, the potential benefits for people with schizophrenia are too significant to ignore. As we continue to explore the complex interplay between the brain, serotonin, and psychedelics, we may find that microdosing becomes a valuable tool in our efforts to help people with this challenging and often misunderstood disorder.

References

[1] Cassetta, E., et al. (2025). A path to precision psychiatry for the psychedelic-based treatment of deficit schizophrenia. International Journal of Molecular Sciences, 26(18), 8949. https://doi.org/10.3390/ijms26188949

[2] Wolf, G., Singh, S., Blakolmer, K., Lerer, L., Lifschytz, T., et al. (2023). Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation. Molecular Psychiatry, 28(1), 1-10. https://doi.org/10.1038/s41380-022-01832-z

[3] Sabé, M., et al. (2025). Reconsidering evidence for psychedelic-induced psychosis. Molecular Psychiatry. https://doi.org/10.1038/s41380-024-02800-5

[4] Maćkowiak, M. (2023). Psychedelics action and schizophrenia. Pharmacological Reports, 75(6), 1265–1279. https://doi.org/10.1007/s43440-023-00546-5

[5] Mahmood, D., Alenezi, S. K., Anwar, M. J., Azam, F., et al. (2022). New paradigms of old psychedelics in schizophrenia. Pharmaceuticals, 15(5), 640. #https://www.mdpi.com/1424-8247/15/5/640

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. The use of psychedelics in people with schizophrenia is a new and emerging area of research, and it is not a recognized treatment.