A new longitudinal study has found that people who use psychedelics in illegal contexts may experience an increase in psychotic and manic symptoms. These effects were not seen in people who used psychedelics in legally permitted settings. The study also found that individuals with a personal history of schizophrenia or bipolar I disorder were especially likely to report worsening manic symptoms after psychedelic use. The findings were published in the journal Psychological Medicine.
Clinical trials have shown that psychedelics, when paired with therapy and administered under strict protocols, can help treat depression, anxiety, and other mental health conditions. But these trials usually exclude participants with a personal or family history of psychotic disorders or bipolar I disorder, due to concerns that psychedelics could worsen symptoms in these populations. As the use of psychedelics becomes more widespread, particularly in settings outside medical supervision, the risks for vulnerable groups are not well understood.
“We know very little about the risk of psychotic or manic episodes following naturalistic psychedelic use, particularly for individuals typically excluded from participation in clinical trials. That’s why it’s so important to investigate this further,” said study author Otto Simonsson, a postdoctoral researcher at Karolinska Institute’s Department of Clinical Neuroscience.
To investigate this issue, researchers used a longitudinal design and surveyed more than 21,000 people in the United States between the ages of 18 and 50. The study began in 2023 and continued through 2024. Participants were recruited online and asked to complete a baseline survey and a follow-up survey about two months later. Of the original sample, over 12,000 participants completed the follow-up. During that time, about 500 participants reported using psychedelics.
Participants answered a range of questions about their use of substances, mental health history, and recent psychological symptoms. Those who used psychedelics during the study period reported how often they used them, which specific substances were taken, and the context in which they were used. The researchers distinguished between psychedelic use that occurred in illegal settings versus use in locations where these substances were decriminalized or permitted. Participants who used psychedelics also completed additional surveys about the quality of their most intense experience during the two-month window, including whether they had psychologically difficult experiences or felt they gained insight during the trip.
Mental health symptoms were measured at both time points. Participants completed questionnaires assessing psychotic symptoms, such as hallucinations and delusional thoughts, as well as symptoms of mania, such as elevated mood, racing thoughts, and increased activity. The study also collected detailed information on participants’ psychiatric history, including whether they had been diagnosed with conditions such as schizophrenia or bipolar I disorder, or had family members with these diagnoses.
The results showed that psychedelic use was associated with an increase in both psychotic and manic symptoms over the study period. However, this association was only observed among people who used psychedelics in illegal contexts. Those who used psychedelics in decriminalized or legal settings did not show similar increases. Nearly all the people in the sample who reported psychedelic use—especially those with a history of schizophrenia or bipolar I disorder—had used them in illegal contexts.
The increase in psychotic symptoms appeared to be stronger among people who used psychedelics more frequently and among those who reported more psychologically difficult experiences during their trips. For example, feelings of fear, confusion, or paranoia during the experience were linked to more psychotic symptoms later on. In contrast, the increase in manic symptoms was most pronounced among people with a personal history of schizophrenia or bipolar I disorder and among those who reported experiencing deep insights during their psychedelic trips.
The researchers also found some indication that other psychiatric histories may increase sensitivity to psychedelics. For instance, people with schizotypal personality disorder who used psychedelics reported greater increases in manic symptoms. These findings suggest that genetic or psychological factors related to certain disorders might heighten the risk of adverse outcomes following psychedelic use.
One possible reason why illegal contexts were associated with worse outcomes is that these settings may be less safe or predictable. Participants who used psychedelics in illegal environments were more likely to report negative mindsets prior to the experience or lack of psychological support during it. Stressful surroundings or uncertainty about the content and dosage of the drug could also contribute to challenging experiences. These factors may amplify the effects of the drug in ways that increase vulnerability to psychotic or manic episodes.
“The relationship between naturalistic psychedelic use and psychotic or manic symptoms is intricate and likely influenced by factors such as legal context, frequency of use, the acute psychedelic experience, and psychiatric history,” Simonsson told PsyPost.
Interestingly, the study did not find an association between psychedelic use and worsening psychotic symptoms among people with a personal history of schizophrenia or bipolar I disorder. This finding contrasts with earlier concerns that psychedelic use in these populations could trigger psychosis. However, the number of participants in the study with these specific diagnoses was small—only four people with schizophrenia and 22 with bipolar I disorder reported using psychedelics during the study period—so conclusions should be made cautiously.
The study’s design allowed the researchers to examine symptom changes over time, which strengthens the interpretation of the results. However, the authors caution that the study has several limitations. The sample was not randomly selected and included a high number of people likely to use psychedelics, which may not reflect the general population. The study also relied entirely on self-report measures, which could be affected by inaccurate recall or biased reporting. In addition, since the study was observational, it cannot determine whether psychedelic use directly caused the changes in symptoms.
The study also raises questions about how to identify individuals who may be more vulnerable to negative effects. Future research may explore genetic markers or other biological indicators that could help predict who is at greater risk. The authors suggest that future studies should include clinician assessments of symptoms and aim for more consistent measurement tools across studies. They also note that increases in symptoms like elevated mood or unusual perceptions are not necessarily harmful in all cases, and further work is needed to clarify the clinical significance of these changes.
The study, “Longitudinal associations of naturalistic psychedelic use with psychotic and manic symptoms,” was authored by Otto Simonsson, Simon B. Goldberg, Walter Osika, Cecilia U. D. Stenfors, Sankalp Chaturvedi, Caroline M. Swords, Jayanth Narayanan, and Peter S. Hendricks.
