New research sheds light on psychedelics’ complex relationship to psychosis and mania

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In a new study published in JAMA Psychiatry, researchers led by Otto Simonsson of Karolinska Institutet’s Department of Clinical Neuroscience have cast new light on the controversial topic of psychedelic drug use among adolescents.

Their findings suggest that, when accounting for use of other substances, the naturalistic use of psychedelics like LSD and psilocybin may be linked to fewer psychotic symptoms in teenagers. However, the study also uncovers that the relationship between psychedelic use and manic symptoms may hinge on an individual’s genetic vulnerability to conditions such as schizophrenia or bipolar I disorder.

With a rising trend in the use of psychedelics among U.S. adolescents, understanding the potential risks and benefits of these substances is more crucial than ever. While psychedelics have been shown to be relatively safe in controlled settings, there’s a gap in our knowledge about the effects of their uncontrolled, naturalistic use, especially among younger populations.

This gap in knowledge, coupled with concerns about the risk of psychotic or manic episodes in individuals with a personal or family history of psychiatric conditions, has led researchers to seek more genetically nuanced insights.

The study tapped into the Child and Adolescent Twin Study in Sweden, which is a part of the Swedish Twin Registry. The research focused on a substantial cohort of 16,255 twins who, at the age of 15, provided self-reported data on their past use of LSD or psilocybin. Importantly, a subset of these twins, numbering 9,426, also contributed genotype data.

These adolescents were part of a series of follow-up assessments that had been initiated when they were just 9 years old, with subsequent follow-ups at ages 15, 18, and 24. The twins answered detailed questions about their experiences of psychotic and manic symptoms. Psychotic symptoms involve losing touch with reality, such as experiencing hallucinations or delusions, while manic symptoms are characterized by abnormally elevated mood, energy levels, or irritability.

Initially, a straightforward analysis suggested that psychedelic use was associated with an increase in these symptoms. However, this picture changed dramatically once adjustments were made for the use of other substances. After accounting for the concomitant use of drugs like alcohol, tobacco, cannabis, and others, a striking reversal was observed: adolescents who reported using psychedelics like LSD or psilocybin actually exhibited fewer psychotic symptoms compared to those who had not used these substances.

The researchers went a step further by exploring the influence of genetic predisposition on the relationship between psychedelic use and mental health outcomes. The researchers did not find a significant effect of genetic vulnerability to schizophrenia or bipolar I disorder on the incidence of psychotic symptoms related to psychedelic use.

But the pattern was different for manic symptoms. Adolescents with a higher genetic risk for these conditions experienced more manic symptoms following psychedelic use compared to those with a lower genetic risk. This finding suggests that genetic factors may play a critical role in modulating individual responses to psychedelics, particularly concerning manic symptoms.

“Taken together, the findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelics may be associated with lower rates of psychotic symptoms among adolescents,” the researchers explained. “At the same time, the association between psychedelic use and manic symptoms seems to depend on genetic vulnerability to psychopathology such as schizophrenia or bipolar I disorder.”

As with any study, the new research has limitations to consider. The reliance on self-reported data, potential biases, and the lack of longitudinal follow-up invite caution in interpreting the findings. Moreover, the specific circumstances of psychedelic use (such as the environment and dosage) remained unexplored, which could significantly influence outcomes.

Importantly, the researchers are unable to rule out the possibility of reverse causality. In other words, it is possible that those who exhibit fewer psychotic symptoms might be more inclined to use psychedelics, compared to those who exhibit more psychotic symptoms.

“In conclusion, this study highlights the potential of genetically informative research designs to delineate the complex interplay between psychedelic use, genetic factors, and psychotic or manic symptoms,” the researchers wrote. “Future studies are needed to replicate our findings and extend them to other age groups, ideally with larger samples, longitudinal data, and more objective outcome measures (eg, diagnoses in the health care system).”

The study, “Adolescent Psychedelic Use and Psychotic or Manic Symptoms,” was authored by Otto Simonsson, Miriam A. Mosing, Walter Osika, Fredrik Ullén, Henrik Larsson, Yi Lu, and Laura W. Wesseldijk.