How Psilocybin Affects Depression, Anxiety, and Substance Use in Real-Life Settings

By Katie Pickard, Director of Education

Psilocybin, the psychoactive compound found in magic mushrooms, continues to attract attention as a potential mental health treatment. While clinical trials have shown its promise in treating depression, anxiety, and substance use disorders, much less is known about how psilocybin affects people who use it outside of a research or therapeutic setting. A new study from Unlimited Sciences, published in the International Journal of Mental Health and Addiction offers groundbreaking insights into this area by analyzing mental health outcomes in thousands of people who used psilocybin in naturalistic environments.

The Largest Longitudinal Study on Naturalistic Psilocybin Use to Date

Our study followed 2,850 adults who were planning to use psilocybin. Participants completed a series of six surveys over a span of two to three months, measuring depression, anxiety, substance use, and cognitive flexibility. Researchers identified four distinct groups, based on changes in mental health and substance use behaviors before and after using psilocybin. At baseline, the most commonly reported weekly substance use behaviors were cannabis (53%), alcohol (37%) and tobacco (23%) use. Two weeks before their psilocybin use, personality traits were measured via the Big Five Inventory on a scale from 1 to 5. After self-rating 44 questions, participants scored, on average:

• Extraversion: 3.2 / 5
• Agreeableness: 3.9 / 5
• Conscientiousness: 3.5 / 5
• Neuroticism: 3.0 / 5
• Openness to Experience: 4.1 / 5

For a comprehensive overview of the individuals who participated in this study, including detailed sociodemographic, personality, and substance use data, you can reference the full participant characteristics reported in the original study. It includes breakdowns by age, gender, race, education level, relationship status, personality traits, and substance use behaviors. The study also categorizes participants into distinct psychological profiles, providing a nuanced view of the diversity within the sample.

Four Mental Health Profiles After Psilocybin Use

1. ↗️ Improved Mental Health with Low Substance Use (IMLS): Representing 30% of participants, this group showed marked reductions in depression and anxiety after psilocybin use, along with slight gains in cognitive flexibility. They had relatively low substance use both before and after the experience.
   • Those with less prior psilocybin use were more likely to fall into this group.
   • Those who scored higher on the ability to surrender to the psychedelic experience tended to have better mental health outcomes.
2. ➡️ Stable Mental Health with Low Substance Use (SMLS): The largest group at 53%, these individuals already had low levels of depression, anxiety, and substance use before taking psilocybin. Their mental health remained stable with minor improvements post-use.
   • This group had the most psychologically adaptive traits, such as low neuroticism and high openness.
   • This group was older on average.
3. ➡️ Persistent Mental Health Symptoms with Persistent Substance Use (PMPS): Making up 9% of the sample, this group started with high levels of anxiety and depression and continued to struggle after their psilocybin experience. They also reported high use of substances like benzodiazepines.
   • This group showed more maladaptive traits, including high neuroticism.
   • This group included more women than men and were younger on average.
   • Participants in this group reported the lowest levels of mystical and awe-inspiring experiences, which have been linked to lasting positive effects in previous research.
4. ↗️ Improved Mental Health with Persistent Substance Use (IMPS): This final group (8%) showed psychological improvements similar to the IMLS group but continued to engage in high levels of alcohol and drug use after their experience.
   • This group included more men than women.
   • This group had the most prior experience with psilocybin.

Implications for Psychedelics and Substance Use

One of the key takeaways is that psilocybin use may support meaningful shifts in substance use behaviors, but those outcomes are not universal. While some participants experienced reductions in use, particularly those with low baseline consumption, others showed little change or continued problematic use. Participants with persistent substance use post-psilocybin often had higher psychological vulnerability and fewer adaptive traits.

This research adds nuance to the growing narrative that psychedelic experiences are generally beneficial. While many participants experienced lasting improvements in mood and cognitive flexibility, others didn’t benefit as much or saw no change in their substance use behaviors. The findings highlight the importance of considering individual differences, including baseline mental health, substance use, and personality traits, when evaluating potential outcomes of psychedelic use.

The study also cautions against overgeneralizing the findings due to several limitations:

• There was no control group of non-users, so causality cannot be definitively established.
• The data relied on self-reported measures, which are subject to bias.
• The participant pool was predominantly white and well-educated, limiting the generalizability of the results.

Despite these issues, this study represents one of the most comprehensive approaches to understand how psilocybin affects real-world users over time.

Our Call for Personalized Psychedelic Care

The study’s results suggest that psilocybin’s effects on mental health and substance use are not one-size-fits-all. While the majority of participants experienced either stable or improved psychological states, a small yet important segment continued to struggle. These findings underscore the need for individualized preparation, intention setting, and post-experience integration, especially for those with preexisting vulnerabilities. As the field of psychedelic research expands, person-centered approaches and diverse participant recruitment will be key to realizing the full potential of these powerful substances.

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.