In recent years, both psilocybin-assisted therapy and mindfulness-based practices have gained recognition for their powerful effects on mental health. Macrodose psilocybin interventions (20–30mg) have shown promise in alleviating symptoms of depression, anxiety, and even PTSD (Holas & Kamińska, 2023). Meanwhile, mindfulness meditation is a well-established treatment for similar conditions (Khoury et al., 2013). But what happens when we combine the two?

A growing body of evidence suggests that psilocybin microdosing—taking sub-perceptual doses of psilocybin—paired with meditation could offer a new, more accessible way to manage anxiety and depression. While large doses of psilocybin have demonstrated impressive results, the time, cost, and intensity of these treatments can be barriers for many. This informal study was the initial step in exploring whether combining microdosing with mindfulness could yield similarly powerful outcomes with fewer drawbacks.

Study Design

In this two-week informal, six participants—five with mild to moderate symptoms of anxiety and depression—combined daily meditation practice with psilocybin microdosing twice a week. The aim was to refine the intervention protocol before we hope to replicate in a formal research study at the National University of Natural Medicine (NUNM). This initial study was generously supported and hosted by Immersive Therapies, a licensed psilocybin service center in Portland, Oregon.

1. Morning Meditation Practice:
   Participants meditated for 30 minutes each morning (7:00–7:30 am), alternating between two types of meditation:

   • Focused Attention: Counting breaths to develop concentration.

   • Open Monitoring: Bringing awareness to thoughts, body sensations, and surroundings.

2. Microdosing and Meditation Sessions:
   On Tuesdays and Thursdays (6:30–8:00 pm), participants attended facilitated microdosing meditation sessions. Starting with a 1mg dose, they gradually adjusted their doses (up to 4mg) to find a balance—enough to notice subtle psychedelic effects while meditating.  The psychedelic effects are a marker of the cross-brain firing and disruption of ruminating thoughts considered to be essential mechanisms in psilocybin’s therapeutic effect (Husain et al., 2023).

3. Education about the Ruminating Brain:
   We taught participants about the Default Mode Network (DMN)—the brain’s “rumination center” responsible for perpetuating negative thought loops. Psilocybin quiets this network (Gukasyan et al., 2022), while mindfulness retrains the mind to focus on the present.

4. Outcome Measures:
   We tracked changes in anxiety, depression, mindfulness, and sleep with three validated scales:

   • Hospital Anxiety and Depression Scale (HADS)

   • Toronto Mindfulness Scale

   • Leeds Sleep Evaluation Questionnaire

Promising Early Results

While the trial period was short, two participants (out of the five with mild to moderate symptoms of anxiety and depression) experienced substantial improvements.

• Participant 0002 reduced their anxiety by 78% and depression by 63%, moving from mild symptoms to subclinical levels for both.

• Participant 0006 saw a 50% reduction in anxiety and a 17% drop in depression, shifting from moderate to subclinical for anxiety and moderate to mild for depression.

Although other participants only showed modest changes, the significant improvements seen in these two individuals suggest that this approach has potential.

Uncovering Sleep Challenges

Although the Leeds Sleep Evaluation did not reflect major disruptions, several participants reported difficulty falling asleep after evening microdosing sessions. This raised concerns, as poor sleep can undermine mental health improvements. The NUNM study will use sleep-tracking devices to collect more accurate data on the relationship between microdosing and sleep.

Fine-Tuning Dosing for Optimal Impact

Dosing patterns varied significantly across participants. Some needed the maximum 4mg dose to experience noticeable effects, while others found even 1mg too intense. This variability highlights the importance of allowing participants to self-select their doses—but better guidelines might help participants find their optimal dose more quickly.

Suggested Improvements for Future Interventions

Based on trial feedback, we are planning several key adjustments:

1. Extend the Duration:
   The two-week period was too short for participants to fully establish their meditation practice and adjust their microdose. Extending the trial to three or four weeks would allow more time for personal insight and deeper progress.

2. Offer Therapeutic Support:
   Some participants encountered difficult emotional insights during the trial. Adding therapeutic support would provide a crucial resource for processing these experiences.

3. Adjust the Timing:
   Moving microdosing sessions earlier (between 4:00 and 5:30 pm) might reduce sleep disruptions without interfering with participants' daily schedules.

4. Provide Clearer Dose Guidelines:
   For quicker dose adjustment, we suggest offering participants clearer next steps:

   • If sufficient psychedelic effects while meditating, stay at 1mg.

   • If some, but insufficient, psychedelic effects while meditating, increase to 2mg.

   • If no psychedelic effects while meditating, increase to 3mg.

Conclusion: A New Path Forward

This trial shows that psilocybin microdosing combined with mindfulness meditation holds real promise as an intervention for anxiety and depression. While further research is needed—with a longer trial period, therapeutic support, earlier microdosing sessions, and better dosing guidelines—the potential for this approach to offer an affordable, convenient, and effective treatment option is significant.

As we continue refining this approach, psilocybin-assisted meditation could become an integral tool in the fight against mental health challenges, offering hope and healing for many.

References

Gukasyan, N., Davis, A., Barrett, F., Cosimano, M., Sepeda, N., Johnson, M., & Griffiths, R. (2022). Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. Journal of Psychopharmacology (Oxford, England), 36, 151 - 158. https://doi.org/10.1177/02698811211073759. 

Heuschkel, K., & Kuypers, K. (2020). Depression, Mindfulness, and Psilocybin: Possible Complementary Effects of Mindfulness Meditation and Psilocybin in the Treatment of Depression. A Review. Frontiers in Psychiatry, 11. https://doi.org/10.3389/fpsyt.2020.00224. 

Holas, P., & Kamińska, J. (2023). Mindfulness meditation and psychedelics: Potential synergies and commonalities. Pharmacological Reports, 75(6), 1398–1409. https://doi.org/10.1007/s43440-023-00551-8 

Husain, M., Ledwos, N., Fellows, E., Baer, J., Rosenblat, J., Blumberger, D., Mulsant, B., & Castle, D. (2023). Serotonergic psychedelics for depression: What do we know about neurobiological mechanisms of action?. Frontiers in Psychiatry, 13. https://doi.org/10.3389/fpsyt.2022.1076459. 

Khoury, B., Lecomte, T., Fortin, G., Masse, M., Therien, P., Bouchard, V., ... & Hofmann, S. G. (2013). Mindfulness-based therapy: A comprehensive meta-analysis. Clinical Psychology Review, 33(6), 763–771. https://doi.org/10.1016/j.cpr.2013.05.005 

Mahapatra, A., & Gupta, R. (2020). Role of psilocybin in the treatment of depression. Therapeutic Advances in Psychopharmacology, 10, 1-6. https://doi.org/10.1177/2045125320950567