Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of Psychopharmacology, 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513 

Psilocybin produces substantial and
sustained decreases in depression and
anxiety in patients with life-threatening
cancer: A randomized double-blind trial

Data suggest that about 40% of patients with terminal illnesses such as cancer develop mood disorders that are clinically significant such as anxiety, depression, and even death anxiety which is related to the fear of death related to their illness, and a fear of the dying process. Furthermore,  mood disorders even seem to be conflicting with the adherence and effectiveness of cancer treatments.

Chronic development of depressive and anxiety symptoms in patients with terminal diseases

Research dating back to the late 50s has provided evidence of how this substance seems to be a relatively safe central nervous system-acting drug in healthy subjects, in which the therapeutic effects can outweigh the risks considering its low potential of abuse. 

Advantages of psilocybin use in psycho-therapy

Double-blind study  design:

 - Low-dose group
- High-dose group
- Administration at Baseline, 5 weeks after session 2, and a 6-month follow-up
- Control for physiological measures to establish a risk assesment


Double-blind study to understand the effects of psylocibin in decreasing symptoms of anxiety, depression and other mood disorders

Studies suggest that psilocybin-assisted psychotherapy has the capacity to reduce clinically significant symptoms of several mood disorders, such as anxiety, depression, and death anxiety.

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Psilocybin is a 5HT-2A (serotonin 2A) receptor agonist that is a naturally-occurring psychedelic compound. It is derived from over 200 species of fungi, many from the genus Psilocybe. A purified bioactive compound derived from medicinal mushrooms.

Psilocybin

Psilocybin is a 5HT-2A (serotonin 2A) receptor agonist, which seems to play a role in both the hallucinogenic and therapeutic impacts. Studies in treatment-resistant depression patients show increased functional connectivity during emotional processing tasks, particularly in the amygdala and the prefrontal cortex. This is similar to the neural plasticity induced by psychedelics in general. 

All of these processes/regions have been implicated in the antidepressant action of typical antidepressants like SSRIs, which may explain why psilocybin has observed antidepressant properties.

Therapeutic mechanisms of psilocybin

Psilocybin’s cellular and systemic effects may range from unlocking a transcriptional blockade via epigenetic reprogramming, direct interactions on the receptor level e.g., through stable 5-HT₂A/mGluR2 heterodimerization, interference with altered brain networks to reactivate glutamatergic signaling in the mPFC or may impact on the alcohol or withdrawal induced microglia response.

Potential mechanisms of action of the fungal bioactive psilocybin in AUD

Psilocybin has been shown to have significant decreases in FC within the DMN. Furthermore, it has shown significant increases in global brain connectivity; decoupling between key DMN nodes such as the mPFC and the PCC has been documented.  In this regard, there has been a reported decrease in DMN integration and a reduction in local modularity and segregation. This has been signed up to 3 weeks after administration in depressed patients

DMN modulation by psilocybin 

Research suggests that psilocybin has the ability to trigger mystical experiences that can also be referred to as quantum change experiences. These are described as abrupt, notable, kindly, and frequently deeply significant encounters that are believed to lead to individual changes impacting a wide array of personal feelings, thoughts, and actions.

Quantum Experiences due to use of Psylocibin

Research suggests that high-dose psilocybin can lead to significant and lasting positive changes in interpersonal relationships, gratitude, life's meaning, forgiveness, spiritual experiences, and more. These effects were influenced by intense psilocybin experiences and regular spiritual practices, suggesting the potential for improved social attitudes and psychological well-being.

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