The studied sample reported through self-reported measures and clinical assessments a clinically significant decrease in anxiety,  depression, and death anxiety and a clinically significant increase in quality of mood, life quality, life meaning, and optimism.

Higher dose effects in double-blind psilocybin study

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

Alma College

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

Drugs such as Psylocibin, LSD, and Ayahuasca can produce a sensation of ego dissolution, openness with nature, and relaxation of self-subject distinction that seem to produce positive therapeutic effects.

Psychedelic effects of modulation and therapeutic outcomes

Gattuso, J. J., Perkins, D., Ruffell, S., Lawrence, A. J., Hoyer, D., Jacobson, L. H., Timmermann, C., Castle, D., Rossell, S. L., Downey, L. A., Pagni, B. A., Galvão-Coelho, N. L., Nutt, D., &amp; Sarris, J. (2022). Default mode network modulation by psychedelics: A systematic review. International Journal of Neuropsychopharmacology, 26(3), 155–188. https://doi.org/10.1093/ijnp/pyac074 

Default Mode Network Modulation by Psychedelics: A
Systematic Review

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

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

Psylocibin-assisted psychotherapy  for anxiety , death anxiety and other mood disorders

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.

Prevalent increase in Prosocial behaviors due to psilocybin mystical experiences in combination with meditation 

LSD effects the DMN in a remarkably
similar way to psilocybin. For instance,
LSD decreases within-network
connectivity (specifically the medialposterior DMN) and increases betweennetwork connections.


Modulation of DMN by LSD 

A brewed Amazonian drink with psychoactive properties made by boiling Banisteriopsis caapi vine and Psychotria viridis bush leaves ( which contains harmala alkaloids, which render the hallucinogenic component DMT orally active).  It was originally used by indigenous shamans for religious rituals and healing. Now it is being used for recreation, being incorporated into folk medicine, and treatment for addiction, anxiety, and depression. 

Ayahuasca

Ayahuasca has been shown to interfere with   DMN function after the administration of the drug. Furthermore, long-term ayahuasca use has led to the increased thickness of the ACC and decreased thickness of the PCC which are key components of DMN.  Studies also show an increase in local network integration as well as a decrease in global network integration.  This also occurs as there is an increase in Shannon entropy across networks. 

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