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Aztec statues of psilocybin mushrooms.

Psilocybin mushrooms played an important role in Aztec rituals and were often referred to as Teonanactal (“flesh of the gods”).


Distribution of the serotonin 2A receptor in the human brain. Source: Saulin et al., 2011

What are psychedelics and how do they work?
What is psilocybin? 

Mechanism of action

Psilocybin acts on a variety of receptors in the brain, however, as a classical psychedelic, its characteristic psychological effects are mediated via its action on serotonin 2a receptors located in the deep layers of the neocortex (most advanced and recently developed part of the neural system). They play an important role in orchestrating interactions of high-order cognitive functions and perceptions, and are believed to be particularly important for active stress-coping behaviors (9) and neurobiological plasticity (10), or brain’s capacity for change.

On a system level, psychedelics appear to promote more flexible patterns of neural activity, widening the repertoire of the functional states that the brain can be in over a fixed amount of time (11). This is physiologically the opposite to what we typically observe in patients suffering from some psychiatric disorders like depression, which is associated with neurophysiological (12) and cognitive (13) inflexibility, allowing for rigid mental states of rumination and self-defeating thoughts. Ultimately, the ability of psychedelics to promote neural and behavioral plasticity, provides scientific justification for using these substances as catalysts and/or adjuncts to various forms of behavioral interventions and psychotherapy in particular, by creating a shift in perception and aiding in development of new mental models.


Psilocybin’s effects have been demonstrated even in otherwise difficult to treat psychiatric conditions, such as, for example, treatment resistant depression (TRD). In a small-scale trial, 9 out of 12 TRD patients did not meet criteria on the week following a high-dose session and 5 of them remained depression-free at 3-month follow-up (6).

An image showing effects of psilocybin on patterns of brain wiring.

Acute effects of psilocybin on brain connectivity.

Source: Petri et al., 2014

A plot showing changes in symptom severity in patients with treatment resistant depression following a high-dose psilocybin session.

Changes in symptom severity in patients with treatment resistant depression following a high-dose psilocybin session.

BDI - Beck's Depression Inventory.

Source: Carhart-Harris et al., 2016

The process of change

There are dozens of psychological models of psychedelic’s action stemming from various schools of psychology. Some link their effects to the lowering of psychological resistances thereby providing more direct access to the unconscious and facilitating a discharge of emotionally charged tensions, while others emphasise the importance of the so-called mystical-type experiences, characterised by the profound ineffable experience of owe, interconnectedness with the Universe (14). 

At Katharsis, we implement a holistic approach to psychedelic therapy, aligning with state-of-the-art biomedical research and medical-grade professionalism and safety, whilst paying respect to ceremonial use of these powerful substances and recognising limitations of the scientific method. Here, we establish a mutually supportive dialogue between modern medicine, academic science and spirituality to assist you on your journey toward self-discovery and healing.


1. R. E. Doblin, M. Christiansen, L. Jerome, B. Burge, The Past and Future of Psychedelic Science: An Introduction to This Issue. J. Psychoactive Drugs. 51, 93–97 (2019).

2. T. S. Krebs, P.-Ø. Johansen, Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J. Psychopharmacol. (Oxf.). 26, 994–1002 (2012).

3. J. J. Rucker, L. A. Jelen, S. Flynn, K. D. Frowde, A. H. Young, Psychedelics in the treatment of unipolar mood disorders: a systematic review. J. Psychopharmacol. (Oxf.). 30, 1220–1229 (2016).

4. D. E. Nichols, Psychedelics. Pharmacol. Rev. 68, 264–355 (2016).

5. S. B. Goldberg, B. Shechet, C. R. Nicholas, C. W. Ng, G. Deole, Z. Chen, C. L. Raison, Post-acute psychological effects of classical serotonergic psychedelics: a systematic review and meta-analysis. Psychol. Med. 50, 2655–2666 (2020).

6. R. L. Carhart-Harris, M. Bolstridge, J. Rucker, C. M. Day, D. Erritzoe, M. Kaelen, M. Bloomfield, J. A. Rickard, B. Forbes, A. Feilding, D. Taylor, S. Pilling, V. H. Curran, D. J. Nutt, Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 3, 619–27 (2016).

7. A. Garcia-Romeu, R. Griffiths, M. Johnson, Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction. Curr. Drug Abuse Rev. 7, 157–164 (2015).

8. M. Johnson, W. Richards, R. Griffiths, Human hallucinogen research: guidelines for safety. J Psychopharmacol. 22, 603–20 (2008).

9. R. Carhart-Harris, D. Nutt, Serotonin and brain function: a tale of two receptors. J. Psychopharmacol. (Oxf.). 31, 1091–1120 (2017).

10. C. Ly, A. C. Greb, L. P. Cameron, J. M. Wong, E. V. Barragan, P. C. Wilson, K. F. Burbach, S. Soltanzadeh Zarandi, A. Sood, M. R. Paddy, W. C. Duim, M. Y. Dennis, A. K. McAllister, K. M. Ori-McKenney, J. A. Gray, D. E. Olson, Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 23, 3170–3182 (2018).

11. E. Tagliazucchi, R. Carhart-Harris, R. Leech, D. Nutt, D. R. Chialvo, Enhanced repertoire of brain dynamical states during the psychedelic experience. Hum Brain Mapp. 35, 5442–56 (2014).

12. M. Demirtaş, C. Tornador, C. Falcón, M. López‐Solà, R. Hernández‐Ribas, J. Pujol, J. M. Menchón, P. Ritter, N. Cardoner, C. Soriano‐Mas, G. Deco, Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder. Hum. Brain Mapp. 37, 2918–2930 (2016).

13. N. Meiran, G. M. Diamond, D. Toder, B. Nemets, Cognitive rigidity in unipolar depression and obsessive compulsive disorder: Examination of task switching, Stroop, working memory updating and post-conflict adaptation. Psychiatry Res. 185, 149–156 (2011).

14. A. Garcia-Romeu, W. A. Richards, Current perspectives on psychedelic therapy: use of serotonergic hallucinogens in clinical interventions. Int. Rev. Psychiatry. 30, 291–316 (2018).

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