Use of Psilocybin for Treatment-resistant Depression


Used in indigenous communities for over centuries, mushroom extracts are finding their way into modern treatments. Psilocybin can be found in over 100+ mushrooms and it has shown promise in the treatment of psychological treatment of depression.

It has shown to be effective even in treatment-resistant depressive ailments, with decreased symptoms recorded in the majority of patients treated with psilocybin. It is a non-selective serotonergic and is classified as a classic ‘psychedelic’ drug [1]. Used historically in supportive environments, its application in similar conditions has proven to be effective.

To date, research has pointed at its use along with psychological support has resulted in safely treating psychiatric conditions, including but not limited to end-of-life anxiety and depression, alcohol and tobacco addiction, obsessive compulsive disorder, and treatment-resistant major depression [2].

These findings have been backed by studies and trials that used other psychedelics with results appearing after one to two doses. It raises questions how these hallucinogens are impacting brain mechanics to result in these significant impacts that were not witnessed before. How the ‘psychedelic state’ is produced by the neural networks and the long term impact is yet to be gauged in an exhaustive study [3].

Psychedelics’ impact on brain functionality

It has been observed that in subsequent days after taking in psilocybin, there is a distinct phase of ‘afterglow’ where moods are improved and stress relieved [4]. Overview of arterial spin labelling (ASL), blood oxygen level dependent (BOLD), and resting state functional connectivity (RSFC) changes measurement of the cerebral blood flow (CBF) and functional connectivity have further evidenced to this ‘afterglow’ state.

Patients diagnosed with treatment resistant major depression when treated with psilocybin produced rapid and sustained antidepressant effects. They responded significantly in ASL, and BOLD analyses, with positive outcomes. CBF decreases were also recorded, while RSFC analyses showed implications in pathophysiology of depression [5].

The psychedelic experience mediated post-acute brain changes. This was evidenced from decrease in PH in individuals scoring high on ‘mystical’ experience [6]. It shows that while there is a knowledge gap considering serotonergic psychedelics impact on the brain, there are distinct movements in functions towards alleviated impact on depression.

However, meta-analyses of depression related studies does not point to consistent results. There has been an increased thalamic and metabolism activity, which is consistent but it is not supported by whole-brain analyses [7] Decreased CBF in the temporal cortex is consistent with previously reported research [8].

Positive influence on symptoms of depression

Nevertheless, it can be concluded that there are changes in resting-state brain blood flow and functional connectivity when subjects are exposed to psilocybin. This is especially true for individuals suffering from treatment-resistant depression. Depressive mood alleviation can be correlated to the decreased blood flow in the amygdala, which was witnessed during ‘mystical’ psychedelic experience.

There is a need for more exhaustive study where the rigorous controls are applied. Moreover, the sample population needs to increase in further clinical trials as it was a limiting factor in the established body of work. This will not only help to establish the interactions of different treatment factors with the impending results, especially with respect to Resting State Networks (RSN).

However, it can be ascertained with success that psychedelics such as psilocybin are effective in treatment of resistant depression. It works on the brain functions and disassociates linkages that allow the mind to get rid of its negative emotions. It has resulted in individuals to fare better following their exposure to the hallucigens.


Carhart-Harris RL, Roseman L, Bolstridge M, et al. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Sci Rep. 2017;7(1):13187. Published 2017 Oct 13. doi:10.1038/s41598-017-13282-7


  1. Carhart-Harris, R. L. & Goodwin, G. M. The Therapeutic Potential of Psychedelic Drugs: Past, Present and Future. Neuropsychopharmacology, 10.1038/npp.2017.84 (2017).
  2. Watts, R. D., Krzanowski, C, Nutt, J. D. & Carhart-Harris, R, L. Patients’ accounts of increased ‘connection’ and ‘acceptance’ after psilocybin for treatment-resistant depression. Journal of Humanistic Psychology (2017).
  3. Carhart-Harris RL, et al. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences of the United States of America. 2016;113:4853–4858. doi: 10.1073/pnas.1518377113
  4. Winkelman M. Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. Current drug abuse reviews. 2014;7:101–116. doi: 10.2174/1874473708666150107120011.
  5. Drevets WC, et al. A functional anatomical study of unipolar depression. The Journal of neuroscience: the official journal of the Society for Neuroscience. 1992;12:3628–3641.
  6. Carhart-Harris RL, et al. Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences of the United States of America. 2016;113:4853–4858. doi: 10.1073/pnas.1518377113.
  7. Hamilton JP, Farmer M, Fogelman P, Gotlib IH. Depressive Rumination, the Default-Mode Network, and the Dark Matter of Clinical Neuroscience. Biological psychiatry. 2015;78:224–230. doi: 10.1016/j.biopsych.2015.02.020.
  8. Bolwig TG. Neuroimaging and electroconvulsive therapy: a review. J ECT. 2014;30:138–142. doi: 10.1097/YCT.0000000000000140.

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