Psychedelic-Assisted Therapy: Psilocybin
Updated: May 1
by Dylan Biel
“Psychedelics are to the study of the mind what the microscope is to biology and the telescope is to astronomy” - Dr. Stanislav Grof
What is Psilocybin?
Psilocybin is a naturally-occurring psychedelic prodrug produced by over 200 different species of fungi. When ingested, the inactive prodrug form is converted into a molecule called psilocin which is the active psychedelic compound. This compound closely resembles serotonin, a neurotransmitter associated with mood, focus, sleep, digestion, and more. Psilocybin is known as a classical psychedelic; LSD, mescaline, and DMT also fall into this category.
Breakthrough Therapy Status
In October 2018, the FDA granted Breakthrough Therapy status to the ongoing work from COMPASS Pathways investigating psilocybin as a therapy for treatment-resistant depression. Again in November 2019, the FDA granted Breakthrough Therapy status to Usona Institute’s research, exploring the effects of a single psilocybin dose for treating major depressive disorder. These researchers are treating a much broader definition of depression, which means this therapy may be able to help more people than the first Breakthrough Therapy status. Hundreds of millions of people around the globe are afflicted with these types of acute major depressive episodes each year.
The Default Mode Network
When people with severe depression undergo functional magnetic resonance imaging (fMRI), the resulting images show increased default mode network (DMN) activity compared to those without depression. The default mode network is a group of interconnected brain structures that is most active when someone is not focused on the outside world. In other words, the person is “in their own head.” The default mode network is associated with thinking about the past or the future, rumination, and low-focus states of mind. Some have even called it the seat of the ego. When we are not being present, typically this means the DMN is more active. Both meditation and psychedelic-assisted therapy have been shown to reduce the activity of the default mode network, even when the person is not meditating or it has been days since the psychedelic experience.
SSRI vs. Psilocybin
A study published in 2021 by the New England Journal of Medicine compared treating depression with a common anti-depressant SSRI drug, escitalopram, and psilocybin. Patients in both groups received ongoing psychological support for the duration of the study. The details of the study can be further explored by clicking the link above. The two graphs below show that psilocybin showed better results on two self-reported wellbeing scales, showing the greatest difference in secondary outcomes. Panel A shows the mean change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16; on which scores range from 0 to 27, with higher scores indicating greater depression). Panel B shows the mean change in the score on the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS; on which scores range from 14 to 70, with higher scores indicating greater mental well-being).
Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009;60:355-66. doi: 10.1146/annurev.med.60.042307.110802. PMID: 19630576; PMCID: PMC5864293.
Brewer, JA PNAS 2011 108 (50):20254-59.
Speth J, Speth C, Kaelen M, Schloerscheidt AM, Feilding A, Nutt DJ, Carhart-Harris RL. Decreased mental time travel to the past correlates with default-mode network disintegration under lysergic acid diethylamide. J Psychopharmacol. 2016 Apr;30(4):344-53. doi: 10.1177/0269881116628430. PMID: 26979587.
Robin Carhart-Harris, Ph.D., et al. N Engl J Med 2021; 384:1402-1411