Well-Being

Psilocybin, the active ingredient in ‘magic mushrooms,’ makes scientific gains

“The idea here is that mystical experience can create the opportunity for personal insights,” researchers said.
The Associated Press/Peter Dejong

Story at a glance

  • Studies over the past several years have shown promise in using psilocybin-assisted therapy to treat psychiatric disorders like depression.

  • A recent follow-up study by Johns Hopkins Medicine researchers found two doses of the hallucinogenic compound coupled with psychotherapy resulted in large decreases in major depressive disorder symptoms for most of the study’s participants. 

  • New research is hinting at how the hallucinogenic compound may facilitate reduced depression symptoms.

Research on the use of psychedelic drugs as potential treatment for psychiatric disorders has gained momentum in the U.S. in recent years, with compounds like psilocybin — the active ingredient in “magic mushrooms” — shifting from the fringes of medicine toward the mainstream.  

Limited studies out of institutions like Johns Hopkins University and others over the last decade have shown promise in using psilocybin in tandem with talk therapy to help longtime smokers quit smoking, ease anxiety in people with terminal cancer and reduce symptoms of major depression.  

Earlier this year, a follow-up study by Johns Hopkins Medicine researchers found two doses of the hallucinogenic compound coupled with psychotherapy resulted in large decreases in major depressive disorder symptoms for most of the study’s participants.  

In a testament to how powerful the mystical experience associated with the drug can be, Roland Griffiths, the professor in the Neuropsychopharmacology of Consciousness at Johns Hopkins University School of Medicine who received approval in 2000 to carry out the first experiments on psilocybin since the 1960s, found in a survey of early study participants that more than half regarded it as one of the most meaningful experiences of their lives.   


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But precisely how the hallucinogen may produce a positive outcome among those suffering from addiction, depression or post-traumatic stress disorder remains unclear.  

“That’s certainly the multi-million-dollar question of the day: how are these drugs working?” Frederick Barrett, Associate Professor of Psychiatry and Behavioral Sciences at the Johns Hopkins School of Medicine, told Changing America.  

In a paper published late last year, Barrett proposed the drug’s antidepressant effects may be the result of changes in neuroplasticity.  

“One common feature of depression is something you can think of as cognitive or psychological inflexibility,” Barrett said.  

“You get stuck in a rut of rumination. You get stuck in negative self-attribution, negative self-thoughts, and this is a kind of characteristic of depression that helps people develop and maintain their depression,” he said.  

“It boils down to a reduced capacity to think creatively or to think openly, and to think differently about yourself and your condition, situation and behavior. If psilocybin can increase our cognitive flexibility, if it can increase our neural flexibility, we think that essentially it gives people back the capacity to think broadly about how they fit into the world and reassess or reappraise things that might happen to them.”  

A separate paper published just last week in Nature Medicine by researchers from the University of California, San Francisco and Imperial College London echoed similar findings, although Barrett notes there are several caveats associated with the study’s findings.  

In that study, researchers analyzed fMRI brain scans from roughly 60 participants who took part in two psilocybin trials. Participants in the first trial had treatment-resistant depression and knew they were receiving psilocybin with psychotherapy. Participants in the second trial had less severe depression and were given either psilocybin or the common SSRI antidepressant escitalopram, although they were not told which drug they were given.  

According to the research, participants given psilocybin not only experienced a reduction in depression symptoms, but brain scans taken before and after the doses showed greater interconnectivity between regions of the brain that are typically segregated in depressed patients. The changes were not seen in the brains of participants who received the escitalopram.

“We’re looking at brain modularity and network modularity. So, this is a measure of how segregated systems are in the brain and there is a suspicion that certain systems become too segregated in mental illness, not just in depression, but also in addiction and maybe other psychiatric disorders as well,” Robin Carhart-Harris, former head of the Imperial Center for Psychedelic Research who is now based at the University of California, San Francisco, told Changing America.  

“What we’re seeing in these data after psychedelics is that there’s an increase in the connectivity between systems, such that they are becoming less segregated from each other,” he said.  

Carhart-Harris emphasized the studies only looked at a combination therapy, that being the dose of the drug coupled with psychotherapy and noted there is no evidence the drug alone can be therapeutic.  

What may be most intriguing is that some researchers hypothesize the mystical experience associated with psilocybin — which can include change in consciousness, mood, thought and perception — may be necessary to lead to the reduction in depression symptoms. 

“The mystical experience itself does seem to be really important for therapeutic effects, but we published survey data to suggest it’s not actually the mystical experience itself, but the personal insights you can encounter or gain during that mystical experience that actually lead to therapeutic change,” Barrett said.  

“The idea here is that mystical experience can create the opportunity for personal insights.”  

Researchers note more rigorous studies need to be conducted to get a real grasp on how psilocybin affects psychiatric disorders, but the preliminary results appear to be promising, so much so that Oregon in 2020 approved a ballot measure to legalize and regulate psilocybin therapy. Roll out of the program is expected next year.  


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