New John Hopkins Study Finds Psilocybin 4x More Effective Than Antidepressants

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A new John Hopkins study is furthering the evidence that psilocybin may treat depression four times more effectively than antidepressant medication. The study, published on November 4th in JAMA Psychiatry, was the first randomized clinical trial to focus narrowly on psilocybin’s potential in treating long term clinical depression.


Simply titled Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder, the study included 24 participants with the following demographics:

  • 16 females, 8 males
  • Collectively an average of 39 years old
  • Collectively experienced depression on average for 21.5 years
  • No psychotic disorders among them
  • No participants were currently taking antidepressant medication


Participants underwent one 20mg psilocybin dosage while they laid on a couch wearing eye shades and listening to music. The participants did this for a second time 1.6 weeks later, this time undergoing a 30mg psilocybin dosage. Like most John Hopkins psychedelic studies, participants met with mental health professionals before and after each session.

Psilocybin Shown to Produce Large, Rapid & Sustained Antidepressant Effects

The study found “psilocybin-assisted therapy was efficacious in producing large, rapid, and sustained antidepressant effects in patients with major depressive disorder.” More specifically, the study concluded the following:

  • Following the first psilocybin session, 67 percent of participants reported more than 50 percent decrease in depression symptoms
  • Following the second psilocybin session, 71 percent of participants reported more than 50 percent decrease in depression symptoms
  • At four week follow up, 54 percent of participants were in remission (a severe decrease in symptoms)

While this study size is small, there are a couple things worth noting about this experiment. First, what the study lacks in terms of size, it makes up for in robust data which warrants more research. The reality of psychedelic science is that, regardless of shared enthusiasm within the community, it is still a niche research topic. That being said, when judged on methodology, merrit, and outcomes, this study is groundbreaking in its own right.

Second, the results of this study are complementary to several previous studies confirming psilocybin’s potential to treat depression symptoms. Such studies most notably include the works of Robin Carhart-Harris and Roland R. Griffiths. In all cases, psilocybin was concluded to be a promising adjunct to psychotherapy, particularly for clients with treatment-resistant depression.

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A Different Mechanism To Treating Depression

We now know that psilocybin therapy is not only more effective than antidepressants, but it’s effective for a completely different reason. The most common and effective conventional antidepressant medications are SSRIs. These work by blocking the “reuptake” of serotonin, leaving more serotonin in the brain of the user. SSRIs are easily more effective than their tricyclic predecessors, and the aim of psychedelic medicine is not to render existing SSRIs useless. Rather, psychedelic medicine aims to help the 30 percent of individuals who do not reap any benefits from SSRIs.

Moreover, psilocybin therapy is promising for this demographic in triggering activity in different parts of the brain than regular antidepressants. Rather than creating a buffer to stimuli awareness (an effect of antidepressants commonly referred to as felt “fogginess”), psilocybin increases the user’s ability to engage with stimuli.

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Psychedelics Offer “Exposure Therapy” Style of Problem Solving

For this reason, psilocybin trips may be challenging, taking on an “exposure therapy” style of problem solving. In other words, where antidepressants shield the user from responding emotionally, psilocybin increases this emotional response. According to 2017 Neuropharmacology article, psilocybin increases this emotional response via activating one’s limbic system:

“Psilocybin with psychological support was associated with increased amygdala responses to emotional stimuli, an opposite effect to previous findings with SSRIs. This suggests fundamental differences in these treatments’ therapeutic actions, with SSRIs mitigating negative emotions and psilocybin allowing patients to confront and work through them.”

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No One Is Left Behind In the Psychedelic Medicine Revolution

Psilocybin therapy will indefinitely play an important role for those with treatment resistant depression. However, the underlying mechanism of all psychedelics seems to have an opposite approach to pharmaceutical interventions. The nature of psychedelic therapy is that the experience is the intervention. This “one and done” approach, where a powerful experience all at once disrupts vigorous and detrimental thought patterns, has a collaborative place in medicine – not a competitive one. 

Traditional pharmaceutical interventions and psychedelic interventions should each be considered for clients afflicted with clinical mental health crisis. Indeed, many will benefit from having a guided psychedelic experience in the context of psychotherapy, but some may be better off with antidepressant medication. Mental health will always be treated on a case-by-case basis.

No one, including those failed by antidepressants, will be left in a mental health crisis during the psychedelic medicine revolution.

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Ali Shana

Ali Shana

Ali Shana is a Palestinian-American writer and grad student studying clinical mental health counseling. He tends to report on a variety of drug-related topics, such as policy reform, psychopharmacology, and medication-assisted therapies.