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Psilocybin vs. Traditional Antidepressants: How Do They Compare?

February 28, 2025

For decades, traditional antidepressants like SSRIs have been the go-to treatment for mood disorders such as depression and anxiety. However, in light of the veil of stigma around mental health finally being lifted in public discourse and the growing interest in alternative therapies, more solutions are becoming available. Among those, psilocybin, a naturally occurring psychedelic compound, has emerged as a potential breakthrough in mental health care.

Mechanism of Action: How They Work

Traditional antidepressants typically work by increasing the availability of serotonin in the brain. They prevent reabsorption and help regulate the patient’s mood, though it usually takes weeks for any noticeable effects to kick in.

Psilocybin treatment, on the other hand, interacts directly with serotonin receptors, triggering profound changes in brain connectivity and neuroplasticity. Rather than increasing the amount of available serotonin, the chemical reactions stimulate its receptors, which means the brain’s natural chemistry doesn’t get disrupted.

Speed and Duration of Effects

One of the biggest differences between these treatments lies in how quickly they take effect:

  • SSRIs: Typically, SSRIs require four to six weeks to produce noticeable relief, and patients must take them daily to maintain their benefits. What happens when you stop? Most people suffer from some degree of withdrawal symptoms as a result of the altered brain chemistry we mentioned a moment ago,
  • Psilocybin: Psychedelic mushrooms can often produce significant improvements after just one or two guided therapy sessions. In many cases, the positive effects can last for months, reducing the need for continuous medication.

Side Effects and Tolerance

Lots has been said about the range of side effects associated with the use of traditional antidepressants. These include:

  • Weight gain
  • Fatigue
  • Sexual dysfunction
  • Emotional and cognitive blunting

For many, this short list is enough to put them off the idea of taking these compounds. The fact that many experience a worsening of their symptoms before the medication stabilizes their mood doesn’t help either.

Conversely, psilocybin therapy does carry certain different risks, including temporary nausea, increased heart rate, and psychological discomfort. However, it’s typically considered non-addictive and does not require daily use, so the risk of long-term dependence remains low.

Effectiveness for Treatment-Resistant Depression

For individuals with TRD, SSRIs often provide little to no relief in as many as 30% of patients who genetically do not respond to standard antidepressants. Meanwhile, clinical trials from institutions like Johns Hopkins or the Imperial College of London indicate that psilocybin therapy may be significantly more effective for fighting treatment-resistant depression. Because of this, those who feel they have exhausted other options, including conventional medication, can try once again to rejuvenate themselves on their journey to restoring their health.

The Takeaway

While both traditional antidepressants and psilocybin therapy have their place in mental health treatments, scientific exploration of psilocybin’s effects seems to give it a potential advantage. SSRIs do remain a widely used option, but psilocybin treatment could break the traditional mold and introduce a revolutionary alternative, particularly for SSRI non-responders.

 

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About Me

Hello all!!!! I'm Darcy and I recently started writing on My Zeo about health and fitness (and part of that important health equation is sleep!). As we are all super busy with life, I try to integrate how to stay fit, relax and be healthy and happy through everyday life.

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