Five Key Differences You Need to Know Between MDMA and Psilocybin

mdma psilocybin Feb 04, 2026

One of the most common things people ask me is what the pros and cons of choosing MDMA vs. Psilocybin are or how the effects of each substance differ.

While both substances interact with the serotonergic system, they produce markedly different psychological and physiological effects. MDMA and psilocybin are often grouped together as 'psychedelics', but their effects, mechanisms, and therapeutic roles differ.

In this video blog, I explore the key distinctions between MDMA and psilocybin as they relate to subjective experience, therapeutic focus, session structure, and safety considerations.

The video covers five key differences including:

1. Mechanisms of action, including monoamine release versus 5-HT2A receptor agonism

2. Subjective effects, with a focus on differences in emotional, cognitive, and perceptual experiences

3. Therapeutic applications, from trauma processing and relational work to insight-driven cognitive and existential change

4. Session length, verbal engagement, and experiential flow

5. Relative risk profiles and physiological considerations

a BONUS feature: How each substance may interact with SSRI antidepressants with thoughts on potential management strategies

As psychedelic-assisted therapies continue to gain attention across clinical and educational settings, understanding these differences is essential for informed expectations, preparation, and safety. I hope you enjoy the video and find the content useful.

Stay safe, be well, and many blessings!