This article summarizes peer-reviewed data on caffeine and psilocybin pharmacology. It is not medical or mental health advice. Effects vary by dose, tolerance, and individual neurochemistry.
Coffee’s caffeine primarily blocks adenosine receptors (A1 and A2A)—reducing fatigue and indirectly boosting dopamine and glutamate.
Psilocybin, metabolized into psilocin, primarily activates serotonin 5-HT2A receptors, producing its cognitive and perceptual effects.
Although both heighten brain activity, their mechanisms differ:
| Compound | Primary Targets | Neurochemical Result | Duration |
|---|---|---|---|
| Caffeine | Adenosine A1/A2A antagonist | ↑ dopamine, ↑ glutamate | 3–6 hrs |
| Psilocin | Serotonin 5-HT2A agonist | ↑ cortical entropy, ↓ default-mode network | 4–6 hrs |
(Sources: PMID 28476262, PMID 32168483)
Both compounds modulate cortical connectivity—but in opposite ways:
Combining the two can either:
fMRI data show psilocybin reduces default-mode coherence while caffeine increases frontoparietal connectivity (PMID 33914816). Together, they may temporarily amplify brain “energy” but reduce integration if overstimulated.
In microdosing (≈ 100–200 mg psilocybin equivalent, sub-perceptual), caffeine is often co-used for focus.
Surveys of microdosers report mild synergy when doses are small and timing is staggered (PMID 37515259).
Suggested sequencing (non-clinical):
Reported benefits (anecdotal + survey-based):
For full psychedelic sessions (2–5 g dried mushrooms), caffeine can:
Caffeine’s stimulation competes with psilocybin’s parasympathetic shift.
Facilitators usually recommend zero caffeine 24 hours before and after a macrodose experience.
Post-journey, many people report increased sensitivity to caffeine for several days.
This may stem from serotonin receptor plasticity and temporarily altered homeostasis (PMID 34664236).
Re-introduce caffeine gently:
| Use-Case | Recommended Approach | Why |
|---|---|---|
| Microdosing | Low caffeine (≤100 mg), 1–2 h before dose | Enhances focus, avoids overstimulation |
| Macrodosing | Avoid caffeine 24 h before/after | Prevents anxiety, heart strain |
| Integration | Reintroduce gradually | Nervous system sensitivity resets |
Our friends over at Agape Church in Conroe, Texas have received traditional training by a Colombian medicine to properly and safely facilitate these sacred ayahuasca ceremonies. And, they have been safely facilitating psylocibin ceremonies for many years. Agape Church has served over 1,500 people since 2019. Participants have traveled from all over the country and world to attend their retreats.
Agape’s voice: “Agape Church is an interfaith spiritual community that welcomes individuals from all paths. We host
enriching spiritual retreats designed to foster personal growth, community connection, and a deeper
understanding of diverse spiritual traditions.
Celebrating diversity in all forms, Agape Church warmly welcomes everyone, inviting you to explore a deeper connection with your Soul, Mind, and Body, transcending boundaries of religion, race, and personal backgrounds.”
Agape Church is a registered 508c1a non-profit that has listed their listed entheogenic practices to legally facilitate these ceremonies. You can learn more about their location, retreats and more on their website: https://www.agape4smb.com
Read Part 1: ‘Coffee & Psychedelics: What Science Actually Says’ HERE
Read Part 2: ‘Ayahuasca Timing & Risks Guidelines’ HERE
Serving: The Woodlands, Spring, Conroe, New Caney, Humble, Porter, and the greater North Houston area.
Codec Coffee is a veteran-owned coffee company based in Houston, Texas.
