Pharmacology & Neuroscience
Half-Life
What is half-life?
Half-life is a pharmacological measure of how quickly your body eliminates a substance. After one half-life, 50% of the substance remains. After two half-lives, 25% remains. After three, 12.5%, and so on.
A substance is generally considered to be fully eliminated after 4–5 half-lives (when less than 3–6% remains).
Half-lives of common microdosing substances
| Substance | Half-life | Total duration | Practical implication |
|---|---|---|---|
| Psilocin | ~2.5–3 hours | 4–6 hours | Effects wear off by evening if dosed in the morning |
| LSD | ~3.5–5 hours | 8–12 hours | Longer-lasting; morning dosing essential to avoid sleep disruption |
| Mescaline | ~6 hours | 8–12 hours | Longest common half-life |
| DMT (smoked) | ~15 minutes | 30–45 minutes | Too short for practical microdosing |
Why half-life matters for microdosing
Protocol design
Half-life determines how long a microdose remains active in your body, which directly affects:
- When to dose — substances with longer half-lives need earlier morning dosing
- Sleep impact — LSD's longer half-life means it's more likely to affect sleep if taken late
- Transition day effects — the "afterglow" may partly reflect residual substance below the half-life threshold
Substance choice
- Psilocybin (shorter half-life): More forgiving timing, less sleep disruption risk, effects contained within the workday
- LSD (longer half-life): Requires stricter morning timing, greater risk of sleep disruption, longer window of subtle effects
Tolerance timing
Half-life informs how quickly you develop tolerance:
- After the substance is eliminated (4–5 half-lives), the pharmacological effect is over
- But receptor changes (downregulation) persist much longer — this is why tolerance lasts days even after the substance is gone
Practical guidelines
Dosing time recommendations
- Psilocybin: Dose by 9–10 AM for minimal evening impact
- LSD: Dose by 7–8 AM (some prefer as early as 6 AM) to avoid any sleep interference
- General rule: Earlier is safer. You can always adjust earlier, but you can't un-take a late dose.
The "still feeling it" question
If you're wondering whether your microdose is "still working" at hour 6:
- Psilocin: After 2 half-lives (~6 hours), only ~25% remains. You're likely in afterglow territory.
- LSD: After 2 half-lives (~8 hours), ~25% remains. Subtle effects may still be present.