Mushroom tolerance calculators: what they assume vs what's been measured

The short answer

Tolerance calculators turn "days since last time" into a percentage using a curve their makers picked, not one fitted to human data. In our check of 36 online calculators, 13 include a tolerance tool, and the models they state run from a half-life of about 2.3 days to a reset of about 4 weeks. The main human study behind the idea, from 1961, showed that tolerance to psilocybin develops and crosses over with LSD, but its abstract gives no recovery time.¹

What tolerance calculators assume

A tolerance calculator usually asks what you took last time, how many days ago, and sometimes what you plan next. Then it applies a curve. That's true of the tools below and of the tolerance estimator on My Mushroom Dispensary's dosing page. My Mushroom Dispensary is an online shop for adults 21+ run by the team that publishes this site, and its estimator, like the others, applies a modeled curve rather than measured human recovery. Here's what the tools in our audit say they assume.

None of these tools links its constant to a human study. Azarius points to "published research on 5-HT2A receptor pharmacology" in general terms, and mycodosing.wtf links a book chapter. Two pages disagree with themselves: Tripsitter's tolerance page gives both about a week and 14 days, and EasyMushroomCultivation's recovery timelines differ between sections of the same page.

Outside the calculators, a widely repeated figure on PsychonautWiki says it "takes about 3 days for the tolerance to be reduced to half and 7 days to be back at baseline". No citation is attached to it.²

What has been measured in people

Isbell and colleagues, 1961. In two series of experiments on 19 volunteers, researchers gave LSD or psilocybin in rising amounts over 6 to 13 days and measured how the response changed. "Direct" tolerance to LSD "developed to a high degree", and tolerance to psilocybin "also developed, although to a lesser degree." People tolerant to LSD were "to a considerable degree, also cross tolerant to psilocybin", and people tolerant to psilocybin were cross-tolerant to LSD.¹ The abstract doesn't report how fast tolerance appeared or how long it lasted once the doses stopped.

Hollister, 1961 (one person). In a clinical report on psilocybin in volunteers, one person was given psilocybin in rising amounts over 21 days. The same amount that had almost no effect on day 22 worked again later: "several weeks later the same dose produced the characteristic clinical syndrome."¹⁰ It's a single case, and the abstract gives no finer timing.

Isbell and colleagues, 1955 (LSD only). The only human recovery figure in days that we found is for LSD, from a conference abstract. In patients given LSD every day, tolerance "to all the effects measured was evident in less than 7 days", and it "was completely lost 3 days after discontinuation of LSD."³ That's LSD after days of daily use, measured in the 1950s, not psilocybin after a single session.

Madsen and colleagues, 2020. A brain-imaging study scanned 10 healthy volunteers who had never used psychedelics, before and 1 week after one psilocybin session. Serotonin 2A receptor binding at 1 week showed no group-level change from baseline (mean change 0.007, p = 0.8).⁴ It measured one time point, so it can't describe a curve.

The gap. We found no modern controlled study that measured, day by day, how tolerance to psilocybin fades in people after one session or a short run of sessions. Our searches covered PubMed and the web.

What animal studies add

Most of what's known about the mechanism comes from animals, where researchers can count serotonin 2A receptors directly.

• Rats (Buckholtz 1990). Daily LSD for 5 days lowered serotonin 2 receptor binding in the cortex. The drop "was evident within 3 days" but not after the first dose, and it "was still present 48 hours, but not 96 hours, after the last administration." Eight days of psilocybin also lowered binding. The authors wrote that the drop "strikingly parallels" behavioral tolerance but "cannot explain the gamut" of tolerance and cross-tolerance effects.⁵
• Pigs (Raval 2021). In a study of 24 pigs given either a single psilocybin injection or saline, 5-HT2A receptor density in the hippocampus and prefrontal cortex was lower one day after psilocybin. Seven days later "there were no longer any differences".⁶
• Mice (de la Fuente Revenga 2022). Four days of repeated LSD or DOI cut the head-twitch response, a standard mouse measure of psychedelic effect, by about half. Tolerance depended on 5-HT2A activation.⁷

Receptor counts in animals aren't the same as how a person feels, and these designs (daily injections, single injections, different drugs) don't match how people use mushrooms. In these studies the receptor drop faded within days to a week, but none of them supplies a decay constant for people.

Assumed vs measured, side by side

What a tolerance number leaves out

A tolerance estimate covers one variable. Others change the response as much or more:

• Potency. The amount of psilocybin varies between mushrooms and batches, so "the same amount as last time" may not be the same. See the potency data.
• Medicines. In 23 healthy adults, two weeks of the antidepressant escitalopram before a psilocybin session reduced "any drug effects", "bad drug effects" and fear compared with placebo, while blood levels of psilocin didn't change.⁸ A weaker response can come from a medicine, not tolerance. See the interactions reference.
• Age and experience. A review of 14 studies found older age and more psychedelic experience were linked to "generally less intense effects".⁹
• Body weight. Some tolerance tools sit beside a weight question. Trials found weight didn't predict intensity; see does body weight matter.