The One-Trip Rule: Understanding LSD’s Tolerance Limits
Double-dosing LSD on back-to-back days doesn’t double the fun. Thanks to tolerance, day two’s trip will be only about 47% as strong as the first.
It only takes about 140 micrograms of acid to blow your mind — but if you took that same 140 micrograms of acid a second time the following day, you'd barely feel anything more than a buzz.
This is because of a phenomenon called tolerance.
All drugs lead to tolerance over time — but the tolerance formed by classical psychedelics like LSD is exceptionally fast.
LSD, shrooms, mescaline, MDMA, and just about every other serotonergic-based psychedelic can result in tolerance and diminished effects in just one session. This happens because the receptors adjust to the presence of the drug in order to maintain equilibrium.
The only way to experience the same intensity of effects 2 days in a row is to double or triple the dose.
What is Tolerance?
Tolerance happens when the body resists the effects of a substance. The more often you use something, the less impact it has on the body.
We can become tolerant to almost anything — including caffeine, prescription medications, alcohol, etc... Basically, anything that causes a physiological change in the body can lead to tolerance.
If you’re a coffee drinker, you’ve likely noticed that drinking two or three cups a day over time has less of an impact. After a short break (a few days), a single cup can feel much stronger again.
The same is true for LSD but on a much faster scale.
The body becomes resistant to the effects of LSD in as little as one session. If you take the same dose the following day, you’re not likely to feel much of anything.
You’ll need to account for this newly-formed tolerance by taking a much larger dose if you want to feel the same intensity of effects.
What Causes Tolerance to LSD?
Scientists aren’t entirely sure why the body becomes tolerant to psychedelics so quickly, but we know it has something to do with the serotonin receptors.
LSD affects several types of serotonin receptors in the brain. The most significant in terms of the psychedelic effects are the 5HT2A receptors.
There are two leading theories about how the serotonin receptors become resistant to the effects of LSD on subsequent doses:
1. Receptor Desensitization
The desensitization theory suggests the serotonin receptors become rapidly desensitized to LSD and other indole psychedelics.
Desensitization implies the receptors lose sensitivity to stimulation over time. There aren't any less receptor binding points (like the next theory suggests); rather, they simply stop responding to LSD. These changes only appear to happen to the specific 5HT2A receptors LSD targets and have little to no impact on other 5HT receptors.
2. Reduced Receptor Density
The receptor density theory suggests the serotonin receptors aren’t desensitized directly but are instead hidden or blocked on the surface of the cell.
By hiding some of the receptors, we need to take higher doses of LSD in order to exert the same level of force that caused the initial effects.
This is a common mechanism the body uses to maintain balance, preventing overstimulation by downregulating the number of available receptors.
How Long Does it Take To Develop Tolerance to LSD?
Tolerance to LSD forms immediately — within just one single session.
Some research has even shown signs of tolerance just 3 hours after taking LSD.
If you take a second dose, you’ll only feel about half the effects. The dose after that will produce about 25 percent of the original dose.
By the seventh dose, complete tolerance is achieved — meaning LSD will no longer produce any noticeable effects unless the dosage is significantly increased.
How Long Does LSD Tolerance Last?
Thankfully, LSD tolerance reverses just as quickly as it develops.
If you were to take LSD today, you would need to wait about 1-week before your receptors are completely back to normal.
Most people find tolerance is negligible after just three days — while others say they need about 5 or 6 before they can trip again on a single tab.
LSD tolerance also appears to linger longer with heavy use. That is, people who use LSD more frequently — such as multiple times per week — report signs of tolerance as many as two weeks after their last session.
Regardless of how often you use LSD, tolerance rarely lasts more than two weeks beyond your most recent dose.
LSD Tolerance Calculator
Want to figure out your adjusted dose after a recent trip?
Use our handy LSD tolerance calculator to estimate the dose you’ll need based on your last dose, the number of days since, and the desired effects.
There’s a formula for calculating this dose, but it’s not exactly “user-friendly” (formula listed below).
We’ve converted this formula into a handy tolerance calculator to help you find the estimated equivalent dose based on your last dose of LSD.
⚠️ Disclaimer: This calculator is based on general guidelines and doesn’t account for individual factors. Always prioritize safety and avoid excessive dosing.
The formula used to make this calculator:
Y= X/100 * 280.059565 * N^-0.412565956
Y = New dose
X = The last dose you used
N = The number of days since your last dose
What’s the Maximum Safe Dose of LSD?
The theoretical lethal dose of LSD is around 14,000 micrograms — nearly 100X the standard dose of around 140 micrograms (~100 blotter tabs or ~50 LSD gel tabs).
This estimate is theoretical, as no scientific study has yet to exceed 500 micrograms.
With that said, there are plenty of anecdotal reports of users taking well over the 500 microgram dose without any major side effects.
The only report of hospitalization from LSD involved a group of people in the 70s who reportedly snorted somewhere between 1000 and 7000 micrograms of powdered LSD by accident. All members of this group survived after a short stint in the hospital.
In the early 2000s, a group of 20 Canadians made a calculation error that resulted in all participants taking nearly 10X a typical dose (~1100 micrograms). Eight members of the group ended up in the hospital, but all recovered by the following day.
With all of that said… it's unwise to ever take more than 500 micrograms of LSD. If your calculated dose for equivalent effects exceeds this amount, it's best to just take some time and wait for your tolerance to reset.
How to Reverse LSD Tolerance (Tolerance Breaks)
LSD tolerance will reverse on its own. You just need to give the body time for the affected receptors to readjust without taking any more LSD or other psychedelics — especially indole psychedelics like mescaline, magic mushrooms, 2C-X or DOX drugs, or any of the LSD analogs (lysergamides).
A tolerance break is a specific period of time set aside to allow LSD tolerance to reverse naturally. Anybody who uses LSD more than once per week (including microdoses) should consider taking a tolerance break from time to time.
The standard microdose protocols already take tolerance into account.
For example, the classic Fadiman microdosing protocol calls for 1 day ON, three days OFF. The three-day break is essentially the tolerance break to ensure the LSD continues to work again on the next dose.
Can Different Psychedelics Cause Cross-Tolerance With Each Other?
You bet! Multiple studies have confirmed that various tryptamine and phenethylamine psychedelics will cause cross-tolerance with LSD.
That means if you take mescaline or magic mushrooms today, your dose of LSD will have diminished effects tomorrow or the day after.
Most psychedelics work on the same receptors — so when tolerance affects the serotonin receptors, it will impact all serotonergic psychedelics as well.
Phenethylamines
The phenethylamine family is massive — it includes everything from mescaline and 2C-X drugs to amphetamines and bath salts.
While many members of this group affect the same serotonin receptors as LSD, this isn't very cut and dry. It's difficult to calculate exactly how much weaker your LSD will feel after taking phenethylamines.
Some have more impact on the 5HT2A receptors; others bind more readily to 5HT1 or 5HT3 serotonin subtypes. Others bind to different receptors entirely and may not produce any cross-tolerance at all.
The only phenethylamine with PROVEN cross-tolerance to LSD is mescaline — but there are numerous user reports of cross-tolerance with other members of this group.
It’s very likely that most phenethylamine psychedelics will cause cross-tolerance with LSD, but it’s unknown to what extent, and this will vary substantially from one substance to another.
DMT (Dimethyltryptamine)
One interesting exception to cross-tolerance appears to be DMT (N,N-dimethyltrypramine).
A study from the 60s demonstrated that humans tolerant to high doses of LSD still experience the full effects of DMT.
Dr. Rick Strassman, one of the leading researchers on DMT, explored this effect by giving participants four identical doses of DMT to assess tolerance formation. Strassman found some indicators of physical tolerance formation — adrenocorticotropic hormone, prolactin, and heart rate all decreased with repeated use — but the psychedelic effects remained in full effect.
LSD Tolerance in Context: How It Compares to Other Drugs
Nothing I've been able to find form tolerance faster than indole psychedelics like LSD.
To help you visualize just how abnormal the tolerance formation is to this substance, let's compare the time it takes to experience a 50% drop in potency due to tolerance formation with other classes of drugs:
LSD — 1 day.
Clonazapam (Long-Acting Benzodiazepine) — 5–7 days.
Alprazolam (Short-Acting Benzodiazepine) — ~4 days.
Amphetamine (Adderall) — Tolerance forms between 7–11 days but can remain in place for up to 31 days after ceasing.
Ketamine — ~7 days.
Methadone (Long-Scting Opiate) — 5–6 days.
Morphine (Short-Acting Opiate) — ~6 days but stabilizes at 6-weeks.
Caffeine — >18 days.
Nicotine — 4 days of continual infusion (likely much longer with conventional use).
Ethanol (Alcohol) — 46–55 days.
Further Reading
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