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Can You Develop Psilocybin Tolerance?

Can you develop a tolerance to Psilocybin Mushroom Species Guide:Psilocybin Molecule

Question: Can you develop psilocybin tolerance?

Answer: Tolerance to psilocybin and psilocin is not something that has been well researched, so the simple answer is it depends.  Read on and learn about psilocybin tolerance.

Understanding Psilocybin Tolerance

Let’s start off first by coming up with a reasonable definition of tolerance, something like:

Tolerance occurs when individuals need more of a specific substance to get the effects that once occurred at lower doses.

According Meyler’ Side Effects of Drugs, psilocybin is not considered classic drugs of abuse they lack the reinforcing properties and do not produce drug-seeking behaviors. This means their use tends to be episodic, short-term and experimental. Based on literature from the Drug Policy Alliance, Psilocybin, psilocybin/psilocin are not considered to be addictive and is not associated with compulsive use due to the fact that the intense experience associated with the ingestion of the substance can be physically and mentally challenging so that people using psilocybin self limit the frequency of its use.

Another reason is that the human body quickly builds tolerance to psilocybin, such that people require much higher doses after only a few days of repeated use, making it extremely difficult to have any effect after more than four days of repeated usage.

Having said that, tolerance occurs with repeated dosing and is thought to be due to down-regulation of 5HT2A receptors. The use of magic mushrooms on a regular basis is associated with very rapid development of tolerance to psilocybin. However, there is no evidence that individuals who regularly use magic mushrooms can develop physical dependence on them.

Psilocybin and LSD Cross Tolerance

As psilocybin/psilocin are similar to LSD in that their structural backbones are the same (both are “indoles”), it is not surprising that their effects are similar to both LSD and mescaline and there appears to be some cross-tolerance among these three hallucinogens.


Fundamentals of Forensic Science; Third Edition, 2015.

Drug Policy Alliance: 10 Facts about Psilocybin Mushrooms.

Meyler’s Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions.

Harris Isbell, A. B. Wolbach, A. Wikler & E. J. Miner, Cross tolerance between LSD and psilocybin; Psychopharmacologia volume 2, pages147–159 (1961)


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