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Psilocybin can exacerbate or trigger the onset of underlying psychotic conditions, people with a personal or family history of conditions like schizophrenia are at high risk of long-lasting harm and should steer clear of psilocybin. If not used in a controlled environment with a mental health professional present, psilocybin is a powerful tool that, if used in a dangerous way, could harm the person or the people around them.

Psilocybin is not considered to be addictive nor does it cause compulsive use. One reason is that the intense experience, which can be physically and mentally challenging, may cause people using psilocybin to limit their frequency of 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.

The risks associated with psychedelic drugs are mostly psychological, not physical. Physically, psilocybin mushrooms are considered one of the least toxic drugs known.

Reported symptoms like nausea, increased perspiration, numbing and tremors, can sometimes make psychological symptoms like anxiety, panic attacks, paranoia, and mood swings seem worse. Long-term physical effects directly attributed to the pharmacology of psilocybin are rare, and research suggests they may also be due to latent psychological disorders.