Psilocybin

Taken by mouth, psilocybin is converted to psilocin and typically begins to act within 20–60 minutes, peaks at around 2–3 hours, and resolves over roughly 4–6 hours. Onset and intensity vary with dose, the species and preparation of the mushroom, and individual factors (Nichols, 2016).

Psilocybin is generally not advised for people with a personal or family history of psychotic disorders (such as schizophrenia) or bipolar disorder, because the experience can trigger or worsen these conditions. Clinical studies routinely screen out such individuals as a basic safety measure (Johnson, Richards & Griffiths, 2008).

• Psychiatric history: personal or family history of schizophrenia, other psychotic disorders, or bipolar I disorder.
• Cardiovascular conditions: caution is advised with significant heart disease or uncontrolled high blood pressure, as psilocin can modestly raise heart rate and blood pressure.
• Current medication: see drug interactions below, especially serotonergic psychiatric medicines.

The most important interactions involve medicines that act on the serotonin system.

• SSRIs and SNRIs (antidepressants): long-term use often reduces or blunts the effects of psilocybin. Stopping antidepressants to feel stronger effects is itself risky and should only be considered with medical guidance.
• MAOIs: can substantially intensify and prolong the effects of psilocybin and are generally considered unsafe to combine without expert oversight.
• Lithium: combining lithium with psychedelics has been linked to seizures and is considered dangerous; avoid this combination.
• Tramadol and other serotonergic drugs: may increase the risk of serotonin-related effects.

This list is not exhaustive. Always check an up-to-date interaction resource and consult a clinician about any prescription medication (NIDA; TripSit drug-combination data).

The most common adverse reaction to psilocybin is acute psychological distress, often called a 'bad trip'. It can involve intense anxiety, fear, paranoia, or confusion. A structured review of hallucinogen safety identified overwhelming distress during the drug's action as the most likely risk of use (Johnson, Richards & Griffiths, 2008).

Because effects last several hours, a difficult experience cannot simply be stopped. Risk is strongly influenced by 'set and setting' — the person's mindset and their physical and social environment — and reassurance in a calm, safe place usually helps. In rare cases distress can lead to dangerous behaviour, such as trying to leave a place of safety.

Serious lasting harm from psilocybin is uncommon, and the compound itself has very low physiological toxicity. Important risks include:

• Mushroom misidentification: foraged mushrooms can be confused with toxic species, some of which cause fatal organ damage. This is one of the greatest dangers associated with mushroom use.
• Prolonged psychosis: rarely, psilocybin can trigger a persistent psychotic reaction, most often in people predisposed to psychotic illness (Johnson, Richards & Griffiths, 2008; Nichols, 2016).
• Hallucinogen Persisting Perception Disorder (HPPD): a rare condition in which visual disturbances continue after the drug has worn off (Halpern, Lerner & Passie, 2018).
• Accidental injury: altered perception and judgement can lead to unsafe behaviour.

Some groups face higher risk and are generally advised not to use psilocybin:

• People with a personal or family history of psychosis or bipolar disorder, in whom psychedelics may trigger or worsen episodes.
• Adolescents and young adults, whose brains are still developing and who may be more vulnerable to adverse psychological effects.
• Pregnant or breastfeeding people, for whom safety has not been established.
• People in acute psychological crisis or unstable circumstances, where a safe set and setting cannot be ensured.

Psilocybin is not considered addictive. It does not produce compulsive drug-seeking or a physical withdrawal syndrome, and classic psychedelics are generally not regarded as drugs of dependence (Johnson, Richards & Griffiths, 2008; Nichols, 2016). Tolerance also builds quickly: effects diminish sharply if it is taken on consecutive days, which discourages frequent use, and tolerance resets after a few days.

Life-threatening overdose from psilocybin itself is extremely rare, because the compound has very low physiological toxicity. The greater danger is accidentally eating misidentified toxic mushrooms, which can cause severe or fatal poisoning. Very high doses of psilocybin can cause intensely frightening experiences, nausea, and vomiting. Seek emergency care if there is any concern about poisoning or a serious medical reaction (Nichols, 2016).

The scientific evidence for microdosing is still limited and mixed. Many reported benefits come from uncontrolled self-reports, and placebo-controlled studies suggest that expectation explains much of the perceived benefit. Long-term safety has not been established, so microdosing is best regarded as experimental rather than proven (Passie, 2019).