From the Guidelines
The toxic dose of psilocybin is not well-defined, but doses above 25-30mg are considered high and potentially risky, with significant individual variability in response. When considering the use of psilocybin, it is essential to understand that the precise quantity that constitutes a toxic dose is difficult to define, and there have been no consistently accepted criteria amongst researchers 1. The most commonly reported definition of a microdose is a dose between approximately one tenth and one twentieth of a typical recreational dose, although this range is uncomfortably imprecise for scientific purposes 1. Some key factors contributing to the uncertainty in defining dosing criteria include the unregulated nature of the substances, variation in pharmacological and subjective effects, and individual differences in response to a given substance 1. Given these considerations, it is crucial to approach psilocybin use with caution, starting with very low doses in a safe environment with trusted individuals present, and avoiding it entirely for those with personal or family history of psychosis or severe mental illness. Factors affecting individual response to psilocybin include body weight, metabolism, mental health history, medication interactions, and setting, making it essential to carefully evaluate these factors before use 1. While psilocybin is not physically toxic in the traditional sense, and fatal overdoses from the compound alone are extremely rare, the psychological risks of high doses should not be underestimated, and can lead to overwhelming psychological experiences, anxiety, panic, confusion, and in rare cases, dangerous behavior due to impaired judgment. In clinical settings, moderate therapeutic doses of psilocybin are often 20-25mg of pure psilocybin, while microdoses typically range from 0.1-0.5g of dried mushrooms, highlighting the need for careful dosing and monitoring 1. Ultimately, the use of psilocybin requires a thorough understanding of the potential risks and benefits, as well as careful consideration of individual factors that may influence response to the substance.
From the Research
Psilocybin Dosage
- The optimal dosage of psilocybin is still being researched, with studies suggesting that a high dose (22 or 30 mg/70 kg) may be more effective in reducing depression and anxiety in patients with life-threatening cancer 2.
- A study found that psilocybin doses in the range of 20 to 30 mg/70 kg (inclusive) were effective in producing therapeutic outcomes, with no significant associations found between subjective effects and demographic variables including body weight or sex 3.
- Another study suggested that a fixed dose of psilocybin may be as effective as a weight-adjusted dose, with the convenience and lower cost of administering psilocybin as a fixed dose outweighing any potential advantage of weight-adjusted dosing 3.
Toxicity and Adverse Events
- Psilocybin has been shown to be generally well-tolerated, with common minor to moderate adverse events including elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms 4.
- A systematic review and meta-analysis found that the most common adverse event with psilocybin was headache, with nearly a third of the articles reporting that no participants reported lasting adverse effects 5.
- High doses of psilocybin (above 30 mg/70 kg) may increase the risk of adverse events, but the exact toxic dose of psilocybin is not well-established 4, 2.
Therapeutic Effects
- Psilocybin has been shown to have therapeutic effects on mental disorders such as depression and anxiety, with a systematic review and meta-analysis finding that psilocybin had the strongest therapeutic effect among four psychedelics 5.
- A randomized double-blind trial found that high-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism 2.
- Psilocybin-assisted therapy may be effective for treating anxiety, depression, and possibly existential distress in people facing a life-threatening disease, with the certainty of evidence being low to very low due to high risk of bias and imprecision 4.