Luckily, there is a sound body of research into the working mechanisms of psilocybin (and other psychedelic substances) ¹. Psilocybin shares with other psychedelics that they act as an agonist at the serotonin 2A receptor subtype (5-HT2AR). This means that psychedelics work via a very specific system in our brain, traceable to the molecular level. Even more remarkable is that when this receptor is blocked (by another agent), the psychedelic en profound experience do not occur!
While the psychedelic effect is of course the desired effect of psilocybin, there is more. There has been extensive research into the safety of psilocybin (and other psychedelics) ². The results are encouraging; psilocybin has a low toxicity and doesn’t lead to organ damage or neuropsychological deficits. During the experience there are some physiological symptoms that may occur, such as dizziness, weakness, tremors, nausea, drowsiness, paresthesia, blurred vision, dilated pupils, and increased tendon reflexes². Additionally, psilocybin has temporal effects on both systolic and diastolic blood pressure and on heart rate (approximately 10 bpm during the experience) ³. Blood pressure peaks after 30 minutes and stays that way for about 2,5 hours and then slowly returns to normal.
On a psychological level the most talked about risk is the ‘bad trip’, characterized by anxiety, fear/panic, dysphoria, and/or paranoia². Although this is a serious risk, even in unsupervised and uncontrolled conditions this is a rare event. Another risk is that of prolonged psychosis². It is thought that psychosis occurs in individual who had a premorbid risk for psychosis, but it is difficult to determine this causation. The last risk we like to address is that of hallucinogen persisting perception disorder (HPPD)⁴. This is a rare condition, often confused with ‘flashbacks’, which seem more benign. HPPD can be a debilitating condition. As the ‘bad trip’ occurrence seems much less likely in a safe, controlled environment. Not much is known about why or how it happens.
Although the above might sound a bit ‘heavy’, the use of psilocybin, especially in a good ‘set’ and ‘setting’ is considered safe. Recent research, combined in a review by Dos Santos et al⁵, shows that besides a profound experience, a psychedelic experience can help reducing anxiety, depression and addiction. Also there is evidence that a psychedelic experience has a positive effect on personality, the trait Neuroticism decreased, while traits Extraversion, Conscientiousness (trend-level), and Openness all increased from baseline to the 3-month follow-up after psilocybin-facilitated therapy for treatment-resistant depression⁶