Psilocybin

The active psychedelic ingredient (when converted to psilocin) found within magic mushrooms. Psilocybin has been found to be effective therapy for treatment resistant depression (TRD).

Figure 1. Psilocybin chemical structure

Psilocybin (Figure 1) degrades quickly into its active metabolite psilocin after ingestion. Both psilocin and psilocybin exhibit affinity for a range of serotonin receptors (5-HT1A/B/D/E, 2B, 5, 6, 7) with high affinity for the 5-HT2A receptor.

History

A chemical found in more than 100 mushroom species and used for millennia in Indigenous communities in Mexico and Central America as part of celebrations, healing rituals, and religious ceremonies. Investigated by psychiatrists in the 1950s and 1960s before the 1971 Controlled Substances Act designated it a Schedule I drug.

Effects During the Psychedelic Experience

Figure 2. The dynamic of the Psilocybin psychedelic experience.

It takes 20-40 minuets for Psilocybin / Psilocin to have an psychological effect after ingestion. The peak of this effect occurs within 60-90 minutes which then subsides substantially (by over 50%) within 180 minutes (see Figure 2), the entore session can last between 2–6 h.

Long Term Effects

Increased positive mood, hallucinations, and an inability to discern fantasy from reality. Causes alterations of thought and of the perception of time. Panic reactions and a psychotic-like episode can occur, particularly at a high dose.

Depression Dosage

Figure 3. Depression symptom reduction from placebo, low dose and therapeutic dose of psilocybin.

Best practice indicates that a body weight derived dosage of psilocybin of 0.3mg / kg or 25mg should be used. In the realm of magic mushrooms this is approximately 2.5 grams of dried Psilocybe cubensis.

These standard doses has been found to have substantially better clinical outcomes than lower doses such 10mg or microdosing (see Figure 3). This equates to 10–20µg l–1 psilocin in plasma, which corresponds to ~60% occupancy of serotonin 2A (5-HT2A) receptors in the neocortex of humans.

A heroic dose, which is usually reserved for experienced psychedelic users is considered to be at the upper end of the dosage spectrum — typically around or more than 5 grams of dried psilocybin mushrooms or anywhere from 25 to 40 mg of pure psilocybin.

Psychedelic Experience

During clinical studies it is common for those carrying out the trial to match the dynamic of the psychedelic experience (trip) with a musical playlist which includes:

1. Low Vocalization (for the onset) - commonly classical, low volume (first 45 minutes)
2. Peak Emotion - percussion, higher volumes (45-90 minutes)
3. Comedown - Can be choral, melodic, commonly have female voices, nature sounds or mimics the "outside world" (after 90 mins)

Reference