Psilocybin decreases depression and anxiety in cancer patients (2016)

Study design and placebo/blinding challenges

• Commenters note psychedelic trials struggle with blinding: most participants can tell if they received an active dose.
• Strategies mentioned: low vs high dose (“micro vs macro”), active placebos like niacin or strong antihistamines to mimic bodily sensations, or comparing psilocybin to other hallucinogens.
• Some argue mood interventions are inherently hard to blind and third‑party observers (family, monitors) may be better outcome raters.

Role of preparation, therapy, and music/setting

• Multiple anecdotes stress that the benefit came from a structured protocol: screening for treatment‑resistant depression, extensive prep sessions, and dosing under supervision of trained therapists/trip sitters.
• Guided soundtracks and carefully chosen music are described either as essential for steering thoughts and avoiding “loops,” or as something that interferes with the timelessness of the experience.
• “Set and setting” (mindset, environment, sitter) are repeatedly emphasized as critical.

Reported benefits

• Several people claim life‑changing relief from severe anxiety/depression, including in cancer contexts and long‑term treatment‑resistant cases; some report lasting improvements in empathy, sobriety, or sense of meaning.
• Others describe psilocybin as enabling perspective shifts or “ego death” that break maladaptive patterns.

Adverse experiences and risks

• Many counter‑anecdotes: onset of panic attacks, derealization, suicidal ideation, or psychotic‑like states after otherwise “normal” trips, sometimes lasting months or longer.
• Concerns are raised about triggering latent psychosis or schizophrenia, especially with family history; some argue the risk is non‑trivial, others insist it is rare but real.
• Debate over physical toxicity: one side characterizes euphoria as mild poisoning with potential renal harm; others demand evidence and point out misidentified or unclear mushroom species in cited cases.

Evidence quality, effect sizes, and placebo

• Critical commenters highlight: small, self‑selected samples; many prior hallucinogen users; weak blinding; uncorrected multiple outcomes; and crossover designs.
• Depression scores improve in both active and placebo arms, attributed to strong placebo effects, regression to the mean, and “turbo placebo” from a mystical‑seeming intervention.
• Some psychologists argue psilocybin may help some individuals but current data do not yet justify broad clinical adoption and hype is outpacing evidence.

Dosing and pharmacology discussion

• The trial’s 30 mg/70 kg dose is informally equated to roughly 2–5 g of dried Psilocybe cubensis, with wide variability by species, strain, and cultivation.
• Debate over mechanisms: acute 5‑HT2A activation vs. longer‑term receptor density changes, anti‑inflammatory effects, and how this compares to chronic SSRIs or microdosing (with possible heart‑valve risks at sustained exposure).

Policy, economics, and regulation

• Several threads ask why psilocybin remains Schedule I while amphetamines are widely prescribed.
• Explanations raised: 1970s drug‑war politics targeting counterculture and minorities; path‑dependence from historical medical use of stimulants; stigma from recreational use; and limited pharma incentives for an infrequent‑use, easily home‑grown drug.
• Some favor full legalization but criticize advocacy that minimizes risks, likening it to earlier marijuana debates.

Alternatives and broader mental health context

• Mindfulness, moral/behavioral change, reduced sensory overstimulation, and charitable acts are offered as a non‑drug success story for depression, framed in Buddhist terms.
• Others push back that “just be more moral” is not meaningful treatment advice, though cultivating loving‑kindness and reducing compulsive desire is seen by some as beneficial.