Use of ecstasy, possibly together with cannabis, may cause cognitive decline in healthy young people. An impairment of working memory might underlie declines in various task performances. The cognitive disturbance likely relates to ecstasy's neurotoxic potential, and even typical recreational doses appear sufficient to cause neurotoxicity in humans.
A single high dose of psilocybin can produce profound, personality-changing spiritual experiences in healthy people and is effective in psychotherapy for end-of-life anxiety, yet the same drug also models psychosis by stimulating the serotonin 2A receptor. This presentation resolves the paradox by proposing that the prodromal phase of first-episode psychosis, spontaneous spiritual experiences, and the psychedelic drug state share a common neurobiological state called the primitive state. This evolutionarily regressive state features magical thinking and a breakdown in the perception of separateness, supported by brain imaging showing decreased orthogonality of brain states in psychosis, the psychedelic state, and meditation.
Psychedelics like LSD, psilocybin, MDMA, and DMT work in the brain through a multi-level mechanism. Classic serotonergic psychedelics act on the serotonin 2A receptor, whose function and evolutionary purpose are illuminated by this pharmacology. Brain imaging reveals acute effects that increase entropy, supporting the entropic brain hypothesis. The REBUS model explains how psychedelics relax prior beliefs, allowing for predictive processing changes that map onto the acute experience and therapeutic outcomes. Current evidence supports psychedelic therapy, including a clinical trial of psilocybin for treatment-resistant depression and an ongoing comparison with escitalopram for major depressive disorder.