New England Journal of Medicine · 2021PubMed → Trial of Psilocybin versus Escitalopram for Depression
Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ
In the first head-to-head comparison of psilocybin against a leading SSRI antidepressant, psilocybin therapy showed comparable efficacy to escitalopram over six weeks, with faster onset and fewer side effects. On secondary outcome measures, psilocybin outperformed escitalopram on well-being, social functioning, and emotional responsiveness. This landmark trial, published in the world's most prestigious medical journal, signaled mainstream acceptance of psychedelic medicine.
depression
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study
Carhart-Harris RL, Bolstridge M, Rucker J, Day CMJ, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ
Twelve patients with treatment-resistant depression received two psilocybin sessions with psychological support. All patients showed reduced depression scores one week post-treatment, and five of twelve remained in remission at three months. This was the first modern clinical trial of psilocybin for depression, demonstrating that patients who had failed multiple conventional treatments could experience rapid and sustained relief.
depression
Proceedings of the National Academy of Sciences · 2012PubMed → Neural correlates of the psychedelic state as determined by fMRI
Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ
Using functional MRI, this study revealed that psilocybin reduces activity in key brain hub regions, particularly the default mode network (DMN) - contradicting the assumption that psychedelics work by increasing brain activity. Decreased DMN activity correlated with the subjective experience of ego dissolution. This finding reshaped our understanding of how psychedelics produce their therapeutic effects and established the DMN as a central target of psychedelic neuroscience.
depressionanxiety
Frontiers in Human Neuroscience · 2014PubMed → The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs
Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, Chialvo DR, Nutt D
This influential theoretical paper proposed that the quality of conscious experience lies on a spectrum of entropy - from highly ordered (rigid, depressive) states to highly disordered (psychedelic) states. Depression and addiction are characterized by overly rigid brain dynamics, while psychedelics temporarily increase neural entropy, allowing the brain to escape fixed patterns. This 'entropic brain hypothesis' provided a unifying framework for understanding both mental illness and psychedelic therapy.
depressionaddiction
Psilocybin with psychological support for treatment-resistant depression: six-month follow-up
Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ
Six-month follow-up of the 2016 treatment-resistant depression trial showed that psilocybin's antidepressant effects persisted well beyond the acute experience. At six months, most patients maintained clinically significant improvements in depression, with many continuing to describe the treatment as one of the most meaningful experiences of their lives. This extended follow-up provided critical evidence that psilocybin therapy produces durable changes rather than transient symptom relief.
depression
Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance
Griffiths RR, Richards WA, McCann U, Jesse R
In the study that reignited modern psychedelic research, 36 healthy volunteers received psilocybin in a controlled setting. Two-thirds rated the experience among the top five most meaningful events of their entire lives, comparable to the birth of a child or death of a parent. At 14-month follow-up, participants continued to report positive changes in attitudes, mood, and behavior. This rigorous double-blind trial at a major university proved psychedelics could be studied safely and effectively.
depressionanxietyend of life
Journal of Psychopharmacology · 2016PubMed → Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA
Cancer patients with life-threatening diagnoses received a single high dose of psilocybin. At six months, 80% showed clinically significant decreases in depression and anxiety, with approximately two-thirds meeting criteria for clinical remission. The depth of the mystical experience directly predicted therapeutic outcome. This study demonstrated that a single psychedelic session could fundamentally alter a person's relationship with death and existential suffering.
depressionanxietyend of life
Psilocybin occasioned mystical-type experiences: immediate and persisting dose-related effects
Griffiths RR, Johnson MW, Richards WA, Richards BD, McCann U, Jesse R
This dose-response study found that higher doses of psilocybin produced more complete mystical experiences, and that the intensity of mystical experience predicted lasting positive changes in attitudes, mood, life satisfaction, and behavior. At 14-month follow-up, 94% of participants who had a complete mystical experience rated it among the top five most meaningful experiences of their lives. The study established dose-response relationships critical for clinical protocol development.
depressionanxiety
Survey of subjective 'God encounter experiences': Comparisons among naturally occurring experiences and those occasioned by the classic psychedelics psilocybin, LSD, ayahuasca, or DMT
Griffiths RR, Hurwitz ES, Davis AK, Johnson MW, Jesse R
A large survey of over 4,000 individuals who reported encountering 'God' or 'ultimate reality' found striking similarities between naturally occurring and psychedelic-occasioned experiences. Both groups reported vivid encounters with a conscious, benevolent entity, and the experiences led to lasting decreases in fear of death and increases in life meaning. The majority described the encounter as among the most meaningful and spiritually significant experiences of their lives.
end of lifedepressionanxiety