Trial of Psilocybin versus Escitalopram for Depression

New England Journal of Medicine, Год журнала: 2021, Номер 384(15), С. 1402 - 1411

Опубликована: Апрель 14, 2021

Psilocybin may have antidepressant properties, but direct comparisons between psilocybin and established treatments for depression are lacking.In a phase 2, double-blind, randomized, controlled trial involving patients with long-standing, moderate-to-severe major depressive disorder, we compared escitalopram, selective serotonin-reuptake inhibitor, over 6-week period. Patients were assigned in 1:1 ratio to receive two separate doses of 25 mg 3 weeks apart plus 6 daily placebo (psilocybin group) or 1 oral escitalopram (escitalopram group); all the received psychological support. The primary outcome was change from baseline score on 16-item Quick Inventory Depressive Symptomatology-Self-Report (QIDS-SR-16; scores range 0 27, higher indicating greater depression) at week 6. There 16 secondary outcomes, including QIDS-SR-16 response (defined as reduction >50%) remission ≤5) 6.A total 59 enrolled; 30 group 29 group. mean 14.5 16.4 (±SE) changes -8.0±1.0 points -6.0±1.0 group, between-group difference 2.0 (95% confidence interval [CI], -5.0 0.9) (P = 0.17). A occurred 70% 48% those 22 percentage CI, -3 48); 57% 28%, respectively, 28 2 54). Other outcomes generally favored analyses not corrected multiple comparisons. incidence adverse events similar groups.On basis 6, this did show significant effects selected patients. Secondary these lacked correction Larger longer trials required compare antidepressants. (Funded by Alexander Mosley Charitable Trust Imperial College London's Centre Psychedelic Research; ClinicalTrials.gov number, NCT03429075.).

Язык: Английский

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REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics

Pharmacological Reviews, Год журнала: 2019, Номер 71(3), С. 316 - 344

Опубликована: Июнь 20, 2019

This paper formulates the action of psychedelics by integrating free-energy principle and entropic brain hypothesis. We call this formulation relaxed beliefs under (REBUS) anarchic brain, founded on that—via their effect spontaneous cortical activity—psychedelics work to relax precision high-level priors or beliefs, thereby liberating bottom-up information flow, particularly via intrinsic sources such as limbic system. assemble evidence for model show how it can explain a broad range phenomena associated with psychedelic experience. With regard potential therapeutic use, we propose that weighting pathologically overweighted underpinning various expressions mental illness. process entails an increased sensitization signaling (stemming from sources), heightened sensitivity enables revision deweighting priors. end discussing further implications model, bring about other heavily weighted priors, not directly related health, those underlying partisan and/or overly-confident political, religious, philosophical perspectives.

Significance Statement

Psychedelics are capturing interest, efforts underway psilocybin therapy marketing authorisation legal access within decade, spearheaded findings series phase 2 trials. In climate, compelling unified how alter function consciousness would have appeal. Towards end, sought integrate leading global function, hierarchical predictive coding, often-cited acute psychedelics, the hypothesis. The resulting synthesis states sensitising them liberated which, right intention, care provision context, help guide cultivate entrenched pathological

Язык: Английский

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Psychedelic drugs: neurobiology and potential for treatment of psychiatric disorders

Nature reviews. Neuroscience, Год журнала: 2020, Номер 21(11), С. 611 - 624

Опубликована: Сен. 14, 2020

Язык: Английский

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Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo

Neuron, Год журнала: 2021, Номер 109(16), С. 2535 - 2544.e4

Опубликована: Июль 5, 2021

Язык: Английский

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The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects

ACS Pharmacology & Translational Science, Год журнала: 2020, Номер 4(2), С. 568 - 572

Опубликована: Дек. 10, 2020

Classic psychedelics produce altered states of consciousness that individuals often interpret as meaningful experiences. Across a number human studies, when the participant-rated intensity overall drug effects are statistically controlled for, certain subjective predict therapeutic and other desirable outcomes. Underlying neurobiological mechanisms likely necessary but not sufficient to confer full enduring beneficial effects. We propose for their these account majority benefit.

Язык: Английский

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A non-hallucinogenic psychedelic analogue with therapeutic potential

Nature, Год журнала: 2020, Номер 589(7842), С. 474 - 479

Опубликована: Дек. 9, 2020

Язык: Английский

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Emotions and brain function are altered up to one month after a single high dose of psilocybin

Scientific Reports, Год журнала: 2020, Номер 10(1)

Опубликована: Фев. 10, 2020

Psilocybin is a classic psychedelic compound that may have efficacy for the treatment of mood and substance use disorders. Acute psilocybin effects include reduced negative mood, increased positive amygdala response to affective stimuli. However, no study has investigated long-term, enduring impact on affect associated brain function. Twelve healthy volunteers (7F/5M) completed an open-label pilot including assessments 1-day before, 1-week after, 1-month after receiving 25 mg/70 kg dose test hypothesis administration leads changes in neural correlates affect. One-week post-psilocybin, facial stimuli were reduced, whereas dorsal lateral prefrontal medial orbitofrontal cortex responses emotionally-conflicting increased. One-month returned baseline levels while remained elevated, trait anxiety was reduced. Finally, number significant resting-state functional connections across from post-psilocybin. These preliminary findings suggest increase emotional plasticity, reported support be therapeutic target psilocybin.

Язык: Английский

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Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice

Proceedings of the National Academy of Sciences, Год журнала: 2021, Номер 118(17)

Опубликована: Апрель 13, 2021

Depression is a widespread and devastating mental illness the search for rapid-acting antidepressants remains critical. There now exciting evidence that psychedelic compound psilocybin produces not only powerful alterations of consciousness, but also rapid persistent antidepressant effects. How exerts its therapeutic actions known, it widely presumed these require altered which known to be dependent on serotonin 2A receptor (5-HT2AR) activation. This hypothesis has never been tested, however. We therefore asked whether would exert antidepressant-like responses in mice and, if so, required 5-HT2AR Using chronically stressed male mice, we observed single injection reversed anhedonic assessed with sucrose preference female urine tests. The antianhedonic response was accompanied by strengthening excitatory synapses hippocampus-a characteristic traditional fast-acting antidepressants. Neither behavioral nor electrophysiological were prevented pretreatment 5-HT2A/2C antagonist ketanserin, despite positive ketanserin's efficacy. conclude psilocybin's mechanism action can studied animal models suggest perception may further 5-HT2AR-independent restoration synaptic strength cortico-mesolimbic reward circuits contribute action. possibility combining compounds offers potential means increase their acceptance clinical utility should human depression.

Язык: Английский

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Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors

Science, Год журнала: 2023, Номер 379(6633), С. 700 - 706

Опубликована: Фев. 16, 2023

Decreased dendritic spine density in the cortex is a hallmark of several neuropsychiatric diseases, and ability to promote cortical neuron growth has been hypothesized underlie rapid sustained therapeutic effects psychedelics. Activation 5-hydroxytryptamine (serotonin) 2A receptors (5-HT2ARs) essential for psychedelic-induced plasticity, but it currently unclear why some 5-HT2AR agonists neuroplasticity, whereas others do not. We used molecular genetic tools demonstrate that intracellular 5-HT2ARs mediate plasticity-promoting properties psychedelics; these results explain serotonin does not engage similar plasticity mechanisms. This work emphasizes role location bias signaling, identifies as target, raises intriguing possibility might be endogenous ligand cortex.

Язык: Английский

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Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer

Journal of Psychopharmacology, Год журнала: 2020, Номер 34(2), С. 155 - 166

Опубликована: Янв. 9, 2020

A recently published randomized controlled trial compared single-dose psilocybin with niacin in conjunction psychotherapy participants cancer-related psychiatric distress. Results suggested that psilocybin-assisted facilitated improvements and existential distress, quality of life, spiritual well-being up to seven weeks prior the crossover. At 6.5-month follow-up, after crossover, 60-80% continued meet criteria for clinically significant antidepressant or anxiolytic responses.The present study is a long-term within-subjects follow-up analysis self-reported symptomatology involving subset completed parent trial. All 16 who were still alive contacted, 15 agreed participate at an average 3.2 4.5 years following administration.Reductions anxiety, depression, hopelessness, demoralization, death anxiety sustained first second follow-ups. Within-group effect sizes large. (4.5 year) approximately met responses. Participants overwhelmingly (71-100%) attributed positive life changes therapy experience rated it among most personally meaningful spiritually experiences their lives.These findings suggest holds promise promoting relief from Limited conclusions, however, can be drawn regarding efficacy this due crossover design study. Nonetheless, adds emerging literature base suggesting psilocybin-facilitated may enhance psychological, emotional, patients life-threatening cancer.

Язык: Английский

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