Enduring changes in personality/attitudes , depression , spirituality , anxiety , wellbeing , substance misuse , meditative practice s , and mindfulness were documented .
Mystical experiences , connectedness , emotional breakthrough , and increased neural entropy were related to these long-term changes in psychological functioning .
Finally , with proper screening , preparation , supervision , and integration , limited aversive side effects were noted by study participants .
Research into the basic effects and therapeutic applications of  psychedelic drugs  has grown considerably in recent years .
Yet , pressing questions remain regarding the substances ' lasting effects .
Although individual studies have begun monitoring sustained changes , no study to- date has synthesized this information .
Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study.
BACKGROUND Psilocybin is a serotonin receptor agonist that occurs naturally in some mushroom species . Recent studies have assessed the therapeutic potential of psilocybin for various conditions , including end-of-life anxiety , obsessive-compulsive disorder , and smoking and alcohol dependence , with promising preliminary results . Here , we aim ed to investigate the feasibility , safety , and efficacy of psilocybin in patients with unipolar treatment-resistant depression . METHODS In this open-label feasibility trial , 12 patients ( six men , six women ) with moderate-to-severe , unipolar , treatment-resistant major depression received two oral doses of psilocybin ( 10 mg and 25 mg , 7 days apart ) in a supportive setting . There was no control group . Psychological support was provided before , during , and after each session . The primary outcome measure for feasibility was patient-reported intensity of psilocybin 's effects . Patients were monitored for adverse reactions during the dosing sessions and subsequent clinic and remote follow-up . Depressive symptoms were assessed with st and ard assessment s from 1 week to 3 months after treatment , with the 16-item Quick Inventory of Depressive Symptoms ( QIDS ) serving as the primary efficacy outcome . This trial is registered with IS RCT N , number IS RCT N14426797 . FINDINGS Psilocybin 's  acute psychedelic effects typically became detectable 30 - 60 min after dosing , peaked 2 - 3 h after dosing , and subsided to negligible levels at least 6 h after dosing . Mean self-rated intensity ( on a 0 - 1 scale ) was 0·51 ( SD 0·36 ) for the low-dose session and 0·75 ( SD 0·27 ) for the high-dose session . Psilocybin was well tolerated by all of the patients , and no serious or unexpected adverse events occurred . The adverse reactions we noted were transient anxiety during drug onset ( all patients ) , transient confusion or thought disorder ( nine patients ) , mild and transient nausea ( four patients ) , and transient headache ( four patients ) . Relative to baseline , depressive symptoms were markedly reduced 1 week ( mean QIDS difference -11·8 , 95 % CI -9·15 to -14·35 , p=0·002 , Hedges ' g=3·1 ) and 3 months ( -9·2 , 95 % CI -5·69 to -12·71 , p=0·003 , Hedges ' g=2 ) after high-dose treatment . Marked and sustained improvements in anxiety and anhedonia were also noted . INTERPRETATION This study provides preliminary support for the safety and efficacy of psilocybin for treatment-resistant depression and motivates further trials , with more rigorous design s , to better examine the therapeutic potential of this approach . FUNDING Medical Research Council
Enduring changes in personality/attitudes , depression , spirituality , anxiety , wellbeing , substance misuse , meditative practice s , and mindfulness were documented .
Mystical experiences , connectedness , emotional breakthrough , and increased neural entropy were related to these long-term changes in psychological functioning .
Finally , with proper screening , preparation , supervision , and integration , limited aversive side effects were noted by study participants .
Research into the basic effects and therapeutic applications of  psychedelic drugs  has grown considerably in recent years .
Yet , pressing questions remain regarding the substances ' lasting effects .
Although individual studies have begun monitoring sustained changes , no study to- date has synthesized this information .