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Clinical Trial
. 2018 Feb;235(2):399-408.
doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8.

Psilocybin With Psychological Support for Treatment-Resistant Depression: Six-Month Follow-Up

Free PMC article
Clinical Trial

Psilocybin With Psychological Support for Treatment-Resistant Depression: Six-Month Follow-Up

R L Carhart-Harris et al. Psychopharmacology (Berl). .
Free PMC article


Rationale: Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy.

Objectives: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression.

Methods: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure.

Results: Treatment was generally well tolerated. Relative to baseline, marked reductions in depressive symptoms were observed for the first 5 weeks post-treatment (Cohen's d = 2.2 at week 1 and 2.3 at week 5, both p < 0.001); nine and four patients met the criteria for response and remission at week 5. Results remained positive at 3 and 6 months (Cohen's d = 1.5 and 1.4, respectively, both p < 0.001). No patients sought conventional antidepressant treatment within 5 weeks of psilocybin. Reductions in depressive symptoms at 5 weeks were predicted by the quality of the acute psychedelic experience.

Conclusions: Although limited conclusions can be drawn about treatment efficacy from open-label trials, tolerability was good, effect sizes large and symptom improvements appeared rapidly after just two psilocybin treatment sessions and remained significant 6 months post-treatment in a treatment-resistant cohort. Psilocybin represents a promising paradigm for unresponsive depression that warrants further research in double-blind randomised control trials.

Keywords: 5-HT2AR; Depression; Hallucinogen; Mood; Psilocybin; Psychedelic; Psychotherapy; Serotonin; Treatment-resistant depression.

Conflict of interest statement

The authors declare that they have no conflict of interest.


Fig. 1
Fig. 1
Depression severity vs time: depression severity determined by the primary outcome measure, self-rated QIDS-SR16. Mean values were calculated for the 19 completers. Data are shown for the QIDS scores of 16–20 considered to reflect severe depression. All post-treatment assessments were obtained after the high-dose session, i.e. 1-week post-treatment refers to 1 week after the 25-mg psilocybin dose. Mean values are represented by the black horizontal bars with positive standard errors also included. Cohen’s d values vs baseline are shown in red, all contrasts vs baseline yielded p values of < 0.001 with the exception of the 6 month contrast which was p = 0.0035. Patient 17’s data is not included in the chart due to absent data points at 1 week to 4 months; however, his baseline and 6-month data is included in the text contained in “Results” section and retrospective ratings for 1 and 3 weeks post-treatment were also obtained and are reported in the text only
Fig. 2
Fig. 2
Acute ‘insight’ measured by the ‘insightfulness’ factor of the 11D-ASC rated in the evening after the 25-mg psilocybin experience correlated significantly with reductions in depressive symptoms 5 weeks later (r = − 0.57, p = 0.01, two-tailed)

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