The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index; 18 of the 30 sources its claims cite were checked for support.
Single-Dose Psilocybin Treatment for Major Depressive Disorder: A Randomized Clinical Trial
Open accessAbstract
Importance: Psilocybin shows promise as a treatment for major depressive disorder (MDD). Objective: To evaluate the magnitude, timing, and durability of antidepressant effects and safety of a single dose of psilocybin in patients with MDD. Design, Setting, and Participants: In this phase 2 trial conducted between December 2019 and June 2022 at 11 research sites in the US, participants were randomized in a 1:1 ratio to receive a single dose of psilocybin vs niacin placebo administered with psychological support. Participants were adults aged 21 to 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of MDD of at least 60 days' duration and moderate or greater symptom severity. Exclusion criteria included history of psychosis or mania, active substance use disorder, and active suicidal ideation with intent. Participants taking psychotropic agents who otherwise met inclusion/exclusion criteria were eligible following medication taper. Primary and secondary outcomes and adverse events (AEs) were assessed at baseline (conducted within 7 days before dosing) and at 2, 8, 15, 29, and 43 days after dosing. Interventions: Interventions were a 25-mg dose of synthetic psilocybin or a 100-mg dose of niacin in identical-appearing capsules, each administered with psychological support. Main Outcomes and Measures: The primary outcome was change in central rater-assessed Montgomery-Asberg Depression Rating Scale (MADRS) score (range, 0-60; higher scores indicate more severe depression) from baseline to day 43. The key secondary outcome measure was change in MADRS score from baseline to day 8. Other secondary outcomes were change in Sheehan Disability Scale score from baseline to day 43 and MADRS-defined sustained response and remission. Participants, study site personnel, study sponsor, outcome assessors (raters), and statisticians were blinded to treatment assignment. Results: A total of 104 participants (mean [SD] age, 41.1 [11.3] years; 52 [50%] women) were randomized (51 to the psilocybin group and 53 to the niacin group). Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3 [95% CI, -17.5 to -7.2]; P <.001) and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001). Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11]; P < .001) from baseline to day 43. More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin. There were no serious treatment-emergent AEs; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs. Conclusions and Relevance: Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events. These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD. Trial Registration: ClinicalTrials.gov Identifier: NCT03866174.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
45 Own result · 17 Own method · 8 Partly supported · 5 Own interpretation · 4 No full text of the sources · 3 Supported so far · 3 Couldn’t confirm · 2 No basis given · 1 Sources not found · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Psilocybin shows promise as a treatment for major depressive disorder (MDD).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
What the sources say
- Partly supportedcites [6] 6. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12): 1181-1197. doi:10.1177/0269881116675513 sourceExperimental — accuracy not yet measured
The Abstract reports substantial, sustained decreases in depressed mood after psilocybin, and Methods > Study participants says 18 of the 51 patients had an MDD diagnosis, including four also diagnosed with generalized anxiety disorder. But the results concern a mixed group of patients with life-threatening cancer and do not establish the effect specifically for MDD patients or for MDD more generally. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [7] 7. Agin-Liebes GI, Malone T, Yalch MM, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020;34(2):155-166. doi:10.1177/ 0269881119897615 source
- Partly supportedcites [8] 8. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12): 1165-1180. doi:10.1177/0269881116675512 sourceExperimental — accuracy not yet measured
The Discussion (Primary outcomes; page unavailable) reports sustained reductions in depression symptoms among patients with life-threatening cancer and cites a separate open-label study in treatment-resistant depression. This supports the cautious phrase “shows promise,” but this trial did not test psilocybin as a treatment for MDD specifically; its participants had cancer-related distress and anxiety-related diagnoses (Methods, Study sample and setting; page unavailable). (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Nonetheless, placebo response rates in the current study are smaller than are typically observed with daily placebo pills, 34 which may have inflated the placebo-adjusted effect size compared with studies of standard antidepressants in patients with MDD.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Could not verifycites [34] 34. Williams MT, Reed S, Aggarwal R. Culturally informed research design issues in a study of MDMA-assisted psychotherapy for posttraumatic stress disorder. J Psychedelic Stud. 2019;4(1):40-50. doi:10.1556/2054.2019.016 sourceExperimental — accuracy not yet measured
The Introduction contrasts MDMA given 2–3 times with medications often taken daily, but it does not compare placebo response rates. Searches for daily placebo pills, MDD, and placebo-adjusted effect size found no passage addressing the cited claim that placebo responses were smaller than those typically observed with daily pills. (LLM, conf=0.76)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The 8% rate of severe adverse events in participants receiving psilocybin was similar to the 10% rate reported in the study by Goodwin et al in participants with TRD treated with a single 25-mg dose of psilocybin.14”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
What the sources say
- Partly supportedcites [14] 14. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387(18):1637-1648. doi:10.1056/NEJMoa2206443 sourceExperimental — accuracy not yet measured
The Safety section reports severe adverse events in 9% of the 25-mg group from day 2 through week 3, but does not report the claimed 10% rate. Table 3 also gives separate rates of 4% on day 1 and 3% after week 3; these interval-specific rates do not establish a 10% overall rate. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“First, the success of allocation blinding was not assessed, and it is likely that the acute psychoactive effects of psilocybin produced some degree of functional unblinding that may have contributed to the observed effect in psilocybin-treated (psilocybin -niacin).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Partly supportedcites [33] 33. Michaels TI, Purdon J, Collins A, Williams MT. Inclusion of people of color in psychedelic-assisted psychotherapy: a review of the literature. BMC Psychiatry. 2018;18(1):245. doi:10.1186/s12888-018- 1824-6 sourceExperimental — accuracy not yet measured
The Results > Study methodologies section says that finding a placebo that mimics psychedelics’ physiological effects is an important issue for double-blinded trials. That supports a general concern about blinding, but the paper does not say that psilocybin caused functional unblinding in the psilocybin–niacin comparison or that unblinding contributed to its observed effect. No page number is available in our copy. (LLM, conf=0.78)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Nonetheless, placebo response rates in the current study are smaller than are typically observed with daily placebo pills, 34 which may have inflated the placebo-adjusted effect size compared with studies of standard antidepressants in patients with MDD.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Could not verifycites [34] 34. Williams MT, Reed S, Aggarwal R. Culturally informed research design issues in a study of MDMA-assisted psychotherapy for posttraumatic stress disorder. J Psychedelic Stud. 2019;4(1):40-50. doi:10.1556/2054.2019.016 sourceExperimental — accuracy not yet measured
The Introduction describes MDMA-assisted psychotherapy for PTSD and contrasts its dosing schedule with medications taken daily, but it does not compare placebo response rates. Searches of our copy for daily placebo pills and placebo-adjusted effects found no passage addressing the claimed comparison. (LLM, conf=0.76)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Could not verify
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and from baseline to day 8 (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001).”
- Also stated in: § Efficacy · plain
“and from baseline to day 8 (key secondary end point) (mean difference, -12.0 [95% CI, -16.6 to -7.4]; P < .001).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelationaln = 104 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Efficacy · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There were no serious treatment-emergent AEs”
- Also stated in: § Discussion · plain
“No serious TEAEs were reported in the current study”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plainn = 104- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“More participants receiving psilocybin than niacin had sustained depressive symptom response (20/48 [42%] vs 5/44 [11%]; adjusted absolute difference, 30.3 [95% CI, 13.5-47.1];P = .002;OR, 5.6 [95% CI, 1.9-16.7];P = .002)”
- Also stated in: § Abstract · plain
“More participants receiving psilocybin had sustained response (but not remission) than those receiving niacin.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and a higher rate of severe AEs.”
- Also stated in: § Safety · plain
“Severe related AEs through day 9 were reported by 4 of 50 participants (8%) receiving psilocybin (migraine in 1 participant, headache in 1 participant, illusion in 1 participant [all solicited], and panic attack and paranoia in 1 participant) vs 0 in the niacin group.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Safety · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Psilocybin treatment was also associated with significantly reduced Sheehan Disability Scale scores compared with niacin (mean difference, -2.31 [95% CI, 3.50-1.11];P < .001)from baseline to day 43.”
- Also stated in: § Efficacy · plain
“Mean change difference in SDSassessed functional disability score from baseline to day 43 was greater in the psilocybin vs niacin group (-2.31 [95% CI, 3.50-1.11];P < .001)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelationaln = 104 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Efficacy · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Psilocybin treatment was associated with significantly reduced MADRS scores compared with niacin from baseline to day 43 (mean difference,-12.3[95% CI, -17.5 to -7.2]; P <.001)”
- Also stated in: § Efficacy · plain
“The psilocybin-treated group showed greater change vs niacin in central rater-assessed MADRS score from baseline to day 43 (mean difference, -12.3 [95% CI, -17.5 to -7.2]; P <.001)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelationaln = 104- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Efficacy · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“psilocybin treatment was associated with a higher rate of overall AEs”
- Also stated in: § Safety · plain
“44 of 50 participants (88%) receiving psilocybin and 33 of 54 (61%) receiving niacin reported at least 1 AE through day 43.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Safety · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sustained depressive symptom | 20/48 (41.7) | 5/44 (11.4) | 30.3 (13.5 to 47.1) g | .002 c,d”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No serious TEAEs occurred during the study, but psilocybin treatment was associated with an increase rate of overall, solicited, and severe TEAEs, most of which occurred during or immediately after the dosing period.”
- Also stated in: § Conclusions · plain
“At least 1 solicited AE d | 38 (76) | 16 (30) | 38 (76) | 16 (30) | 46 (29.4 to 63.4) | | | NC”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Conclusions · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No clinically significant changes in vital signs or clinical laboratory tests were observed.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Headache e | 33 (66) | 13 (24) | 33 (66) | 13 (24) | 42 (27.3 to 57.6) NA | NA | NA |”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Visual perceptual | 22 (44) | 3 (6) | 22 (44) | 3 (6) | 38 (23.4 to 53.5) NA | NA | NA |”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The current study sample was predominantly White, non-Hispanic, and from upper socioeconomic echelons.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At least 1 related AE c | 41 (82) | 24 (44) | 41 (82) | 24 (44) | 38 (20.6 to 54.6) 2 (4) | 1 (2) | 2 (-4.4 to 8.7) |”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were observed for day 15 and day 29 (Figure 2)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sustained depressive symptom | 12/48 (25.0) | 4/44 (9.1) | 15.9 (1.0 to 30.8) i | .05 d”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The majority of solicited events were mild (73 of 91 total events [80%] in the psilocybin group and 22 of 23 total events [96%] in the niacin group).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At least 1 AE | 44 (88) | 33 (61) | 42 (84) | 32 (59) | 25 (8.2 to 41.3) | 18 (36) | 13 (25) | 11 (-6.2 to 29.1)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Nausea e | 24 (48) | 3 (6) | 24 (48) | 3 (6) | 42 (24.5 to 59.3) NA | NA | NA |”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Severe related AEs through day 9 were reported by 4 of 50 participants (8%) receiving psilocybin (migraine in 1 participant, headache in 1 participant, illusion in 1 participant [all solicited], and panic attack and paranoia in 1 participant) vs 0 in the niacin group.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Solicited AEs were reported by 38 of 50 participants (76%) receiving psilocybin vs 16 of 54 (30%) receiving niacin (difference, 46% [95% CI, 29.4%-63.4%];RI, 2.6 [95% CI, 1.7-4.0]).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No serious TEAEs occurred during the study, but psilocybin treatment was associated with an increase rate of overall, solicited, and severe TEAEs, most of which occurred during or immediately after the dosing period.”
- Also stated in: § Conclusions · plain
“At least 1 AE | 44 (88) | 33 (61) | 42 (84) | 32 (59) | 25 (8.2 to 41.3) | 18 (36) | 13 (25) | 11 (-6.2 to 29.1)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Conclusions · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“At least 1 solicited AE d | 38 (76) | 16 (30) | 38 (76) | 16 (30) | 46 (29.4 to 63.4) | | | NC”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No serious TEAEs occurred during the study, but psilocybin treatment was associated with an increase rate of overall, solicited, and severe TEAEs, most of which occurred during or immediately after the dosing period.”
- Also stated in: § Conclusions · plain
“Severe | 4 (8) | | 4 (8) | | NC | 1 (2) | | NC”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Conclusions · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this randomized trial, a single 25-mg dose of psilocybin administered with psychosocial support was associated with clinically and statistically significant reductions in depressive symptoms and improvement in measures of functional disability compared with a 100-mg dose of niacin placebo administered under an identical protocol.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The most common solicited AE was headache in 33 of 50 participants (66%) receiving psilocybin and 13 of 54 participants (24%) receiving niacin (difference, 42% [95% CI, 27.3%-57.6%];RI, 2.7 [95% CI, 1.6-4.6])”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“44 of 50 participants (88%) receiving psilocybin and 33 of 54 (61%) receiving niacin reported at least 1 AE through day 43.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No serious TEAEs occurred during the study, but psilocybin treatment was associated with an increase rate of overall, solicited, and severe TEAEs, most of which occurred during or immediately after the dosing period.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Day 8 (key secondary outcome) | -17.8 (-21.1 to -14.6) | -5.8 (-9.1 to -2.6) | -12.0 (-16.6 to -7.4) | <.001 c”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaindirectn = 51 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“followed by nausea in 24 of 50 participants (48%) receiving psilocybin and 3 of 54 participants (6%) receiving niacin (difference, 42% [95% CI, 24.5%-59.3%];RI, 8.6 [95% CI, 2.8-26.9]).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Day 43 (primary outcome) | -19.1 (-22.7 to -15.5) | -6.8 (-10.5 to -3.1) | -12.3 (-17.5 to -7.2) | <.001 c”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From day 10 through day 43, related TEAEs were reported by 2 of 50 participants (4%) in the psilocybin group vs 1 of 53 (2%) receiving niacin (difference, 2% [95% CI, -4.4% to 8.7%]; RI, 2.1 [95% CI, 0.2-22.7])(Table 3).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“One participant receiving psilocybin and 5 in the niacin group had an increase in C-SSRS suicidal ideation score from baseline to end of trial”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From randomization on the day of dosing (day 1) through day 9, a total of 41 of 50 participants (82%) in the psilocybin group experienced at least 1 drug-related TEAE vs 24 of 54 (44%) in the niacin group (difference, 38% [95% CI, 20.6%-41.3%];relative incidence [RI], 1.8 [95% CI, 1.3-1.8]).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plaincorrelationaln = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No serious TEAEs occurred during the study, but psilocybin treatment was associated with an increase rate of overall, solicited, and severe TEAEs, most of which occurred during or immediately after the dosing period.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In this randomized trial, a single 25-mg dose of psilocybin administered with psychosocial support was associated with clinically and statistically significant reductions in depressive symptoms and improvement in measures of functional disability compared with a 100-mg dose of niacin placebo administered under an identical protocol.”
- Also stated in: § Conclusions · plain
“Day 43 (secondary outcome) | -4.07 (-4.88 to -3.26) | -1.76 (-2.62 to -0.91) | -2.31 (-3.50 to -1.11) | <.001 c”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
- Also stated in: § Conclusions · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, in contradistinction to the study by Goodwin et al, no clinically confirmed active suicidal ideation or suicidal behavior occurred in either randomized group.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Day 43 (secondary outcome) | -4.07 (-4.88 to -3.26) | -1.76 (-2.62 to -0.91) | -2.31 (-3.50 to -1.11) | <.001 c”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
In the paper
“Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events.”
- Also stated in: § Discussion · plain
“treatment with a 25-mg dose of psilocybin administered with psychological support was associated with a statistically and clinically significant reduction in depressive symptoms compared with a niacin placebo, assessed as change in total MADRS score and as rates of sustained response.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
What the sources say
- Not checked — no full text of the sourcecites [25] 25. Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression. BMJ Evid Based Med. 2022;27(2):69-73. doi:10.1136/ bmjebm-2020-111600 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Discussion · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings add to increasing evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Psilocybin treatment was associated with a clinically significant sustained reduction in depressive symptoms and functional disability, without serious adverse events.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the 19.1-point reduction in MADRS score from baseline to day 43 in the psilocybin group is larger than the 12-point difference shown to reflect substantial clinical improvement in patients with TRD. 25”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
What the sources say
- Not checked — no full text of the sourcecites [25] 25. Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression. BMJ Evid Based Med. 2022;27(2):69-73. doi:10.1136/ bmjebm-2020-111600 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Fourth, that psilocybin and niacin were administered within an identical, fully protocolized program of psychological support is a strength of the current study.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To reduce the risk of functional unblinding of raters, all MADRS assessments, including those at screening and baseline, were conducted via telephone 27,28 by trained, remote central raters who maintained interrater reliability and were blinded to participant treatment assignment, study visit, and the specifics of the protocol and study design.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy Assessments
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Fifth, as with the majority of recent clinical trials of psychedelics, 35 a major limitation of the current study is a lack of participant ethnic and racial diversity.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Not matchedcites [35]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Not matched
In the paper
“the 12.3-point difference in change in score between the psilocybin and niacin groups is larger than the upper limit active placebo difference in the literature of 9 points”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
What the sources say
- Not checked — no full text of the sourcecites [25] 25. Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression. BMJ Evid Based Med. 2022;27(2):69-73. doi:10.1136/ bmjebm-2020-111600 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This may reflect the fact that to maintain central rater blinding, the 7-day recall period used for all other MADRS assessments was maintained at day 2, with the result that the majority of recall period for the day 2 assessment covered the predosing period during which depressive symptoms remained elevated”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings add to evidence that psilocybin-when administered with psychological support-may hold promise as a novel intervention for MDD.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No participants withdrew due to an AE.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Similar results were observed for day 15 and day 29 (Figure 2) and in multiple imputation sensitivity analyses accounting for missing data”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy
plainn = 9- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, the success of allocation blinding was not assessed, and it is likely that the acute psychoactive effects of psilocybin produced some degree of functional unblinding that may have contributed to the observed effect in psilocybin-treated (psilocybin -niacin).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 21
- Probably not a substantial claim. 18
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“recent critiques highlight notable limitations in many of these studies, [16][17][18][19] including small sample sizes, assessments by raters likely to be functionally unblinded, an open or waitlist comparator design, and an inadequate assessment of adverse events (AEs).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
What the sources say
- Partly supportedcites [16] 16. Hall WD, Humphreys K. Is good science leading the way in the therapeutic use of psychedelic drugs? Psychol Med. 2022;52(14):2849-2851. doi: 10.1017/S0033291722003191 sourceExperimental — accuracy not yet measured
In “Lowering of standards by major medical journals” (page unavailable), the paper describes a psilocybin trial with 30 and 29 patients in its two arms, calls it underpowered, and questions whether participants remained blinded. It does not say that outcome raters were functionally unblinded or that the studies used open or waitlist comparators or inadequately assessed adverse events. The trial it discusses used escitalopram as its comparator. (LLM, conf=0.87)
- Partly supportedcites [17] 17. Breeksema JJ, Kuin BW, Kamphuis J, van den Brink W, Vermetten E, Schoevers RA. Adverse events in clinical treatments with serotonergic psychedelics and MDMA: a mixed-methods systematic review. J Psychopharmacol. 2022;36(10):1100-1117. doi:10. 1177/02698811221116926 sourceExperimental — accuracy not yet measured
The Discussion > Limitations section (page unavailable) says the included studies were mostly small and that few assessed adverse events systematically. The Psilocybin section identifies open-label studies, and the Limitations section notes difficulty blinding participants. Our copy does not establish that outcome raters were functionally unblinded or that studies used waitlist comparators. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [18] 18. Yaden DB, Potash JB, Griffiths RR. Preparing for the bursting of the psychedelic hype bubble. JAMA Psychiatry. 2022;79(10):943-944. doi:10.1001/ jamapsychiatry.2022.2546 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Larger recent studies have addressed these issues to various degrees, but report primary end points of short duration, 14,15 leaving open the question of the long-term clinical utility of psilocybin for an often chronic condition such as MDD.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
What the sources say
- Supportedcites [14] 14. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387(18):1637-1648. doi:10.1056/NEJMoa2206443 source
The Discussion says this trial addressed limitations of earlier studies and had a primary end point at 3 weeks, despite 12 weeks of follow-up. The Abstract says larger and longer trials are needed to determine psilocybin’s efficacy and safety for treatment-resistant depression, supporting the claim that its longer-term clinical utility remains open. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [15] 15. von Rotz R, Schindowski EM, Jungwirth J, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine. 2022;56:101809. doi:10.1016/j. eclinm.2022.101809 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“recent studies suggesting that psilocybin engenders a rapid antidepressant response that far outlasts the presence of the drug in the body.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Abstract
What the sources say
- Partly supportedcites [6] 6. Griffiths RR, Johnson MW, Carducci MA, et al. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: a randomized double-blind trial. J Psychopharmacol. 2016;30(12): 1181-1197. doi:10.1177/0269881116675513 sourceExperimental — accuracy not yet measured
The Results (Outcome measures; page unavailable) report a substantial antidepressant response in patients with life-threatening cancer at five weeks, sustained at six months. The Methods (Outcome measures; page unavailable) say the subjective drug effects had subsided by seven hours, supporting that the benefit outlasted the acute effects. But depression was first assessed five weeks after dosing, so this study does not establish how rapidly the antidepressant response began or when the drug left the body. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [7] 7. Agin-Liebes GI, Malone T, Yalch MM, et al. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020;34(2):155-166. doi:10.1177/ 0269881119897615 source
- Partly supportedcites [8] 8. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12): 1165-1180. doi:10.1177/0269881116675512 sourceExperimental — accuracy not yet measured
The Discussion (Primary outcomes) reports immediate antidepressant effects lasting weeks to months after a single psilocybin dose, given with psychotherapy to patients with life-threatening cancer. The paper does not establish how long the drug remains in the body, so the comparison with its bodily presence is not directly supported. (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“First, the success of allocation blinding was not assessed, and it is likely that the acute psychoactive effects of psilocybin produced some degree of functional unblinding that may have contributed to the observed effect in psilocybin-treated (psilocybin -niacin).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Partly supportedcites [33] 33. Michaels TI, Purdon J, Collins A, Williams MT. Inclusion of people of color in psychedelic-assisted psychotherapy: a review of the literature. BMC Psychiatry. 2018;18(1):245. doi:10.1186/s12888-018- 1824-6 sourceExperimental — accuracy not yet measured
The Results > Study methodologies section (page unavailable) says that a placebo must mimic psychedelic effects for a double-blinded trial, supporting the general concern about blinding. It does not report functional unblinding in a psilocybin–niacin comparison or link it to treatment effects or niacin-group dropout. (LLM, conf=0.82)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one. The quote only partly states this claim.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Niacin was used as an active placebo that produces an acute physiological response (flushing) thought to aid in blinding.8,22”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Study Procedures
What the sources say
- Partly supportedcites [8] 8. Ross S, Bossis A, Guss J, et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12): 1165-1180. doi:10.1177/0269881116675512 sourceExperimental — accuracy not yet measured
The Methods section (Study design and interventions; page unavailable) identifies niacin as the active control in a double-blind psilocybin trial. Our copy does not state that niacin caused flushing or that this physiological response was intended to aid blinding; the section refers readers to supplementary blinding procedures without describing them. (LLM, conf=0.84)
- Could not verifycites [22] 22. Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008;22(6):603-620. doi:10. 1177/0269881108093587 sourceExperimental — accuracy not yet measured
The Preparation of volunteers section discusses blinding and an active placebo, but identifies that placebo as methylphenidate. Searches for niacin and flushing found no passage in our copy addressing niacin’s use, its physiological response, or whether it aided blinding. (LLM, conf=0.72)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Second, the use of niacin as active placebo may have increased believability of the comparator condition and enhanced the placebo response, given that placebo response rates in the current study were equivalent to those seen in response to a low-dose psilocybin comparator in participants with TRD and larger than the effect of an inactive placebo in a recent study in participants with MDD.14,15”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Supportedcites [14] 14. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387(18):1637-1648. doi:10.1056/NEJMoa2206443 source
The Efficacy section reports an 18% response rate at week 3 in the 1-mg psilocybin comparator group among participants with treatment-resistant depression. That supports the low-dose comparator figure used in the citing paper's comparison; this source is not offered as evidence for the citing study's own placebo rate or the separate MDD study. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [15] 15. von Rotz R, Schindowski EM, Jungwirth J, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine. 2022;56:101809. doi:10.1016/j. eclinm.2022.101809 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Niacin 100 mg is an inactive placebo with no antidepressant effect.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“No serious TEAEs were reported in the current study; however, psilocybin treatment was associated with a higher rate of overall AEs and a higher rate of severe AEs compared with niacin, with these severe AEs being known effects of psilocybin.17”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
What the sources say
- Partly supportedcites [17] 17. Breeksema JJ, Kuin BW, Kamphuis J, van den Brink W, Vermetten E, Schoevers RA. Adverse events in clinical treatments with serotonergic psychedelics and MDMA: a mixed-methods systematic review. J Psychopharmacol. 2022;36(10):1100-1117. doi:10. 1177/02698811221116926 sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“Moreover, psychedelics may produce AEs not captured by standard rating scales or may induce unrecognized new psychiatric conditions even as they improve target syndromes.32”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
What the sources say
- Could not verifycites [32] 32. Jones BDM, Razza LB, Weissman CR, et al. Magnitude of the placebo response across treatment modalities used for treatment-resistant depression in adults: a systematic review and meta-analysis. JAMA Netw Open. 2021;4(9):e2125531. doi:10.1001/jamanetworkopen.2021.25531 sourceExperimental — accuracy not yet measured
The Results (page not provided) list an ayahuasca trial and the depression rating scale it used, but do not discuss psychedelic adverse events or new psychiatric conditions. A search of our copy for those risks and for limitations of standard rating scales found no passage addressing the claim. (LLM, conf=0.76)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Second, the use of niacin as active placebo may have increased believability of the comparator condition and enhanced the placebo response, given that placebo response rates in the current study were equivalent to those seen in response to a low-dose psilocybin comparator in participants with TRD and larger than the effect of an inactive placebo in a recent study in participants with MDD.14,15”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
What the sources say
- Supportedcites [14] 14. Goodwin GM, Aaronson ST, Alvarez O, et al. Single-dose psilocybin for a treatment-resistant episode of major depression. N Engl J Med. 2022; 387(18):1637-1648. doi:10.1056/NEJMoa2206443 source
The citation supports the comparison to a low-dose psilocybin group in participants with treatment-resistant depression: the Efficacy section reports an 18% response rate at week 3 in the 1-mg group. The suggestion that niacin increased comparator believability and placebo response is the citing authors’ own explanation, not a finding attributed to this paper. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [15] 15. von Rotz R, Schindowski EM, Jungwirth J, et al. Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial. EClinicalMedicine. 2022;56:101809. doi:10.1016/j. eclinm.2022.101809 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Sustained depressive symptom remission rate appeared greater with psilocybin, but the difference was not statistically significant (12/48 [25%] for psilocybin vs 4/44 [9.1%] for niacin; adjusted absolute difference, 15.9 [95% CI, 1.0-30.8];P = .05;OR, 3.4 [95% CI, 1.0-11.5])”
- Also stated in: § Discussion · plain
“The 15.9% difference in sustained remission rates between the groups was not significantly different.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Among 1529 potential participants who completed prescreening, 347 signed informed consent, 240 were excluded at screening, 3 were excluded prior to randomization, and 104 were randomized, received the study drug, and comprised the ITT population (51 in the psilocybin group and 53 in the niacin group)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Participants
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The rates of mild and moderate drug-related TEAEs in the same period were higher for psilocybin vs niacin (mild: difference, 35% [95% CI, 17.9%-52.9%];RI, 1.8 [95% CI, 1.1-1.8]);moderate: difference, 18% [95% CI, 5.8%-30.8%];RI, 2.3 [95% CI, 1.0-5.7]).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Visual perceptual effects (assessed following resolution of acute drug effects) were reported by 22/50 (44%) psilocybin participants on the day of dosing and by 3/50 (6%) after the dosing day, all resolved by study conclusion”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 50- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on C-SSRS or MADRS Item 10 scores and confirmed by clinical assessment, no suicidal or self-injurious behavior occurred during the trial and all instances of suicidal ideation were considered passive.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Psilocybin treatment was associated with improvements in various exploratory end points, including reductions in global disease severity, self-reported depressive and anxiety symptoms, and improvement in quality of life, while having no effect on emotional blunting”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Three serious AEs occurred between enrollment and randomization (nephrolithiasis; incisional hernia, obstructive; and appendicitis; Table 3).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Severe solicited events were reported by 3 participants receiving psilocybin (2 headaches and 1 visual perceptual effects) and 1 headache was reported in a participant receiving niacin.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
plainn = 3- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In contrast to prior psilocybin trials for depression, 8,14,15 there was not a significant reduction in depressive symptoms or a psilocybin/ placebo difference in depressive symptom status at the day 2 assessment (ie, 1 day after dosing)”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomization was administered centrally by the study's clinical research organization via the Advantage eClinical data system.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Study Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“One participant randomized to receive psilocybin received the incorrect treatment, resulting in 50 participants receiving psilocybin and 54 receiving niacin.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Participants
plaindirectSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The primary efficacy analysis was a de facto estimand conducted on the intent-to-treat (ITT) population that included all randomized participants analyzed according to randomized treatment group.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“By 6 weeks, 1 participant in the psilocybin group and 9 in the niacin group had withdrawn or been lost to followup”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Participants
plainSingle case- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Psilocybin was generally well-tolerated, with most AEs being of mild or moderate severity and generally limited to the acute dosing period.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“No procedure for α-level control was applied for exploratory end points, therefore P values reported for these outcomes in eTables 4-8 in Supplement 3 should be considered nominal (ie, not adjusted for multiple comparisons).”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Participants, study sponsor, and study site personnel were blinded to treatment group until unblinding following data lock.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Study Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Similarly, the current study does not allow inferences to be drawn regarding whether the antidepressant effect would have diminished over subsequent weeks or been maintained”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“a sample size of 100 participants resulted in 92% power for the primary day 43 end point and 98% power for the key secondary day 8 end point.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Statistical Analysis
plainn = 100- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“A minimal clinically important difference (MCID) in change in MADRS score was not prespecified, although depression trial literature supports a placebo-adjusted change in score as low as 2 and as high as 9 and an absolute change from pretreatment of 6 as clinically meaningful and a change of 12 as clinically substantial.25,26”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Efficacy Assessments
What the sources say
- Not checked — no full text of the sourcecites [25] 25. Hengartner MP, Plöderl M. Estimates of the minimal important difference to evaluate the clinical significance of antidepressants in the acute treatment of moderate-to-severe depression. BMJ Evid Based Med. 2022;27(2):69-73. doi:10.1136/ bmjebm-2020-111600 source
- Not checked — no full text of the sourcecites [26] 26. Kobak KA, Williams JB, Jeglic E, Salvucci D, Sharp IR. Face-to-face versus remote administration of the Montgomery-Asberg Depression Rating Scale using videoconference and telephone. Depress Anxiety. 2008;25(11):913-919. doi:10.1002/da.20392 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“eligible participants were randomized in a 1:1 ratio using permuted blocks with random block sizes of 2, 4, and 6, with randomization stratified by site”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Study Procedures
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To help address this issue, the current study used off-site centralized raters to reduce the potential impact of unblinding on the assessment of outcomes.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Limitations
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“A sequential significance testing procedure was used to control the overall α level at .05 for primary and secondary end points.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Sensitivity analyses using multiple imputation methods were run for the primary and key secondary outcomes.”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Statistical Analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Niacin 100 mg is an inactive placebo with no antidepressant effect.
“compared with a 100-mg dose of niacin placebo administered under an identical protocol.”
“the use of niacin as active placebo may have increased believability of the comparator condition and enhanced the placebo response”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“In some instances, control groups consisted of waiting lists rather than active comparators, 60,73 and therapeutic settings were sometimes not consistently provided. 74,76”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [76]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Blinding procedures were not consistently robust, 26,32,60,72-76 and comparison with placebo or standard treatments was lacking in many studies. 25,26,31-33,39,57,60,72,73,75-81”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [76]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Research on MDD, anxiety and depressive symptoms associated with life-threatening cancer, and TRD showed the most robust evidence, supported by a non-randomized study 72 and several RCTs. 26,31-33,60,73-77”
From The revival of psilocybin between scientific excitement, evidence of efficacy, and real-world challenges (2024) · cites this paper as [76]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Safety
“difference, 38% [95% CI, 20.6%-41.3%]”
§ Single-Dose Psilocybin Treatment for Major Depressive Disorder A Randomized Clinical Trial > Conclusions
“| At least 1 related AE c | 41 (82) | 24 (44) | 41 (82) | 24 (44) | 38 (20.6 to 54.6) 2 (4) | 1 (2) | 2 (-4.4 to 8.7) | |”
Citations
Cites
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962
Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116675513 · Cited by 2,201
Self-citationRoss, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., et al. (2016) · Journal of Psychopharmacology · doi:10.1177/0269881116675512 · Cited by 1,698
Self-citationCarhart-Harris, R. L., Bolstridge, M., Rucker, J., Day, C. M. J., Erritzoe, D., Kaelen, M., Bloomfield, M., Rickard, J. A., Forbes, B., Feilding, A., et al. (2016) · The Lancet Psychiatry · doi:10.1016/s2215-0366(16)30065-7 · Cited by 1,540
Sheehan, D. V., Harnett-Sheehan, K., & Raj, B. A. (1996) · International Clinical Psychopharmacology · doi:10.1097/00004850-199606003-00015 · Cited by 1,440
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, D. J. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032994 · Cited by 1,391
Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2020.3285 · Cited by 1,301
Self-citationPilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.116 · Cited by 1,206
Human hallucinogen research: guidelines for safety
Johnson, M., Richards, W., & Griffiths, R. (2008) · Journal of Psychopharmacology · doi:10.1177/0269881108093587 · Cited by 1,203
Self-citationSingle-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression
Goodwin, G. M., Aaronson, S. T., Alvarez, O., Arden, P. C., Baker, A., Bennett, J. C., Bird, C., Blom, R. E., Brennan, C., Brusch, D., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206443 · Cited by 1,167
Self-citation
Cited by
Sorted by citations
Psilocybin desynchronizes the human brain
Siegel, J. S., Subramanian, S., Perry, D., Kay, B. P., Gordon, E. M., Laumann, T. O., Reneau, T. R., Metcalf, N. V., Chacko, R. V., Gratton, C., et al. (2024) · Nature · doi:10.1038/s41586-024-07624-5 · Cited by 308
Self-citationManagement of Depression in Adults: A Review
Simon, G. E., Moise, N., & Mohr, D. C. (2024) · JAMA · doi:10.1001/jama.2024.5756 · Cited by 234
Yao, Y., Guo, D., Lu, T., Liu, F.-L., Huang, S., Diao, M.-Q., Li, S., Zhang, X.-J., Kosten, T. R., Shi, J., et al. (2024) · Psychiatry Research · doi:10.1016/j.psychres.2024.115886 · Cited by 162
“…Goodwin et al., 2023a, 2023b; Hollister et al., 1969; Ludwig et al., 1969; Mitchell et al., 2021, 2023; Mithoefer et al., 2019; Pahnke et al., 1970; Raison et al., 2023; Tomsovic and Edwards, 1970), most of them used small sample sizes with an average of 23.46 participants (SD = 13.30, range = 3…”
InfluentialPsilocybin-assisted therapy for depression: A systematic review and meta-analysis
Haikazian, S., Chen-Li, D. C. J., Johnson, D. E., Fancy, F., Levinta, A., Husain, M. I., Mansur, R. B., McIntyre, R. S., & Rosenblat, J. D. (2023) · Psychiatry Research · doi:10.1016/j.psychres.2023.115531 · Cited by 134
Rosenblat, J. D., Meshkat, S., Doyle, Z., Kaczmarek, E. S., Brudner, R. M., Kratiuk, K., Mansur, R. B., Schulz-Quach, C., Sethi, R., Abate, A., et al. (2024) · Med · doi:10.1016/j.medj.2024.01.005 · Cited by 134
Metadata
- Authors
- Raison, C. L., Sanacora, G., Woolley, J., Heinzerling, K., Dunlop, B. W., Brown, R. T., Kakar, R., Hassman, M., Trivedi, R. P., Robison, R., Gukasyan, N., Nayak, S. M., Hu, X., O’Donnell, K. C., Kelmendi, B., Sloshower, J., Penn, A. D., Bradley, E., Kelly, D. F., Mletzko, T., Nicholas, C. R., Hutson, P. R., Tarpley, G., Utzinger, M., Lenoch, K., Warchol, K., Gapasin, T., Davis, M. C., Nelson-Douthit, C., Wilson, S., Brown, C., Linton, W., Johnson, M. W., Ross, S., & Griffiths, R. R.
- Affiliations
- Usona Institute (US)
- Yale University (US)
- San Francisco VA Medical Center (US)
- Pacific Neuroscience Institute, Santa Monica, California
- Emory University (US)
- University of Wisconsin–Madison (US)
- Center for Psychedelic Research, Segal Trials, Lauderhill, Florida
- Hassman Research Institute (US)
- Flourish Research, Chicago, Illinois
- University of Utah (US)
- Johns Hopkins University (US)
- NYU Langone Health (US)
- University of California, San Francisco (US)
- Usona Institute, Fitchburg, Wisconsin
- Emmes (United States) (US)
- Corresponding author
- Raison, Charles L.
- ORCID
- Raison, Charles L.
- Sanacora, Gerard
- Woolley, Joshua
- Heinzerling, Keith
- Dunlop, Boadie W.
- Brown, Randall T.
- Trivedi, Rupal P.
- Robison, Reid
- Gukasyan, Natalie
- Nayak, Sandeep M.
- O’Donnell, Kelley C.
- Kelmendi, Benjamin
- Sloshower, Jordan
- Penn, Andrew D.
- Bradley, Ellen
- Kelly, Daniel F.
- Mletzko, Tanja
- Nicholas, Christopher R.
- Hutson, Paul R.
- Brown, Carrie
- Johnson, Matthew W.
- Ross, Stephen
- Griffiths, Roland R.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2023-09-05
- Volume
- 330
- Issue
- 9
- Pages
- 843
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC10472268
- OpenAlex
- W4386305655
- Cited by
- 545
- References
- 35
- Citations by year
- 2026: 165 · 2025: 212 · 2024: 152 · 2023: 16
- FWCI
- 158.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR001863)
- National Center for Advancing Translational Sciences
- Topics
- Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- psilocybin, major depressive disorder, antidepressant effects, psychological support, depression remission, sustained response, adverse events, antidepressant safety, psychedelic therapy, Sheehan Disability Scale, Montgomery-Asberg Depression Rating Scale, treatment durability
- MeSH terms
- Adult, Major Depressive Disorder, Female, Hallucinogens, Humans, Male, Mental Health, Niacin, Psilocybin
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
