Psilocybin: End-of-Life Distress
Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial
Methodology: Randomized double-blind cross-over trial. Each participant received a very low placebo-like dose (1 or 3 mg/70 kg) in one session and a high therapeutic dose (22 or 30 mg/70 kg) in another session ~5 weeks later (order randomized). Sessions were conducted in a supportive setting with monitored psychotherapy, and outcomes were assessed up to 6 months.
Sample: Evaluating psilocybin for depression/anxiety in 51 patients with life-threatening cancer.
Dosage: 1 or 3 mg/70 kg and 22 or 30 mg/70 kg
Key Findings:
– The high-dose psilocybin session produced large, immediate reductions in depression and anxiety, alongside increases in quality of life, meaning, and optimism, and decreased death anxiety.
– Impressively, at 6-month follow-up ~80% of participants still showed clinically significant relief from depression and anxiety symptoms. – – Participants attributed positive changes in life attitude, mood, relationships, and spirituality to the psilocybin experience, with >80% reporting increased well-being or life satisfaction.
– Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.
Implications: This landmark RCT demonstrated substantial and sustained anxiolytic and antidepressant effects of a single psilocybin session in distress related to terminal illness.
Citation: Griffiths, R. R., Johnson, M. W., Carducci, M. A., Umbricht, A., Richards, W. A., Richards, B. D., Cosimano, M. P., & Klinedinst, M. A. (2016). Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. Journal of psychopharmacology (Oxford, England), 30(12), 1181–1197. https://doi.org/10.1177/0269881116675513
Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial
Methodology: Randomized double-blind placebo-controlled cross-over trial. Patients received a single moderate dose of psilocybin in one session and a placebo (niacin) in another session (with random order), each combined with preparatory and follow-up psychotherapy. Symptoms of anxiety and depression were measured at 7 weeks (prior to crossover) and again long-term.
Sample: Focused on cancer-related existential distress in 29 patients.
Dosage: 0.3 mg/kg of psilocybin
Key Findings:
– The psilocybin treatment led to “rapid and sustained” reductions in anxiety and depression, along with decreased demoralization and hopelessness and improved spiritual well-being and quality of life compared to placebo.
– By the 6.5-month follow-up (after all participants had received psilocybin), approximately 60–80% of participants were still experiencing clinically significant reductions in depression or anxiety.
Implications:
– Participants also reported lasting improvements in existential distress and attitudes toward death, indicating that a single psilocybin session (with therapy) can produce robust, enduring relief from end-of-life anxiety and depression.
– Notably, the intensity of the mystical-type experience induced by psilocybin was found to mediate its therapeutic outcomes, suggesting a link between profound subjective experiences and clinical efficacy.
Citation: Ross, S., Bossis, A., Guss, J., Agin-Liebes, G., Malone, T., Cohen, B., Mennenga, S. E., Belser, A., Kalliontzi, K., Babb, J., Su, Z., Corby, P., & Schmidt, B. L. (2016). Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. Journal of psychopharmacology (Oxford, England), 30(12), 1165–1180. https://doi.org/10.1177/0269881116675512
Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer
Methodology: Long-term follow-up study of Ross et al. (2016), assessing durability of psilocybin’s effects approximately 3–4.5 years later. Of the original Ross et al. sample, all 16 participants still alive were contacted, and 15 completed longitudinal assessments at ~3.2 years and ~4.5 years post-treatment. No additional drug sessions were given; this was a naturalistic observation of lasting outcomes.
Sample: 15 patients.
Dosage: N/A
Key Findings:
– The reductions in anxiety, depression, hopelessness, and demoralization observed after psilocybin therapy were largely sustained at long-term follow-ups.
– At 4.5 years, an estimated 60–80% of participants still met criteria for clinically significant antidepressant or anxiolytic responses.
– Many participants reported the psilocybin session as among the most personally meaningful experiences of their lives, with 71–100% attributing positive life changes (improved well-being, life satisfaction, spiritual sustenance) to the therapy.
Implications: Suggests that a one-time psilocybin-assisted therapy can confer enduring relief from end-of-life psychiatric distress, although the authors caution that conclusions are limited by the parent trial’s cross-over design
Citation: Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., Bossis, A. P., Grigsby, J., Fischer, S., & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of psychopharmacology (Oxford, England), 34(2), 155–166. https://doi.org/10.1177/0269881119897615
Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy
Methodology: Prospective observational study of “compassionate use” psilocybin therapy in Canada, examining real-world outcomes for palliative patients. Participants completed surveys at baseline and at 2 weeks after a single psilocybin session (with an optional next-day check-in).
Sample: Eight patients (four females, Mage = 52.3 years, all with advanced cancer diagnoses) obtained legal exemptions (Section 56 in Canada) to undergo psilocybin-assisted psychotherapy in a clinical setting.
Dosage: All participants reported consuming the psilocybin in the form of psilocybin mushrooms or truffles (dried; 2/5 reported taking Golden Teacher [Psilocybe cubensis strain]; the other three reported not knowing). The majority reported taking only one dose ranging from 2.5 g (n = 1) to 5 g (n = 4) (one patient reported two doses over the course of the session as 3.33 and 1.66 doses, less than 1 h apart). Two participants consumed the psilocybin mushrooms/truffles whole, while the three others consumed it cooked or brewed into a tea.
Key Findings:
– At two-weeks post-session, there were significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being compared to baseline
– Importantly, attitudes toward death and desire for hastened death did not change, suggesting psilocybin eased distress without diminishing realistic outlooks on mortality.
– Most participants found the experience highly meaningful (albeit challenging) and their psychological well-being improved, except one patient who reported a substantial decline in well-being attributable to the session.
Implications: These real-world preliminary data (among the first collected outside of a formal trial) indicate that psilocybin-assisted psychotherapy can yield benefits in “real-world” palliative-care patients akin to those seen in controlled trials, while underscoring the need for ongoing monitoring and structured support as access expands.
Citation: de la Salle, S., Kettner, H., Thibault Lévesque, J., Garel, N., Dames, S., Patchett-Marble, R., Rej, S., Gloeckler, S., Erritzoe, D., Carhart-Harris, R., & Greenway, K. T. (2024). Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy. Scientific reports, 14(1), 16524. https://doi.org/10.1038/s41598-024-66817-0
Psilocybin mushrooms for psychological and existential distress. Treatment for a patient with palliative lung cancer
Methodology: With special authorization, the patient underwent one psilocybin therapy session facilitated by two family physicians in a community setting.
Sample: A woman in her 50s with advanced lung cancer suffering from severe existential and psychological distress despite standard palliative care.
Dosage: 5g of dried psilocybin mushrooms (steeped as a tea).
Key Findings:
– Consistent with clinical trial observations, this single session triggered a profound mystical-type experience, which the patient later described as “the single-most personally meaningful experience of her life.”
– She experienced an immediate transformation with substantial and sustained improvement in her anxiety, mood, and overall quality of life following the session.
– Importantly, no adverse physical or psychiatric events were noted.
Implications: This case underscores that, even in a non-research, compassionate-use context, psilocybin therapy can lead to rapid and durable relief of end-of-life existential distress, in line with outcomes reported in larger trials.
Citation: Patchett-Marble, R., O’Sullivan, S., Tadwalkar, S., & Hapke, E. (2022). Psilocybin mushrooms for psychological and existential distress. Canadian Family Physician, 68(11), 823-827. https://doi.org/10.46747/cfp.6811823
HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer
Methodology: An open-label pilot trial exploring psilocybin in a group therapy format to treat demoralization and depression in cancer patients. Therapy was delivered partly in group sessions: each cohort of four patients met for three preparatory therapy sessions, then received a single high dose (25 mg) of psilocybin simultaneously in a group setting, facilitated by therapists (one therapist per patient present). After the dosing day, three group integration sessions were held. Outcomes (depression, anxiety, etc.) were measured at baseline, 2 weeks, and 26 weeks post-treatment.
Sample: 12 adults with cancer and DSM-5 depressive disorders (major depression or adjustment disorder).
Dosage: 25mg of psilocybin
Key Findings:
– All 12 participants completed the intervention, and no serious adverse events or safety issues were attributable to psilocybin.
– Depression symptoms improved markedly: the mean clinician-rated depression score (HAM-D) fell from 21.5 at baseline to 10.1 at 2 weeks, and 14.8 at 26 weeks (both timepoints showed statistically significant improvement).
– At 2 weeks post-session, 6 of 12 patients (50%) achieved clinical remission of depression (HAM-D <7).
– Some relapse of depressive symptoms occurred by 26 weeks, but scores remained significantly better than baseline.
Implications: The pilot demonstrated feasibility and potential efficacy of group-administered psilocybin – showing rapid antidepressant responses similar in magnitude to individual therapy trials. The group modality also reduced total therapist hours per patient, hinting at greater scalability. Authors concluded that psilocybin-assisted group therapy appears safe, acceptable, and worthy of further study to improve end-of-life mental health in a resource-efficient way
Citation: Lewis, B. R., Garland, E. L., Byrne, K., Durns, T., Hendrick, J., Beck, A., & Thielking, P. (2023). HOPE: A Pilot Study of Psilocybin Enhanced Group Psychotherapy in Patients With Cancer. Journal of pain and symptom management, 66(3), 258–269. https://doi.org/10.1016/j.jpainsymman.2023.06.006
Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial
Study Type: Single-site open-label trial (12-week follow-up).
Methodology: Participants underwent a carefully structured psilocybin-assisted therapy program at Sheppard Pratt Hospital: they had three preparatory therapy sessions, a single psilocybin dosing day (with two therapists present), and three integration therapy sessions in the weeks post-dose. All psychiatric medications were tapered and stopped at least 2 weeks prior to psilocybin dosing (and patients remained off antidepressants for at least 3 weeks after dosing) to avoid confounds. Depression severity was primarily measured with the MADRS at baseline, week 3, and week 12 post-treatment. Other secondary measures included self-reported depression scales and functional assessments. As an open-label study with no control group, the focus was on within-subject changes from baseline and safety observations.
Sample: 12 adults (18–65 years old) with very difficult-to-treat depression. Notably, 5 of 12 participants also had comorbid PTSD, and many had other comorbidities common in chronic depression (anxiety, etc.). These comorbid conditions were recorded to see if they affected outcomes.
Dosage: A single dose of 25 mg of synthetic psilocybin (Compass Pathways’ formulation) was administered in a controlled setting. The dosing session lasted ~8 hours with therapists present throughout. Patients were instructed to set intentions and were supported during the psychedelic experience. On the dosing day, vital signs and psychological state were monitored closely. After the session, patients stayed in a safe environment overnight. They then participated in integration sessions over the next 3 weeks to discuss and make meaning of their experience.
Key Findings:
– The pilot results were very promising: psilocybin led to rapid and substantial antidepressant effects in this veteran TRD group. At the primary 3-week endpoint, 9 out of 15 veterans (60%) met response criteria (MADRS ≥50% improvement), and 8 out of 15 (53%) achieved remission (virtually no depressive symptoms). This degree of remission in such severe cases is striking. By 12 weeks (3 months post-dose), although some had relapsed, a considerable portion maintained their gains: 47% were still classified as responders and 40% remained in remission
– In other words, nearly half the group had a sustained antidepressant effect lasting at least 3 months from a single treatment – a positive outcome given their prior chronic depression. Veterans also showed improvements in secondary measures like anxiety and hopelessness. For those with co-morbid PTSD, it’s notable that the presence of PTSD did not significantly diminish the antidepressant response in this study
– Veterans with PTSD improved on depression just as much as those without (and some even reported that psilocybin helped them process traumatic memories, though formal PTSD symptom measures were not the primary focus). Additionally, the intensity of the psychedelic experience (as measured by the 5D-ASC questionnaire) did not straightforwardly correlate with outcome in this sample, even those with less intense subjective experiences sometimes had strong clinical improvement, suggesting that benefit can occur across a range of session experiences.
– No unexpected or serious adverse events occurred. Some veterans had transient blood pressure elevations and anxiety during the session onset, all managed supportively without need for pharmacologic intervention. A few experienced brief increases in trauma-related thoughts during the trip, but with therapeutic support they reframed these experiences positively. Importantly, no cases of psychosis or prolonged dissociation were seen. Four participants went back on an antidepressant sometime after the 3-week point due to returning symptoms; those cases were counted as “non-responders from that timepoint” in the analysis
– There were no reports of persistent worsening of PTSD symptoms; on the contrary, many described improvements in mood regulation and perspective.
Citation: Aaronson, S. T., van der Vaart, A., Miller, T., LaPratt, J., Swartz, K., Shoultz, A., Lauterbach, M., Suppes, T., & Sackeim, H. A. (2025). Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial. The American journal of psychiatry, 182(1), 104–113. https://doi.org/10.1176/appi.ajp.20231063
Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study
Study Type: Open-label pilot trial.
Methodology: Participants underwent one psilocybin dosing session (open-label, everyone received the active treatment) with psychological support. Antidepressant medications were tapered off beforehand to avoid drug interactions (similar to other trials). Depression severity was measured using the MADRS at baseline, at 3 weeks, and 12 weeks post-treatment; standard criteria for response (≥50% drop in MADRS) and remission (MADRS ≤10) were applied. The study also monitored PTSD symptoms and other mental health outcomes qualitatively. Without a control group, efficacy was inferred by pre-post changes and comparison to historical expectations.
Sample: 15 U.S. military veterans (mixed ages, many middle-aged; gender not specified) with severe treatment-resistant depression were enrolled. Inclusion required a major depressive episode that either failed ≥5 prior treatments or lasted >2 years continuously without remission. Notably, a majority of these veterans also had co-occurring PTSD from their service (though this was not exclusionary). All had multiple failed antidepressant trials; some had also tried ECT or ketamine.
Dosage: A single 25 mg oral dose of psilocybin (synthetic) was administered in a comfortable clinical setting. Two trained facilitators were present during the session, employing a vet-specific supportive approach. Veterans were encouraged to focus inward (using eyeshades and music) during the peak psychedelic effects. The acute session lasted ~6–8 hours, followed by debriefing. Therapy sessions were provided before the dose (to build trust and set intentions) and after (for integration of insights). Given the veteran population, special attention was paid to creating a feeling of safety and addressing any combat-related trauma that arose.
Key Findings:
– The pilot results were very promising: psilocybin led to rapid and substantial antidepressant effects in this veteran TRD group. At the primary 3-week endpoint, 9 out of 15 veterans (60%) met response criteria (MADRS ≥50% improvement), and 8 out of 15 (53%) achieved remission (virtually no depressive symptoms). This degree of remission in such severe cases is striking. By 12 weeks (3 months post-dose), although some had relapsed, a considerable portion maintained their gains: 47% were still classified as responders and 40% remained in remission
– In other words, nearly half the group had a sustained antidepressant effect lasting at least 3 months from a single treatment – a positive outcome given their prior chronic depression. Veterans also showed improvements in secondary measures like anxiety and hopelessness. For those with co-morbid PTSD, it’s notable that the presence of PTSD did not significantly diminish the antidepressant response in this study
– Veterans with PTSD improved on depression just as much as those without (and some even reported that psilocybin helped them process traumatic memories, though formal PTSD symptom measures were not the primary focus). Additionally, the intensity of the psychedelic experience (as measured by the 5D-ASC questionnaire) did not straightforwardly correlate with outcome in this sample, even those with less intense subjective experiences sometimes had strong clinical improvement, suggesting that benefit can occur across a range of session experiences.
– No unexpected or serious adverse events occurred. Some veterans had transient blood pressure elevations and anxiety during the session onset, all managed supportively without need for pharmacologic intervention. A few experienced brief increases in trauma-related thoughts during the trip, but with therapeutic support they reframed these experiences positively. Importantly, no cases of psychosis or prolonged dissociation were seen. Four participants went back on an antidepressant sometime after the 3-week point due to returning symptoms; those cases were counted as “non-responders from that timepoint” in the analysis
– There were no reports of persistent worsening of PTSD symptoms; on the contrary, many described improvements in mood regulation and perspective.
Citation: Ellis, S., Bostian, C., Feng, W., Fischer, E., Schwartz, G., Eisen, K., Lean, M., Conlan, E., Ostacher, M., Aaronson, S., & Suppes, T. (2025). Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – A first-in-kind open-label pilot study. Journal of affective disorders, 369, 381–389. https://doi.org/10.1016/j.jad.2024.09.133
Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - 12-month data from an open-label pilot study
Study Type: A long-term observational follow-up of the above 15 veteran TRD patients
Methodology: Participants had MADRS assessments at approximately 6 months, 9 months, and 12 months post-psilocybin. No additional psilocybin sessions were given in this period, though participants were free to seek other treatments as needed (any such interventions were recorded). The main outcomes were depression severity over time and the proportions meeting response/remission at those extended time points, compared to baseline. Given the observational nature, no control group is present, but the data show trends of how the group fared over time.
Sample: Out of the original 15 veterans, 10 completed the full 12-month follow-up (5 were lost to follow-up or withdrew by 12 months).
Dosage: N/A
Key Findings:
– Significant depression improvements persisted compared to baseline across all long-term follow-ups, but there was a gradual return of symptoms in some veterans as time went on
– At 6 months post-treatment, the results were still very strong: out of the 10 veterans assessed, 80% were classified as responders (≥50% depression reduction) and 50% remained in remission. This indicates that at the half-year mark, half of the followed participants were still essentially depression-free, and most had substantial benefit – an unusually prolonged effect for a one-time treatment in TRD. However, by 9 months, signs of waning efficacy emerged
– The data showed that some who had been in remission at 6 months experienced a return of depressive symptoms by 9 months. By the 12-month point, the maintained response rate dropped to 40%, and remission rate to 30% among those 10 veterans
– In other words, after one year, 3 of 10 were still in remission, 4 of 10 still had a meaningful response (but not full remission), and 6 of 10 had experienced a depressive relapse of some kind. Importantly, even at 12 months the average depression scores were better than baseline – meaning everyone was not back to square one, but the group as a whole had lost some of the early gains
– The increase in MADRS from the earlier time-points to 12 months did not reach statistical significance, likely due to the small sample, but the trend was clear (symptoms creeping back)
– No new safety issues were noted over this extended period.
Citation: Ellis, S., Bostian, C., Donnelly, A., Feng, W., Eisen, K., Lean, M., Conlan, E., Ostacher, M., Aaronson, S., & Suppes, T. (2025). Long-term outcomes of single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression – 12-month data from an open-label pilot study. Journal of affective disorders, 119655. Advance online publication. https://doi.org/10.1016/j.jad.2025.119655
Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials
Study Type: Systematic review and dose-response network meta-analysis of randomized controlled trials (RCTs) examining psilocybin for depression.
Methodology: Researchers searched databases (Embase, PubMed, Cochrane, Scopus, etc.) up to July 2024 for RCTs of psilocybin versus placebo in adults with major depression (including TRD). They identified 3 RCTs meeting criteria (total N = 389 patients). These likely included: the 2022 COMPASS Pathways trial (25 mg vs 1 mg), a smaller placebo-controlled trial in major depression (e.g., the 2021 Johns Hopkins waitlist-controlled RCT which had a placebo/delay component), and possibly another trial with low-dose control. Using a network meta-analysis approach, the study compared outcomes of different psilocybin doses (e.g., 1 mg, 10 mg, ~20 mg/70kg, 25 mg) relative to placebo at various time points. The primary outcome aggregated was change in depression scores (MADRS) at Day 8 and Day 15 post-treatment (to capture the rapid effects), as well as at Day 2 (to see immediate effect). Adverse events were also compiled. A dose-response model was used to rank doses by efficacy.
Sample: See methodology
Dosage: See methodology
Key Findings:
– The meta-analysis confirmed that psilocybin has a significant antidepressant effect compared to placebo in the short term. Specifically, by 1 week (Day 8) after treatment, psilocybin-treated patients had much greater symptom improvement than those given placebo (pooled mean difference ~–7.4 MADRS points in favor of psilocybin, p<0.001)
– By 2 weeks (Day 15), this advantage grew (mean difference ~–9.5 MADRS points vs placebo, p<0.001). This roughly corresponds to a large effect size. At 2 days post-dose, however, there was no significant difference yet, indicating psilocybin’s antidepressant action is not immediate same-day, but emerges over several days (likely as psychological insights develop and neuroadaptive changes occur).
– In terms of dose, the network meta-analysis found that 25 mg was the most effective dose tested, outperforming both a 10 mg dose and a weight-adjusted dose around 0.2 mg/kg (~15 mg for 70kg)
– Using a probabilistic ranking (SUCRA – Surface Under Cumulative Ranking curve), 25 mg had a SUCRA of ~92%, meaning it had the highest likelihood of being the best dose for response
– Lower doses had lower efficacy rankings. This quantitatively validates the dose selection used in ongoing phase 3 trials (25 mg seen as optimal). On the safety side, the meta-analysis noted that psilocybin was associated with a higher frequency of mostly mild-to-moderate adverse events compared to placebo
– The most significantly elevated side effect was nausea, psilocybin patients had about 8.35 times the risk of nausea as placebo patients (p<0.001)
– This isn’t surprising given psilocybin often causes transient nausea. Other side effects like headache, transient anxiety, or blood pressure increase were also more common with psilocybin, but generally short-lived. Crucially, no signal of increased serious adverse events emerged (reinforcing safety in controlled setting
Citation: Swieczkowski, D., Kwaśny, A., Pruc, M., Gaca, Z., Szarpak, L., & Cubała, W. J. (2025). Efficacy and safety of psilocybin in the treatment of Major Depressive Disorder (MDD): A dose-response network meta-analysis of randomized placebo-controlled clinical trials. Psychiatry research, 344, 116337. https://doi.org/10.1016/j.psychres.2024.116337
Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials
Study Type: Systematic review and meta-analysis of recent clinical trials of psilocybin for depression.
Methodology: Authors followed PRISMA guidelines and searched for trials (open-label or randomized) involving psilocybin treatment for MDD or TRD. They ended up including 12 studies (published between ~2016 and 2023) that met criteria. These comprised both uncontrolled studies (like Carhart-Harris 2016, 2018) and controlled trials (like Davis 2020, Carhart-Harris 2021, Goodwin 2022, etc.), encompassing several hundred patients in total. The meta-analysis quantitatively compared depression severity before and after psilocybin therapy across studies. It also conducted subgroup analyses on trials that used a single psilocybin session versus those that used two sessions (e.g., some trials gave one dose, others like Davis 2020 gave two doses separated by weeks). Efficacy was measured via standard depression rating scales. Because of variations in scales, they likely used standardized mean differences to pool results.
Sample: See methodology
Dosage: See methodology
Key Findings:
– Across the 12 studies, psilocybin treatment (with therapy) was found to be highly effective in reducing depressive symptoms on average
– The meta-analysis confirmed a large pre-to-post treatment improvement in depression severity scores among patients receiving psilocybin, whether in open-label or controlled contexts
– When comparing one vs two dose regimens: both approaches significantly reduced depression, but in some cases, two-dose administrations yielded more pronounced and/or longer-lasting effects
– For example, trials that gave a second psilocybin session (usually a few weeks after the first) often reported sustained or even enhanced benefits at follow-ups, whereas single-dose trials saw some patients relapse sooner. However, the review noted that it’s not entirely clear if the superiority of two doses is strictly due to the extra psilocybin or could be influenced by other factors (like those particular studies having slightly different patient populations or additional therapy)
– In some of the pooled analyses, the difference between one vs two doses wasn’t statistically huge, indicating that even a single session has a potent effect, but there was a tendency for two-dose protocols to show numerically better outcomes. No serious safety concerns emerged in either single or two-dose studies, reinforcing that even multiple sessions are well-tolerated in clinical settings (with appropriate screening).
Citation: Salvetti, G., Saccenti, D., Moro, A. S., Lamanna, J., & Ferro, M. (2024). Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials. Brain sciences, 14(8), 829. https://doi.org/10.3390/brainsci14080829