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Our vision is that psychedelics can be used worldwide to better the lives of as many as 450 million people who suffer from mental health problems. Our information hopes to make that vision come to life just a little faster.
Here will be a narrative, readable, summary of the research.
In our literature study we came across the following studies of note. Browse the meta, review, commentary articles for an overview. Check out the individual studies for specific experiments and observations.
Esketamine Nasal Spray for the Rapid Reduction of Depressive Symptoms in Major Depressive Disorder With Acute Suicidal Ideation or Behavior
2021 | Canuso, C. M., Fu, D. J., Ionescu, D. F., Lane, R., Li, X., Lopena, T. J., Nash, A. I., Qui, X., Turkoz, I.
This pooled analysis (n=456) of the two ASPIRE studies (comparing ketamine to placebo, both with standard care) finds significant improvements in depression scores immediately (4 & 24 hours) up to 25 days later (all similar reductions). The study also showed improvements on suicidal ideation (which all patients had), most for those with a history of suicide attempt.
Psychopharmacological Agents and Suicide Risk Reduction: Ketamine and Other Approaches
2015 | Al Jurdi, R. K., Mathew, S. J., Swann, A. C.
This review (2015) examines the neurobiology of ketamine’s potential to treat suiciadility and proposes that its working mechanism functions via the suppression of pro-inflammatory cytokines and by restoring tryptophan/serotonin production via inhibition of the kynurenine pathway. It notes that this hypothesis requires further validation via replicated randomized control research with larger samples.
Registered clinical studies investigating psychedelic drugs for psychiatric disorders
2021 | Gill, H., Lipsitz, O., Lui, L. M. W., McIntyre, R. S., Rosenblat, J. D., Siegel, A. N., Teopiz, K. M.
This review (2021) summarizes the study characteristics of all ongoing registered clinical trials investigating psychedelic drugs for psychiatric disorders and identifies that their majority focuses on investigating MDMA and psilocybin for treating depression or PTSD, while only 30% of their results are published.
Ketamine administration in depressive disorders: a systematic review and meta-analysis
2014 | Abbar, M., Boyer, L., Brittner, M., Courtet, P., Fond, G., Lançon, C., Leboyer, M., Loundou, A., Macgregor, A., Micoulaud-Franchi, J., Rabu, C., Richieri, R., Roger, M.
This review (2015, n=118) found that ketamine showed reliable anti-depressive effects in patients diagnosed with either MDD or bipolar disorder (BD). The duration of effects, however, requires further research.
Lysergic acid diethylamide: side effects and complications
1980 | Cohen, S.
This early review (1960) details the prevalence of some possible side effects and complications of LSD from the literature. The discussion includes prolonged psychotic symptoms, (attempted) suicides, and others.
Rapid Onset of Intranasal Esketamine in Patients with Treatment Resistance Depression and Major Depression with Suicide Ideation: A Meta-Analysis
2021 | Bahk, W., Kim, N., Lim, H., Na, H., Pae, C., Wang, S., Woo, Y.
This meta-analysis (s=7; n=1488) of double-blind placebo-controlled studies with those suffering from depression (MDD; TRD) and suicidal ideation (SI) found that esketamine (24-84mg) significantly improved scores on a measure of depression (MADRS) over the placebo up to 28 days alter, the SI scores were only significant within the first 24 hours.
Clinical trials for rapid changes in suicidal ideation: Lessons from ketamine
2021 | Ballard, E. D., Farmer, C. A., Fields, J., Zarate, C. A.
This review (2021) examines methodological innovations within clinical trials investigating ketamine as a rapid-acting treatment option for depression or suicidal ideation (SI). The authors emphasize that the fast-acting dynamic of this treatment will enable the next generation of clinical trial designs to focus more on the development of better psychometric instruments, and more reliable biomarkers for assessing the efficacy of suicidal ideation treatment.
Antisuicidal and antidepressant effects of ketamine and esketamine in patients with baseline suicidality: A systematic review
2021 | Brietzke, E., Di Vincenzo, J. D., Gill, H., Ho, R., Lui, L. M. W., McIntyre, R. S., Ng, J., Rodrigues, N. B., Rosenblat, J. D., Siegel, A. N., Teopiz, K. M.
This review (2021) evaluates the effect of esketamine and ketamine in patients with suicidal ideation at baseline. The authors find that esketamine trials did not demonstrate antisuicidal effects, while IV ketamine appeared to rapidly decrease the short term severity of suicidal ideation and depressive symptoms in individuals with baseline suicidal ideation.
The Effect of a Single Dose of Intravenous Ketamine on Suicidal Ideation: A Systematic Review and Individual Participant Data Meta-Analysis
2017 | Ballard, E. D., Bloch, M. H., Feder, A., Mathew, S. J., Murrough, J. W., Sanacora, G., Sos, P., Wang, G., Wilkinson, S. T., Zarate, C. A.
This systematic review (2018) and meta-analysis (n=176) examined the effects of ketamine on suicidal ideation using patient-level data from various studies that applied a single-dose intravenous administration route to treat any type of psychiatric disorder. Ketamine significantly reduced suicidal ideation for up to one week after the infusion.
On the Relationship between Classic Psychedelics and Suicidality: A Systematic Review
2021 | Breslow, L., Singhal, N., Weissman, C. R., Zeifman, R. J.
This review (2021; 64 studies) investigated the literature and found no clear relationship (finding correlation both ways, and non-significant results) between non-clinical use of psychedelics and suicidality. There is preliminary evidence for acute and sustained decreases in suicidality after psychedelic therapy.
Relationships between reduction in symptoms and restoration of function and wellbeing: Outcomes of the Oral Ketamine Trial on Suicidality (OKTOS)
2021| Beaudequin, D. A., Can, A. T., Dutton, M., Forsyth, C. G., Hermens, D. F., Jensen, E., Jones, M., Lagopoulos, J., Scherman, J., Schwenn, P. E., Yang, C.
In this open-label study (n=30) participants received six oral sub-anaesthetic doses of ketamine, one dose a week over six weeks. The initial dose was 35mg/70kg which increased to a max of 210mg/70kg by week six. Although restoration of function and wellbeing did improve, these effect sizes were smaller than for suicidality and depression outcomes suggesting that reduction in these outcomes may not be necessary for full restoration of function and wellbeing.
Assessing measures of suicidal ideation in clinical trials with a rapid-acting antidepressant
2015| Ameli, R., Ballard, E. D., Brutsche, N. E., Luckenbaugh, D. A., Niciu, M. J., Richards E. M., Vande Voort, J. L., Walls, T. S., Zarate, C. A.
This study (n=60) of randomized, placebo-controlled, crossover clinical trials appraises suicidal ideation (SI) with ketamine infusion in persons with treatment-resistant depression (TRD). The results indicated improvement in suicidal thoughts after ketamine infusion and the measures are sensitive to these changes.
Psychedelics not linked to mental health problems or suicidal behavior: A population study
2015| Johansen, P. Ø., Krebs, T. S.
This 2015 observational survey study (n=135 095) investigated the association between lifetime psychedelic use (LSD, psilocybin, mescaline) and mental health problems, but found no indication of increased likelihood for psychological distress, mental health treatment, suicidal behavior, depression, or anxiety amongst psychedelic users (n=19 299). These results contest the justification for prohibiting psychedelics as a public health measure.
Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic
2021| Di Vincenzo, J. D., Kratiuk, K., Lee, Y., Lipsitz, O., McIntyre, R. S., Rodrigues, N. B., Rosenblat, J. D., Subramaniapillai, M.
This open-label study (n=267) investigated if Covid had any impact on the effectiveness of ketamine treatments (iv, 4x 35-53mg/70kg) for depression (TRD). Patients in both groups experience significant and comparable improvements in depressive symptoms, suicidal ideation (SI), and anxiety.
Esketamine Nasal Spray for Rapid Reduction of Depressive Symptoms in Patients With Major Depressive Disorder Who Have Active Suicide Ideation With Intent: Results of a Phase 3, Double-Blind, Randomized Study (ASPIRE II)
2021| Canuso, C. M., Drevets, W. C., Fu, D. J., Hough, D., Ionescu, D. F., Kasper, S., Lane, R., Lim, P., Manji, H., Qiu, X.
This double-blind, placebo-controlled, randomized study (n=230) evaluated esketamine nasal spray (84 mg) for rapid reduction of depressive symptoms in patients with major depressive disorder (MDD) who have active suicide ideation with intent. It found that patients in both treatment categories demonstrated a very significant decrease in depressive symptoms over placebo and confirmed that esketamine nasal spray could play a role in helping critically ill patients with MDD who have suicidal intent.
Ketamine versus midazolam in bipolar depression with suicidal thoughts: A pilot midazolam-controlled randomized clinical trial
2017| Burke, A. K., Cooper, T. B., Ellis, S. P., Grunebaum, M. F., Keilp, J. G., Mann, J. J., Marver, J. E., Milak, M. S., Moitra, V. K., Oquendo, M. A., Sublette, M. E.
This midazolam-controlled randomized clinical trial study (n=16) compares ketamine and midazolam (another anesthetic) to investigate their feasibility and effect on suicidal ideation (SI) in bipolar depression (BD) using the Scale for Suicidal Ideation (SSI) score. The results substantiate feasibility with improvement in memory and BDNF as promising biomarkers and that ketamine effects showing more reduction in suicidal thoughts than with midazolam, although it was not statistically significant; this was possibly due to a small sample so a full-scale trial is needed.
Attenuation of antidepressant and antisuicidal effects of ketamine by opioid receptor antagonism
2019| Bentzley, B. S., Blasey, C., Hawkins, J., Heifets, B. D., Lyons, D. M., Schatzberg, A. F., Sudheimer, K. D., Williams, N. R.
This double-blind placebo-controlled clinical trial (n=12) examined the effects of naltrexone and ketamine on suicidal ideation (SI) and found that naltrexone attenuates (blocks) the effects of ketamine. It's proposed, just as with the antidepressant effect of ketamine, that it requires opioid receptor activation.
Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial
2019| Akeju, O., Alpert, J. E., Baer, L., Bentley, K. H., Brown, E. N., Cusin, C., Dording, C., Eikermann, M., Fava, M., Ionescu, D. F., Mischoulon, D., Nock, M. K., Pavone, K. J., Petrie, S. R., Swee, M. B., Taylor, N.
This randomized, double-blind, placebo-controlled study (n=26) investigated the efficacy of ketamine (35mg/70kg) treatment for patients with severe depression and found that, in contrast to other studies, ketamine did not outperform placebo in terms of short- or long-term antidepressant or antisuicidal efficacy.
The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study
2021| Abrão, J., Debattista, C., Fava, M., Feeney, A., Flynn, M., Freeman, M. P., Hock, R. S., Hoeppner, B., Ionescu, D. F., Iosifescu, D. V., Mathew, S. J., Papakostas, G. I., Sanacora, G., Trivedi, M. H.
This randomized double-blind placebo-controlled study (n=56) found that a single dose of ketamine significantly reduced the level of suicidal ideation (SI). Still, in both groups, there was a high level of suicidal ideation, and the study showed diminishing results rapidly over the 30 days of the study (the effects being the largest at 3 days post-infusion).
Antisuicidal Response Following Ketamine Infusion Is Associated With Decreased Nighttime Wakefulness in Major Depressive Disorder and Bipolar Disorder
2017| Ballard, E. D., Bernert, R. A., Duncan, W. C., Luckenbaugh, D. A., Machado-Vieira, R., Niciu M. J., Park L. T., Richards E. M., Voort, J. L. V., Zarate, C. A.
This open-label study (n=34) investigated the effects of ketamine (35mg/70kg) on suicidal ideation and sleep rhythm in patients with (bipolar) depression and found that patients with less post-infusion nocturnal wakefulness exhibited an antisuicidal response to ketamine, compared to patients who were wakeful at night and continued suicidal ideation.
Rapid antidepressant effect of S-ketamine in schizophrenia
2018| Bartova, L., Dold, M., Kasper, S., Milenkovic, I., Papageorgiou, K., Weidenauer, A., Willeit, M., Winkler, D.
This open-label case study (n=1) describes a patient with schizophrenia whose treatment regimen was augmented with a ketamine (25mg) infusion to alleviate her symptoms of depression and suicidal ideation (SI). Her symptoms underwent a robust and sustained remission after the infusion, without any accompanying psychotic or dissociative phenomena.
Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting
2017| Argento, E., Braschel, M., Shannon, K., Strathdee, S. A., Tupper, K. W., Wood, E.
This longitudinal community-based cohort study (n=290) investigated whether naturalistic psychedelics use is protective against the development of suicidality, amongst a cohort of marginalized women over a period of four years (2010-2014). Lifetime psychedelics use was associated with a 60% reduced hazard for developing suicidality, whereas crystal meth use and childhood abuse were the strongest independent predictors by comparison.
Improvement in suicidal ideation after ketamine infusion: Relationship to reductions in depression and anxiety
2014| Ameli, R., Brutsche, N. E., Furey, M., Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Richards, E. M., Vande Voort, J. L., Zarate, C. A.
This post-hoc meta-analysis (n=133) examined the relationship between the antidepressant efficacy of intravenous ketamine (35mg/70kg) and its effects on suicidal ideation (SI) among patients with depression. Ketamine increased the patient's wish to live and decreased their wish to die, and these reductions in suicidal ideation independent of reductions in depressive and anxiety symptoms.
Ketamine Use for Suicidal Ideation in the General Hospital: Case Report and Short Review
2018| Baup, E., Lefebvre, D., Lemogne, C., Limosin, F., Passeron, A., Rieutord, M., Seigneurie, A. S., Thauvin, I., Vulser, C., Vulser, H.
This case report (n=1) describes an anorexic patient who was treated with repeated dose ketamine (0.5mg/kg, 20mg) following a suicide attempt and persevering suicidal ideation (SI). Although the first dose had little effect, the second dose administered 2 weeks after led to a dramatic decrease in depression, hopelessness, and suicidal ideation.
Post-Marketing Safety Concerns with Esketamine: A Disproportionality Analysis of Spontaneous Reports Submitted to the FDA Adverse Event Reporting System
2020| Barbui, C., Gastaldon, C., Kane, J. M., Raschi, E., Schoretsanitis, G.
This study (n=962) investigated adverse events after administration of nasal esketamine (Spravato) for treatment-resistant depression (TRD). The study found increased suicidal ideation (versus antidepressants) but not suicide attempts or completions.
Esketamine Nasal Spray for Rapid Reduction of Major Depressive Disorder Symptoms in Patients Who Have Active Suicidal Ideation With Intent: Double-Blind, Randomized Study (ASPIRE I)
2020| Canuso, C. M., Drevets, W. C., Fu, D. J., Hough, D., Ionescu, D. F., Lane, R., Lim, P., Manji, H., Sanacora, G.
This placebo-controlled, double-blind study, phase 3 study (n=226) compared esketamine (84mg, nasal, 2xp/w for 4w) with a placebo spray and found esketamine to be effective in lowering depression scores (MADRS) for those suffering from depression (MDD) and suicidal ideation (SI). Scores on a measure of SI was, however, not significantly different between the two groups.
A Double-Blinded, Randomized, Placebo-Controlled Sub-Dissociative Dose Ketamine Pilot Study in the Treatment of Acute Depression and Suicidality in a Military Emergency Department Setting
2016| Boche, B., Burger, J., Capobianco, M., Darracq, M. A., Lovern, R., McLay, R., Ross, E.
This placebo-controlled proof-of-concept study (n=10, 7 placebo) administered sub-dissociative doses of ketamine to military personnel experiencing depression and suicidal ideation (SI), and found that the ketamine infusion resulted in significant short-term improvement in two out of the three patients who received the drug.
Acute and Sustained Reductions in Loss of Meaning and Suicidal Ideation Following Psilocybin-Assisted Psychotherapy for Psychiatric and Existential Distress in Life-Threatening Cancer
2021| Agin-Liebes, G. I., Benville, J., Bjerre-Real, C., Bossis, A. P., Franco-Corso, S., Ghazal, L., Guss, J., Lo, S., Mennenga, S. E., Ross, E., Zeifman, R. J.
This follow-up study (n=11) of psilocybin-assisted therapy for anxiety and depression, found that it also significantly reduced suicidal ideation (SI) and loss of meaning (LoM) up to the 4.5 years follow-up.
Single, Fixed-Dose Intranasal Ketamine for Alleviation of Acute Suicidal Ideation. An Emergency Department, Trans-Diagnostic Approach: A Randomized, Double-Blind, Placebo-Controlled, Proof-of-Concept Trial
2021| Domany, Y., McCullumsmith, C. B.
This double-blind placebo-controlled study study (n=30) with intranasal ketamine (40mg) found significant reductions in suicidal ideation (SI, 80 vs 33% remission) and depressive symptoms (MADRS) 4 hours after administration for those with SI in the emergency department.
Low dose oral ketamine treatment in chronic suicidality: An open-label pilot study
2021| Beaudequin, D. A., Can, A. T., Dutton, M., Gallay, C. C., Hermens, D. F., Jensen, E., Jones, M., Lagopoulos, J., Scherman, J., Schwenn, P. E., Yang, C.
This open-label study (n=32) with 6 dosages (weekly) of oral ketamine (35-210mg/70kg) found that it significantly reduced suicidal ideation in those with chronic suicidal thought, with clinically significant lower scores in 69% of participants at the end (which held at 50% 4 weeks later).
Replication of Ketamine’s Antidepressant Efficacy in Bipolar Depression: A Randomized Controlled Add-On Trial
2012| Brutsche, N. E., Cravchik, A., Diazgranados, N., Franco-Chaves, J., Ibrahim, L., Liberty, V., Luckenbaugh, D. A., Marquardt, C. A., Selter, J., Zarate, C. A.
This double-blind, randomized, crossover, placebo-controlled replication study (n=15) investigated the effects of ketamine (35mg) on patients with treatment-resistant bipolar depression, and found rapid improvements of depressive symptoms, suicidal ideation, and subjective well-being within 40 minutes after infusion and up to 3 days after.
Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial
2018| Burke, A. K., Choo, T-H., Galfalvy, H. C., Grunebaum, M. F., Keilp, J. G., Mann, J. J., Marver, J. E., Milak, M. S., Moitra, V. K., Oquendo, M. A., Parris, M. S., Sublette, M. E.
This randomized study (n=80) found that participants with depression (MDD) and suicidal ideation (SSI/SI) who were treated with ketamine (IV, 35mg/70kg) have significantly lower SSI scores versus treatment with midazolam (another anesthetic). This effect consistently held up to 6 weeks later.
Rapid and sustained decreases in suicidality following a single dose of ayahuasca among individuals with recurrent major depressive disorder: results from an open-label trial
2020| de Lima Osório, F., Dos Santos, R. G., Hallak, J. E., Sanches, R. F., Weissman, C. R., Zeifman, R. J.
This analysis of an earlier open-label study (n=15) on Ayahuasca, found significant (Hedges' g = 1.75) and sustained decreases in suicidality in people with depression (MDD).
Post-Psychedelic Reductions in Experiential Avoidance Are Associated With Decreases in Depression Severity and Suicidal Ideation
2020| Carhart-Harris, R. L., Kettner, H., Mertens, L. J., Wagner, A. C., Watts, R., Zeifman, R. J.
A prospective survey study (n=358) found that psychedelics may lead to significant decreases in experiential avoidance, depression severity, and suicidal ideation.
This section compares the research with psychedelics to other therapies, medicines, or treatments.
This section highlights the various measures used and their use in research.
Who are the top researches in this area, the ones who have done the groundbreaking research.
What do we not know at this time? Where are the gaps in our knowledge and are we closing it?
The companies that are actively engaged in researching this topic or (planning to) provide therapy focussed on this topic.
This section highlights everything done outside of academia, from popular press to books and non academic research.