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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.
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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.
Ketamine for the treatment of major depressive disorder and bipolar depression: A review of the literature
2017 | Grady, S. E., Klein, K., Marsh, T. A., Tenhouse, A.
This literature review (2017) of randomized, placebo-controlled trials explores the effects of ketamine in treatment-resistant depression (TRD) and bipolar depression (BD). Ketamine reduced symptoms in both and is a promising compound for those who have found other treatments lacking.
Meta-analysis of short- and mid-term efficacy of ketamine in unipolar and bipolar depression
2015 | Choucha, W., Fossati, P., Romeo, B., Rotge, J.
This meta-analysis (2015) of six randomized, double-blind, placebo-controlled trials (n=101) examined the short-and mid-term efficacy of ketamine (bipolar) to depression. Ketamine effectively reduced symptoms in unipolar depression for seven days, , whereas the maintenance of its efficacy in bipolar depression failed to reach significance after 4 days.
Psychedelic Psychiatry’s Brave New World
2020 | Carhart-Harris, R. L., Erritzoe, D., Nutt, D. J.
This popular commentary article (2020) describes the current resurrection of research into psychedelics (both neuroscience and therapeutic applications). It describes the evidence for the serotonin receptor (5-HT2a) agonism (psychedelics binding to that receptor) and the possible mechanisms through which long-lasting therapeutic effects can be found.
Ketamine's effect on inflammation and kynurenine pathway in depression: A systematic review
2021 | Kopra, E., Mondelli, V., Nikkheslat, N., Pariante, C.
This literature review (2021) explores ketamine's anti-inflammatory properties and tryptophan-kynurenine (KYN) pathway in patients with unipolar and bipolar depression as well as in animal models of depression. It found that ketamine induces anti-inflammatory effects in at least a proportion of patients with depression and decreased activation of the KYN pathway's neurotoxic arm.
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.
Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder
2018 | Brietzke, E., Cha, D. S., Fus, D., Lee, Y. L., Lui, L. M. W., Mansur, R. B., McIntyre, R. S., Pan, Z., Park, C., Rong, C., Rosenblat, J. D., Subramaniapillai, M., Zuckerman, H.
This meta-analysis (2018) examined whether clinical and biological pretreatment variables could predict the treatment response of ketamine for patients with (bipolar) depression, but found that its antidepressant efficacy was highly variable and did not depend on any single predictor, although certain inflammatory biomarkers were associated with a positive response.
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.
Ketamine for bipolar depression: a systematic review
2021 | Bahji, A., Vazquez, G. H., Zarate, C. A.
This review (2021; s=6; n=135) found that ketamine (35mg/70kg; 1-6 doses) achieved a response (>50% reduction) on a score of depression for 61% of those suffering from bipolar depression (BD), compared to 5% for placebo.
Administration of ketamine for unipolar and bipolar depression
2017 | Bartova, L., Carlberg, L., Gryglewski, G., Kasper, S., Kraus, C., Lanzenberger, R., Papageorgiou, K., Popovic, A., Rabl, U., Rybakowski, J. K., Spies, M., Vanicek, T., Willeit, M., Winkler, D.
This review (2017) examined clinical trials that investigated the antidepressant efficacy of ketamine for unipolar (MDD) and bipolar depression (BD). Results indicate that intravenous and intranasal ketamine produces strong reductions of depressive symptoms within a short period and with response rates up to 88%, however, depressive relapse occurs in up to 90% of patients within 2 weeks after treatment.
Efficacy and safety of ketamine in bipolar depression: A systematic review
2017 | Alberich, S., González-Pinto, A., López, P., Martínez-Cengotitabengoa, M., Nuñez, N. A., Vieta, E., Zorrilla, I.
This review (2017) compared the safety and efficacy of ketamine for bipolar depression across scientific studies (1 clinical trial, 4 case studies, 5 cohort studies), which showed that symptoms are reduced swiftly and effectively in response to treatment, but they reappear relatively quickly within 3-14 days depending on the scale used to measure symptoms. Ketamine may be considered safe and effective for treating some cases of bipolar depression, although it has a short duration of action, in the absence of confirming studies designed specifically for bipolar depression.
Do the dissociative side effects of ketamine mediate its antidepressant effects?
2014 | Brutsche, N. E., Guevara, S., Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Nolan, N. M., Richards, E. M., Zarate, C. A.
This meta-analysis (n=108) examined whether the rapid antidepressant effect of a single subanesthetic ketamine (35mg/70kg) infusion is mediated by its dissociative side-effects or other symptoms related to its psychotomimetic profile. The analysis revealed that its dissociative effect was the only mediator that predicted a robust and sustained antidepressant efficacy.
The use of ketamine as an antidepressant: a systematic review and meta-analysis
2015 | Coyle, C. M., Laws, K. R.
This meta-analysis (2015; n=437) examined the antidepressant effects of ketamine, with regard to its efficacy over short and long-term periods, across single or repeated infusions, moderating variables related to the experimental design, and efficacy amongst patients with depression (MDD) or bipolar disorder (BD). Results conveyed that ketamine is an effective and rapid treatment for depression in the short term, with large antidepressant effects emerging after 4 hours and lasting up to 2 weeks post-infusion in participants with a primary diagnosis of MDD or BD. Repeated infusion showed larger effect sizes but did not extend the duration of antidepressant effect.
Ketamine for treatment-resistant depression: recent developments and clinical applications
2016 | Iosifescu, D. V., Murrough, J. W., Schwartz, J.
This clinical review (2016) examines the fasting-acting effects of ketamine for alleviating symptoms of major depressive disorder (MDD), with regard to its administration method, its safety profile, and its general effects on suicidal ideation, anhedonia, cognition. It also examines which patient profiles predict the most effective response duration while highlighting that the manifestation of depressive symptoms make it challenging to predict the efficacy of ketamine, and although further research is underway to elucidate the role of genetic, central neurobiological, and peripheral measures, it is still too early to recommend their adoption in clinical practice.
Ketamine for Treatment-Resistant Unipolar and Bipolar Major Depression: Critical Review and Implications for Clinical Practice
2016 | Bobo, W. V., Croarkin, P. E., Frye, M. A., Leung, J. G., Tye, S. J., Vande Voort, J. L.
This review (2016) examines the clinical efficacy of ketamine as fast-acting pharmacotherapy for major depressive disorder and bipolar disorder (BP), in light of the available evidence. In the authors' view, there is insufficient empirical support for the early adoption of ketamine into routine practice, given the lack of data on the longer-term safety of ketamine as an antidepressant therapy, which will require the development of clinical protocols with standardized screening, clinical phenotyping, and follow-up procedures.
Rapid infusion of esketamine for unipolar and bipolar depression: a retrospective chart review
2017| Araújo-de-Freitas, L., Argolo, F. C., Correia-Melo, F. S., Kapczinski, F., Lacerda, A. L. T., Leal, G. C., Quarantini, L. C.
This retrospective chart review (n=27) investigates the efficacy and safety of rapid infusion of esketamine in patients with treatment-resistant depression (TRD) and bipolar depression (BD). The study found that rapid infusion of esketamine is not the best choice for treatment-resistant depression due to tolerability issues. Additionally, patients reported dissociative symptoms ranging from mild to severe and found them to be disturbing.
Mental health of a self-selected sample of psychedelic users and self-medication practices with psychedelics
2018| Kuypers, K. P. C., Mason, N. L.
The observational survey study (n=1,967) investigated the frequency and efficacy of self-medication practices amongst psychedelic users and found that the prevalence of lifetime psychopathologies amongst psychedelic users was higher than in the general population. Although psychedelics were seldom used for self-medication, those who did use psychedelics in this manner reported it to be more effective than the current lines of treatment for mental illness.
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.
Long-Term Efficacy of Combination Therapy of Transcranial Magnetic Stimulation with Ketamine for Patients with Treatment-Resistant Depression
2021| Best, S. R. D., Haustrup, N., Pavel, D. G.
This retrospective review (n=28) investigated the clinical benefits of combining two therapies, repetitive transcranial magnetic stimulation (rTMS) and ketamine infusion (together CTK), for patients with treatment-resistant depression (TRD). The review found that all 28 patients experienced significant and enduring (two years) decreases in their depressive moods post the CTK therapy. The review also called for further research into method optimization and randomized controlled trials.
Rapid effectiveness of intravenous ketamine for ultraresistant depression in a clinical setting and evidence for baseline anhedonia and bipolarity as clinical predictors of effectiveness
2018| Baker, G., Dursun, S., Lind, J., Thomas, R. K.
This retrospective, open-label, database study (n=50) examined the efficacy of ketamine (35mg/70kg) treatment for patients with ultra-resistant depression and found that baseline anhedonia and bipolar disorder strongly predicted treatment response (44%) and the rate of symptom remission (16%) across participants.
Neurocognitive effects of six ketamine infusions and the association with antidepressant response in patients with unipolar and bipolar depression
2018| Chen, L., Li, H., Li, M., Liu, W., Ning, Y-P., Wang, C., Zhan, Y.
This open-label study (n=84) found that 6 ketamine (35mg/70kg) infusions over 12 days led to cognitive improvements (speed of processing, verbal learning) in those with depression. The improvements were mediated by the level of improvement in depressive symptoms. Those with a higher baseline of visual learning had the greatest antidepressant response.
Use of repeated intravenous ketamine therapy in treatment-resistant bipolar depression with suicidal behaviour: a case report from Spain
2017| Fernández-González, J. L., Galiano-Rus, S., López-Díaz, A., Luján-Jiménez, J. E.
This case study describes the successful treatment of 'treatment-resistant' bipolar depression (BD) with ketamine, but with a relapse in the fifth week of discharge as result of a suicide attempt.
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.
Blood pressure safety of subanesthetic ketamine for depression: A report on 684 infusions
2018| Dunlop, B. W., Edwards, J. A., Galendez, G. C., Garlow, S. J., Job, G. P., McDonald, W., Reiff, C. M., Riva-Posse, P., Saah, T. C.
This retrospective open-label study (n=66) assessed the blood pressure safety profile of subanesthetic ketamine (35mg/70kg) infusion for patients with depression. Although hypertensive patients had higher blood pressure peaks during the infusions, the overall changes in blood pressure were small, well-tolerated, and clinically insignificant.
Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression
2018| Ballard, E. D., Brutsche, N. E., Farmer, C. A., Jaso, B. A., Luckenbaugh, D. A., Niciu, M. J., Park, L. T., Shovestul, B. J., Zarate, C. A.
This follow-up study (n=126) investigated whether the antidepressant effects of ketamine (35mg/70kg) were related to dissociative symptoms experienced by patients with (bipolar) depression, and found that the subjective effects of depersonalization were most closely related to the antidepressant response.
A single infusion of ketamine improves depression scores in patients with anxious bipolar depression
2014| Ionescu, D. F., Luckenbaugh, D. A., Niciu, M. J., Richards, E. M., Zarate, C. A.
This randomized, double-blind, placebo-controlled, crossover, within-subjects study (n=36) investigated the effects of ketamine (35mg/70kg) treatment for anxious and non-anxious bipolar patients. Ketamine rapidly reduced symptoms of depression in patients with anxious bipolar depression to the same extent as those without anxiety.
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.
Single Ketamine Infusion and Neurocognitive Performance in Bipolar Depression
2014| Bartkowska-Sniatkowska, A., Kisielewski, J., Permoda-Osip, A., Rybakowski, J. K.
This open-label study (n=18) assessed antidepressant efficacy and neurocognitive performance of intravenous ketamine (35mg/70kg) in patients with bipolar depression (BD) and found that around half the patients responded to treatment. Independent of depressive symptoms, ketamine generally improved impairments in their cognitive performance, on measures related to psychomotor speed, verbal abilities, and executive functioning.
Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression
2014| Ameli, R., Lally, N., Luckenbaugh, D. A., Nugent, A. C., Roiser, J. P., Zarate, C. A.
This randomized, placebo-controlled, double-blind crossover within-subjects study (n=36) investigated the antidepressant efficacy of a single ketamine (35mg/70kg) infusion using positron emission tomography (PET) imaging on patients with bipolar depression (BD). Ketamine rapidly improved patients' anhedonia (emotional blunting), which was linked to increased glucose metabolism in their dorsal anterior cingulate cortex and putamen.
A Physician’s Attempt to Self-Medicate Bipolar Depression with N,N-Dimethyltryptamine (DMT)
2017| Ayub, S., Brown, T. L., Chong, D., Cornelius, C., Shao, W.
This article (2017) presents a case study of a physician who attempted to self-medicate with DMT in order to treat their bipolar depression (BD). However, the paper goes beyond the case study to discuss DMT in general terms, as well.
A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression
2010| Brutsche, N. E., Diazgranados, N., Ibrahim, L., Kammerer, W. A., Khalife, S., Kronstein, P., Luckenbaugh, D. A., Machado-Vieira, R., Manji, H., Newberg, A. B., Quezado, Z., Salvadore, G., Zarate, C. A.
This double-blind, placebo-controlled, randomized study (n=18) with those suffering from bipolar depression (BD; treatment-resistant) found that ketamine (35mg/70kg; 2x 2w apart) produced anti-depressant effects as measured on the MADRS scale. The effects were found immediately (40 minutes) and lasted up to three days.
Plasma BDNF concentrations and the antidepressant effects of six ketamine infusions in unipolar and bipolar depression
2021| Lan, X-F., Ning, Y-P., Wang, C-Y., Yan, S., Zhang, B., Zheng, W., Zhou, S-M., Zhou, Y-L.
This open-label study (n=94) finds that baseline plasma BDNF concentrations (a protein related to nerve growth) correlate with ketamine (6 infusions, 35mg/70kg) antidepressant effects (MADRS).
Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports
2021| Barrett, F. S., Erowid, E., Erowid, F., Griffiths, R. R., Gukasyan, N., Nayak, S.
This analysis of online reports (n=96) found that the use of psychedelics in combination with lithium led to seizures (47%), bad trips (64%), and emergency medical treatment (39%). The authors express the caution people should take when self-medicating/combining psychedelics with antidepressants (with lithium being commonly used for bipolar disorder).
Mania following use of ibogaine: A case series
2015| Koek, R. J., Kopelowicz, A., Marta, C. J., Ryan, W. C.
This case report (n=3) examines patients who developed manic symptoms and diagnosed with Bipolar-I disorder in response to ibogaine use. None of the patients had a prior diagnosis or family history of bipolar disorder, but all of them were poly-drug users or recovering from addiction. Manic symptoms which often included grand delusions that lasted up to two weeks after using ibogaine.
Switch to mania after ayahuasca consumption in a man with bipolar disorder: a case report
2015| Smith, J. M., Szmulewicz, A. G., Valerio, M. P.
This case report describes the clinical profile of a man from Argentina with a family history of bipolar disorder who participated in a four-day Ayahuasca ceremony that led to the eruption of a hypomanic episode two days after, consisting of mystical and paranoid delusional ideas, auditory hallucinations, racing thoughts, disorganized behavior, elevated energy, and manic euphoria. Given that the remission of psychotic symptoms was immediately followed by an onset of depressive symptoms, the authors theorize that antidepressant effects of harmine may have occasioned the manic shift of his bipolar disorder.
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.
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.