DOCSLIB.ORG

Comparative Efficacy and Side-Effect Profile of Ketamine And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparative Efficacy and Side-Effect Profile of Ketamine And BMJ Open: first published as 10.1136/bmjopen-2020-043457 on 12 February 2021. Downloaded from PEER REVIEW HISTORY BMJ Open publishes all reviews undertaken for accepted manuscripts. Reviewers are asked to complete a checklist review form (http://bmjopen.bmj.com/site/about/resources/checklist.pdf) and are provided with free text boxes to elaborate on their assessment. These free text comments are reproduced below. ARTICLE DETAILS TITLE (PROVISIONAL) Comparative efficacy and side effect profile of ketamine and esketamine in the treatment of unipolar and bipolar depression: protocol for a systematic review and network meta-analysis AUTHORS Zhan, Zhiqing; Wang, Xichao; Chen, Qing; Xiao, Zhidai; Zhang, Bin VERSION 1 – REVIEW REVIEWER Kenji Hashimoto Chiba University Center for Forensic Mental Health, Japan But I am an inventor of patent of the use of arketamine in the treatment of depression. REVIEW RETURNED 26-Sep-2020 GENERAL COMMENTS I have some minor comments. Abstract: Introduction: The sentence "Ketamine and esketamine are enantiomers" is wrong. I suggests that "Esketamine is (S)- enantiomer of ketamine" is better. Introduction: There is one article reporting head-to-head study of intravenous esketamine and intravenous ketamine in patients http://bmjopen.bmj.com/ (Correia-Melo et al, J Affect Disord 2020). Introduction There is a pilot report showing antidepressant actions of arketamine in treatment-resistant patients with MDD (Leal et al, Eur Arch Psychiatry Clin Neurosci 2020). Please cite this paper in the introduction. on September 24, 2021 by guest. Protected copyright. REVIEWER Jennifer Phillips University of Ottawa Institute of Mental Health Research, Canada REVIEW RETURNED 20-Nov-2020 GENERAL COMMENTS This systematic review will compare intravenous ketamine to intranasal esketamine in terms of therapeutic efficacy and side effects for the treatment of depression in patients with major depressive disorder and bipolar disorder. The study protocol is clear, well written and methodologically sound. However, I question the rationale for its publication when according to the authors stated timeline, the study has likely already occurred and the results may soon be ready for publication (within the paper, the authors state that they expect to submit the manuscript reporting their results before December 20, 2020). General comments 1 BMJ Open: first published as 10.1136/bmjopen-2020-043457 on 12 February 2021. Downloaded from The registration information should be updated as it appears the systematic review has been registered on PROSPERO (CRD42020201559). For data collection/extraction, it is not clear how the authors plan to deal with concomitant medications. There appears to be no mention of distinguishing between ketamine/esketamine as monotherapy versus adjunctive therapy. It is unclear what the authors mean by placebo? Will RCTs only be included if they used a true placebo as a comparator (ex. saline)? What about RCTs that compare ketamine to an active control (such as midazolam)? I commend the authors for including examination of potential sex differences for these treatments. Specific suggested revisions follow. Introduction -Page 5, Line 5. Unusual to highlight cognitive deficit over all other aspects of depression and its elevated burden to the individual and society at large- recommend revising opening sentence to better define depression. -Page 5, Line 11. Please change “full dose and long-term treatment” to “adequate dose and sufficient duration”. Also, the reference for this sentence is incorrect; I assume the sentence references the STAR-D trial? Please revise. -Page 5, Line 15. For more clarity when first introducing ketamine please specify that you are referring to the racemic mixture or ketamine hydrochloride, a mixture of the R and S enantiomers. -Page 5, Line 21. Revise language, treatment with ketamine does not necessarily “require intravenous administration”. It is most commonly administered intravenously to treat depression but other http://bmjopen.bmj.com/ routes of administration exist including oral, sublingual, transmucosal, intranasal, intramuscular, and subcutaneous. -Page 5, Line 36. While true that no RCTs comparing intranasal esketamine and intravenous ketamine have been published to date, several such studies are currently ongoing- that can be mentioned here. -Page 5, Line 38. Problem with tense, this sentence refers to having conducted the systematic review already. Protocol paper should use future tense throughout. on September 24, 2021 by guest. Protected copyright. Methods and Analysis -Page 6, Line 9. Inclusion criteria B please clarify intravenous ketamine -Page 6, Line 40-45. Inconsistent spelling of crossover (sometimes two words, sometimes hyphenated), please correct “precross- overphase”. -Page 6, Line 45. Please specify how you will deal with papers that fail to report pre-crossover phase data? Will you contact study authors directly to obtain this data? -Page 7, Table 1, Section 1.2 CNKI searing strategy. Unable to review (language). 2 BMJ Open: first published as 10.1136/bmjopen-2020-043457 on 12 February 2021. Downloaded from VERSION 1 – AUTHOR RESPONSE Reviewing: 1 Comments to the Author: I have some minor comments. #1 Abstract: Introduction: The sentence "Ketamine and esketamine are enantiomers" is wrong. I suggests that "Esketamine is (S)- enantiomer of ketamine" is better. Response: Thank you for this comment. As you advised, we have changed the sentence "Ketamine and esketamine are enantiomers" to "Esketamine is (S)- enantiomer of ketamine". Revision: Abstract: Esketamine is (S)- enantiomer of ketamine. (Page 2, Line 5) #2 Abstract: Introduction: There is one article reporting head-to-head study of intravenous esketamine and intravenous ketamine in patients (Correia-Melo et al, J Affect Disord 2020). Response: Thank you for this comment. As you advised, we have revised this sentence and cited the article (Correia-Melo et al, J Affect Disord 2020). http://bmjopen.bmj.com/ Revision: Abstract: However, there is limited evidence comparing esketamine and ketamine in treating unipolar and bipolar depression have been published so far. (Page 2, Line 7-9) Introduction: However, only one head- to-head study assessed the efficacy and safety of ketamine compared to esketamine. (Page 3, Line 28-30) on September 24, 2021 by guest. Protected copyright. #3 Introduction： There is a pilot report showing antidepressant actions of arketamine in treatment-resistant patients with MDD (Leal et al, Eur Arch Psychiatry Clin Neurosci 2020). Please cite this paper in the introduction. Response: Thank you for this comment. As you advised, we have cited this paper in the introduction. Revision: Introduction: To date, there are several studies16-22 evaluating the efficacy and side effect profile of the enantiomers of ketamine, including esketamine16-21, the S (-)-enantiomer of ketamine, and arketamine22, the R (-)-enantiomer of ketamine. (Page 3, Line 26-28) 3 BMJ Open: first published as 10.1136/bmjopen-2020-043457 on 12 February 2021. Downloaded from Reference 16.Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry 2018; 75(2):139-148 17.Popova V, Daly EJ, Trivedi M, et al. Efficacy and Safety of Flexibly Dosed Esketamine Nasal Spray Combined With a Newly Initiated Oral Antidepressant in Treatment-Resistant Depression: A Randomized Double-Blind Active-Controlled Study. Am J Psychiatry 2019; 176(6):428-438 18.Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry 2018; 175(7):620-630 19.Kryst J, Kawalec P, Pilc A. Efficacy and safety of intranasal esketamine for the treatment of major depressive disorder. Expert Opin Pharmacother 2020; 21(1):9-20. 20.Fedgchin M, Trivedi M, Daly EJ, et al. Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1). Int J Neuropsychopharmacol 2019;22(10):616-630. 21.Fu DJ, Ionescu DF, Li X, et al. 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). J Clin Psychiatry 2020 81(3):19m13191. 22.Leal GC, Bandeira ID, Correia-Melo FS, et al. Intravenous arketamine for treatment-resistant depression: open-label pilot study. Eur Arch Psychiatry Clin Neurosci 2020. doi: 10.1007/s00406-020- 01110-5. http://bmjopen.bmj.com/ Reviewer: 2 Comments to the Author: #1 This systematic review will compare intravenous ketamine to intranasal esketamine in terms of on September 24, 2021 by guest. Protected copyright. therapeutic efficacy and side effects for the treatment of depression in patients with major depressive disorder and bipolar disorder. The study protocol is clear, well written and methodologically sound. However, I question the rationale for its publication when according to the authors stated timeline, the study has likely already occurred and the results may soon be ready for publication (within the paper, the authors state that they expect to submit the manuscript reporting their results before December 20, 2020). Response: Thank
Load more

Recommended publications
  • SPRAVATO® Esketamine Hydrochloride DATA SHEET
    SPRAVATO® esketamine hydrochloride DATA SHEET 1. PRODUCT NAME SPRAVATO® esketamine hydrochloride 32.3mg (equivalent to 28mg esketamine) nasal spray 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each single use nasal spray device delivers two sprays, one spray into each nostril. Total volume of drug product per device to be delivered is 0.2 mL containing a total of 32.3 mg of esketamine hydrochloride (equivalent to 28 mg of esketamine). For the full list of excipients, see Section 6.1 List of Excipients. 3. PHARMACEUTICAL FORM Nasal spray, solution. Clear, colourless, aqueous solution. 4. CLINICAL PARTICULARS 4.1 Therapeutic Indications SPRAVATO in conjunction with an oral antidepressant, is indicated for: - treatment resistant depression (Major Depressive Disorder in adults who have not responded adequately to at least two different antidepressants of adequate dose and duration to treat the current depressive episode). - rapid reduction of depressive symptoms in patients with Major Depressive Disorder who have acute suicidal ideation or behaviour. SPRAVATO is not indicated to prevent suicide or in reducing suicidal ideation or behaviour (see section 4.4. Special Warnings And Precautions For Use) 4.2 Dose and method of administration In patients with TRD, SPRAVATO should be administered in conjunction with a newly initiated oral antidepressant (AD) therapy. In patients with MDSI, SPRAVATO should be administered in conjunction with standard of care therapy. During the Phase III MDSI clinical program, standard of care oral AD treatment (either AD monotherapy or AD plus augmentation therapy) was initiated or optimised. Important Considerations Prior to Initiating and During Therapy SPRAVATO must be administered under the direct supervision of a healthcare provider.
    [Show full text]
  • Around the Corner Canadian Equity Research Emerging Companies and Industries to Watch 3 March 2020
    Around the Corner Canadian Equity Research Emerging companies and industries to watch 3 March 2020 Tania Gonsalves, CFA | Analyst | Canaccord Genuity Corp. (Canada) | [email protected] | 1.416.996.8346 Scott McFarland | Associate | Canaccord Genuity Corp. (Canada) | [email protected] | 1.416.998.7202 Around the Corner highlights what we believe are some of the most exciting Psychedelic-derived medicines and therapies emergent private companies in Canada, and/or industry themes and trends which are yet to be fully represented in the Mental health miracle or another bad trip? public markets. When most of us think of psychedelic drugs, we think of the 1960s counterculture. We We aim to offer insight into early industry think of anti-establishment, anti-war, anti-capitalist hippies, Woodstock, tie-dye, Lucy in trends, educate investors about private the Sky, peace, love and bell bottom jeans. But before psychedelics became ingrained in companies that are making a mark, and the counterculture, they were found in a lab. The first wave of scientific research on identify companies that may enter the psychedelics took place between 1950-65. Sandoz Pharmaceutics, what is now Novartis public markets in the future. AG (NVS-NYSE), the third largest pharmaceutical company in the world, used to market We do not provide any ratings or price LSD and psilocybin for psychotherapeutic purposes. Psychedelics weren’t born of the targets, nor should any be inferred, for counterculture. They were killed by it. The proliferation of recreational use spurred any uncovered company featured in government intervention and by 1971, psilocybin, LSD, ibogaine, mescaline, peyote, Around the Corner.
    [Show full text]
  • Janssen Research & Development, LLC Advisory Committee Briefing
    Janssen Research & Development, LLC Advisory Committee Briefing Document Esketamine Nasal Spray for Patients with Treatment-resistant Depression JNJ-54135419 (esketamine) Status: Approved Date: 16 January 2019 Prepared by: Janssen Research & Development, LLC EDMS number: EDMS-ERI-171521650, 1.0 ADVISORY COMMITTEE BRIEFING MATERIALS: AVAILABLE FOR PUBLIC RELEASE 1 Status: Approved, Date: 16 January 2019 JNJ-54135419 (esketamine) Treatment-resistant Depression Advisory Committee Briefing Document GUIDE FOR REVIEWERS This briefing document provides 3 levels of review with increasing levels of detail: The Executive Overview (Section 1, starting on page 11) provides a narrative summarizing the disease, need for novel treatments, key development program characteristics for esketamine nasal spray, study results, and conclusions. References are made to the respective supporting sections in the core document. The core document (Section 2 to Section 11, starting on page 30) includes detailed summaries and discussion in support of the Executive Overview. The appendices (starting on page 180) provide additional or more detailed information to complement brief descriptions provided in sections of the core document (e.g., demographic and baseline characteristics of the study populations, additional efficacy analyses in the Phase 3 studies, statistical methods). These appendices are referenced in the core document when relevant. This review structure allows review at varying levels of detail; however, reviewers who read at multiple levels will necessarily
    [Show full text]
  • Glutamatergic Synapse: a Promising Target to Treat Major Depressive Disorder (Mdd)
    GLUTAMATERGIC SYNAPSE: A PROMISING TARGET TO TREAT MAJOR DEPRESSIVE DISORDER (MDD) Glutamatergic Synapse: A Promising Target to Treat Major Depressive Disorder (MDD) Varinder Garg1, Harish Kumar2, Surinder Rana3, Bikramjeet Singh Kalsi4, Lakshmi Akhila Rajnala5, Ramandeep Kaur6, Jyoti Rustagi7, Swati8, Chesta9 1 MBBS, MD Principal Investigator, ICMR-Centre for Innovation and Bio-Design, Room No. 2022 and 2027, Advanced Cardiac Centre, PGIMER, Sector 12, Chandigarh, 160012. Email: [email protected] 2 B.E., M.E., PhD CSE Dept, UIET Panjab University, Chandigarh 160014. 3 M.D., D.M Gastroenterology, Professor, Department of Gastroenterology, PGIMER, Sector 12, Chandigarh, 160012. Email: [email protected] 4 B. Tech., Computer Science, UIET Panjab University, Chandigarh 160014. 5 B.E (Hons)., Biotechnology, Vignan University, Andhra Pradesh 6,9 B.Sc. Hons In Microbiology and Food Technology, MCM Dav College for Women, Sec 36 A, Chandigarh 7,8 M.Sc. Zoology, Post Graduate Government College for Girls, Sector -11 Chandigarh ABSTRACT After few decades, mono-amine hypothesis could grab the attention of millions with the captivating evidence that, prevailing changes in the areas of brain with complex networks of cognitive and emotional behaviors for long time witnessing mood and anxiety disorders. Major Depressive Disorder (MDD) encompasses a large number of psychological illness include, loss of interest, mood disturbance, loss of appetite, insomnia, feeling of fatigue and decreased concentration and standing as the major illness worldwide. Later on, a wealth of data from experimental models started exploring on the environmental factors enhancing the stress which enhances some powerful exerts and induces limbic remodeling or the reduction of synapses pivoted by “Glutamatergic Synapse”.
    [Show full text]
  • The Neurobiology of Treatment-Resistant Depression: from Antidepressant Classifications to Novel Pharmacological Targets
    1521-0081/70/3/475–504$35.00 https://doi.org/10.1124/pr.117.014977 PHARMACOLOGICAL REVIEWS Pharmacol Rev 70:475–504, July 2018 Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: ELIOT H. OHLSTEIN International Union of Basic and Clinical Pharmacology CIV: The Neurobiology of Treatment-resistant Depression: From Antidepressant Classifications to Novel Pharmacological Targets F. Caraci, F. Calabrese, R. Molteni, L. Bartova, M. Dold, G. M. Leggio, C. Fabbri, J. Mendlewicz, G. Racagni, S. Kasper, M. A. Riva,1 and F. Drago1 Departments of Drug Sciences (F.Car.) and Biomedical and Biotechnological Sciences, School of Medicine (G.M.L., F.D.), University of Catania, Catania, Italy; Oasi-Research-Institute-IRCCS, Troina, Italy (F.Car.); Departments of Pharmacological and Biomolecular Sciences (F.Cal., G.R., M.A.R.) and Medical Biotechnology and Translational Medicine (R.M.), Università degli Studi di Milano, Milan, Italy; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria (L.B., M.D., S.K.); Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy (C.F.); and School of Medicine, Universite’ Libre de Bruxelles, Bruxelles, Belgium (J.M.) Abstract ...................................................................................476 I. Introduction . ..............................................................................476 Downloaded from II. The New Neuroscience-Based Nomenclature and the Classification of Antidepressant
    [Show full text]
  • Ketamine (C13h16clno)
    Ketamine (C13H16ClNO) Ketamine General Facts Molecular formular: C13H16ClNO Systematic name: 2-(2-chlorophenyl)-2-(methylamino)cyclohexan-1-one (IUPAC name) Alternatenames: a. In medical jargon: Ketaject, Ketanest, dl-Ketamine, Ketalar, CI 581 base, CLSTA 20, Ketolar b. In drug jargon: special K, green, jet, K, and super C Molar mass: 237.092042 g/mol Appearance: white powder, colorless liquid History and Discovery Initial genesis: finding a substitude for Morphin as a anaesthetic initially: Heroin, however too addicting temporary substitute: phencyclidine (PCP) Phencyclidine strong analgesic properties, hallucinogenic effects leading to an introduction in drug world as „angel dust“ 1962: Ketamine as drug with milder side-effects but similar structure 1964: experiments on paid prisoners, first suspicion on effects on psyche 1966: patent by Clarke-Davis 1970: officially in use proven as safe and very effective anaesthetic and painkiller for humans and animals effects strike quickly and does not cause depression or collapse of airways Used for casualties of traffic accidents or battlefield victims Historical usage: Vietnam war as anaesthetic however, still with psychic side effects Synthesis (following the mechanism developed by Calvin L. Stevens) Initial reagent: cyclopentyl Grignard Step 0: Producing cyclopentyl Grignard Reacting cyclopentyl bromide with magnesium in solvent (ether or THF) Best results: distill solvent from Grignard under vacuum and replace with hydrocarbon solvent (e.g. benzene) Step 1: processing to (o-chlorophenyl)-cyclopentyl
    [Show full text]
  • Esketamine Spray Drug to Cure Paralysis
    Editorial Journal of Volume 5:2, 2021 Formulation Science & Bioavailability ISSN: 2577-0543 Open Access Esketamine Spray Drug to Cure Paralysis Ziemandonald* Department of formulation and bioavailability, University of Cologne, Germany Esketamine drug is employed within the treatment of restrictive depression These receptors are liable for the transmission of excitatory chemical signals in adults. In 1997 Esketamine is introduced in medical use and now in March through the Centre systema nervosum and are the key point to strengthen or 5th, 2019 it's approved by FDA for the treatment of depression in adults by weaken the power of the synapses i.e. synaptic plasticity. Like other drugs the nasal route. Oneamong good advantage of Nasal Spray is that it'll act faster common side effects that are observed within the trials are Vomiting, Anxiety, and potentially help those patients which experience suicidal thoughts more and Increase in vital sign , Vomiting, Nausea, dissociation, and Sedation but quickly. it's the non-competitive N-methyl-D-aspartate (NMDA) receptor just in case of efficacy this drug may be a potent and helpful drug to cure antagonist and up to some extent it'll also act on dopamine reuptake inhibitor serious depression. Recently, FDA approved Esketamine drug nasal spray but don't interact with sigma receptor as like ketamine drug. it's a sort of under the name of Spravato or Ketanest to cure severe depression. ketamine drug which is approved by FDA in 1970 which having two chemical The all procedure for that drug has been done by Johnson & Johnson forms R and S and Esketamine contain on of it and that i .e.
    [Show full text]
  • 211243Orig1s000
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 211243Orig1s000 OTHER REVIEW(S) MEMORANDUM REVIEW OF REVISED LABEL AND LABELING Division of Medication Error Prevention and Analysis (DMEPA) Office of Medication Error Prevention and Risk Management (OMEPRM) Office of Surveillance and Epidemiology (OSE) Center for Drug Evaluation and Research (CDER) Date of This Memorandum: March 5, 2019 Requesting Office or Division: Division of Psychiatry Products (DPP) Application Type and Number: NDA 211243 Product Name and Strength: Spravato (esketamine) nasal spray, 56 mg dose kit and 84 mg dose kit (28 mg per device) Applicant/Sponsor Name: Janssen Pharmaceuticals, Inc. FDA Received Date: March 5, 2019 (via email) OSE RCM #: 2018-1873-2 DMEPA Safety Evaluator: Loretta Holmes, BSN, PharmD DMEPA Team Leader: Sevan Kolejian, PharmD, MBA 1 PURPOSE OF MEMORANDUM The Division of Psychiatry Products (DPP) requested that we review the device label, blister labeling, carton labeling and Instructions for Use for Spravato (Appendix A) to determine if they are acceptable from a medication error perspective. The revisions are in response to recommendations that we made during a previous label and labeling reviewa and other Agency recommendations provided to Janssen via email. 2 CONCLUSION The revised device label, blister labeling, carton labeling and Instructions for Use for Spravato are acceptable from a medication error perspective. We have no further recommendations at this time. a Holmes, L. Human Factors Results and Label and Labeling Review for Spravato (NDA 211243). Silver Spring (MD): FDA, CDER, OSE, DMEPA (US); 2019 Feb 28. RCM No.: 2018-1875-1 and 2018-1873-1. 1 Reference ID: 4399400 APPENDIX A.
    [Show full text]
  • Brain NMDA Receptors in Schizophrenia and Depression
    biomolecules Review Brain NMDA Receptors in Schizophrenia and Depression Albert Adell 1,2 1 Institute of Biomedicine and Biotechnology of Cantabria, IBBTEC (CSIC-University of Cantabria), Calle Albert Einstein 22 (PCTCAN), 39011 Santander, Spain; [email protected] or [email protected] 2 Biomedical Research Networking Center for Mental Health (CIBERSAM), 39011 Santander, Spain Received: 3 June 2020; Accepted: 21 June 2020; Published: 23 June 2020 Abstract: N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP), dizocilpine (MK-801) and ketamine have long been considered a model of schizophrenia, both in animals and humans. However, ketamine has been recently approved for treatment-resistant depression, although with severe restrictions. Interestingly, the dosage in both conditions is similar, and positive symptoms of schizophrenia appear before antidepressant effects emerge. Here, we describe the temporal mechanisms implicated in schizophrenia-like and antidepressant-like effects of NMDA blockade in rats, and postulate that such effects may indicate that NMDA receptor antagonists induce similar mechanistic effects, and only the basal pre-drug state of the organism delimitates the overall outcome. Hence, blockade of NMDA receptors in depressive-like status can lead to amelioration or remission of symptoms, whereas healthy individuals develop psychotic symptoms and schizophrenia patients show an exacerbation of these symptoms after the administration of NMDA receptor antagonists. Keywords: NMDA; depression; schizophrenia; subunit; glutamate; GABA 1. Introduction The N-Methyl-D-aspartate (NMDA) receptor (NMDAR) is an ionotropic glutamate receptor that possesses unique characteristics. The flow of ions through the channel is blocked by Mg2+. Two different processes are necessary for activating NMDARs.
    [Show full text]
  • Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine
    The Journal of Neuroscience, February 3, 2021 • 41(5):891–900 • 891 Symposium/Mini-Symposium Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Danilo De Gregorio,1 Argel Aguilar-Valles,2p Katrin H. Preller,3p Boris Dov Heifets,4p Meghan Hibicke,5p Jennifer Mitchell,6p and Gabriella Gobbi1 1Department of Psychiatry, McGill University, Montreal, Quebec H3A 1A1, Canada, 2Department of Neuroscience, Carleton University, Ottawa, Ontario K1S 5B6, Canada, 3Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, CH-8032 Zurich, Switzerland, 4Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California 94305, 5Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, and 6Department of Neurology, University of California San Francisco, San Francisco, California 94158 A revamped interest in the study of hallucinogens has recently emerged, especially with regard to their potential application in the treatment of psychiatric disorders. In the last decade, a plethora of preclinical and clinical studies have confirmed the efficacy of ketamine in the treatment of depression. More recently, emerging evidence has pointed out the potential therapeu- tic properties of psilocybin and LSD, as well as their ability to modulate functional brain connectivity. Moreover, MDMA, a compound belonging to the family of entactogens, has been demonstrated to be useful to treat post-traumatic stress disor- ders. In this review, the pharmacology of hallucinogenic compounds is summarized by underscoring the differences between psychedelic and nonpsychedelic hallucinogens as well as entactogens, and their behavioral effects in both animals and humans are described. Together, these data substantiate the potentials of these compounds in treating mental diseases.
    [Show full text]
  • The Path Forward for Psychedelic Assisted Psychotherapy Investor Presentation July 2020 Our Mission
    The Path Forward for Psychedelic Assisted Psychotherapy Investor Presentation July 2020 Our Mission To bring the world to life through psychedelics and psychedelic enhanced psychotherapy. ©2020 Core One Labs 22 The Problem Mental health conditions are on the rise. Rapid Growth. Limited Treatments. ©2020 Core One Labs 3 75% Non-adherence rates to anti-depressants +2 Current treatments haven’t Point improvement on Hamilton changed in decades Depression Score (out of 52) and have proven to be ineffective with 40-71% undesired side-effects Relapse rates Side Effects Addiction, Insomnia, Agitation, Loss of Libido, Violent Impulses, Suicidal Impulses 1. Star*D Study ©2020 Core One Labs 4 Psychedelics: A Promising Solution The results from the clinical and academical studies on psychedelic-assisted psychotherapy are compelling Evidence for Psychedelic Therapies For depression For addiction For general well-being Extended relief from Addiction decreases after Sustained improvement in quality depression >3months psilocybin treatment oflife and satisfaction 75 40 Severe days First psilocybin treatment following depression week 4 assessments 30 drinking participants Mo d e r a t e 50 of depression of (%) (%) 20 (%) Mild depression 25 Percent 10 Percent Before 1 2 3 5 3 Weeks Weeks Weeks Weeks Weeks 2 months after 2 months 14 months treatment W eek Weeks Weeks Weeks Months 1-4 5-6 9-12 13-24 25-36 methylphenidate after after treatment psilocybin psilocybin (control) treatment treatment Source: Psilocybin with Psychological Support for Treatment Resistant Source: Psilocybin-assisted treatment for alcohol dependence: Source: Psilocybin-occasioned mystical-type experience in combination with Depression, R. Carhart-Harris, The Lancet A proof- ofconcept study, M.
    [Show full text]
  • APSF3502.Pdf
    APSF.ORG NEWSLETTER THE OFFICIAL JOURNAL OF THE ANESTHESIA PATIENT SAFETY FOUNDATION Volume 35, No. 2, 33–68 More than 1,000,000 readers annually worldwide June 2020 Disclaimer: Viewers of this material should review the information contained within it with appropriate medical and legal counsel and make their own determinations as to relevance to their particular practice setting and compliance with state and federal laws and regulations. The APSF has used its best efforts to provide accurate information. However, this material is provided only for informational purposes and does not constitute medical or legal advice. These articles also should not be construed as representing APSF endorsement or policy (unless otherwise stated), making clinical recommendations, or substituting for the judgment of a physician and consultation with independent legal counsel. An Update on the Perioperative Considerations for COVID-19 Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) by Liana Zucco, MD; Nadav Levy, MD; Desire Ketchandji, MD; Michael Aziz, MD; and Satya Krishna Ramachandran, MD INTRODUCTION over 3.1 million people, as of April 29, 2020, with 1,2 The COVID-19 pandemic caused by the over 1 million cases in the United States alone. severe acute respiratory syndrome coronavirus-2 Current estimates suggest a fatality rate (SARS-CoV-2) continues to have a profound ranging from 2 to 20% for hospitalized patients, impact on life across the globe and has placed and up to 88% for those requiring mechanical 3–5 an enormous strain on health care systems and ventilation. SARS-CoV-2 has an estimated basic reproductive number (R0) of 2.2–2.7,6 economies, including with likely untold psycho- which means a single infected person has the logical and social implications.
    [Show full text]