Dextromethorphan Abuse
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Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss
Supplemental Material can be found at: /content/suppl/2020/12/18/73.1.202.DC1.html 1521-0081/73/1/202–277$35.00 https://doi.org/10.1124/pharmrev.120.000056 PHARMACOLOGICAL REVIEWS Pharmacol Rev 73:202–277, January 2021 Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license. ASSOCIATE EDITOR: MICHAEL NADER Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanismss Antonio Inserra, Danilo De Gregorio, and Gabriella Gobbi Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University, Montreal, Quebec, Canada Abstract ...................................................................................205 Significance Statement. ..................................................................205 I. Introduction . ..............................................................................205 A. Review Outline ........................................................................205 B. Psychiatric Disorders and the Need for Novel Pharmacotherapies .......................206 C. Psychedelic Compounds as Novel Therapeutics in Psychiatry: Overview and Comparison with Current Available Treatments . .....................................206 D. Classical or Serotonergic Psychedelics versus Nonclassical Psychedelics: Definition ......208 Downloaded from E. Dissociative Anesthetics................................................................209 F. Empathogens-Entactogens . ............................................................209 -
Dextromethorphan and Memantine After Ketamine Analgesia: a Randomized Control Trial
Drug Design, Development and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article ORIGINAL RESEARCH Dextromethorphan and memantine after ketamine analgesia: a randomized control trial This article was published in the following Dove Press journal: Drug Design, Development and Therapy Elodie Martin,1 Marc Sorel,2 Purpose: Intravenous ketamine is often prescribed in severe neuropathic pain. Oral N- 3 Véronique Morel, Fabienne methyl-D-aspartate receptor (NMDAR) antagonists might prolong pain relief, reducing the 4 4 Marcaillou, Pascale Picard, frequency of ketamine infusions and hospital admissions. This clinical trial aimed at asses- Noémie Delage,4 Florence sing whether oral dextromethorphan or memantine might prolong pain relief after intrave- Tiberghien,5 Marie-Christine 6 6 nous ketamine. Crosmary, Mitra Najjar, Renato Colamarino,6 Christelle Créach,7,8 Patients and methods: A multicenter randomized controlled clinical trial included 60 Béatrice Lietar,7 Géraldine Brumauld patients after ketamine infusion for refractory neuropathic pain. Dextromethorphan (90 mg/ de Montgazon,9 Anne Margot- day), memantine (20 mg/day) or placebo was given for 12 weeks (n=20 each) after ketamine 10 11,12 Duclot, Marie-Anne Loriot, infusion. The primary endpoint was pain intensity at one month. Secondary endpoints 11,12 13 Céline Narjoz, Céline Lambert, included pain, sleep, anxiety, depression, cognitive function and quality of life evaluations 13 1,3 Bruno Pereira, Gisèle Pickering up to 12 weeks. 1Université Clermont Auvergne, Pharmacologie Results: At 1 month, dextromethorphan maintained ketamine pain relief (Numeric Pain Fondamentale Et Clinique de la Douleur, Neuro- Dol, Inserm 1107, F-63000 Clermont-Ferrand, Scale: 4.01±1.87 to 4.05±2.61, p=0.53) and diminished pain paroxysms (p=0.03) while pain France; 2Centre D’evaluation et de Traitement de intensity increased significantly with memantine and placebo (p=0.04). -
ICE 2020/1 Seized Materials Test Group
INTERNATIONAL COLLABORATIVE EXERCISES (ICE) Summary Report ICE Round 2020/1 1 SEIZED MATERIALS / 20 ICE 20 International Collaborative Exercises (ICE) Summary report 2020/1-Seized Materials Final summary report for ICE 2020/1 Seized Materials Test Group Original language: English © United Nations, January 2021. All rights reserved, worldwide. The designations employed and the presentation of material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. This publication has not been formally edited. ICE 2020/1-SM Copyright © 2021 UNODC Page 1 of 104 International Collaborative Exercises (ICE) Summary report 2020/1-Seized Materials Acknowledgements The Laboratory and Scientific Section (LSS) of the UNODC, headed by Dr. Justice Tettey, wishes to express its appreciation and thanks to all laboratories for participating in the International Collaborative Exercises (ICE) round 2020/1. The valuable comments and contribution from the following members of the International Panel of Forensic Experts are gratefully acknowledged: Mr. Benoit Archambault, Health Canada, Canada Mr. Elvio Dias Botelho, Brazilian Federal Police, Brazil Prof. Heesun Chung, Sungkyunkwan University, Republic of Korea Prof. Niamh Nic Daéid, University of Dundee, Scotland, UK Mr. Scott Oulton, Drug Enforcement Administration, USA Ms. Catherine Quinn, Victoria Police, Australia Prof. Franco Tagliaro, University of Verona, Italy Dr. Angeline Tiong Whei Yap, Health Sciences Authority, Singapore In addition, LSS would like to acknowledge the valuable contribution of the Chemical Metrology Laboratory of the Health Sciences Authority, Singapore, for the provision of specific software used for the quantitative statistical calculations in the ICE programme. -
Separation, Quantification and Control of Enatiomers of the Key Starting Material of Dextromethorphan Hydrobromide
Journal of Applied Pharmaceutical Science Vol. 8(08), pp 032-038, August, 2018 Available online at http://www.japsonline.com DOI: 10.7324/JAPS.2018.8805 ISSN 2231-3354 Separation, Quantification and Control of Enatiomers of the Key Starting Material of Dextromethorphan Hydrobromide Ajit Anerao*, Vishal Solase, Amol More, Nitin Pradhan R&D Centre (API), Wanbury Ltd., EL-16, TTC Industrial Estate, Mahape, Navi Mumbai 400710, India. ARTICLE INFO ABSTRACT Article history: Objective: Enantiomeric resolution of racemic 1-(4-Methoxybenzyl)-1,2,3,4,5,6,7,8-octahydroisoquinoline, a key Received on: 16/05/2018 starting material in the synthesis of the antitussive agent dextromethorphan hydrobromide. Material and method: Accepted on: 11/07/2018 Chiral liquid chromatographic method is developed and enantiomers are resolved on a Chiralpak ID-3 column using Available online: 31/08/2018 gradient mode of elution. Mobile phase A and B containing a mixture of 0.1% diethylamine in acetonitrile and 0.1% diethylamine in methanol respectively are optimized with the timed programme. The flow rate is 1.0 mL/minute and the column temperature was maintained at 40°C. Ultraviolet detection was performed at 280 nm wavelength and Key words: the injection volume was 20 μL. Results: The resolution between the enantiomers is found to be more than 2.5. The HPLC; chiral purity; developed method is extensively validated and proved to be robust. The limit of detection and limit of quantification dextromethorphan; of unwanted (R)-enantiomer is found to be 0.0075% and 0.025% with respect to test concentration, respectively. The development; validation. -
Test Update Notification, Effective December 7, 2015
Effective Date: Monday, December 07, 2015 Test Updates In our continuing effort to provide you with the highest quality toxicology laboratory services available, we have compiled important changes regarding a number of tests we perform. Listed below are the types of changes that may be included in this notification, effective Monday, December 07, 2015 Test Changes - Tests that have had changes to the method/ CPT code, units of measurement, scope of analysis, reference comments, or specimen requirements. Discontinued Tests - Tests being discontinued with alternate testing suggestions. Please use this information to update your computer systems/records. These changes are important to ensure standardization of our mutual laboratory databases. If you have any questions about the information contained in this notification, please call our Client Support Department at (866) 522-2206. Thank you for your continued support of NMS Labs and your assistance in implementing these changes. The CPT Codes provided in this document are based on AMA guidelines and are for informational purposes only. NMS Labs does not assume responsibility for billing errors due to reliance on the CPT Codes listed in this document. NMS LABS 3701 Welsh Road Willow Grove, PA 19090 www.NMSLabs.com Page 1 of 15 Effective Date: Monday, December 07, 2015 Test Updates Test Test Name Test Method / Specimen Stability Scope Units Reference Discontinue Code Name CPT Code Req. Comments Antidepressants / Antihistamines 52467U • Confirmation Panel 1, Urine (Forensic) 1330N Copper, Nails -
Hallucinogens Life-Threatening Manifestations and Resuscitative Measures in the Intensive Care Setting
CHAPTER 34. Ben-Abraham R, Szold O, Rudick V, Weinbroum AA: ‘Ecstasy’ intoxication: Hallucinogens life-threatening manifestations and resuscitative measures in the intensive care setting. Eur J Emerg Med 10: 309, 2003. Katherine M. Prybys 35. Turillazzi E, Riezzo I, Neri M, Bello S, Fineschi V: MDMA toxicity and pathological 188 consequences: a review about experimental data and autopsy findings. Curr Pharm Karen N. Hansen Biotechnol 11: 500, 2010. 36. Oesterheld JR, Armstrong SC, Cozza KL: Ecstasy: pharmacodynamic and pharmacoki- netic interactions. Psychosomatics 45: 84, 2004. 37. Halpern JH, Sherwood AR, Hudson JI, Gruber S, Kozin D, Pope HG Jr: Residual REFERENCES neurocognitive features of long-term ecstasy users with minimal exposure to other drugs. Addiction 106: 777, 2011. 1. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE: Monitoring the Future 38. Hall AP, Henry JA: Acute toxic effects of ‘Ecstasy’ (MDMA) and related compounds: national survey results on drug use, 1975-2010. Volume I: secondary school students. overview of pathophysiology and clinical management. Br J Anaesth 96: 678, 2006. Ann Arbor, MI. Institute for Social Research, The University of Michigan; 2011. 39. Bordo DJ, Dorfman MA: Ecstasy overdose: rapid cooling leads to successful outcome. 2. Johnston LD, O’Malley PM, Bachman JG, Schulenberg JE: Monitoring the Future national Am J Emerg Med 22: 326, 2004. survey results on drug use, 1975-2010. Volume II: college students and adults ages 19-50. 40. Moon J, Cros J: Role of dantrolene in the management of the acute toxic effects of Ann Arbor. MI. Institute for Social Research, The University of Michigan; 2011. -
When Good Times Go Bad: Managing 'Legal High' Complications in The
Journal name: Open Access Emergency Medicine Article Designation: REVIEW Year: 2018 Volume: 10 Open Access Emergency Medicine Dovepress Running head verso: Caffrey and Lank Running head recto: Legal highs open access to scientific and medical research DOI: http://dx.doi.org/10.2147/OAEM.S120120 Open Access Full Text Article REVIEW When good times go bad: managing ‘legal high’ complications in the emergency department Charles R Caffrey Abstract: Patients can use numerous drugs that exist outside of existing regulatory statutes in Patrick M Lank order to get “legal highs.” Legal psychoactive substances represent a challenge to the emergency medicine physician due to the sheer number of available agents, their multiple toxidromes and Department of Emergency Medicine, Feinberg School of Medicine, presentations, their escaping traditional methods of analysis, and the reluctance of patients to Northwestern University, Chicago, divulge their use of these agents. This paper endeavors to cover a wide variety of “legal highs,” IL, USA or uncontrolled psychoactive substances that may have abuse potential and may result in seri- ous toxicity. These agents include not only some novel psychoactive substances aka “designer drugs,” but also a wide variety of over-the-counter medications, herbal supplements, and even a household culinary spice. The care of patients in the emergency department who have used “legal high” substances is challenging. Patients may misunderstand the substance they have been exposed to, there are rarely any readily available laboratory confirmatory tests for these substances, and the exact substances being abused may change on a near-daily basis. This review will attempt to group legal agents into expected toxidromes and discuss associated common clinical manifestations and management. -
The Emerging Role of NMDA Antagonists in Pain Management Dana Jamero, Pharmd, BCOP; Amne Borghol, Pharmd; Nina Vo, Pharmd Candidate; Fadi Hawawini, DO US Pharmacist
http://www.medscape.com/viewarticle/744071_print www.medscape.com The Emerging Role of NMDA Antagonists in Pain Management Dana Jamero, PharmD, BCOP; Amne Borghol, PharmD; Nina Vo, PharmD Candidate; Fadi Hawawini, DO US Pharmacist Abstract and Introduction Introduction An estimated 50 million Americans currently suffer from chronic pain, along with another 25 million who suffer from acute pain.[1] Each year, nearly half of all Americans present to their physician with a chief complaint of pain.[2] The mainstay of treatment of moderate-to-severe pain is opioid analgesics, with the addition of other analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) and other adjuvant therapies, including tricyclic antidepressants (TCAs), anticonvulsants, and topical anesthetics as necessary.[3,4] However, more than four out of 10 people with moderate-to-severe pain do not get relief, according to an American Pain Society (APS) survey conducted in 1999.[5] Of those who do not get pain relief, some may be experiencing pain that is not responsive to opioids or other drug therapies despite appropriate use of these agents, as in opioid resistance and neuropathic pain. Opioid Resistance and Neuropathic Pain Opioid resistance is defined as unresponsiveness to IV morphine sulfate of at least 100 mg per hour (or equivalent dosing of another opioid), consistently high pain ratings, and unrelieved pain even after the opioid dose is doubled. Opioid resistance has been found in a multitude of disease states including cancer, chronic pain, neuropathy, complex regional pain syndrome, postherpetic neuralgia, and pancreatitis.[6]Neuropathic pain results from injury to peripheral or central nerves and is commonly treated with agents such as TCAs and anticonvulsants. -
“Robo-Tripping”: Dextromethorphan Abuse and Its Anesthetic Implications
Anesth Pain Med. 2014 December; 4(5): e20990. DOI: 10.5812/aapm.20990 Case Report Published online 2014 1RYHPEHU 14. “Robo-Tripping”: Dextromethorphan Abuse and its Anesthetic Implications 1 1 1,* Kelly A Linn ; Micah T Long ; Paul S Pagel 1Anesthesia Service, Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, USA *Corresponding author : Paul S Pagel, Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin, 53295, USA. Tel: +1-4143842000; Fax: 1-4143842939, E-mail: [email protected] Received: ; Revised: ; Accepted: June 6, 2014 June 29, 2014 July 6, 2014 Introduction: We describe a patient scheduled for elective surgery who regularly consumed approximately 12 to 15 times the maximum recommended daily dose of dextromethorphan. We describe the clinical pharmacology of dextromethorphan and discuss its anesthetic implications. Case Presentation: A 30-year-old man with a history of a nasal fracture was scheduled to undergo an elective septorhinoplasty. He reported daily consumption of large quantities (1440 to 1800 mg) of dextromethorphan for six years. He was previously treated for dextromethorphan dependency on several occasions with urine dextromethorphan levels exceeding 2000 ng/mL. He described marked dissociative effects when abusing the drug, but had abstained from use for 48 hours before his elective surgery. Considering that dextromethorphan has a relatively short half-life and that the patient did not suffer major withdrawal symptoms after voluntarily discontinuing the drug, the authors proceeded with the case while recognizing that the drug has significant neuropsychiatric and sympathetic nervous system stimulant effects resulting from its actions as a N-methyl-D-aspartate receptor antagonist. -
Safety and Efficacy Issues
WHO Drug Information Vol. 27, No. 4, 2013 Safety and Efficacy Issues Contaminated dextromethorphan and had consumed medical products produced by a local manufacturer World Health Organization — On 24 containing dextromethorphan. The January 2013, a WHO Drug Alert was children were aged from 2–9 years and issued following the discovery in Pakistan serious adverse reactions included of two types of locally produced cough altered consciousness, cyanosis, syrup containing the contaminated active respiratory distress and seizures. Onset pharmaceutical ingredient (API) dextro- of symptoms occurred from 2–7 hours methorphan. after ingesting dextromethorphan. Since then, the number of patients experiencing This incident led to the death of approxi- adverse reactions rose to 44 confirmed mately 50 persons in Pakistan, all with a cases, ranging in age from 5 months to history of drug addiction, who had been 48 years. There was one fatality that may abusing dextromethorphan-containing be linked to the event. syrup for many years without any reported unexpected adverse reactions. The Paraguayan Ministry of Health issued The subsequent investigation found that warnings concerning the medicines manufacturers in Pakistan were obtaining thought to be connected to this incident. the dextromethorphan API from a source Investigations by the Paraguayan in India. authorities subsequently indicated the source of the API dextromethorphan to be Full laboratory testing of the dextro- the same Laboratories in India. The batch methorphan showed that it was conta- number of the dextromethorphan API minated with levomethorphan, the used by the Paraguayan manufacturer enantiomer of dextromethorphan, which was the same as one of the contaminated is a potent opioid analgesic internationally batches found in Pakistan. -
Serotonin Toxicity Associated Agents and Clinical Characteristics
ORIGINAL CONTRIBUTION Serotonin Toxicity Associated Agents and Clinical Characteristics Michael J. Moss, MD,*† and Robert G. Hendrickson, MD,‡§ on behalf of the Toxicology Investigators Consortium (ToxIC) data on serotonin toxicity are difficult to obtain. There is no spe- Abstract: cific code in the International Statistical Classification of Diseases Background: Serotonin toxicity is a common cause of drug-induced al- for serotonin toxicity or serotonin syndrome. The US National tered mental status. However, data on the causes of serotonin toxicity, Poison Data System also does not specifically track serotonin tox- symptomatology, complications, and rate of antidotal treatment are limited. icity. However, the National Poison Data System does report that Methods: This study evaluated cases of serotonin toxicity in the ToxIC antidepressants as a category are in the top 5 for total exposures, registry, an international database of prospectively collected cases seen year-to-year increase in exposures, and deaths.5 Treatment of se- by medical toxicologists. Serotonin toxicity was diagnosed by bedside rotonin toxicity is largely supportive in nature. Cyproheptadine, evaluation of medical toxicology specialists and explicit criteria were not an antihistamine with antiserotonergic effects, is often cited as a “ ” used. The database was searched for serotonin syndrome between potential antidote though its use is only supported by case reports January 1, 2010, and December 31, 2016. and case series.6–9 Information on the agents associated with Results: There were 1010 cases included. Females made up 608 (60%) serotonin toxicity, rate of complications, and use pharmaco- cases. Ages are as follows: younger than 2 years (3, 0.3%), 2 to 6 years logic treatment are based on smaller scale case reports, case se- (8, 0.8%), 7 to 12 years (9, 0.9%), 13 to 18 years (276, 27.3%), 19 to ries, and database studies.2,3,10 We sought to report the clinical 65 years (675, 67%), older than 66 years (33, 3.4%), unknown (6, 0.6%). -
Drug/Substance Trade Name(S)
A B C D E F G H I J K 1 Drug/Substance Trade Name(s) Drug Class Existing Penalty Class Special Notation T1:Doping/Endangerment Level T2: Mismanagement Level Comments Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a 3,4-methylenedioxypyprovaleroneMDPV, “bath salts” norepinephrine-dopamine reuptake inhibitor. It was first developed in the 1960s by a team at 1 A Yes A A 2 Boehringer Ingelheim. No 3 Alfentanil Alfenta Narcotic used to control pain and keep patients asleep during surgery. 1 A Yes A No A Aminoxafen, Aminorex is a weight loss stimulant drug. It was withdrawn from the market after it was found Aminorex Aminoxaphen, Apiquel, to cause pulmonary hypertension. 1 A Yes A A 4 McN-742, Menocil No Amphetamine is a potent central nervous system stimulant that is used in the treatment of Amphetamine Speed, Upper 1 A Yes A A 5 attention deficit hyperactivity disorder, narcolepsy, and obesity. No Anileridine is a synthetic analgesic drug and is a member of the piperidine class of analgesic Anileridine Leritine 1 A Yes A A 6 agents developed by Merck & Co. in the 1950s. No Dopamine promoter used to treat loss of muscle movement control caused by Parkinson's Apomorphine Apokyn, Ixense 1 A Yes A A 7 disease. No Recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. It is often claimed that BZP was originally Benzylpiperazine BZP 1 A Yes A A synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals.