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Prete MM, Feitosa GTB, Ribeiro MAT, Fidalgo TM, Sanchez ZM. Adverse clinical effects associated with the use of synthetic cannabinoids: A systematic review. Drug Alcohol Depend 2025; 272:112698. [PMID: 40334326 DOI: 10.1016/j.drugalcdep.2025.112698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Revised: 04/18/2025] [Accepted: 04/21/2025] [Indexed: 05/09/2025]
Abstract
Synthetic cannabinoids (SCs) are potent agonists of CB1 and CB2 receptors, with affinities approximately 100 times greater than that of natural cannabis. This increased potency is associated with severe clinical outcomes, including psychosis, dependence, and various autonomic disturbances, such as seizures and rhabdomyolysis. The objective of this study was to synthesize the existing literature on the clinical effects of SCs, emphasizing health risks and identifying knowledge gaps. Following PRISMA guidelines, a comprehensive search was conducted across three databases-PubMed, Embase, and Lilacs-resulting in 944 studies. Eligible articles focused on clinical effects associated to SC use, while exclusion criteria encompassed studies unrelated to clinical outcomes, other reviews, animal studies, and those concentrating solely on psychiatric symptoms or therapeutic uses of SCs. In total, 49 studies published between 2010 and 2022 were included, representing diverse populations and study designs. Participants were predominantly young adult males, although ages ranged from 12 to 72 years. SCs' clinical effects predominantly affected the neurological and cardiovascular systems, with common symptoms including seizures, altered consciousness, tachycardia, and hypertension. Hospital and ICU admissions varied, reflecting the complex nature of SC toxicity. Compared to cannabis, SC use was linked to more severe cardiovascular and neurological complications. Additional rare complications included thromboembolic events, immune thrombocytopenic purpura, and psychiatric disturbances. This review highlights the urgent need for targeted public health policies to mitigate the risks associated with SC use and improve medical management. It also stresses the importance of further controlled studies to elucidate the underlying mechanisms of these clinical effects and their pharmacological basis.
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Affiliation(s)
- Mariana M Prete
- Departamento de Medicina Preventiva, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Gabriel T B Feitosa
- Departamento de Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Maria A T Ribeiro
- Departamento de Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - T M Fidalgo
- Departamento de Psiquiatria, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Zila M Sanchez
- Departamento de Medicina Preventiva, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
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Taflaj B, La Maida N, Tittarelli R, Di Trana A, D’Acquarica I. New Psychoactive Substances Toxicity: A Systematic Review of Acute and Chronic Psychiatric Effects. Int J Mol Sci 2024; 25:9484. [PMID: 39273431 PMCID: PMC11395625 DOI: 10.3390/ijms25179484] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 08/27/2024] [Accepted: 08/28/2024] [Indexed: 09/15/2024] Open
Abstract
New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae.
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Affiliation(s)
- Beldisa Taflaj
- Azienda Ospedaliera San Giovanni Addolorata, Via dell’Amba Aradam 8, 00184 Rome, Italy;
| | - Nunzia La Maida
- National Centre on Addiction and Doping, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;
| | - Roberta Tittarelli
- Laboratory of Forensic Toxicology, Section of Legal and Forensic Medicine, Social Security and Forensic Toxicology, Department of Biomedicine and Prevention, Faculty of Medicine and Surgery, University of Rome “Tor Vergata”, Via Montpellier 1, 00133 Rome, Italy;
| | - Annagiulia Di Trana
- National Centre on Addiction and Doping, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy;
| | - Ilaria D’Acquarica
- Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, Piazzale A. Moro 5, 00185 Rome, Italy;
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Craft S, Ferris JA, Barratt MJ, Maier LJ, Lynskey MT, Winstock AR, Freeman TP. Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis. Psychopharmacology (Berl) 2022; 239:1349-1357. [PMID: 34533608 PMCID: PMC9110517 DOI: 10.1007/s00213-021-05945-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 07/25/2021] [Indexed: 11/02/2022]
Abstract
Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11-50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p's < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.
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Affiliation(s)
- Sam Craft
- Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK. .,National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
| | - Jason A. Ferris
- grid.1003.20000 0000 9320 7537Centre for Health Services Research, University of Queensland, QLD, Queensland Brisbane, Australia
| | - Monica J. Barratt
- grid.1017.70000 0001 2163 3550Social and Global Studies Centre and Digital Ethnography Research Centre, RMIT University, Victoria Melbourne, Australia ,grid.1005.40000 0004 4902 0432National Drug and Alcohol Research Centre, University of New South Wales Sydney, New South Wales Sydney, Australia
| | - Larissa J. Maier
- grid.266102.10000 0001 2297 6811Department of Clinical Pharmacy, University of California San Francisco, San Francisco, USA
| | - Michael T. Lynskey
- grid.13097.3c0000 0001 2322 6764National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
| | - Adam R. Winstock
- Global Drug Survey Ltd, London, UK ,grid.83440.3b0000000121901201Institute of Epidemiology and Health Care, University College London, London, UK
| | - Tom P. Freeman
- grid.7340.00000 0001 2162 1699Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK ,grid.13097.3c0000 0001 2322 6764National Addiction Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
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Creatine kinase levels in psychotic patients who use cannabinoids. Int Clin Psychopharmacol 2021; 36:45-49. [PMID: 33165025 DOI: 10.1097/yic.0000000000000343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Elevated serum levels of creatine kinase enzymes have been found in brain injuries and psychosis. Cannabinoid use is associated with increased frequency and duration of hospitalizations. We examined whether creatine kinase levels differ in psychotic cannabinoid users and the association between creatine kinase levels and clinical measures (duration of hospitalization and need for mechanical restraint). Computerized medical records of 124 men hospitalized due to acute psychotic episodes were reviewed. Creatine kinase levels and various clinical measures at admission were documented. Cannabis users were significantly younger than nonusers. Duration of illness was longer among nonusers. Log creatine kinase among cannabinoid users (N = 32) was numerically higher compared to nonusers (N = 92) (5.6 ± 1 vs. 5.2 ± 0.9, respectively). Significantly higher rate of elevated creatine kinase levels (creatine kinase > 195 U/l) was detected in the cannabinoid users compared to nonusers (59.4% vs. 38%, respectively; P < 0.04). No association was found between creatine kinase levels and use of mechanical restraints and hospitalization days. Higher rate of elevated creatine kinase levels was observed in hospitalized psychotic cannabinoid users, possibly due to a cannabis activity at peripheral or brain tissues. Studies in larger, more diverse clinical populations are needed to confirm this finding and to clarify the biological mediators of elevated creatine kinase levels in psychotic cannabinoid users.
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Trexler KR, Vanegas SO, Poklis JL, Kinsey SG. The short-acting synthetic cannabinoid AB-FUBINACA induces physical dependence in mice. Drug Alcohol Depend 2020; 214:108179. [PMID: 32688070 PMCID: PMC7461724 DOI: 10.1016/j.drugalcdep.2020.108179] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/30/2020] [Accepted: 07/01/2020] [Indexed: 12/16/2022]
Abstract
BACKGROUND Recent years have seen a rise in the diversity and use of synthetic cannabinoids. The present study evaluated the behavioral effects of the third-generation indazole-3-carboxamide-type synthetic cannabinoid, AB-FUBINACA. METHODS Adult male and female C57BL/6J mice were treated with AB-FUBINACA (0-3 mg/kg, i.p.) and tested repeatedly in the tetrad battery measuring catalepsy, antinociception, hypothermia, and locomotor activity. Mice treated with AB-FUBINACA (≥2 mg/kg, i.p.) displayed classic cannabinoid effects in the tetrad that were blocked by the CB1 receptor selective antagonist rimonabant. To address tolerance and withdrawal effects, a second group of mice was injected with AB-FUBINACA (3 mg/kg, s.c.) or vehicle consisting of 5% ethanol, 5% Kolliphor EL, and 90 % saline every 12 h and tested daily in modified tetrad over the course of 5 days. On the 6th day, withdrawal was precipitated using rimonabant (3 mg/kg, s.c.), and somatic signs of withdrawal (i.e., head twitches and paw tremors) were quantified. RESULTS Although mice did not develop tolerance to AB-FUBINACA or cross-tolerance to Δ9-tetrahydrocannabinol (THC; 50 mg/kg, i.p.), somatic precipitated withdrawal signs were observed. Repeated tetrad testing up to 48 h post injection indicated that AB-FUBINACA effects are relatively short-lived, as compared with THC. Brain levels of AB-FUBINACA, as quantified by UHPLC-MS/MS, were undetectable 4 h post injection. CONCLUSIONS These data indicate that the cannabinoid effects of AB-FUBINACA are relatively short-lived, yet sufficient to induce dependence in mice.
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Affiliation(s)
- Kristen R. Trexler
- Department of Psychology, West Virginia University, Morgantown, WV, United States
| | - S. Olivia Vanegas
- Department of Psychology, West Virginia University, Morgantown, WV, United States,Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States,School of Nursing, University of Connecticut, Storrs, CT, United States
| | - Justin L. Poklis
- Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States
| | - Steven G. Kinsey
- Department of Psychology, West Virginia University, Morgantown, WV, United States,School of Nursing, University of Connecticut, Storrs, CT, United States,Corresponding author at: 231 Glenbrook Rd., Unit 4026, University of Connecticut, Storrs, CT, 06269-3237, United States. (S.G. Kinsey)
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Luethi D, Liechti ME. Designer drugs: mechanism of action and adverse effects. Arch Toxicol 2020; 94:1085-1133. [PMID: 32249347 PMCID: PMC7225206 DOI: 10.1007/s00204-020-02693-7] [Citation(s) in RCA: 143] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 02/25/2020] [Indexed: 12/18/2022]
Abstract
Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at μ-opioid receptors and γ-aminobutyric acid-A (GABAA) or GABAB receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.
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Affiliation(s)
- Dino Luethi
- Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Währinger Strasse 13a, 1090, Vienna, Austria.
- Institute of Applied Physics, Vienna University of Technology, Getreidemarkt 9, 1060, Vienna, Austria.
- Division of Clinical Pharmacology and Toxicology, University Hospital Basel and University of Basel, Schanzenstrasse 55, 4056, Basel, Switzerland.
| | - Matthias E Liechti
- Division of Clinical Pharmacology and Toxicology, University Hospital Basel and University of Basel, Schanzenstrasse 55, 4056, Basel, Switzerland.
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Orsolini L, Chiappini S, Papanti D, De Berardis D, Corkery JM, Schifano F. The Bridge Between Classical and "Synthetic"/Chemical Psychoses: Towards a Clinical, Psychopathological, and Therapeutic Perspective. Front Psychiatry 2019; 10:851. [PMID: 31849723 PMCID: PMC6896660 DOI: 10.3389/fpsyt.2019.00851] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/30/2019] [Indexed: 12/12/2022] Open
Abstract
The critical spread and dissemination of novel psychoactive substances (NPS), particularly among the most vulnerable youngsters, may pose a further concern about the psychotic trajectories related to the intake of new synthetic drugs. The psychopathological pattern of the "new psychoses" appears to be extremely different from the classical presentation. Therefore, clinicians need more data on these new synthetic psychoses and recommendations on how to manage them. The present mini-review aims at deepening both the clinical, psychopathological features of synthetic/chemical NPS-induced psychoses and their therapeutic strategies, according to the different NPS classes implicated, by underlining the main differences with the "classical" psychoses. A comprehensive review was conducted using the PubMed/Medline database by combining the search strategy of free-text terms and exploding a range of MESH headings relating to the topics of novel psychoactive substances and synthetic/chemical psychoses as follows: {(Novel Psychoactive Substances[Title/Abstract]) AND Psychosis[Title/Abstract])} and for each NPS categories as well, focusing on synthetic cannabinoids and cathinones, without time and/or language restrictions. Finally, an overview of the main clinical and psychopathological features between classical versus NPS-induced chemical/synthetic psychoses is provided for clinicians working with dual disorders and addiction psychiatry. Further insight is given here on therapeutic strategies and practical guidelines for managing patients affected with synthetic/chemical NPS-induced psychoses.
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Affiliation(s)
- Laura Orsolini
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
- Neomesia Mental Health, Villa Jolanda Hospital, Jesi, Italy
- Polyedra, Teramo, Italy
| | - Stefania Chiappini
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Duccio Papanti
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Domenico De Berardis
- Polyedra, Teramo, Italy
- NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital "G. Mazzini", Teramo, Italy
- Department of Neuroscience, Imaging and Clinical Science, Chair of Psychiatry, University of "G. D’Annunzio", Chieti, Italy
| | - John M. Corkery
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
| | - Fabrizio Schifano
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, United Kingdom
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Cannabis and Psychosis Through the Lens of DSM-5. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2019; 16:ijerph16214149. [PMID: 31661851 PMCID: PMC6861931 DOI: 10.3390/ijerph16214149] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/08/2019] [Accepted: 10/10/2019] [Indexed: 12/27/2022]
Abstract
Evidence for an association between cannabis and psychosis has been documented in literature in many forms including experimental studies, epidemiological data, and case series. The association has implications for psychotic outcomes ranging from mild to severe and occurring over minutes to years. Due to the huge variety of exposures and outcome measures reported, creating a coherent account of all the available information is difficult. A useful way to conceptualize these wide-ranging results is to consider the association between cannabis and psychosis as it occurs within the context of widely used DSM-5 diagnoses. In the present review we examine cannabis/psychosis associations as they pertain to Cannabis Intoxication, Cannabis-Induced Psychotic Disorder, and Schizophrenia. This allows for an understanding of the cannabis and psychosis association along something approaching a continuum. Cannabis intoxication becomes Cannabis-Induced Psychotic Disorder once certain severity and duration criteria are met and Cannabis-Induced Psychotic Disorder is heavily associated with future schizophrenia diagnoses.
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9
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Armstrong F, McCurdy MT, Heavner MS. Synthetic Cannabinoid-Associated Multiple Organ Failure: Case Series and Literature Review. Pharmacotherapy 2019; 39:508-513. [PMID: 30811628 DOI: 10.1002/phar.2241] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
OBJECTIVE We describe a multicenter descriptive case series of six patients admitted with synthetic cannabinoid (SC) intoxication displaying similar symptoms and sequelae, all resulting in multiple organ failure. METHODS Patients were included in this report if they presented with known SC use and experienced multiple organ failure between March 1, 2016, and July 19, 2016, to the intensive care units of three hospitals in Maryland. Patients were followed to either discharge or death, and complications related to SC were documented. RESULTS All six patients presented with altered mental status and severe rhabdomyolysis, with a peak creatine phosphokinase ranging from 4000 to >320,000 units/L. The majority of patients (five of six) presented with acute kidney injury, with most (four of six) requiring continuous renal replacement therapy. Most patients experienced fever (five of six) and myocardial injury, as evidenced by a troponin elevation (three of six). Seizures occurred in half of patients (three of six patients). Two patients required emergent fasciotomies of the bilateral lower extremities for acute compartment syndrome. Two patients developed fulminant hepatic failure that necessitated liver transplant evaluation, one requiring Molecular Adsorbent Recirculating System (MARS) therapy as a bridge to successful transplant, while the patient without it did not survive. Delirium, severe rhabdomyolysis, acute kidney injury, and fever are common in patients with synthetic cannabinoid intoxication. CONCLUSIONS Given the growing abuse of these substances, clinicians should consider their use in the differential of such patient presentations. To our knowledge, only a few published case reports discuss multiple organ failure associated with SC toxicity, and only two have described an associated acute liver failure. Our report describes the first case of SC-associated acute liver failure requiring organ transplantation. Clinicians should be aware of life-threatening complications and consider SC ingestion in the differential diagnosis of patients presenting with multiple organ failure.
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Affiliation(s)
- Faith Armstrong
- Adult Critical Care Medicine, University of Maryland Baltimore Washington Medical Center, Glen Burnie, Maryland
| | - Michael T McCurdy
- Division of Pulmonary & Critical Care Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland
- Department of Emergency Medicine, University of Maryland School of Medicine, Baltimore, Maryland
| | - Mojdeh S Heavner
- Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland
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Akinnusi M, El Solh AA. Drug treatment strategies for insomnia in patients with post-traumatic stress disorder. Expert Opin Pharmacother 2019; 20:691-699. [PMID: 30794468 DOI: 10.1080/14656566.2019.1574745] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION Insomnia is among the most reported sleep disturbances in patients with post-traumatic stress disorder (PTSD). The pervasiveness of this disorder among trauma-inflicted civilians and military personnel has been associated with reduced quality of life, impaired psychosocial functioning including cognitive impairments, negative mood swings, cardiovascular complications, and increased utilization of medical services. AREAS COVERED This review describes the current state of science with respect to the impact of the most dispensed pharmacological interventions for posttraumatic insomnia. At the present, there are no established treatment algorithms for PTSD-related insomnia. Pharmacotherapy offers an alternative treatment modality for patients with PTSD who fail or decline cognitive behavioral therapy (CBT). Selection of a hypnotic/sedative agent should be based on the patient's history, precipitating and perpetuating factors of insomnia, side effect profile, and potential medication-related interactions. Antipsychotics and benzodiazepines appear ineffective or are associated with significant harm in treating PTSD-related insomnia. EXPERT OPINION In the absence of randomized controlled trials, prescription patterns have been guided by anecdotal reports and expert opinion. Due to the complexity and multifactorial etiology of insomnia in PTSD, clinical investigations should examine available pharmacologic agents in comparative trials or in combination with CBT or complementary therapies to assess both short-term and long-term sleep outcomes in this population.
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Affiliation(s)
- Morohunfolu Akinnusi
- a Department of Medicine , StrongTower Behavioral HealthCare , Marietta , GA , USA
| | - Ali A El Solh
- b Department of Medicine , VA Western New York Healthcare System , Buffalo , NY , USA.,c Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine , State University of New York at Buffalo , USA.,d Department of Epidemiology and Environmental Health , State University of New York at Buffalo School of Medicine and Biomedical Sciences and School of Public Health and Health Professions , USA
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Abstract
Synthetic cannabinoid (SC) products have gained popularity as abused drugs over the past decade in many countries. The SCs broadly impact psychological state (e.g., mood, suicidal thoughts and psychosis) and physiological functions (e.g., cardiovascular, gastrointestinal and urinary). This review is about the effects of SCs on psychotic symptoms in clinical settings and the potentially relevant chemistry and mechanisms of action for SCs. Induction of psychotic symptoms after consuming SC products were reported, including new-onset psychosis and psychotic relapses. The role of SCs in psychosis is more complex than any single chemical component might explain, and these effects may not be a simple extension of the typical effects of cannabis or natural cannabinoids.
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Su S, Mao L, Zhao J, Chen L, Jing J, Cheng F, Zhang L. Epidemics of HIV, HCV and syphilis infection among synthetic drugs only users, heroin-only users and poly-drug users in Southwest China. Sci Rep 2018; 8:6615. [PMID: 29700352 PMCID: PMC5919913 DOI: 10.1038/s41598-018-25038-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/28/2018] [Indexed: 11/18/2022] Open
Abstract
The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p < 0.05). About a third (36.7%) of poly-drug users experienced sexual arousal due to drug effects, which is higher than the rate among other drug users. Poly-drug users had the highest prevalence of HIV (10.5%) and syphilis (3.6%), but heroin-only users had the highest prevalence of HCV (66.0%) (all p < 0.05) among three groups. Logistic regression shows among poly-drug users, having sex following drug consumption and using drugs ≥1/day were the major risk factors for both HIV (Adjusted odds ratio (AOR) = 2.4, 95% CI [1.8–3.4]; 2.3, [1.6–3.1]) and syphilis infection (AOR = 4.1, [2.1–6.9]; 3.9, [1.8–5.4]). Elevated risk of both HIV and syphilis infection have been established among poly-drug users.
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Affiliation(s)
- Shu Su
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Limin Mao
- Center for Social Research in Health, Arts and Social Sciences, UNSW Australia, Sydney, NSW, Australia
| | - Jinxian Zhao
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Liang Chen
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Jun Jing
- Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China
| | - Feng Cheng
- Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China.
| | - Lei Zhang
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia. .,Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China. .,Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.
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Fantegrossi WE, Wilson CD, Berquist MD. Pro-psychotic effects of synthetic cannabinoids: interactions with central dopamine, serotonin, and glutamate systems. Drug Metab Rev 2018; 50:65-73. [PMID: 29385930 PMCID: PMC6419500 DOI: 10.1080/03602532.2018.1428343] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elicited pro-psychotic effects is unknown, but given the ubiquitous neuromodulatory functions of the endocannabinoid system, it seems likely that agonist actions at cannabinoid type-1 receptors (CB1Rs) might modulate the functions of other neurotransmitter systems known to be involved in schizophrenia. The present review surveys what is currently known about the interactions of CB1Rs with dopamine, serotonin, and glutamate systems, because all three of those neurotransmitters are well-established in the pathophysiology of schizophrenia and psychosis. Identification of molecular mechanisms underlying the pro-psychotic effects of SCB drugs of abuse may establish certain classes of these substances as particularly dangerous, guiding regulations to control availability of these drugs. Likewise, an understanding of the pharmacological interactions which lead to schizophrenia and psychosis subsequent to SCB exposure might guide the development of novel therapies to treat afflicted users.
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Affiliation(s)
- William E Fantegrossi
- a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences, College of Medicine , Little Rock , AR , USA
| | - Catheryn D Wilson
- a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences, College of Medicine , Little Rock , AR , USA
| | - Michael D Berquist
- a Department of Pharmacology and Toxicology , University of Arkansas for Medical Sciences, College of Medicine , Little Rock , AR , USA
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14
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Kırgız A, Kaldırım H. Bilateral multiple exudative retinal detachments and macular edema in a patient diagnosed with synthetic cannabinoid (Bonzai) intoxication. Int Ophthalmol 2017; 39:237-241. [PMID: 29275529 DOI: 10.1007/s10792-017-0805-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 12/11/2017] [Indexed: 11/27/2022]
Abstract
PURPOSE To report the first case of a patient with bilateral multiple exudative retinal detachments and macular edema after smoking Bonzai. METHODS A 17-year-old girl presented with a complaint of a sudden onset of reduced vision in both eyes. She was admitted to the emergency service 3 days ago with the symptoms of hallucination and convulsion and diagnosed with synthetic cannabinoid intoxication. RESULTS After consultation with an internal medicine specialist, intravenous fluid treatment was initiated. Laboratory findings resolved rapidly and recovery of fundus findings was achieved at 6 months of follow-up. CONCLUSIONS Synthetic cannabinoid abuse has been increasing in young populations in recent years and has become an important health concern. It is important for health providers to be aware of ocular signs and symptoms of intoxication.
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Affiliation(s)
- Ahmet Kırgız
- Eye Clinic, Department of Opthalmology, Bagcilar Training and Research Hospital, University of Health Sciences, Mimar Sinan CD 6. SK, Istanbul, Turkey.
| | - Havva Kaldırım
- Eye Clinic, Department of Opthalmology, Bagcilar Training and Research Hospital, University of Health Sciences, Mimar Sinan CD 6. SK, Istanbul, Turkey
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15
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McArdle disease: a "pediatric" disorder presenting in an adult with acute kidney injury. CEN Case Rep 2017; 6:156-160. [PMID: 28660497 DOI: 10.1007/s13730-017-0265-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Accepted: 06/26/2017] [Indexed: 12/18/2022] Open
Abstract
Rhabdomyolysis is characterized by the acute breakdown of skeletal muscle, resulting in the release of muscle cell contents, subsequent myoglobinuria, and in severe cases, acute renal failure. A number of etiologies have been identified in acute rhabdomyolysis, in which drugs and trauma account for the majority of cases. One etiological category that is commonly overlooked in the adult population is an underlying genetic defect. This may be challenging to diagnose due to its rarity in the adult demographic and the marked heterogeneity, often requiring a high level of clinical suspicion before investigation is pursued. Once diagnosed, however, appropriate steps can be taken to reduce future episodes of rhabdomyolysis, further renal injury, and other systemic complications. Here, we report a case of an adult patient presenting with acute rhabdomyolysis secondary to McArdle disease, a genetic disease causing defective glycogenolysis. The case highlights the importance of recognizing the potential of undiagnosed "pediatric" disorders in adulthood and particularly for underlying genetic causes of rhabdomyolysis.
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16
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Mdege ND, Meader N, Lloyd C, Parrott S, McCambridge J. The Novel Psychoactive Substances in the UK Project: empirical and conceptual review work to produce research recommendations. PUBLIC HEALTH RESEARCH 2017. [DOI: 10.3310/phr05040] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BackgroundAlthough illegal drug use has largely been declining in the UK over the past decade, this period has witnessed the emergence of a range of novel psychoactive substances (NPS) (‘legal highs’). These are new, mostly synthetic, substances that mimic the effects of existing drugs). Despite there being many causes for concern in relation to NPS, there has been little prior study of the burden associated with their use in public health terms. Clarity is lacking on research priorities in this rapidly developing literature.ObjectivesTo inform the development of public health intervention research on NPS by reviewing existing data on their use, associated problems and potential responses to such problems.DesignA scoping review and narrative synthesis of selected bodies of evidence was undertaken to summarise and evaluate what is known about NPS use and the related harms of, and responses to, such use. Relevant literature was identified from electronic databases (covering January 2006 to June 2016 inclusive), Google (Google Inc., Mountain View, CA, USA), relevant websites and online drug forums and by contacting experts. Articles were included if they were primary studies, secondary studies involving the analysis and interpretation of primary research or discussion papers. A conceptual framework postulating an evidence-informed public health approach to NPS use in the UK was developed through a pragmatic literature review, the iterative development of concepts and finalisation in light of the results from the empirical review work. The process also involved feedback from various stakeholders. Research recommendations were developed from both strands of work.ResultsA total of 995 articles were included in the scoping review, the majority of which related to individual-level health-related adverse effects attributable to NPS use. The prevalence of lifetime NPS use varied widely between (e.g. with higher prevalence in young males) and within population subgroups. The most commonly reported adverse effects were psychiatric/other neurological, cardiovascular, renal and gastrointestinal manifestations, and there is limited evidence available on responses. In these and other respects, available evidence is at an early stage of development. Initial evidence challenges the view that NPS should be treated differently from other illicit drugs. The conceptual framework indicated that much of the evidence that would be useful to inform public health responses does not yet exist. We propose a systems-based prevention approach that develops existing responses, is multilevel and life course informed in character, and emphasises commonalities between NPS and other legal and illegal drug use. We make 20 recommendations for research, including nine key recommendations.LimitationsScoping reviews do not interrogate evidence in depth, and the disjunction between the scoping review and the conceptual framework findings is worthy of careful attention.ConclusionsKey research recommendations build on those that have previously been made and offer more evidence-based justification and detail, as previous recommendations have not yet been acted on. The case for decision-making on commissioning new research based on these recommendations is both strong and urgent.Future workThe validity of recommendations generated through this project could be enhanced via further work with research commissioners, policy-makers, researchers and the public.Study registrationThe systematic review element of this study is registered as PROSPERO CRD42016026415.FundingThe National Institute for Health Research Public Health Research programme.
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Affiliation(s)
- Noreen D Mdege
- Department of Health Sciences, University of York, York, UK
| | - Nick Meader
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Charlie Lloyd
- Department of Health Sciences, University of York, York, UK
| | - Steve Parrott
- Department of Health Sciences, University of York, York, UK
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17
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Ford BM, Tai S, Fantegrossi WE, Prather PL. Synthetic Pot: Not Your Grandfather's Marijuana. Trends Pharmacol Sci 2017; 38:257-276. [PMID: 28162792 PMCID: PMC5329767 DOI: 10.1016/j.tips.2016.12.003] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Revised: 11/08/2016] [Accepted: 12/13/2016] [Indexed: 01/05/2023]
Abstract
In the early 2000s in Europe and shortly thereafter in the USA, it was reported that 'legal' forms of marijuana were being sold under the name K2 and/or Spice. Active ingredients in K2/Spice products were determined to be synthetic cannabinoids (SCBs), producing psychotropic actions via CB1 cannabinoid receptors, similar to those of Δ9-tetrahydrocannabinol (Δ9-THC), the primary active constituent in marijuana. Often abused by adolescents and military personnel to elude detection in drug tests due to their lack of structural similarity to Δ9-THC, SCBs are falsely marketed as safe marijuana substitutes. Instead, SCBs are a highly structural diverse group of compounds, easily synthesized, which produce very dangerous adverse effects occurring by, as of yet, unknown mechanisms. Therefore, available evidence indicates that K2/Spice products are clearly not safe marijuana alternatives.
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Affiliation(s)
- Benjamin M Ford
- Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Sherrica Tai
- Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI, USA
| | - William E Fantegrossi
- Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA
| | - Paul L Prather
- Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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18
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Scocard A, Benyamina A, Coscas S, Karila L. [Synthetic cannabinoids: A new addiction matrix]. Presse Med 2017; 46:11-22. [PMID: 28063756 DOI: 10.1016/j.lpm.2016.11.014] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2016] [Revised: 11/01/2016] [Accepted: 11/28/2016] [Indexed: 12/16/2022] Open
Abstract
Synthetic cannabinoids (SC) belong to the emergent market of new psychoactive substances, sold on the Internet or specialized shops. Since the 1970s, more than 160 new SC have invaded the drug market. These substances imitate the psychoactive effects of cannabis. Underestimated for too long, SC's market growth and consequences are no longer to be ignored, first of all in terms of public health. SC were first synthesized during researches on the endocannabinoid system. Though they are agonists of the cannabinoid receptors 1 and 2, as Δ9-tetrahydrocannabinol in cannabis, they can also have a really high affinity with these receptors, rising up their potency. Each country in the world has chosen various ways how to deal with SC: scheduling, blanket ban, regulation… In order to contour the legal system, producers regularly modify the chemical formulas of those substances and hand out an attracting packaging looking harmless. However, the content of those small packets is extremely unstable and unreliable, including harmful compounds to health. Reports show an increasing number of non-fatal intoxications but also fatalities. Consequences on the body are numerous but there have been also reports of mental health imbalance and appearances of addiction-linked clinical signs. This review of literature aims at establishing a picture on SC in order to raise awareness among professionals in the health field on this new addiction matrix.
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Affiliation(s)
- Amandine Scocard
- Université Paris Sud, AP-HP, hôpital Paul-Brousse, département d'addictologie, 94800 Villejuif, France.
| | - Amine Benyamina
- Université Paris Sud, AP-HP, hôpital Paul-Brousse, département d'addictologie, 94800 Villejuif, France
| | - Sarah Coscas
- Université Paris Sud, AP-HP, hôpital Paul-Brousse, département d'addictologie, 94800 Villejuif, France
| | - Laurent Karila
- Inserm U1000, université Paris Sud, AP-HP, hôpital Paul-Brousse, département d'addictologie, 94800 Villejuif, France
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19
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Hassan Z, Bosch OG, Singh D, Narayanan S, Kasinather BV, Seifritz E, Kornhuber J, Quednow BB, Müller CP. Novel Psychoactive Substances-Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs. Front Psychiatry 2017; 8:152. [PMID: 28868040 PMCID: PMC5563308 DOI: 10.3389/fpsyt.2017.00152] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Accepted: 08/02/2017] [Indexed: 12/15/2022] Open
Abstract
A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.
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Affiliation(s)
- Zurina Hassan
- Centre for Drug Research, Universiti Sains Malaysia, Minden, Malaysia
| | - Oliver G Bosch
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
| | - Darshan Singh
- Centre for Drug Research, Universiti Sains Malaysia, Minden, Malaysia
| | - Suresh Narayanan
- School of Social Sciences, Universiti Sains Malaysia, Minden, Malaysia
| | | | - Erich Seifritz
- Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
| | - Johannes Kornhuber
- Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
| | - Boris B Quednow
- Experimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
| | - Christian P Müller
- Department of Psychiatry and Psychotherapy, University Hospital, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
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20
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Zorlu N, Angelique Di Biase M, Kalaycı ÇÇ, Zalesky A, Bağcı B, Oğuz N, Gelal F, Beşiroğlu L, Gülseren Ş, Sarıçiçek A, Bora E, Pantelis C. Abnormal white matter integrity in synthetic cannabinoid users. Eur Neuropsychopharmacol 2016; 26:1818-1825. [PMID: 27617779 DOI: 10.1016/j.euroneuro.2016.08.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2016] [Revised: 08/08/2016] [Accepted: 08/24/2016] [Indexed: 02/05/2023]
Abstract
Synthetic cannabinoids have become increasingly popular in the last few years especially among adolescents and young adults. However, no previous studies have assessed the effects of synthetic cannabinoids on the structure of the human brain. Understanding the harms of synthetic cannabinoid use on brain structure is therefore crucial given its increasing use. Diffusion tensor imaging (DTI) was performed in 22 patients who used synthetic cannabinoids more than five times a week for at least 1 year and 18 healthy controls. Fractional anisotropy (FA) was significantly reduced in the cannabinoid group compared to controls in a cluster of white matter voxels spanning the left temporal lobe, subcortical structures and brainstem. This cluster was predominantly traversed by the inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, fornix, cingulum-hippocampus and corticospinal tracts. Long-term use of synthetic cannabinoids is associated with white matter abnormalities in adolescents and young adults. Disturbed brain connectivity in synthetic cannabinoid users may underlie cognitive impairment and vulnerability to psychosis.
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Affiliation(s)
- Nabi Zorlu
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey.
| | - Maria Angelique Di Biase
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia
| | - Çiğdem Çolak Kalaycı
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Andrew Zalesky
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia
| | - Başak Bağcı
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Nihan Oğuz
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Fazıl Gelal
- Department of Radiodiagnostics, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Lütfullah Beşiroğlu
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Şeref Gülseren
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Aybala Sarıçiçek
- Department of Psychiatry, Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
| | - Emre Bora
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia
| | - Christos Pantelis
- Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Carlton South, VIC, Australia; Centre for Neural Engineering (CfNE), Department of Electrical and Electronic Engineering, University of Melbourne, Carlton South, VIC, Australia; Florey Institute for Neuroscience & Mental Health, Parkville, VIC, Australia
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21
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Joseph AM, Manseau MW, Lalane M, Rajparia A, Lewis CF. Characteristics associated with synthetic cannabinoid use among patients treated in a public psychiatric emergency setting. THE AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE 2016; 43:117-122. [PMID: 27797288 DOI: 10.1080/00952990.2016.1240799] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND Growing evidence of adverse outcomes following synthetic cannabinoid use has engendered interest into populations at risk. The existing literature reports that synthetic cannabinoid use is predominant among young, white males. However, reports from local Departments of Health have found contrary evidence, showing that synthetic cannabinoid use is prevalent in populations other than those of young, white men. OBJECTIVES This study sought to examine sociodemographic characteristics associated with self-reported synthetic cannabinoid use among a clinical psychiatric population within a public hospital in New York City. METHODS A cross-sectional medical record review was conducted on synthetic cannabinoid users and non-users in an emergency psychiatric setting. A total of 948 patients who presented at the emergency psychiatric setting in 2014 were included in this sample, 110 (11.6%) of whom were synthetic cannabinoid users. Logistic regressions were used to determine the sociodemographic correlates of synthetic cannabinoid use. RESULTS The most prominent correlate of synthetic cannabinoid use was homelessness/residing in a shelter during time of treatment (AOR = 17.77, 95% CI = 9.74-32.5). Male (AOR = 5.37, 95% CI = 2.04-14.1), non-white (AOR = 2.74, 95% CI = 1.36-5.54), and younger age (AOR = .961, 95% CI = .940-.980) were also significant correlates of synthetic cannabinoid use. CONCLUSION Synthetic cannabinoid use among the homeless and mentally ill is a growing public health concern, representing a population with unique clinical and social needs. Areas and populations with high rates of homelessness should be targeted for synthetic cannabinoid prevention and treatment efforts, particularly in urban and racial/ethnic minority communities.
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Affiliation(s)
- Adriana M Joseph
- a The Nathan Kline Institute, Research Foundation for Mental Hygiene , Orangeburg , NY , USA
| | - Marc W Manseau
- b New York University School of Medicine , Department of Psychiatry , One Park Avenue, New York , NY, USA.,c Bellevue Hospital Center , Department of Psychiatry , New York , NY , USA
| | - Monique Lalane
- b New York University School of Medicine , Department of Psychiatry , One Park Avenue, New York , NY, USA.,c Bellevue Hospital Center , Department of Psychiatry , New York , NY , USA
| | - Amit Rajparia
- b New York University School of Medicine , Department of Psychiatry , One Park Avenue, New York , NY, USA.,c Bellevue Hospital Center , Department of Psychiatry , New York , NY , USA
| | - Crystal Fuller Lewis
- b New York University School of Medicine , Department of Psychiatry , One Park Avenue, New York , NY, USA.,c Bellevue Hospital Center , Department of Psychiatry , New York , NY , USA
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22
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Abstract
Although several chemical structural classes of synthetic cannabinoids (SCs) were recently classified as Schedule I substances, rates of use and cases of serious toxic effects remain high. While case reports and media bring attention to severe SC toxicity, daily SC use resulting in dependence and withdrawal is a significant concern that is often overlooked when discussing the risks of these drugs. There is a rich literature on evidence-based approaches to treating substance use disorders associated with most abused drugs, yet little has been published regarding how to best treat symptoms related to SC dependence given its recency as an emerging clinically significant issue. This review provides a background of the pharmacology of SCs, recent findings of adverse effects associated with both acute intoxication and withdrawal as a consequence of daily use, and treatment approaches that have been implemented to address these issues, with an emphasis on pharmacotherapies for managing detoxification. In order to determine prevalence of use in cannabis smokers, a population at high risk for SC use, we obtained data on demographics of SC users, frequency of use, and adverse effects over a 3.5-year period (2012-2015) in the New York City metropolitan area, a region with a recent history of high SC use. While controlled studies on the physiological and behavioral effects of SCs are lacking, it is clear that risks associated with using these drugs pertain not only to the unpredictable and severe nature of acute intoxication but also to the effects of long-term, chronic use. Recent reports in the literature parallel findings from our survey, indicating that there is a subset of people who use SCs daily. Although withdrawal has not been systematically characterized and effective treatments have yet to be elucidated, some symptom relief has been reported with benzodiazepines and the atypical antipsychotic, quetiapine. Given the continued use and abuse of SCs, empirical studies characterizing (1) SCs acute effects, (2) withdrawal upon cessation of use, and (3) effective treatment strategies for SC use disorder are urgently needed.
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Affiliation(s)
- Ziva D Cooper
- Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY, 10032, USA.
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23
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Fattore L. Synthetic Cannabinoids-Further Evidence Supporting the Relationship Between Cannabinoids and Psychosis. Biol Psychiatry 2016; 79:539-48. [PMID: 26970364 DOI: 10.1016/j.biopsych.2016.02.001] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Revised: 02/01/2016] [Accepted: 02/01/2016] [Indexed: 12/26/2022]
Abstract
Consumption of synthetic mind-altering compounds, also known as "new psychoactive substances," is increasing globally at an alarming rate. Synthetic cannabinoids (SCs) are among the most commonly used new psychoactive substances. They are usually purchased as marijuana-like drugs, marketed as herbal blends and perceived as risk-free by inexperienced users. Yet, contrary to Δ(9)-tetrahydrocannabinol, SCs may lead to severe health consequences, including anxiety, tachycardia, hallucinations, violent behavior, and psychosis. This review focuses on the latest (2010-2015) evidence of psychotic symptoms induced by ingestion of products containing SCs. Reports suggesting that SCs may either exacerbate previously stable psychotic symptoms (in vulnerable individuals) or trigger new-onset psychosis (in individuals with no previous history of psychosis) are reviewed. Pharmacology and toxicology of these compounds are discussed, with particular reference to their psychoactive effects.
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Affiliation(s)
- Liana Fattore
- CNR Neuroscience Institute, National Research Council (Italy), and Centre of Excellence "Neurobiology of Dependence," Department of Biomedical Sciences, University of Cagliari, Cittadella Universitaria, Monserrato, Cagliari, Sardinia, Italy.
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24
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Salani DA, Zdanowicz MM. Synthetic cannabinoids: the dangers of spicing it up. J Psychosoc Nurs Ment Health Serv 2016; 53:36-43. [PMID: 25974923 DOI: 10.3928/02793695-20150422-01] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Accepted: 04/15/2015] [Indexed: 01/09/2023]
Abstract
Cannabinoids are the most commonly used illegal substances in the world. Spice and K2 are synthetic cannabinoid (SC) products that contain a mixture of herbs and plant matter combined with synthetic compounds similar to tetrahydrocannabinol, the psychoactive component of cannabis. Because the effects of Spice and K2 are similar to cannabis, many users are smoking these products as legal substitutes despite package labeling that they are not designed for human consumption. These SC products appeal to users because they are easily accessible and not readily detected in standard urine drug screens. The active components in SC products are highly potent and poorly characterized. Use of these agents has been associated with serious psychological and physiological side effects. Because abuse of SC products has become a national public health issue, nurses should be aware of the effects of SC compounds and must take a lead role in educating patients about the dangers of their use.
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25
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Castellanos D, Gralnik LM. Synthetic cannabinoids 2015: An update for pediatricians in clinical practice. World J Clin Pediatr 2016; 5:16-24. [PMID: 26862498 PMCID: PMC4737689 DOI: 10.5409/wjcp.v5.i1.16] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Revised: 11/15/2015] [Accepted: 01/07/2016] [Indexed: 02/06/2023] Open
Abstract
Synthetic cannabinoids are a group of substances in the world of designer drugs that have become increasingly popular over the past few years. Synthetic cannabinoids are a chemically diverse group of compounds functionally similar to THC. Since first appearing on the world market a few years ago these compounds have evolved rapidly. Newer more potent analogues have been developed. Identifying youth who abuse these substances can be difficult. Newer forms of consumption have also evolved. These products are now manufactured in products that look like natural cannabis resin and in liquid cartridges used in electronic cigarettes. Synthetic cannabinoids appear to be associated with potentially dangerous health effects that are more severe than that of marijuana. Some synthetic cannabinoid compounds have been associated with serious physical consequences, such as, seizures, myocardial infarction and renal damage. In addition, psychoactive effects, such as aggression, confusion, anxiety and psychosis have also been reported. The diagnosis remains primarily clinical with toxicological confirmation difficult due to manufacturers constantly developing new analogues to avoid detection. Pediatricians are urged to familiarize themselves with these drugs and the typical presentations of patients who use them.
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Müller HH, Kornhuber J, Sperling W. The behavioral profile of spice and synthetic cannabinoids in humans. Brain Res Bull 2015; 126:3-7. [PMID: 26548494 DOI: 10.1016/j.brainresbull.2015.10.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2015] [Revised: 10/27/2015] [Accepted: 10/30/2015] [Indexed: 02/06/2023]
Abstract
The use of synthetic cannabinoids (spice) is increasing. The number of descriptions of (new) clinical side effects is also increasing. We screened relevant publications for articles about spice with a focus on the clinical manifestations of the use of this drug. Spice creates diffuse psychiatric and somatic effects that are only partially similar to those of natural cannabinoids. Most of the observed effects are related to sympathomimetic-cardiac effects and neuropsychiatric manifestations. Clinical treatment is primarily based on intensive apparative and laboratory monitoring and supportive therapy. Because the exact active ingredients of spice are often difficult to determine with standard specific toxicology testing, the assessment and analysis of consumed substances by specialized laboratories is recommended.
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Affiliation(s)
- Helge H Müller
- Friedrich-Alexander University of Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Erlangen, Germany; Medical Campus University of Oldenburg, School of Medicine and Health Sciences, University Hospital, Department of Psychiatry and Psychotherapy (Head of Department: Prof. Dr. Alexandra Philipsen), Karl-Jaspers-Klinik, Hermann-Ehlers-Straße 7, D-26160 Bad Zwischenahn, Germany.
| | - Johannes Kornhuber
- Friedrich-Alexander University of Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Erlangen, Germany
| | - Wolfgang Sperling
- Friedrich-Alexander University of Erlangen-Nuremberg, Department of Psychiatry and Psychotherapy, Erlangen, Germany
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Synthetic Cannabinoid Abuse in Adolescents: A Case Series. J Emerg Med 2015; 49:644-50. [DOI: 10.1016/j.jemermed.2015.06.053] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 06/14/2015] [Accepted: 06/23/2015] [Indexed: 11/23/2022]
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Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids. Case Rep Nephrol 2015; 2015:235982. [PMID: 26550500 PMCID: PMC4621326 DOI: 10.1155/2015/235982] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2015] [Revised: 09/21/2015] [Accepted: 09/29/2015] [Indexed: 01/06/2023] Open
Abstract
The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity.
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Sherpa D, Paudel BM, Subedi BH, Chow RD. Synthetic cannabinoids: the multi-organ failure and metabolic derangements associated with getting high. J Community Hosp Intern Med Perspect 2015; 5:27540. [PMID: 26333853 PMCID: PMC4558292 DOI: 10.3402/jchimp.v5.27540] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Revised: 05/03/2015] [Accepted: 05/11/2015] [Indexed: 12/12/2022] Open
Abstract
Synthetic cannabinoids (SC), though not detected with routine urine toxicology screening, can cause severe metabolic derangements and widespread deleterious effects in multiple organ systems. The diversity of effects is related to the wide distribution of cannabinoid receptors in multiple organ systems. Both cannabinoid-receptor-mediated and non-receptor-mediated effects can result in severe cardiovascular, renal, and neurologic manifestations. We report the case of a 45-year-old African American male with ST-elevation myocardial infarction, subarachnoid hemorrhage, reversible cardiomyopathy, acute rhabdomyolysis, and severe metabolic derangement associated with the use of K2, an SC. Though each of these complications has been independently associated with SCs, the combination of these effects in a single patient has not been heretofore reported. This case demonstrates the range and severity of complications associated with the recreational use of SCs. Though now banned in the United States, use of systemic cannabinoids is still prevalent, especially among adolescents. Clinicians should be aware of their continued use and the potential for harm. To prevent delay in diagnosis, tests to screen for these substances should be made more readily available.
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Affiliation(s)
- Dolkar Sherpa
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD, USA;
| | - Bishow M Paudel
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD, USA;
| | - Bishnu H Subedi
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD, USA.,Division of Cardiology, New York Methodist Hospital, Brooklyn, NY, USA
| | - Robert Dobbin Chow
- Department of Medicine, University of Maryland Medical Center Midtown Campus, Baltimore, MD, USA
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Khullar V, Jain A, Sattari M. Emergence of new classes of recreational drugs-synthetic cannabinoids and cathinones. J Gen Intern Med 2014; 29:1200-4. [PMID: 24553958 PMCID: PMC4099455 DOI: 10.1007/s11606-014-2802-4] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2013] [Revised: 10/24/2013] [Accepted: 01/22/2014] [Indexed: 11/28/2022]
Abstract
Designer drugs represent an increasingly popular form of recreational substance abuse, especially amongst young adults. The two classes of designer drugs that have recently risen to prominence are the synthetic cannabinoids and synthetic cathinones. These substances are not detected by conventional drug screening methods and can often be associated with serious health consequences, including seizures, renal failure and death. Thus, clinicians should be familiar with the signs, symptoms, and toxicities associated with the use of these substances, and maintain a high level of suspicion for synthetic drugs as an alternative means of "getting high." We present a case of a 20-year-old college student who presented to the emergency department with altered mental status and severe agitation who later admitted to using bath salts. The goal of this article is to raise awareness about these new designer drugs, their clinical presentation, and management of their intoxication.
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Affiliation(s)
- Vikas Khullar
- Department of Medicine, University of Florida College of Medicine, 1600 SW Archer Rd, PO Box 100277, Gainesville, FL, 32610, USA
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Smith CD, Robert S. 'Designer drugs': update on the management of novel psychoactive substance misuse in the acute care setting. Clin Med (Lond) 2014; 14:409-15. [PMID: 25099844 PMCID: PMC4952836 DOI: 10.7861/clinmedicine.14-4-409] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The use of novel psychoactive substances ('legal highs' or 'designer drugs') is increasing worldwide. Patients misusing such substances have been reported to experience severe or prolonged side effects requiring admission to acute or critical care wards. These complications can be life threatening if misdiagnosed or mismanaged. As physicians have traditionally had less involvement with the management of such patients compared with their colleagues in emergency departments an update in the management of such patients is indicated. Here we present a summary of the management of those novel substances with the potential for serious complications based on a review of current literature.
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Affiliation(s)
- Christopher D Smith
- Accident and Emergency Department, Whipps Cross Hospital, Barts Health NHS Trust, London, UK
| | - Stefanie Robert
- Homerton University Hospital NHS Foundation Trust, London, UK
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Brents LK, Prather PL. The K2/Spice phenomenon: emergence, identification, legislation and metabolic characterization of synthetic cannabinoids in herbal incense products. Drug Metab Rev 2013; 46:72-85. [PMID: 24063277 DOI: 10.3109/03602532.2013.839700] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
In 2008, the European Monitoring Center for Drugs and Drug Addiction (EMCDDA) detected unregulated, psychoactive synthetic cannabinoids (SCBs) in purportedly all-natural herbal incense products (often known as K2 or Spice) that were being covertly abused as marijuana substitutes. These drugs, which include JWH-018, JWH-073 and CP-47,497, bind and activate the cannabinoid receptors CB1R and CB2R with remarkable potency and efficacy. Serious adverse effects that often require medical attention, including severe cardiovascular, gastrointestinal and psychiatric sequelae, are highly prevalent with SCB abuse. Consequently, progressively restrictive legislation in the US and Europe has banned the distribution, sale and use of prevalent SCBs, initiating cycles in which herbal incense manufacturers replace banned SCBs with newer unregulated SCBs. The contents of the numerous, diverse herbal incense products was unknown when SCB abuse first emerged. Furthermore, the pharmacology of the active components was largely uncharacterized, and confirmation of SCB use was hindered by a lack of known biomarkers. These knowledge gaps prompted scientists across multiple disciplines to rapidly (1) monitor, identify and quantify with chromatography/mass spectrometry the ever-changing contents of herbal incense products, (2) determine the metabolic pathways and major urinary metabolites of several commonly abused SCBs and (3) identify active metabolites that possibly contribute to the severe adverse effect profile of SCBs. This review comprehensively describes the emergence of SCB abuse and provides a historical account of the major case reports, legal decisions and scientific discoveries of the "K2/Spice Phenomenon". Hypotheses concerning potential mechanisms SCB adverse effects are proposed in this review.
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Affiliation(s)
- Lisa K Brents
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences , Little Rock, AR , USA and
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