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Jones AT, Marwan Abu Taha A, Miller GP. The resurgence of synthetic cannabinoid receptor agonists as adulterants in the Era of Cannabis legalization: Lessons from prior epidemics and clinical implications. Neurosci Biobehav Rev 2025; 170:106043. [PMID: 39922438 PMCID: PMC11870277 DOI: 10.1016/j.neubiorev.2025.106043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 01/30/2025] [Accepted: 02/03/2025] [Indexed: 02/10/2025]
Abstract
Momentum towards legalization of medical and recreational cannabis drives a convergence between natural cannabinoids and their synthetic counterparts, creating new clinical challenges in a second wave of exposures. This review critically examines the emerging challenges posed by synthetic cannabinoid receptor agonists (SCRAs) and semi-synthetic cannabinoids, emphasizing their clinical implications. SCRAs are potent full agonist activity that have been identified as adulterants in several recreational substances, including cannabis and opioids. Adulteration often leads to unpredictable clinical outcomes and exacerbates the potential for drug interactions. Drawing parallels with other drug epidemics, this paper highlights the urgent need for clinical preparedness to address the nuanced presentations of cannabinoid toxicity, stressing the importance of patient history, physical examination, and judicious use of supportive laboratory tests. This review serves as a cautionary tale and call to action for researchers and policymakers. There is a clear need for robust quality control measures, enhanced public awareness campaigns, and development of evidence-based clinical guidelines to mitigate the health risks associated with intentional and unintentional use of synthetic cannabinoids.
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Affiliation(s)
- Austin T Jones
- College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
| | - Alaa Marwan Abu Taha
- Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
| | - Grover P Miller
- Department of Biochemistry and Molecular Biology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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Thomsen LR, Glass M, Rosengren RJ. The impact of piperazine and antipsychotic co-exposures and CB1 blockade on the effects elicited by AMB-FUBINACA, a synthetic cannabinoid, in mice. Eur J Pharmacol 2024; 979:176844. [PMID: 39053868 DOI: 10.1016/j.ejphar.2024.176844] [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: 02/16/2024] [Revised: 07/10/2024] [Accepted: 07/23/2024] [Indexed: 07/27/2024]
Abstract
BACKGROUND & PURPOSE The constant emergence and broad toxicological effects of synthetic cannabinoids create a discernible public health threat. The synthetic cannabinoid AMB-FUBINACA (AMB-FUB) is a potent agonist at the CB1 receptor and has been associated with numerous fatalities. Synthetic cannabinoids are commonly abused alongside other drugs and medications, including a "party pill" drug, para-fluorophenylpiperazine (pFPP), and the antipsychotic risperidone. This research aimed to investigate the mechanisms underpinning AMB-FUB toxicity and the impact of clinically relevant co-exposures in vivo. EXPERIMENTAL APPROACH Male and female C57Bl/6 mice received a single dose of AMB-FUB (3 or 6 mg kg-1), pFPP (10 or 20 mg kg-1) or vehicle intraperitoneally. Mice were co-exposed to AMB-FUB (3 mg kg-1) and pFPP (10 mg kg-1) or risperidone (0.5 mg kg-1) to investigate these drug combinations. To study receptor-dependency and potential rescue of AMB-FUB toxicity, rimonabant (3 mg kg-1) was administered both pre- and post-AMB-FUB. Adverse effects caused by drug administration, including hypothermia and convulsions, were recorded. KEY RESULTS AMB-FUB induced CB1-dependent hypothermia and convulsions in mice. The combination of AMB-FUB and pFPP significantly potentiated hypothermia, as did risperidone pre-treatment. Interestingly, risperidone provided significant protection from AMB-FUB-induced convulsions in female mice. Pre- and post-treatment with rimonabant was able to significantly attenuate both hypothermia and convulsions in mice administered AMB-FUB. CONCLUSION & IMPLICATIONS Factors such as dose, CB1 signalling, and substance co-exposure significantly contribute to the toxicity of AMB-FUBINACA. Mechanistic understanding of synthetic cannabinoid toxicity and fatality can help inform overdose treatment strategies and identify vulnerable populations of synthetic cannabinoid users.
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Affiliation(s)
- Lucy R Thomsen
- Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
| | - Michelle Glass
- Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
| | - Rhonda J Rosengren
- Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand.
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Takeda A, Doi T, Asada A, Yuzawa K, Nagasawa A, Igarashi K, Maeno T, Suzuki A, Shimizu S, Uemura N, Nakajima J, Suzuki T, Inomata A, Tagami T. The biological effects and thermal degradation of NPB-22, a synthetic cannabinoid. Forensic Toxicol 2024; 42:142-151. [PMID: 38294576 PMCID: PMC11269510 DOI: 10.1007/s11419-023-00679-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Accepted: 11/29/2023] [Indexed: 02/01/2024]
Abstract
PURPOSE NPB-22 (quinolin-8-yl 1-pentyl-1H-indazole-3-carboxylate), Adamantyl-THPINACA (N-(1-adamantantyl)-1-[(tetrahydro-2H-pyran-4-yl)methyl]-1H-indazole-3-carboxamide), and CUMYL-4CN-B7AICA (1-(4-cyanobutyl)-N-(2-phenylpropan-2-yl)-1H- pyrrolo[2,3-b]pyridine-3-carboxamide), synthetic cannabinoids were evaluated in terms of CB1 (cannabinoid receptor type 1) and CB2 (cannabinoid receptor type 2) activities, and their biological effects when inhaled similar to cigarettes were examined. METHODS The half maximal effective concentration values of the aforementioned synthetic cannabinoids at the CB1 and CB2 were investigated using [35S]guanosine-5'-O-(3-thio)-triphosphate binding assays. In addition, their biological effects were evaluated using the inhalation exposure test with mice. The smoke generated was recovered by organic solvents in the midget impingers, and the thermal degradation compounds of the smoke components were identified and quantified using a liquid chromatography-photo diode array detector. RESULTS NPB-22 and Adamantyl-THPINACA had equivalent CB1 activity in in vitro assays. Meanwhile, NPB-22 had a weaker biological effect on some items on the inhalation exposure test than Adamantyl-THPINACA. When analyzing organic solvents in the midget impingers, it was revealed that NPB-22 was degraded to 8-quinolinol and pentyl indazole 3-carboxylic acid by combustion. In addition, these degradation compounds did not have CB1 activity. CONCLUSION It was estimated that the biological effects of NPB-22 on the inhalation exposure test weakened because it underwent thermal degradation by combustion, and the resultant degradation compounds did not have any CB1 activity in vitro.
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Affiliation(s)
- Akihiro Takeda
- Division of Hygienic Chemistry, Osaka Institute of Public Health, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan.
| | - Takahiro Doi
- Division of Hygienic Chemistry, Osaka Institute of Public Health, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan
| | - Akiko Asada
- Division of Hygienic Chemistry, Osaka Institute of Public Health, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan
| | - Katsuhiro Yuzawa
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Akemichi Nagasawa
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Kai Igarashi
- Tolyo Metropolitan Island Public Health Center, 2466-2 Okago, Hachijo-machi, Hachijojima, Tokyo, 100-1492, Japan
| | - Tomokazu Maeno
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Atsuko Suzuki
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Seiko Shimizu
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Nozomi Uemura
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Jun'ichi Nakajima
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Toshinari Suzuki
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Akiko Inomata
- Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, Tokyo, 169-0073, Japan
| | - Takaomi Tagami
- Division of Hygienic Chemistry, Osaka Institute of Public Health, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-0025, Japan
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Smith KE, Feldman JD, Dunn KE, McCurdy CR, Grundmann O, Garcia-Romeu A, Panlilio LV, Rogers JM, Sharma A, Fernandez SP, Kheyfets M, Epstein DH. Novel methods for the remote investigation of emerging substances: Application to kratom. Exp Clin Psychopharmacol 2024; 32:215-227. [PMID: 37213182 PMCID: PMC10663387 DOI: 10.1037/pha0000656] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/23/2023]
Abstract
The botanical product commonly called "kratom" is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Affiliation(s)
- Kirsten E. Smith
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
| | - Jeffrey D. Feldman
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
| | - Kelly E. Dunn
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Christopher R. McCurdy
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Oliver Grundmann
- Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Albert Garcia-Romeu
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States
| | - Leigh V. Panlilio
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
| | - Jeffrey M. Rogers
- San Diego State University/University of California San Diego Joint Doctoral Program in Clinical Psychology, San Diego, CA, United States
| | - Abhisheak Sharma
- Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, United States
| | - Salma-Pont Fernandez
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
| | - Marina Kheyfets
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
| | - David H. Epstein
- Real-World Assessment, Prediction, and Treatment Unit, National Institute on Drug Abuse Intramural Research Program, Baltimore, MD, United States
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Lea Houston M, Morgan J, Kelso C. Narrative Review of the Pharmacodynamics, Pharmacokinetics, and Toxicities of Illicit Synthetic Cannabinoid Receptor Agonists. Mini Rev Med Chem 2024; 24:92-109. [PMID: 37190813 DOI: 10.2174/1389557523666230515163107] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 03/20/2023] [Accepted: 04/03/2023] [Indexed: 05/17/2023]
Abstract
BACKGROUND Synthetic cannabinoid receptor agonists (SCRAs) are the most diverse class of new psychoactive substances worldwide, with approximately 300 unique SCRAs identified to date. While the use of this class of drug is not particularly prevalent, SCRAs are associated with several deaths every year due to their severe toxicity. METHODS A thorough examination of the literature identified 15 new SCRAs with a significant clinical impact between 2015 and 2021. RESULTS These 15 SCRAs have been implicated in 154 hospitalizations and 209 deaths across the US, Europe, Asia, and Australasia during this time period. CONCLUSION This narrative review provides pharmacodynamic, pharmacokinetic, and toxicologic data for SCRAs as a drug class, including an in-depth review of known pharmacological properties of 15 recently identified and emerging SCRAs for the benefit of researchers, policy makers, and clinicians who wish to be informed of developments in this field.
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Affiliation(s)
- Matilda Lea Houston
- Griffith Institute for Drug Discovery, Griffith University, Nathan, Queensland, Australia
| | - Jody Morgan
- School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia
- Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
| | - Celine Kelso
- School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, New South Wales, Australia
- Molecular Horizons Institute, University of Wollongong, Wollongong, New South Wales, Australia
- Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, New South Wales, Australia
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Baweja R, Mills-Huffnagle S, Jernigan A, Chongtham N, Waschbusch D, Waxmonsky JG. Synthetic Marijuana: Assessment of Usage, Motivation and Associated Risks in Adolescent Substance Users. SUBSTANCE USE : RESEARCH AND TREATMENT 2024; 18:29768357241254258. [PMID: 38764525 PMCID: PMC11102655 DOI: 10.1177/29768357241254258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2023] [Accepted: 04/23/2024] [Indexed: 05/21/2024]
Abstract
Objectives Use of Synthetic and designer products, including synthetic marijuana (SM), among adolescents poses a major risk to public health. Little is known about the motivating factors of synthetic substance use in adolescents. This study examined the motivations, predictors, perceived risks and benefits, and differences with SM versus natural marijuana among adolescents. Methods Between April 2016 and May 2018, a convenience sample of adolescents receiving substance use treatment from a local counseling center completed an anonymous survey to assess the use of natural and synthetic marijuana use, the Strengths and Difficulties Questionnaire to assess levels of current psychiatric symptoms and the Community Assessment of Psychic Experiences-Positive Scale to assess symptoms of psychosis. Results A total of 80 adolescents (age range of 14-18 years; 71% male; 53% Caucasian) completed the study. Of these, 39 (49%) reported natural marijuana use (natural marijuana users) and 41 (51%) reported both synthetic and natural marijuana use (dual users). The most commonly reported reasons for using SM were its low cost and reduced risk of detection. Participants who were familiar with SM and reported a desire to avoid detection on drug tests were likelier to use SM (all P < .05). Dual users reported more benefits and risks associated with SM use when compared to natural marijuana users (P ⩽ .05). The use of SM also heightened the perceived medical risks of natural marijuana, including seizures and respiratory issues (P < .05), compared with natural marijuana users. While dual users self-reported more conduct (P = .009) and externalizing problems (P = .024) when compared to natural marijuana users, there were no group differences in psychotic symptoms, nor correlations with the frequency of synthetic or natural marijuana use and psychotic symptoms except that persecutory ideation correlated with the frequency of natural marijuana use during the past 12 months (rp = 0.28, P = .04). Conclusions These results suggest that reports of cost savings, and lack of detection on urine drug screens are common reasons for SM use in adolescents despite being aware of the risks of using SM. Perceived benefits of using synthetics and other novel substances appear diverse, and merit further exploration as a better understanding of what motivates adolescents to use specific novel substances may guide prevention and treatment efforts.
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Affiliation(s)
- Raman Baweja
- Pennsylvania State College of Medicine, Hershey, PA, USA
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7
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Craft S, Austin A, Tooth T, Glover C, Garrett T, Blagbrough IS, Sunderland P, Pudney CR, Freeman TP. Synthetic cannabinoid use in an adult male prison in the UK. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2023; 122:104219. [PMID: 37813081 DOI: 10.1016/j.drugpo.2023.104219] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 09/19/2023] [Accepted: 09/26/2023] [Indexed: 10/11/2023]
Abstract
INTRODUCTION Synthetic cannabinoids (i.e. Spice) are a major public health problem in UK prisons, however, research in this area is limited. Here we aimed to draw comparisons between people with and without experience of using synthetic cannabinoids in prison, to characterise the features of, and motivations for use within this setting and evaluate support for different treatment interventions. METHOD Questionnaires were administered to 122 people in a category-B prison for adult males in England between July 2022 and March 2023. Participants were asked questions related to their sociodemographic and custodial characteristics, use of synthetic cannabinoids (and other drugs) inside and outside of prison and psychological distress was measured via the Brief Symptom Inventory (BSI-18). Those that had ever used synthetic cannabinoids in prison completed additional questions related to features of use, motivations for use and support for various interventions. RESULTS In total 46.7 % (n = 57) of participants reported use of synthetic cannabinoids in prison and this group experienced significantly greater levels of psychological distress compared to those reporting no use (mean (± standard deviation) BSI-18 scores = 23.7 (±16.7) vs 12.8 (±13.6), p < 0.001). Participants mostly reported using paper-based preparations (77.4 %) and use via e-cigarettes (75.9 %). The most strongly endorsed motivations for use included to alleviate boredom (91.1 % strongly agree/agree), to make the sentence pass faster (89.3 % strongly agree/agree) and to cope with stress (80.4 % strongly agree/agree). The interventions that received most support were strategies to better manage time and medication to manage withdrawal. CONCLUSIONS The use of synthetic cannabinoids in UK prisons typically involves the use of paper-based preparations via e-cigarettes, and use is associated with greater levels of psychological distress. Motivations for use were mostly pragmatic (e.g. to alleviate boredom or cope with stress) and interventions should prioritise increasing the time individuals spend out of cells and in meaningful activity.
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Affiliation(s)
- Sam Craft
- Addiction and Mental Health Group, Department of Psychology, University of Bath, UK.
| | - Alice Austin
- Addiction and Mental Health Group, Department of Psychology, University of Bath, UK
| | - Tom Tooth
- HM Prison and Probation Service (HMPPS), London, UK
| | - Catherine Glover
- Royal College of General Practitioners Secure Environments Group, London, UK
| | - Tina Garrett
- Office of Health Improvements and Disparities (OHID), London, UK
| | | | | | | | - Tom P Freeman
- Addiction and Mental Health Group, Department of Psychology, University of Bath, UK
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Wang Z, Leow EYQ, Moy HY, Chan ECY. Advances in urinary biomarker research of synthetic cannabinoids. Adv Clin Chem 2023; 115:1-32. [PMID: 37673518 DOI: 10.1016/bs.acc.2023.03.004] [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] [Indexed: 03/29/2023]
Abstract
New psychoactive substances (NPS) are chemical compounds designed to mimic the action of existing illicit recreational drugs. Synthetic cannabinoids (SCs) are a subclass of NPS which bind to the cannabinoid receptors, CB1 and CB2, and mimic the action of cannabis. SCs have dominated recent NPS seizure reports worldwide. While urine is the most common matrix for drug-of-abuse testing, SCs undergo extensive Phase I and Phase II metabolism, resulting in almost undetectable parent compounds in urine samples. Therefore, the major urinary metabolites of SCs are usually investigated as surrogate biomarkers to identify their consumption. Since seized urine samples after consuming novel SCs may be unavailable in a timely manner, human hepatocytes, human liver microsomes and human transporter overexpressed cell lines are physiologically-relevant in vitro systems for performing metabolite identification, metabolic stability, reaction phenotyping and transporter experiments to establish the disposition of SC and its metabolites. Coupling these in vitro experiments with in vivo verification using limited authentic urine samples, such a two-pronged approach has proven to be effective in establishing urinary metabolites as biomarkers for rapidly emerging SCs.
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Affiliation(s)
- Ziteng Wang
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Eric Yu Quan Leow
- Department of Pharmacy, National University of Singapore, Singapore, Singapore
| | - Hooi Yan Moy
- Analytical Toxicology Laboratory, Applied Sciences Group, Health Sciences Authority, Singapore, Singapore
| | - Eric Chun Yong Chan
- Department of Pharmacy, National University of Singapore, Singapore, Singapore.
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Acharya R, Zeng X, Upadhyay K. Synthetic cannabinoid-associated acute interstitial nephritis: An emerging cause of pediatric acute kidney injury? Clin Nephrol Case Stud 2023; 11:55-60. [PMID: 37006641 PMCID: PMC10062021 DOI: 10.5414/cncs111063] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2022] [Accepted: 01/19/2023] [Indexed: 03/29/2023] Open
Abstract
Synthetic cannabinoid (SCB) usage among children is a rapidly emerging public health concern in the United States. Acute kidney injury (AKI) is an uncommon manifestation of SCB usage, with acute tubular necrosis (ATN) as the predominant histology. Here we describe a 16-year-old adolescent who sustained severe non-oliguric AKI in association with SCB usage. Emesis, right flank pain, and hypertension were the presenting clinical features. There was no uveitis, skin rash, joint pains, or eosinophilia. Urinalysis showed absence of proteinuria or hematuria. Urine toxicology was negative. Renal sonogram showed bilateral echogenic kidneys. Renal biopsy demonstrated severe acute interstitial nephritis (AIN), mild tubulitis, and absence of ATN. AIN responded with pulse steroid followed by oral steroid. Renal replacement therapy was not required. Although the exact pathophysiology of SCB-associated AIN is not known, immune response elicited by the renal tubulointerstitial cells against the antigens present in the SCB is the most likely mechanism. A high index of suspicion for SCB-induced AKI is necessary in adolescents who present with AKI of unclear etiology.
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Affiliation(s)
| | - Xu Zeng
- Division of Anatomic Pathology, Department of Pathology, and
| | - Kiran Upadhyay
- Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, Gainesville, FL, USA
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Celeste-Villalvir A, Crouch C, Witte L, Heads AM, Weaver M, Schmitz JM, Isbell F, Schick V. Assessing Stage of Change and Harm Reduction Strategies for Synthetic Cannabinoid Use Among Individuals Experiencing Homelessness in Houston, Texas. JOURNAL OF DRUG ISSUES 2023. [DOI: 10.1177/00220426231161284] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
Synthetic cannabinoids (SCs) are low-cost substances that have been associated with adverse health outcomes and an increase in emergency department visits over recent years, particularly among people experiencing homelessness. This mixed methods study explored the connection between homelessness, SC use, and readiness to quit in order to inform the development of harm reduction strategies. Individuals (18+) residing in homeless encampments in Houston, TX with experiences of SC use were eligible to participate. Participants ( N = 65) completed an interviewer-administered survey about their SC use. Most participants were Black/African American (65.7%), male (82.9%), and most (75.4%) reported using SCs to avoid positive drug tests. Many wanted to quit using SCs (69.2%) and already employed harm reduction strategies while using SCs. Organizations supporting individuals experiencing homelessness who use SCs should focus on reducing barriers to stopping SC use and increasing the availability of housing and supportive services.
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Affiliation(s)
- Alane Celeste-Villalvir
- Department of Management, Policy & Community Health, University of Texas Health Science Center at Houston, Houston, TX, USA
| | | | - Laura Witte
- Department of Management, Policy & Community Health, University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Angela M. Heads
- Department of Psychiatry and Behavioral Health, University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA
| | - Michael Weaver
- Department of Psychiatry and Behavioral Health, University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA
- Center for Neurobehavioral Research on Addiction, Houston, TX, USA
| | - Joy M. Schmitz
- Department of Psychiatry and Behavioral Health, University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA
- Center for Neurobehavioral Research on Addiction, Houston, TX, USA
| | | | - Vanessa Schick
- Department of Management, Policy & Community Health, University of Texas Health Science Center at Houston, Houston, TX, USA
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Giorgetti A, Brunetti P, Haschimi B, Busardò FP, Pelotti S, Auwärter V. Human phase-I metabolism and prevalence of two synthetic cannabinoids bearing an ethyl ester moiety: 5F-EDMB-PICA and EDMB-PINACA. Drug Test Anal 2023; 15:299-313. [PMID: 36366743 DOI: 10.1002/dta.3405] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 11/01/2022] [Accepted: 11/08/2022] [Indexed: 11/13/2022]
Abstract
Around 2017, with the appearance of 5F-EDMB-PINACA, synthetic cannabinoids (SCs) carrying an ethyl ester moiety at the linked group started spreading on the market of new psychoactive substances (NPS). In 2020 and 2021, the indole analog of 5F-EDMB-PINACA (5F-EDMB-PICA) and the non-fluorinated analog of this compound (EDMB-PINACA) were analytically characterized. Here, we present suitable urinary markers to prove the consumption of these two ethyl analogs. Ten authentic urine samples for each compound were analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qToF-MS). Anticipated phase-I metabolites detected in urine samples were confirmed in vitro by applying a pooled human liver microsomes (pHLM) assay. Prevalence data were obtained from urines collected for abstinence control and submitted to a screening method for SC metabolites. Ten phase-I metabolites of 5F-EDMB-PICA and 18 of EDMB-PINACA were detected by LC-qToF-MS analysis of authentic urine specimens. The main in-vivo metabolites were built by ester hydrolysis, often coupled to further metabolic processes. Investigation of phase-I biotransformation led to the identification of ester hydrolysis, monohydroxylation, and defluorination products as the most suitable urinary biomarkers for 5F-EDMB-PICA. Metabolites formed by ester hydrolysis coupled to ketone formation and by monohydroxylation are suggested for the detection of EDMB-PINACA. From October 1, 2020 to February 1, 2022, among positive urine samples, 5.4% and 10.1% tested positive 5F-EDMB-PICA and EDMB-PINACA, respectively. Due to common metabolites shared among structurally related SCs, the unequivocal detection of their consumption remains challenging for forensic laboratories and requires sensitive methods to monitor multiple metabolites, ideally including highly specific species.
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Affiliation(s)
- Arianna Giorgetti
- Department of Medical and Surgical Sciences, Unit of Legal Medicine, University of Bologna, Bologna.,Institute of Forensic Medicine, Forensic Toxicology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Pietro Brunetti
- Institute of Forensic Medicine, Forensic Toxicology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University, Ancona, Italy
| | - Belal Haschimi
- Institute of Forensic Medicine, Forensic Toxicology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Francesco Paolo Busardò
- Unit of Forensic Toxicology, Section of Legal Medicine, Department of Excellence of Biomedical Sciences and Public Health, Marche Polytechnic University, Ancona, Italy
| | - Susi Pelotti
- Department of Medical and Surgical Sciences, Unit of Legal Medicine, University of Bologna, Bologna
| | - Volker Auwärter
- Institute of Forensic Medicine, Forensic Toxicology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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12
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Wiese BM, Alvarez Reyes A, Vanderah TW, Largent-Milnes TM. The endocannabinoid system and breathing. Front Neurosci 2023; 17:1126004. [PMID: 37144090 PMCID: PMC10153446 DOI: 10.3389/fnins.2023.1126004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 03/16/2023] [Indexed: 05/06/2023] Open
Abstract
Recent changes in cannabis accessibility have provided adjunct therapies for patients across numerous disease states and highlights the urgency in understanding how cannabinoids and the endocannabinoid (EC) system interact with other physiological structures. The EC system plays a critical and modulatory role in respiratory homeostasis and pulmonary functionality. Respiratory control begins in the brainstem without peripheral input, and coordinates the preBötzinger complex, a component of the ventral respiratory group that interacts with the dorsal respiratory group to synchronize burstlet activity and drive inspiration. An additional rhythm generator: the retrotrapezoid nucleus/parafacial respiratory group drives active expiration during conditions of exercise or high CO2. Combined with the feedback information from the periphery: through chemo- and baroreceptors including the carotid bodies, the cranial nerves, stretch of the diaphragm and intercostal muscles, lung tissue, and immune cells, and the cranial nerves, our respiratory system can fine tune motor outputs that ensure we have the oxygen necessary to survive and can expel the CO2 waste we produce, and every aspect of this process can be influenced by the EC system. The expansion in cannabis access and potential therapeutic benefits, it is essential that investigations continue to uncover the underpinnings and mechanistic workings of the EC system. It is imperative to understand the impact cannabis, and exogenous cannabinoids have on these physiological systems, and how some of these compounds can mitigate respiratory depression when combined with opioids or other medicinal therapies. This review highlights the respiratory system from the perspective of central versus peripheral respiratory functionality and how these behaviors can be influenced by the EC system. This review will summarize the literature available on organic and synthetic cannabinoids in breathing and how that has shaped our understanding of the role of the EC system in respiratory homeostasis. Finally, we look at some potential future therapeutic applications the EC system has to offer for the treatment of respiratory diseases and a possible role in expanding the safety profile of opioid therapies while preventing future opioid overdose fatalities that result from respiratory arrest or persistent apnea.
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Affiliation(s)
- Beth M. Wiese
- Department of Pharmacology, University of Arizona, Tucson, AZ, United States
| | - Angelica Alvarez Reyes
- Department of Pharmacology, University of Arizona, Tucson, AZ, United States
- College of Medicine, University of Arizona, Tucson, AZ, United States
| | - Todd W. Vanderah
- Department of Pharmacology, University of Arizona, Tucson, AZ, United States
| | - Tally M. Largent-Milnes
- Department of Pharmacology, University of Arizona, Tucson, AZ, United States
- *Correspondence: Tally M. Largent-Milnes,
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13
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Wiese BM, Liktor-Busa E, Couture SA, Nikas SP, Ji L, Liu Y, Makriyannis A, Spigelman I, Vanderah TW, Largent-Milnes TM. Brain Penetrant, but not Peripherally Restricted, Synthetic Cannabinoid 1 Receptor Agonists Promote Morphine-Mediated Respiratory Depression. Cannabis Cannabinoid Res 2022; 7:621-627. [PMID: 34935460 PMCID: PMC9587769 DOI: 10.1089/can.2021.0090] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Introduction: Cannabis acceptance and use continues to rise despite the gaps in knowledge regarding the mechanisms of cannabinoids and the endocannabinoid system in many physiological functions, including respiratory influence. Methods: With recent evidence of cannabinoid receptor 1 (CB1R) presence in the collection of respiratory neurons in the brainstem, as well as in the peripheral lung tissue, it is vital that the mechanisms involved in central and peripheral CB1R modulation of respiratory function be delineated. In this study we sought to define the roles of central versus peripheral CB1R activation on respiratory depression alone and in combination with morphine using whole body plethysmography. Results: We show that the peripherally restricted CB1 agonist (4-{2-[-(1E)-1[(4-propylnaphthalen-1-yl)methylidene]-1H-inden-3yl]ethyl}morpholine [PrNMI] 0.3, 0.6, and 1 mg/kg) does not induce respiratory depression, while our previous studies showed that a central penetrating synthetic cannabinoid does induce respiratory depression. Significantly, the combination of morphine with the peripheral CB1 agonist, PrNMI, attenuated morphine-induced respiratory depression. Conclusions: These studies support that a peripherally restricted CB1R agonist may be a unique strategy to attenuate the respiratory depression associated with opioid therapy.
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Affiliation(s)
- Beth M. Wiese
- Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
| | - Erika Liktor-Busa
- Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
| | - Sarah A. Couture
- Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
| | - Spyros P. Nikas
- Chemistry and Chemical Biology, Bouve College Health Sciences—Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA
| | - Lipin Ji
- Chemistry and Chemical Biology, Bouve College Health Sciences—Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA
| | - Yingpeng Liu
- Chemistry and Chemical Biology, Bouve College Health Sciences—Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA
| | - Alexandros Makriyannis
- Chemistry and Chemical Biology, Bouve College Health Sciences—Center for Drug Discovery, Northeastern University, Boston, Massachusetts, USA
| | - Igor Spigelman
- Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, California, USA
| | - Todd W. Vanderah
- Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
- Comprehensive Pain and Addiction Center, University of Arizona, Health Sciences, Tucson, Arizona, USA
| | - Tally M. Largent-Milnes
- Department of Pharmacology, University of Arizona, Tucson, Arizona, USA
- Comprehensive Pain and Addiction Center, University of Arizona, Health Sciences, Tucson, Arizona, USA
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14
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Evaluation of the in-vitro inhalation uptake of MDMB-4en-PINACA using a smoking simulation chamber. Microchem J 2022. [DOI: 10.1016/j.microc.2022.107737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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15
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Yoganathan P, Claridge H, Chester L, Englund A, Kalk NJ, Copeland CS. Synthetic Cannabinoid-Related Deaths in England, 2012-2019. Cannabis Cannabinoid Res 2022; 7:516-525. [PMID: 33998886 PMCID: PMC9418359 DOI: 10.1089/can.2020.0161] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Aim: To identify drug-related death trends associated with synthetic cannabinoid receptor agonists (SCRAs) reported to the National Programme on Substance Abuse Deaths (NPSAD) from England. Design: Case reports from NPSAD (England) where a SCRA was detected in post-mortem tissue(s) and/or implicated in the death were extracted, analyzed, and compared against non-SCRA-related deaths that occurred over the same time period (2012-2019). Findings: One hundred sixty-five death SCRA-related reports were extracted, with 18 different SCRAs detected. Following the first death in 2012, a subsequent sharp increase in reporting is evident. Acute SCRA use was the underlying cause of death in the majority of cases (75.8%) with cardiorespiratory complications the most frequently cited underlying physiological cause (13.4%). SCRA users were predominantly found dead (68.6%), with a large proportion of those witnessed becoming unresponsive described as suddenly collapsing (81.6%). Psychoactive polydrug use was detected in 90.3% of cases, with alcohol the most commonly co-detected (50.3%), followed by opioids (42.2%), benzodiazepines/Z-drugs (32.1%), stimulants (32.1%, [28.5% cocaine]), and cannabis (24.8%). Compared to all non-SCRA-related NPSAD deaths occurring over the same time period, SCRA-related decedents were more predominantly male (90.3% vs. 72.0%; p<0.01), and lived in more deprived areas (p<0.01). While a comparatively significant proportion of decedents were homeless (19.4% vs. 4.1%), living in a hostel (13.3% vs. 2.3%) or in prison (4.9% vs. 0.2%) at time of death (all p<0.01), the greatest majority of SCRA-related decedents were living in private residential accommodations (57.6%). Conclusions: This is the largest dataset regarding SCRA-related mortalities reported to date. Reporting of SCRA-related deaths in England have increased considerably, with polydrug use a specific concern. Lack of effective deterrents to SCRA use under current UK legislation, compounded by limited knowledge regarding the physiological impacts of SCRA consumption and their interaction with other co-administered substances are contributory factors to the occurrence of SCRA-related mortalities in an increasingly deprived demographic.
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Affiliation(s)
- Pruntha Yoganathan
- Population Health Research Institute, St George's, University of London, London, United Kingdom
| | - Hugh Claridge
- Population Health Research Institute, St George's, University of London, London, United Kingdom
| | - Lucy Chester
- Department of Psychosis Studies and Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
| | - Amir Englund
- Department of Addictions, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
- South London and Maudsley NHS Foundation Trust, London, United Kingdom
| | - Nicola J. Kalk
- Department of Addictions, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
- South London and Maudsley NHS Foundation Trust, London, United Kingdom
- KCH Alcohol Care Team, South London and Maudsley NHS Foundation Trust, London, United Kingdom
| | - Caroline S. Copeland
- Population Health Research Institute, St George's, University of London, London, United Kingdom
- Institute of Pharmaceutical Science, King's College London, London, United Kingdom
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16
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Bakshi HA, Faruck HL, Ravesh Z, Ansari P, Hannan JMA, Hashimoto R, Takayama K, Farzand R, Nasef MM, Mensah A, Aljabali AAA, Mishra V, Charbe NB, Goyal R, Negi P, Serrano-Aroca Á, Bahar B, El-Tanani M, Courtenay AJ, McCarron P, Jack IG, Tambuwala MM. Therapeutic Potential of Cannabinoids on Tumor Microenvironment: A Molecular Switch in Neoplasia Transformation. Integr Cancer Ther 2022; 21:15347354221096766. [PMID: 35796303 PMCID: PMC9425895 DOI: 10.1177/15347354221096766] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2021] [Revised: 03/02/2022] [Accepted: 04/09/2022] [Indexed: 11/24/2022] Open
Abstract
The efficacy of chemotherapy depends on the tumor microenvironment. This microenvironment consists of a complex cellular network that can exert both stimulatory and inhibitory effects on tumor genesis. Given the increasing interest in the effectiveness of cannabis, cannabinoids have gained much attention as a potential chemotherapy drug. Cannabinoids are a group of marker compounds found in Cannabis sativa L., more commonly known as marijuana, a psychoactive drug used since ancient times for pain management. Although the anticancer potential of C. sativa, has been recognized previously, increased attention was generated after discovering the endocannabinoid system and the successful production of cannabinoid receptors. In vitro and in vivo studies on various tumor models have shown therapeutic efficiency by modifying the tumor microenvironment. However, despite extensive attention regarding potential therapeutic implications of cannabinoids, considerable clinical and preclinical analysis is needed to adequately define the physiological, pharmacological, and medicinal aspects of this range of compounds in various disorders covered in this review. This review summarizes the key literature surrounding the role of cannabinoids in the tumor microenvironment and their future promise in cancer treatment.
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Affiliation(s)
| | | | | | | | | | | | | | - Rabia Farzand
- University of Huddersfield, Queensgate, Huddersfield, UK
| | | | | | | | - Vijay Mishra
- Lovely Professional University, Phagwara, Punjab, India
| | | | - Rohit Goyal
- Shoolini University, Solan, Himachal Pradesh, India
| | - Poonam Negi
- Shoolini University, Solan, Himachal Pradesh, India
| | | | | | | | | | - Paul McCarron
- Ulster University, Coleraine, County Londonderry, UK
| | - Iain G. Jack
- Ulster University, Coleraine, County Londonderry, UK
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17
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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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18
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Selzer EB, Blain D, Hufnagel RB, Lupo PJ, Mitchell LE, Brooks BP. Review of Evidence for Environmental Causes of Uveal Coloboma. Surv Ophthalmol 2021; 67:1031-1047. [PMID: 34979194 DOI: 10.1016/j.survophthal.2021.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 12/22/2021] [Accepted: 12/27/2021] [Indexed: 10/19/2022]
Abstract
Uveal coloboma is a condition defined by missing ocular tissues and is a significant cause of childhood blindness. It occurs from a failure of the optic fissure to close during embryonic development,and may lead to missing parts of the iris, ciliary body, retina, choroid, and optic nerve. Because there is no treatment for coloboma, efforts have focused on prevention. While several genetic causes of coloboma have been identified, little definitive research exists regarding the environmental causes of this condition. We review the current literature on environmental factors associated with coloboma in an effort to guide future research and preventative counseling related to this condition.
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Affiliation(s)
- Evan B Selzer
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Delphine Blain
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Robert B Hufnagel
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD
| | - Philip J Lupo
- Department of Pediatrics, Section of Hematology-Oncology, Baylor College of Medicine, Houston, TX
| | - Laura E Mitchell
- Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX
| | - Brian P Brooks
- Ophthalmic Genetics & Visual Function Branch, National Eye Institute, National Institutes of Health, Bethesda, MD.
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19
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Gaunitz F, Andresen-Streichert H. Analytical findings in a non-fatal intoxication with the synthetic cannabinoid 5F-ADB (5F-MDMB-PINACA): a case report. Int J Legal Med 2021; 136:577-589. [PMID: 34921326 PMCID: PMC8847293 DOI: 10.1007/s00414-021-02717-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Accepted: 09/27/2021] [Indexed: 11/23/2022]
Abstract
The case report centres on analytical findings from a spice sample (mixed with tobacco (as a cigarette) for consumption), and its corresponding plasma sample, smoked by a 31-year-old man who was attended by emergency services following collapse. The man was fully conscious and cooperative during initial medical treatment. Suddenly, he suffered a complete loss of self-control, whereupon the police was notified. The man encountered the police officers when exiting the apartment, at which point he threatened them with clenched fists and reached for a plant bucket in order to strike out in the direction of the officers. At the trial, he described himself as confused and as being completely overwhelmed, having lost self-control, suffered a panic attack and “just wanted to get out the situation”. Furthermore, he stated that he had no recollection of the incident. He feared death due to palpitations, heart pain, dizziness and repetitive anxiety states. Routine systematic as well as extended toxicological analysis of the plasma sample, taken approximately 2 h after the incident, confirmed the use of cannabis and spice. Plasma concentrations of THC, OH-THC and THC-COOH were 8.0 μg/L, 4.0 μg/L and 147 μg/L, respectively. Furthermore, analysis confirmed uptake of 5F-ADB (5F-MDMB-PINACA) via detection of both 5F-ADB and the 5F-ADB N-(5-OH-pentyl) metabolite. The spice sample additionally contained 5F-MDMB-PICA, which was not detected in the plasma sample. A differentiation between a possible co-use and a recent use of cannabis was not possible. In summary, this case once more underlines the health risks of spice use.
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Affiliation(s)
- Franziska Gaunitz
- Institute of Legal Medicine, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany.
| | - Hilke Andresen-Streichert
- Institute of Legal Medicine, University of Cologne, Faculty of Medicine and University Hospital, Cologne, Germany
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20
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Caniglia EC, Khan M, Ban K, Braithwaite RS. Integrating Screening and Treatment of Unhealthy Alcohol Use and Depression with Screening and Treatment of Anxiety, Pain, and Other Substance Use Among People with HIV and Other High-Risk Persons. AIDS Behav 2021; 25:339-346. [PMID: 33829369 PMCID: PMC8610949 DOI: 10.1007/s10461-021-03245-5] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/23/2021] [Indexed: 02/06/2023]
Abstract
We review and synthesize results from a series of analyses estimating the benefit of screening for unhealthy alcohol use, depression, and tobacco to detect individuals at heightened risk for co-occurring anxiety, pain, depression, unhealthy alcohol use, and other substance use among people with HIV and HIV-uninfected individuals in the Veterans Aging Cohort Study. We also examine the potential impact of reducing unhealthy alcohol use and depressive symptoms on the incidence of co-occurring conditions. We found that screening for alcohol and depression may help identify co-occurring symptoms of anxiety, depression, and pain interference, treating unhealthy alcohol use may improve co-occurring pain interference and substance use, and improving depressive symptoms may improve co-occurring anxiety, pain interference, and smoking. We propose that an integrated approach to screening and treatment for unhealthy alcohol use, depression, anxiety, pain, and other substance use may facilitate diagnostic assessment and treatment of these conditions, improving morbidity and mortality.
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Affiliation(s)
- Ellen C Caniglia
- Department of Population Health, NYU School of Medicine, 227 E. 30th St., New York, NY, 10016, USA.
| | - Maria Khan
- Department of Population Health, NYU School of Medicine, 227 E. 30th St., New York, NY, 10016, USA
| | - Kaoon Ban
- Department of Population Health, NYU School of Medicine, 227 E. 30th St., New York, NY, 10016, USA
| | - R Scott Braithwaite
- Department of Population Health, NYU School of Medicine, 227 E. 30th St., New York, NY, 10016, USA
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21
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Deen AA, Claridge H, Treble RD, Hamnett HJ, Copeland CS. Deaths from novel psychoactive substances in England, Wales and Northern Ireland: Evaluating the impact of the UK psychoactive substances act 2016. J Psychopharmacol 2021; 35:1315-1323. [PMID: 34182812 PMCID: PMC8600590 DOI: 10.1177/02698811211026645] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
BACKGROUND 'Legal highs' began appearing in the UK in the mid-2000s. Whilst many of these substances were controlled under the 1971 Misuse of Drugs Act, novel compounds and new variants of controlled compounds were continuously being introduced to the recreational drug market. The Psychoactive Substances Act (PSA) was therefore implemented in 2016 as a blanket ban on all novel psychoactive substances (NPS). AIM To evaluate the impact of the PSA on deaths following NPS use in England, Wales and Northern Ireland. METHODS Cases reported to the National Programme on Substance Abuse Deaths where death had occurred 3 years pre- or post-implementation of the PSA were extracted. Cases with NPS detected at post-mortem were analysed and compared against cases non-NPS cases. RESULTS 293 deaths with NPS detected were identified; 91 occurring before the PSA and 202 afterwards, indicating an 222.0% post-PSA increase. Contrastingly, non-NPS drug-related death case reporting increased by only 8.0%. Synthetic cannabinoid, anxiolytic/sedative and stimulant NPS were detected in the largest proportions of deaths pre-PSA; post-PSA stimulant NPS detections reduced whilst synthetic cannabinoid and anxiolytic/sedative detections increased.Post-PSA, average decedent age increased significantly (mean age pre-PSA 34.4 ± 10.8 vs post-PSA 38.3 ± 9.4), and they were significantly more likely to have been living in deprived areas (pre-PSA 50.0% vs post-PSA 65.9%). CONCLUSIONS Reporting of deaths following NPS use has risen despite introduction of the PSA. Whilst deaths amongst younger individuals and those living in more affluent areas has reduced, additional approaches to prohibition are needed to curb their persistence in deprived demographics.
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Affiliation(s)
- Adrian A Deen
- Institute of Pharmaceutical Sciences,
King’s College London, London, United Kingdom
| | - Hugh Claridge
- Population Health Research Institute,
St George’s, University of London, London, United Kingdom
| | | | - Hilary J Hamnett
- School of Chemistry, University of
Lincoln, Lincoln, United Kingdom
| | - Caroline S Copeland
- Institute of Pharmaceutical Sciences,
King’s College London, London, United Kingdom,Population Health Research Institute,
St George’s, University of London, London, United Kingdom,Caroline S Copeland, Institute of
Pharmaceutical Sciences, King’s College London, Franklin Wilkins Building,
Stamford Street, London, SE1 9 NH, United Kingdom.
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Lam AP, Moeller S, Speitling C, Lam MC, Philipsen A, Müller HHO. Consumption of Synthetic Cannabinoids in Adult Attention-Deficit/Hyperactivity Disorder: a Pilot Study. Int J Ment Health Addict 2021. [DOI: 10.1007/s11469-020-00248-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
AbstractAttention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for substance abuse and addiction. Synthetic cannabinoids (SC) have gained rising importance as their consumption increased rapidly in the last few years. However, SC consumption in patients with adult ADHD has not been investigated yet. A prospective clinical pilot study was conducted, including 60 adults with ADHD, assessing the prevalence of SC consumption and its associations with psychiatric comorbidities and patient characteristics. A drug consumption survey was utilized to investigate the use of SC and other drugs. Current ADHD symptoms were evaluated via ADHD Self-Rating Scale (ADHD-SR) and retrospective childhood ADHD symptom severity via Wender Utah Rating Scale (WURS-k) questionnaire. A positive lifetime prevalence of SC consumption was found in 15.0% of the analyzed sample. SC consumption was significantly associated with current smoking, lifetime use of natural cannabis (NC), cocaine, amphetamines, and benzodiazepines. Lifetime NC consumption was indicated by 65.0% and found to antecede SC use in adult ADHD patients. Logistic regression analysis identified substance use disorder and male sex as predictive for SC consumption. Patients with history of SC use scored significantly higher in both WURS-k and ADHD-SR questionnaire compared with nonusers and suffered significantly more frequently from psychiatric comorbidities. Main side-effects of SC included gastrointestinal, cardiovascular, and neuropsychiatric symptoms. SC consumption in adults with ADHD is frequent and associated with stronger ADHD symptom severity. Given the underestimated dangerous effects and related comorbidities, SC use should be subject to scrutiny by clinicians treating ADHD patients. More studies are needed to further elucidate the impact of SC use in ADHD.
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23
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Jackson MA, Brown AL, Johnston J, Clancy R, McGregor I, Bruno R, Lintzeris N, Montebello M, Luksza J, Bowman J, Phung N, Allsop D, Dunlop AJ. The use and effects of synthetic cannabinoid receptor agonists by New South Wales cannabis treatment clients. J Cannabis Res 2021; 3:33. [PMID: 34311790 PMCID: PMC8314558 DOI: 10.1186/s42238-021-00091-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Accepted: 07/09/2021] [Indexed: 11/25/2022] Open
Abstract
Introduction Despite decreasing consumption by general populations, use of synthetic cannabinoid receptor agonists (SCRAs) persists in some marginalised groups, including those who use other substances. This article explores SCRA consumption in an Australian cannabis treatment sample, comparing those who report ever using SCRAs with those who have never used SCRAs. Methods A questionnaire orally administered in person to a convenience sample of 154 cannabis treatment service clients from New South Wales, Australia (71% male, median age 35) collected information regarding cannabis and SCRA use including motivations, effects and health-related consequences of use, demographics, other substance use and overall health. Demographic profiles and between-group differences were explored. McNemar tests compared effects of SCRA and cannabis. Logistic regression analysis determined predictors of SCRA use. Results Half (53%) reported lifetime SCRA use; 20% reported previous-month use. The SCRA + cannabis group displayed greater polysubstance use and psychological distress. Reduced dependence on cannabis but higher levels of other substance use may predict SCRA use. Although curiosity motivated initial SCRA consumption, perceived psychoactive strength drove continued use. SCRAs appear to induce more negative side-effects than cannabis. Of the SCRA + cannabis group, 27% sought medical assistance for SCRA use. Most (90%) preferred cannabis to SCRAs, citing superior safety, effects and consistency of cannabis. Conclusions Among clients seeking treatment for cannabis use, SCRA use was relatively common, although not a preferred substance. Hazardous substance use and poor mental health characterised SCRA consumers, highlighting the need for continued monitoring by researchers and treatment providers of SCRA consumption in populations who use substances. Supplementary Information The online version contains supplementary material available at 10.1186/s42238-021-00091-z.
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Affiliation(s)
- Melissa A Jackson
- Drug and Alcohol Clinical Services, Hunter New England Local Health District, Level 3, 670 Hunter Street, Newcastle, NSW, 2290, Australia.
| | - Amanda L Brown
- Drug and Alcohol Clinical Services, Hunter New England Local Health District, Level 3, 670 Hunter Street, Newcastle, NSW, 2290, Australia
| | - Jennifer Johnston
- University Centre for Rural Health, University of Sydney, Lismore, NSW, Australia
| | - Richard Clancy
- Centre for Brain and Mental Health Research, Hunter New England Local Health District, Newcastle, NSW, Australia
| | - Iain McGregor
- The Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
| | - Raimondo Bruno
- School of Health, University of Tasmania, Hobart, TAS, Australia
| | - Nick Lintzeris
- Drug and Alcohol Services, South East Sydney Local Health District, Sydney, NSW, Australia
| | - Mark Montebello
- Drug and Alcohol Services, Northern Sydney Local Health District, Sydney, NSW, Australia
| | - Jennifer Luksza
- Drug Health, Western Sydney Local Health District, Sydney, NSW, Australia
| | - Jenny Bowman
- Faculty of Science and Information Technology, University of Newcastle, Newcastle, NSW, Australia
| | - Nghi Phung
- Drug Health, Western Sydney Local Health District, Parramatta, NSW, Australia
| | - Dave Allsop
- The Lambert Initiative for Cannabinoid Therapeutics, Brain and Mind Centre, University of Sydney, Sydney, NSW, Australia
| | - Adrian J Dunlop
- Drug and Alcohol Clinical Services, Hunter New England Local Health District, Level 3, 670 Hunter Street, Newcastle, NSW, 2290, Australia
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24
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Symptoms of Intoxication and Withdrawal in a Sample of Egyptian Patients Using Synthetic Cannabinoids: A Cohort Study. ADDICTIVE DISORDERS & THEIR TREATMENT 2021. [DOI: 10.1097/adt.0000000000000259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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25
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Efeoglu Ozseker P, Daglioglu N, Gulmen MK, Tolunay I, Efeoglu F. Determination of AB-FUBINACA and 5F-NPB-22 in rats exposed to "Bonsai" via inhalation and analysis of seized product. Leg Med (Tokyo) 2021; 50:101869. [PMID: 33713938 DOI: 10.1016/j.legalmed.2021.101869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 01/05/2021] [Accepted: 02/27/2021] [Indexed: 10/22/2022]
Abstract
Synthetic cannabinoids (SCs) are the most rapidly growing class of recreational designer drugs. Illicit drug manufacturers began to produce herbal smoking materials under a variety of brands names, e.g. "Spice, K2, Bonsai, Yucatan Fire". They were appeared on the European market in 2008. In this study, types of SCs in the herbal product sold as "Bonsai" in Turkey were determined and the identification of these substances in biological samples collected from rats depending on the inhalation of different amounts of plant material were aimed. To determine the SC species in the content of the plant product, analysis was performed via gas chromatography-mass spectrometry. Liquid-liquid extraction methods were utilized for blood and organ samples, while solid-phase extraction with β-glucuronidase enzyme treatment was applied for urine sample preparation. The relationship between the amount of burned plant and the amount of SCs accumulated in the blood, urine and organ samples of rats exposed to the plant product by inhalation was examined by liquid chromatography-tandem mass spectrometry. AB-FUBINACA and 5F-NPB-22 were detected in the herbal product. A significant correlation was found between the amount of herbal product inhaled and the prevalence of SCs, especially in lung tissues while no SCs were detected in the blood and urine samples of rats. There is currently no study on biological samples of individuals exposed to herbal products containing SCs by inhalation. Regarding the findings obtained in this study, the overall increase in the amounts of herbal product inhaled was demonstrated to pose a potential risk to humans.
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Affiliation(s)
- Pinar Efeoglu Ozseker
- Department of Forensic Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey.
| | - Nebile Daglioglu
- Department of Forensic Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Mete Korkut Gulmen
- Department of Forensic Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey
| | - Ilknur Tolunay
- Adana City Education & Research Hospital, Child Intensive Care Department, Adana, Turkey
| | - Fehiman Efeoglu
- Department of Forensic Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey
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26
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Shapira B, Berkovitz R, Rosca P, Lev-Ran S, Kaptsan A, Neumark Y. Why Switch? - Motivations for Self-Substitution of Illegal Drugs. Subst Use Misuse 2021; 56:627-638. [PMID: 33663337 DOI: 10.1080/10826084.2021.1887246] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Self-substitution is the conscious switch from one drug to another for reasons such as price, availability, desired effect, or perceived benefit of the substitute drug. Purpose/Objectives: This study aimed to describe drug use patterns and motivations associated with substitution. We examined correlates of lifetime substitution among individuals with substance use disorder. Methods: A cross-sectional study of 771 treatment-enrolled individuals. We used self-report for determining the lifetime prevalence, correlates, and motivations for substitution. Results: Of the 771 respondents, 570 (73.9%) reported ever substituting their preferred substance. The main incentives for substitution were availability (23.7%) and curiosity (20.2%). Among heroin or cannabis preferers, improved effects or less adverse effects of the substitute drug, self-medication, and managing withdrawal symptoms were significant substitution incentives. Increased odds for substitution were observed for past 12 months use of cannabis (OR = 1.51, CI = 1.06-4.52), prescription opioids (OR = 2.86, CI = 1.81-4.52), novel psychoactive substances (OR = 2.68, CI = 1.64-4.36), and repeated admission (OR = 1.50, CI = 1.05-2.14). Older age at onset-of-use was negatively associated with substitution (OR = 0.95, CI = 0.93-0.98). Conclusions: Self-substitution of one substance for another is a highly prevalent behavior among treatment-enrolled patients with substance use disorder. Clinicians caring for substance use disorder patients should be aware of substitution patterns involving the use of highly potent substances, which constitutes a risk to patients. Results underscore the benefit of substitution patterns analyses, as they reveal important information on the characteristics of persons who use drugs and their motivations.
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Affiliation(s)
- Barak Shapira
- Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem, Israel
| | - Ronny Berkovitz
- Division of Enforcement and Inspection, Israel Ministry of Health, Jerusalem, Israel
| | - Paola Rosca
- Department for the Treatment of Substance Abuse, Israel Ministry of Health, Jerusalem, Israel
| | - Shaul Lev-Ran
- Lev Hasharon Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel
| | - Alexander Kaptsan
- Dual Diagnosis Department, Be'er Sheva Mental Health Center, Negev, Be'er Sheva, Israel.,Ben Gurion University of the Negev, Be'er Sheva, Israel
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27
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Tebo C, Mazer-Amirshahi M, Wax P, Campleman S, Boyer E, Brent J, Sheth A, Daniuaityte R, Carlson R. Characterizing Trends in Synthetic Cannabinoid Receptor Agonist Use from Patient Clinical Evaluations during Medical Toxicology Consultation. J Psychoactive Drugs 2020; 53:207-214. [PMID: 33225872 DOI: 10.1080/02791072.2020.1851826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
Synthetic cannabinoid receptor agonists (SCRAs) are a new class of compounds with profound psychoactive effects and potential toxicity. This study characterizes patterns in SCRA abuse using qualitative interviews with individuals receiving medical toxicology consultation. Patients with suspected exposure to a new psychoactive substance were interviewed by medical toxicologists upon presentation for acute care. Investigators collected clinical and qualitative data including knowledge, attitudes, beliefs, and practices related to psychoactive substance use. Responses were categorized by identifying themes, and statistics were generated to describe patterns of use. Overall, 69% (86) of the 124 cases of novel psychoactive substance use entered into the registry were associated with exposure to SCRAs. Most patients (68.8%) had used SCRAs at least once before the presenting episode. 47.7% considered SCRAs to be very easy to obtain, and 44.2% reported paying for the substances while 32.6% acquired it for free. Nearly half (48.8%) of patients reported their primary reason for use was to get high; a small proportion used SCRAs to avoid testing positive on drug screening (6.9%) or as an alternative to marijuana (4.6%). Findings suggest an independent and stable culture is developing around the use of SCRAs separate from their appeal as an "undetectable" alternative to marijuana.
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Affiliation(s)
- Collin Tebo
- School of Medicine, Georgetown University, Washington, DC, USA
| | - Maryann Mazer-Amirshahi
- School of Medicine, Georgetown University, Washington, DC, USA.,Department of Emergency Medicine, MedStar Washington Hospital Center, Washington, DC, USA
| | - Paul Wax
- UT Southwestern Medical School.,American College of Medical Toxicology, Phoenix, AZ, USA
| | | | - Edward Boyer
- Department of Emergency Medicine, Brigham and Women's Hospital, Boston, MA, USA
| | - Jeffrey Brent
- University of Colorado School of Medicine and Colorado School of Public Health, Aurora, CO, USA
| | - Amit Sheth
- Computer Science & Engineering, University of South Carolina, Columba, SC, USA
| | | | - Robert Carlson
- Wright State University Boonshoft School of Medicine, Dayton, OH, USA
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28
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Fattore L, Marti M, Mostallino R, Castelli MP. Sex and Gender Differences in the Effects of Novel Psychoactive Substances. Brain Sci 2020; 10:brainsci10090606. [PMID: 32899299 PMCID: PMC7564810 DOI: 10.3390/brainsci10090606] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2020] [Revised: 08/28/2020] [Accepted: 08/31/2020] [Indexed: 12/12/2022] Open
Abstract
Sex and gender deeply affect the subjective effects and pharmaco-toxicological responses to drugs. Men are more likely than women to use almost all types of illicit drugs and to present to emergency departments for serious or fatal intoxications. However, women are just as likely as men to develop substance use disorders, and may be more susceptible to craving and relapse. Clinical and preclinical studies have shown important differences between males and females after administration of “classic” drugs of abuse (e.g., Δ9-tetrahydrocannabinol (THC), morphine, cocaine). This scenario has become enormously complicated in the last decade with the overbearing appearance of the new psychoactive substances (NPS) that have emerged as alternatives to regulated drugs. To date, more than 900 NPS have been identified, and can be catalogued in different pharmacological categories including synthetic cannabinoids, synthetic stimulants (cathinones and amphetamine-like), hallucinogenic phenethylamines, synthetic opioids (fentanyls and non-fentanyls), new benzodiazepines and dissociative anesthetics (i.e., methoxetamine and phencyclidine-derivatives). This work collects the little knowledge reached so far on the effects of NPS in male and female animal and human subjects, highlighting how much sex and gender differences in the effects of NPS has yet to be studied and understood.
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Affiliation(s)
- Liana Fattore
- Institute of Neuroscience-Cagliari, National Research Council (CNR), Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy
- Correspondence:
| | - Matteo Marti
- Department of Morphology, Surgery and Experimental Medicine, Section of Legal Medicine and LTTA Center, University of Ferrara, 44121 Ferrara, Italy;
- Department of Anti-Drug Policies, Collaborative Center for the Italian National Early Warning System, Presidency of the Council of Ministers, 00187 Rome, Italy
| | - Rafaela Mostallino
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy; (R.M.); (M.P.C.)
| | - Maria Paola Castelli
- Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cittadella Universitaria, 09042 Monserrato, Cagliari, Italy; (R.M.); (M.P.C.)
- National Institute of Neuroscience (INN), University of Cagliari, 09124 Cagliari, Italy
- Center of Excellence “Neurobiology of Addiction”, University of Cagliari, 09124 Cagliari, Italy
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29
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Zawatsky CN, Abdalla J, Cinar R. Synthetic cannabinoids induce acute lung inflammation via cannabinoid receptor 1 activation. ERJ Open Res 2020; 6:00121-2020. [PMID: 32832534 PMCID: PMC7430153 DOI: 10.1183/23120541.00121-2020] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Accepted: 06/18/2020] [Indexed: 01/08/2023] Open
Abstract
Synthetic cannabinoid (SC) use has persisted in the United States despite schedule-1 placement under the Synthetic Drug Abuse Prevention Act of 2012 [1]. Analysis of the National Poison Data System indicates that hospitalisations caused by SC use increased significantly between 2010 and 2015 [2]. Moreover, there is a trend of the increasing use of such compounds among adolescents [3]. SCs are often 30–100-fold more potent than Δ9-tetrahydrocannabinol (THC), the major psychoactive ingredient of cannabis, in activating Cannabinoid receptor 1 (CB1R). Users are attracted to SCs because of the cheaper, novel and stronger highs such substances offer compared to cannabis, and because the compounds are not screened for in typical drug tests [1, 2]. Among those hospitalised for SC use, some patients exhibited respiratory failure [4–7], pulmonary infiltrates [5, 7], alveolar damage or haemorrhage [5–7] and histopathologic features similar to organising pneumonia [4–6]. The mechanism by which SCs damage pulmonary tissue has yet to be elucidated – whether by SC binding at CB1R, CB2R or another receptor, and what downstream effects such binding elicits. Solving this conundrum is the first step in optimising treatment for patients presenting with SC-related respiratory distress. Synthetic cannabinoids (SCs) induce a pro-inflammatory condition by activating cannabinoid receptor 1 (CB1R) in the lungs of mice, which raises a potential therapeutic use of CB1R antagonists in SC-induced lung disease resulting in hospitalisationhttps://bit.ly/31bWw4Q
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Affiliation(s)
- Charles N Zawatsky
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.,These authors contributed equally
| | - Jasmina Abdalla
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA.,These authors contributed equally
| | - Resat Cinar
- Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD, USA
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30
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Shapira B, Rosca P, Berkovitz R, Gorjaltsan I, Neumark Y. The switch from one substance-of-abuse to another: illicit drug substitution behaviors in a sample of high-risk drug users. PeerJ 2020; 8:e9461. [PMID: 32742781 PMCID: PMC7370931 DOI: 10.7717/peerj.9461] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 06/10/2020] [Indexed: 01/07/2023] Open
Abstract
Background Substitution can be defined as the consciously motivated choice to use one drug, either licit or illicit, instead of another, due to perceptions of cost, availability, safety, legality, substance characteristics, and substance attributions. Substitution represents a potential risk to drug users, mainly when substitutes are of higher potency and toxicity. This study offers a basic conceptualization of illicit substitution behavior and describes substitution patterns among users of two highly prevalent drugs of abuse-heroin and cannabis. Methods Here, 592 high-risk drug users undergoing pharmacological and psycho-social treatment were interviewed. Patients were asked questions about current drug use, lifetime substitution, and substitution patterns. Descriptive statistics, chi-square tests of independence, and multinomial logistic regressions were used to identify and test correlates of substitution patterns for heroin and cannabis. Results Of the 592 drug users interviewed, 448 subjects (75.7%) reported having substituted their preferred drug for another illicit substance. Interviews yielded a total of 275 substitution events reported by users of cannabis, and 351 substitution events reported by users of heroin. The most frequently reported substitution substances for responders who preferred heroin were illicit non-prescribed "street" methadone (35.9%), followed by oral and transdermal prescription opioids (17.7%). For responders who preferred cannabis, substitution for synthetic cannabinoid receptor agonists (33.5%) followed by alcohol (16.0%) were the most commonly reported. Age at onset-of-use (p < 0.005), population group (p = 0.008), and attending treatment for the first time (p = 0.026) were significantly associated with reported lifetime substitution. Past-year use of stimulants, heroin, hallucinogens, methylenedioxymethamphetamine (MDMA), and novel psychoactive substances were-at the 95% confidence level-also significantly associated with reported lifetime substitution. In multivariate analysis, the odds for methadone substitution among heroin users were significantly affected by age at onset-of-use, type of treatment center, and education. Odds for substitution for synthetic cannabinoid receptor agonists among cannabis users were significantly affected by age, population group, type of treatment center, and education. Conclusion Self-substitution behavior should be considered by clinicians and policymakers as a common practice among most drugusers. Substitution for street methadone provides evidence for the ongoing diversion of this substance from Opioid Maintenance Treatment Centers, while the prominence of substitution of synthetic cannabinoids among dual-diagnosis patients should be regarded as an ongoing risk to patients that needs to be addressed by clinicians. Analysis of additional substitution patterns should provide further valuable insights into the behavior of drugusers.
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Affiliation(s)
- Barak Shapira
- Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.,Division of Enforcement and Inspection, Israel Ministry of Health, Jerusalem, Israel
| | - Paola Rosca
- Department for the Treatment of Substance Abuse, Israel Ministry of Health, Jerusalem, Israel
| | - Ronny Berkovitz
- Division of Enforcement and Inspection, Israel Ministry of Health, Jerusalem, Israel
| | | | - Yehuda Neumark
- Braun School of Public Health and Community Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
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31
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The synthetic cannabinoid 5F-MDMB-PICA: A case series. Forensic Sci Int 2020; 314:110410. [PMID: 32683270 DOI: 10.1016/j.forsciint.2020.110410] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Revised: 06/30/2020] [Accepted: 07/07/2020] [Indexed: 12/23/2022]
Abstract
5F-MDMB-PICA has been detected in products sold on the internet as well as in biological samples since 2016. It is associated with serious adverse health and behavioral effects and even death. Herein we report on twelve cases with proven 5F-MDMB-PICA consumption, including three fatalities, four cases of driving under the influence of drugs and five other criminal acts. In these cases, 5F-MDMB-PICA was detected in postmortem blood or serum. Concentrations ranged from 0.1-16ng/mL. In some blood (serum) and urine samples, the hydrolysis metabolite of 5F-MDMB-PICA (M12) could also be detected. In this case series, co-consumption with other drugs occurred in 9 of 12 cases, most commonly alcohol, cannabis and other contemporary SCs. In five cases, 4F-MDMB-BINACA was also detected. The described cases demonstrate various adverse effects that might be associated with 5F-MDMB-PICA. Observed physical adverse effects were mainly balance deficiencies and ocular effects such as reddened conjunctivae, glassy eyes and delayed or unresponsive pupil light reactions. Observed mental and behavioral effects were mainly changing moods, aggression, confusion, erratic behavior, mental leaps, disorientation, slowed reaction, logorrhea and slurred speech. Due to the fast changing market of synthetic cannabinoids, data on such new appearing substances are basically scarce. Because of the limited number of studies on pharmacological properties of synthetic cannabinoids, reports of findings in human samples along with corresponding case history descriptions can be valuable for the interpretation of upcoming routine cases.
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32
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Bulbena-Cabre A, DiGenova P, Sigel P, Dunn NR, Swift RG. Synthetic Cannabinoid Intoxication Presenting as Malignant Catatonia: a Case Report. Int J Ment Health Addict 2020. [DOI: 10.1007/s11469-018-9954-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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Cohen K, Rosenzweig S, Rosca P, Pinhasov A, Weizman A, Weinstein A. Personality Traits and Psychotic Proneness Among Chronic Synthetic Cannabinoid Users. Front Psychiatry 2020; 11:355. [PMID: 32477173 PMCID: PMC7242629 DOI: 10.3389/fpsyt.2020.00355] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Accepted: 04/07/2020] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Chronic use of synthetic cannabinoids (SCs) has been associated with a wide range of negative consequences for health including psychotic and affective disturbances. Accumulating evidence indicates that cannabinoids use may be a risk factor for schizophrenia, and chronic natural cannabis users score higher than non-users on measures of schizotypal personality traits. However, little is known regarding the personality characteristics of SC users, especially in comparison with recreational cannabis users and healthy individuals. This study aimed to examine the differences in personality characteristics and schizotypy between SC users, regular cannabis users, and non-users and to compare these measures between groups. METHODS Forty-two chronic SC users, 39 natural cannabis users, and 47 non-using control participants, without history of mental disorder, or current substance use diagnosis (mean age 26± 4.47 years; 23 females, 105 males), completed the Big-Five Factor Inventory (BFI), the Schizotypal Personality Questionnaire-Brief (SPQ-B), substance use history, rating scales of depression and anxiety, and a demographic questionnaire. RESULTS On the BFI, SC users scored higher than natural cannabis users and non-users on neuroticism, but lower on agreeableness and extraversion, and endorsed greater schizotypal symptoms on the SPQ-B. In addition, SC users had lower scores on conscientiousness than non-users, and natural cannabis users were more extroverted than non-users. Higher openness and lower conscientiousness predicted schizotypy for both SC and natural cannabis users. Finally, greater neuroticism predicted schizotypy for natural cannabis users, and introversion predicted schizotypy for non-users. CONCLUSIONS These results show that chronic SC users differ from natural cannabis users and non-users on dimensions of specific personality traits and schizotypy that may indicate psychotic proneness.
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Affiliation(s)
- Koby Cohen
- Department of Behavioral Science, Ariel University, Ariel, Israel
| | - Shiri Rosenzweig
- Department of Behavioral Science, Ariel University, Ariel, Israel
| | - Paola Rosca
- Ministry of Health (Israel), Jerusalem, Israel
| | - Albert Pinhasov
- Adelson School of Medicine, Ariel University, Ariel, Israel
- Department of Molecular Biology, Ariel University, Ariel, Israel
| | | | - Aviv Weinstein
- Department of Behavioral Science, Ariel University, Ariel, Israel
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34
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Shapira B, Berkovitz R, Rosca P, Neumark Y. Recent Use of Synthetic Cannabinoids, Synthetic Opioids, and Other Psychoactive Drug Groups among High-risk Drug Users. J Psychoactive Drugs 2020; 52:334-343. [DOI: 10.1080/02791072.2020.1754534] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Barak Shapira
- Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem, Israel
| | - Ronny Berkovitz
- Division of Enforcement and Inspection, Israel Ministry of Health, Jerusalem, Israel
| | - Paola Rosca
- Department for the Treatment of Substance Abuse, Israel Ministry of Health, Jerusalem, Israel
| | - Yehuda Neumark
- Hebrew University-Hadassah Braun School of Public Health and Community Medicine, Jerusalem, Israel
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35
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Takeda A, Doi T, Asada A, Suzuki T, Yuzawa K, Ando H, Kubo Y, Nagasawa A, Kaihoko F, Hasegawa Y, Tanaka K, Igarashi K, Maeno T, Suzuki A, Shimizu S, Uemura N, Nakajima J, Suzuki J, Tagami T. Evaluation of carboxamide-type synthetic cannabinoids on the functional activities at cannabinoid receptors and biological effects via inhalation exposure test. Forensic Toxicol 2020. [DOI: 10.1007/s11419-020-00534-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Ahmed T, Khan A, See VY, Robinson S. Cardiac arrest associated with synthetic cannabinoid use and acquired prolonged QTc interval: A case report and review of literature. HeartRhythm Case Rep 2020; 6:283-286. [PMID: 32461896 PMCID: PMC7244635 DOI: 10.1016/j.hrcr.2020.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
Affiliation(s)
- Talha Ahmed
- University of Maryland Midtown Campus, Baltimore, Maryland
| | - Ahmed Khan
- University of Maryland School of Medicine, Baltimore, Maryland
| | - Vincent Y See
- University of Maryland School of Medicine, Baltimore, Maryland
| | - Shawn Robinson
- University of Maryland School of Medicine, Baltimore, Maryland
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Yasin H, Bulatova N, Wazaify M. Patterns of Substance Use among Patients in Addiction Rehabilitation in Jordan. Subst Use Misuse 2020; 55:1035-1044. [PMID: 32013654 DOI: 10.1080/10826084.2020.1722697] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Background: This study aimed to identify pattern of substance use among patients at two public addiction rehabilitation centers in Amman. It provided a description of substance use career and assessment of addiction severity, quality of life and quality of sleep among participants.Methods: A quantitative cross-sectional study using a structured data collection form consisting of 4 parts: 1. General data including the demographic characteristics, medical history and career of drug abuse. 2. Severity of addiction using the severity of dependence scale (SDS). 3. Quality of life measured by the EQ-5D and 4. Quality of sleep measured by the insomnia severity index (ISI) scale.Results: A total of 93 patients from 2 treatment settings were recruited over 5 months. The total number of actively used substances was 196, with an average of 2 substances per patient. Alcohol and synthetic cannabinoids were the two most commonly used substances (39.8% and 38.7% respectively) followed by benzodiazepines (33.4%). A notable drop in heroin use was observed (5.4%, 5 out of 23 opioid user) compared to the years 2007-2009. The mean SDS score among patients was 11.43 (SD ± 3.48) indicating high dependence. Sleep problems were reported by 45% of patients. Data showed a significant role of community pharmacies in supplying drugs of abuse for users.Conclusion: Pattern of substance use changed significantly in Jordan with synthetic cannabinoids being of the top substances used and heroin use dropping. Actions should be taken to reframe the legalization of dispensing certain drugs by pharmacists without a prescription.
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Affiliation(s)
- Haya Yasin
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan
| | - Nailya Bulatova
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan
| | - Mayyada Wazaify
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, University of Jordan, Amman, Jordan
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Cohen K, Mama Y, Rosca P, Pinhasov A, Weinstein A. Chronic Use of Synthetic Cannabinoids Is Associated With Impairment in Working Memory and Mental Flexibility. Front Psychiatry 2020; 11:602. [PMID: 32695029 PMCID: PMC7339911 DOI: 10.3389/fpsyt.2020.00602] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Accepted: 06/10/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND We have recently shown that chronic use of Synthetic Cannabinoids (SCs) has been associated with mood disorders and impairments in executive functions. There is also evidence indicating that chronic SC users have higher rates of comorbidity with depression and psychotic symptoms. Here, we investigate performance on executive function and emotional processing tasks in regular SC users and a measure of schizotypal traits. METHOD Thirty chronic SC users, 32 recreational cannabis users, and 32 non-using control participants, without history of mental disorder, or current substance abuse diagnosis (mean age 26 ± 4.27 years; 85 males, 9 females), were tested in addiction treatment centers in Israel. Computerized neurocognitive function tests; the N-back task, Go/No-Go task, Wisconsin Sorting Card-like Task (WSCT), and emotional face recognition task and questionnaires of depression, anxiety and schizotypal traits and symptoms were used. RESULTS SC users have performed worse than recreational cannabis users and non-cannabis users on the N-back working-memory task (lower accuracy) and the WSCT cognitive flexibility task. SC users showed greater schizotypal traits and symptoms compared with recreational cannabis users and non-user control participants. A positive association was found in cannabinoid-user groups between schizotypal traits and symptoms and cognitive and emotional processing measures. Finally, SC users have scored higher on depression and state-trait anxiety measures than recreational cannabis users or healthy control participants. CONCLUSIONS Repeated use of SCs is associated with impairment in executive functions and emotional processing. These alterations are associated with depression and schizotypal traits and symptoms. This adds to existing evidence on the long-term consequences of SC drugs and their risks for mental health.
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Affiliation(s)
- Koby Cohen
- Department of Behavioral Science, Ariel University, Ariel, Israel
| | - Yaniv Mama
- Department of Behavioral Science, Ariel University, Ariel, Israel
| | - Paola Rosca
- Ministry of Health (Israel), Jerusalem, Israel
| | - Albert Pinhasov
- Adelson School of Medicine, Ariel University, Ariel, Israel.,Department of Molecular Biology, Ariel University, Ariel, Israel
| | - Aviv Weinstein
- Department of Behavioral Science, Ariel University, Ariel, Israel
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Worob A, Wenthur C. DARK Classics in Chemical Neuroscience: Synthetic Cannabinoids (Spice/K2). ACS Chem Neurosci 2019; 11:3881-3892. [PMID: 31799831 DOI: 10.1021/acschemneuro.9b00586] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
This Review covers the background, pharmacology, adverse effects, synthesis, pharmacokinetics, metabolism, and history of synthetic cannabinoid compounds. Synthetic cannabinoids are a class of novel psychoactive substances that act as agonists at cannabinoid receptors. This class of compounds is structurally diverse and rapidly changing, with multiple generations of molecules having been developed in the past decade. The structural diversity of synthetic cannabinoids is supported by the breadth of chemical space available for exploitation by clandestine chemists and incentivized by attempts to remain ahead of legal pressures. As a class, synthetic cannabinoid products have a more serious adverse effect profile than that of traditional phytocannabinoids, including notable risks of lethality, as well as a history of dangerous adulteration. Most synthetic cannabinoids are rapidly metabolized to active species with prolonged residence times and peripheral tissue distribution, and analytical confirmation of use of these compounds remains challenging. Overall, the emergence of synthetic cannabinoids serves as a noteworthy example of the pressing public health challenges associated with the increasing development of easily synthesized, structurally flexible, highly potent, psychoactive drugs.
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Affiliation(s)
- Adam Worob
- Divisions of Pharmaceutical Sciences and Pharmacy Practice, School of Pharmacy, University of Wisconsin—Madison, Madison, Wisconsin 53705, United States
| | - Cody Wenthur
- Divisions of Pharmaceutical Sciences and Pharmacy Practice, School of Pharmacy, University of Wisconsin—Madison, Madison, Wisconsin 53705, United States
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40
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Ellsworth JT. Spice, vulnerability, and victimization: Synthetic cannabinoids and interpersonal crime victimization among homeless adults. Subst Abus 2019; 43:32-38. [PMID: 31697191 DOI: 10.1080/08897077.2019.1686725] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Background: Although the physiologic and psychological harms associated with the use of synthetic cannabinoids, such as spice, are well-described, researchers have yet to examine how spice abuse affects exposure to crime. This paper describes the dangerous social environment where spice is used and delineates how synthetic cannabinoid abuse increases the risk of victimization. Methods: This qualitative study used semi-structured interviews to examine crime- and victimization-related experiences of 22 homeless adults. Transcripts were analyzed for emergent themes using a two-tiered qualitative coding process. Results: Those experiencing homelessness describe synthetic cannabinoids as powerful intoxicants. Substances such as spice are sought for their ability to detach those under the drug's influence from reality. Participants illustrated their understanding of how synthetic cannabinoids affect the health and safety of unsheltered persons. Spice use frequently results in rapid intoxication; individuals under the influence of spice are thereby physically vulnerable to crime, particularly theft and robbery. Conclusion: Findings add to previous research on the harms of synthetic cannabinoid abuse. This study suggests a victimization process common among homeless persons who use spice: Incapacitation often rapidly follows use, which in turn precipitates victimization.
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Affiliation(s)
- Joshua T Ellsworth
- Department of Criminal Justice, Indiana University, Bloomington, Indiana, USA
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41
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Abstract
OBJECTIVE The main objective of this study was to investigate the structure of psychotic disorders due to synthetic cannabinoid use and to determine differences in clinical characteristics and disease course between such substance-induced psychosis and psychosis associated with a primary diagnosis of schizophrenia. METHODS This was a longitudinal, observational cohort study that included male patients who underwent inpatient treatment in the intensive care unit or in the emergency department due to substance-induced psychoses. The follow-up period was up to 2 years. RESULTS We identified 4 clinical variants of substance-induced psychoses in patients who use synthetic cannabinoids. CONCLUSIONS Our study revealed that psychotic symptoms are typical manifestations in association with intoxication with synthetic cannabinoids, and we identified several nonspecific characteristics of the psychoses that may occur in patients intoxicated with synthetic cannabinoids. We also identified a number of signs that may indicate the presence of substance-induced psychoses.
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42
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Campos S, Benoit E, Dunlap E. Risk management strategies of synthetic cannabis users. DRUGS AND ALCOHOL TODAY 2019; 19:270-281. [PMID: 34046079 DOI: 10.1108/dat-04-2019-0012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Purpose
The purpose of this paper is to explore the various ways users of synthetic cannabinoids (SCs) managed the dangers associated with the consumption of this substance.
Design/methodology/approach
This paper is based on a parent study of the use and market of synthetic cathinones (also known as “bath salts”) in New York City, Houston, Galveston and New Orleans. Focus groups were conducted in all four cities with a total of 20 individuals who identified as users of SCs. Grounded theory was used to analyse focus group transcripts.
Findings
Participants were aware of drug-related risks and implemented strategies to reduce harm to health. Protective measures fell into two broad categories: marketing and consumption. They noted the instability of SC products and consumer manipulation through packaging. Harm reduction (HR) strategies included: carefully selecting SC sources; sticking to one brand; handling their own SC; managing amount of K2 consumed in one sitting; controlling the pace.
Originality/value
Given the small amount of data on user experience with SCs and its risk to health, it is important to learn from users themselves how they create methods to keep themselves safe. This is one of the first studies recording HR practices of SC users and can contribute to intervention programs and organisations serving substance users.
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Orsolini L, Chiappini S, Corkery JM, Guirguis A, Papanti D, Schifano F. The use of new psychoactive substances (NPS) in young people and their role in mental health care: a systematic review. Expert Rev Neurother 2019; 19:1253-1264. [PMID: 31503507 DOI: 10.1080/14737175.2019.1666712] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Introduction: Over the past 10 years, a large number of New Psychoactive Substances (NPS) have entered the recreational drug scenario. NPS intake has been associated with health-related risks, and especially so for vulnerable populations such as the youngsters. Currently, most knowledge on the NPS health effects is learnt from both a range of users' reports, made available through the psychonauts' web fora, and from the few published, related toxicity, clinical observations.Areas covered: This paper aims at providing an overview of NPS effects on youngsters' mental health, whilst performing a systematic review of the current related knowledge.Expert opinion: NPS consumption poses serious health risks, due to both a range of unpredictable clinical pharmacological properties and the typical concomitant use of other psychoactive molecules; overall, this can lead to near misses and fatalities. In comparison with adults, the central nervous system of children/adolescents may be more vulnerable to the activity of these molecules, hence raising even further the levels of health-related concerns. More research is needed to provide evidence of both short- and long-term effects of NPS, related health risks, and their addiction potential.
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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, UK.,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, UK
| | - John M Corkery
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Amira Guirguis
- Swansea University Medical School, Institute of Life Sciences 2, Swansea University, Singleton Park, Swansea, Wales
| | - Duccio Papanti
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
| | - Fabrizio Schifano
- Psychopharmacology, Drug Misuse and Novel Psychoactive Substances Research Unit, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK
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44
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Corkery JM, Streete P, Claridge H, Goodair C, Papanti D, Orsolini L, Schifano F, Sikka K, Körber S, Hendricks A. Characteristics of deaths associated with kratom use. J Psychopharmacol 2019; 33:1102-1123. [PMID: 31429622 DOI: 10.1177/0269881119862530] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Kratom (Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. AIMS This study details the characteristics of such fatalities and provides a 'state-of-the-art' review. METHODS UK cases were identified from mortality registers by searching with the terms 'kratom', 'mitragynine', etc. Databases and online media were searched using these terms and 'death', 'fatal*', 'overdose', 'poisoning', etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. RESULTS Typical case characteristics (n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. CONCLUSIONS These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom's safety profile remains only partially understood; toxic and fatal levels require quantification.
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Affiliation(s)
- John M Corkery
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | | | - Hugh Claridge
- National Programme on Substance Abuse Deaths, Population Health Research Institute, St George's, University of London, London, UK
| | - Christine Goodair
- National Programme on Substance Abuse Deaths, Population Health Research Institute, St George's, University of London, London, UK
| | - Duccio Papanti
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Laura Orsolini
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Fabrizio Schifano
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Kanav Sikka
- Psychopharmacology, Drug Misuse, and Novel Psychoactive Substances Research Unit, Department of Clinical and Pharmaceutical Sciences, University of Hertfordshire, Hatfield, UK
| | - Sophie Körber
- Department of Pharmaceutical Science, University of Basel, Basel, Switzerland
| | - Amy Hendricks
- Retired Forensic Pathology Technician, Santa Clara County, CA, USA
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45
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Anderson SAR, Oprescu AM, Calello D, Monte A, Dayan PS, Hurd YL, Manini AF. Neuropsychiatric Sequelae in Adolescents With Acute Synthetic Cannabinoid Toxicity. Pediatrics 2019; 144:e20182690. [PMID: 31285395 PMCID: PMC6697124 DOI: 10.1542/peds.2018-2690] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 05/01/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVES Adolescents represent the largest age group that presents to emergency departments (ED) for synthetic cannabinoid (SC) toxicity; however, the neurotoxic effects of acute SC exposures in this group are understudied. Our aim was to characterize the neuropsychiatric presentation of adolescents with SC-related exposure in the ED compared with those with traditional cannabis exposure. METHODS A multicenter registry of clinical information prospectively collected by medical toxicologists (Toxicology Investigators Consortium Case Registry) was reviewed for adolescents presenting to the ED after SC or cannabis exposure from 2010 through 2018. Associations were measured between drug exposures and neuropsychiatric symptoms and/or signs. Exposures were classified into 4 groups: SC-only exposure, SC-polydrug exposures, cannabis-only exposure, and cannabis-polydrug exposures. RESULTS Adolescents presenting to the ED with SC-only exposure (n = 107) had higher odds of coma and/or central nervous system depression (odds ratio [OR] 3.42; 95% confidence interval [CI] 1.51-7.75) and seizures (OR 3.89; 95% CI 1.39-10.94) than those with cannabis-only exposure (n = 86). SC-only drug exposure was associated with lower odds of agitation than cannabis-only exposure (OR 0.18; 95% CI 0.10-0.34). In contrast, the group with SC-polydrug exposures (n = 38) had higher odds of agitation (OR 3.11; 95% CI 1.56-7.44) and seizures (OR 4.8; 95% CI 1.80-12.74) than the cannabis-polydrug exposures group (n = 117). CONCLUSIONS In this multisite cohort of US adolescents assessed in the ED, SC exposure was associated with higher odds of neuropsychiatric morbidity than cannabis exposure providing a distinct neurospychiatric profile of acute SC toxicity in adolescents.
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Affiliation(s)
| | - Anna M Oprescu
- Departments of Psychiatry, Neuroscience, and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Diane Calello
- Department of Emergency Medicine, New Jersey Medical School, Rutgers University, Newark, New Jersey; and
| | - Andrew Monte
- Departments of Emergency Medicine and Pharmaceutical Sciences, School of Medicine, University of Colorado, Aurora, Colorado
| | - Peter S Dayan
- Departments of Pediatrics and
- Emergency Medicine, Columbia University Herbert and Florence Irving Medical Center, New York, New York
| | - Yasmin L Hurd
- Departments of Psychiatry, Neuroscience, and Pharmacological Science, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Alex F Manini
- Division of Medical Toxicology, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai and Elmhurst Hospital Center, New York, New York
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Akram H, Mokrysz C, Curran HV. What are the psychological effects of using synthetic cannabinoids? A systematic review. J Psychopharmacol 2019; 33:271-283. [PMID: 30789300 DOI: 10.1177/0269881119826592] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
BACKGROUND Synthetic cannabinoids are, typically, full agonists at the cannabinoid CB1 receptor, and therefore considerably more potent than natural cannabis and may have correspondingly more serious psychological effects. Despite government sanctions against their production they continue to be available in ever-increasing varieties over the Internet. The psychological consequences of synthetic cannabinoid use are relatively unknown. AIM The purpose of this study was to synthesise the available research on the psychological consequences of synthetic cannabinoid use. METHOD A literature search of three databases was conducted in February 2018, including the following keywords: Spice, synthetic cannabis, cognition, affect, behaviour, psychosis, depression and anxiety. RESULTS Seventeen studies involving a variety of participants were eligible for inclusion: one controlled administration study, seven cross-sectional studies, five Internet surveys and four qualitative studies. The controlled administration study showed that, compared to placebo, synthetic cannabinoids acutely affected some aspects of cognitive functioning and subjective psychological ratings. Non-controlled, cross-sectional studies generally showed that synthetic cannabinoid users had lower performance on cognitive tasks and showed elevated symptomatology (e.g. paranoia) compared to both natural cannabis and non-cannabis users. Methodological limitations were noted across different study designs. There is limited research on how doses, frequency or type of synthetic cannabinoid influence outcomes. CONCLUSIONS Acute synthetic cannabinoid use can result in a range of psychological outcomes and, when non-intoxicated, synthetic cannabinoid users appear to differ from natural cannabis and non-users on various affective and cognitive domains. As synthetic cannabinoid use is increasing in at-risk populations there is an urgent need for more and better research to inform users, professionals and policymakers.
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Affiliation(s)
- Hina Akram
- 1 Department of Clinical, Educational and Health Psychology, University College London, London, UK.,2 UCL Clinical Psychopharmacology Unit, University College London, London, UK
| | - Claire Mokrysz
- 2 UCL Clinical Psychopharmacology Unit, University College London, London, UK
| | - H Valerie Curran
- 2 UCL Clinical Psychopharmacology Unit, University College London, London, UK
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Yin S. Adolescents and Drug Abuse: 21st Century Synthetic Substances. CLINICAL PEDIATRIC EMERGENCY MEDICINE 2019. [DOI: 10.1016/j.cpem.2019.03.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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Sharing, Group-Buying, Social Supply, Offline and Online Dealers: how Users in a Sample from Six European Countries Procure New Psychoactive Substances (NPS). Int J Ment Health Addict 2018. [DOI: 10.1007/s11469-018-0043-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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Smith KE, Staton M. Synthetic cannabinoid use among a sample of individuals enrolled in community-based recovery programs: Are synthetic cannabinoids actually preferred to other drugs? Subst Abus 2018; 40:160-169. [PMID: 30457960 DOI: 10.1080/08897077.2018.1528495] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Background: Over the past decade, availability and use of novel psychoactive substances such as synthetic cannabinoid receptor agonists (SCRA) have proliferated globally. However, the prevalence of SCRAs use remains uncertain, as does the degree to which individuals reporting SCRA use prefer SCRA to other drugs. Methods: In April 2017, a total of 500 anonymous surveys were completed by clients enrolled in a residential drug recovery program. Chi-square and t tests were used to examine significant differences between those who had ever used SCRA and those who had not. Logistic regression analysis was conducted in order to determine which other substances used within the past 12 months were significantly associated with past-12-month SCRA use. Results: About 69% (68.4%) of clients reported lifetime SCRA use. Those reporting SCRA use were predominantly younger ( x¯ = 32.5 vs. 40.7, P < .001), single (60.3% vs. 48.1%, P = .011), and white (87.1% vs. 77.7%, P = .008) and were more likely to have experienced past-12-month homelessness (6.5% vs. 3.2%, P = .004). This group had higher rates of probation/parole involvement (79.2% vs. 61.8%, P < .001) and incarceration (91.8% vs. 79.6%, P < .001). Individuals reporting SCRA use also showed extensive substance use histories and favored heroin, opioids, and amphetamines compared with SCRA. Only 5.2% of the SCRA-using group stated that SCRA was a preferred substance, and only 11.8% reported that they would try SCRA again. E-cigarettes (adjusted odds ratio [AOR] = 1.88), traditional cannabis (AOR = 3.87), amphetamines (AOR = 2.20), and synthetic cathinones (AOR = 3.51) were significantly associated with past-12-month SCRA use. Motivations for use included circumnavigating drug screens and peer influence. Approximately half of those who tried SCRA reported adverse effects associated with use. Conclusions: Prevalence of SCRA use among individuals with a history of substance misuse and criminal justice system involvement is high; however, SCRA are not indicated as a preferred drug.
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Affiliation(s)
- Kirsten Elin Smith
- Kent School of Social Work, University of Louisville , Louisville , Kentucky , USA.,Center on Drug and Alcohol and Research, University of Kentucky , Lexington , Kentucky , USA
| | - Michele Staton
- Department of Behavioral Science, University of Kentucky , Lexington , Kentucky , USA.,Center on Drug and Alcohol and Research, University of Kentucky , Lexington , Kentucky , USA
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50
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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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