1.Clinical profile and drugs of abuse identified among people who use drugs admitted to a tertiary hospital in the Philippines using a validated LC-QTOF/MS method.
Carissa Paz C. DIOQUINO ; Joanna V. TORALBA ; Lilianna Mae M. MORA ; Jowela B. ALVARADO ; Fresthel Monica M. CLIMACOSA ; Frances Lois U. NGO ; Maria Lourdes E. AMARILLO ; Ailyn M. YABES ; Monet M. LOQUIAS ; Roy Roberto L. GERONA
Acta Medica Philippina 2025;59(13):52-59
BACKGROUND
Drug use and abuse is a public health issue that has come into focus in the Philippines in the past years. Excluding the years of the COVID-19 pandemic, there has been a yearly increase in the number of admissions to treatment and rehabilitation centers. The census in the University of the Philippines-Philippine General Hospital (UP-PGH) National Poison Management and Control Center (NPMCC) shows a parallel increase in drug-positive patients consulting in the emergency room (ER).
OBJECTIVEThe objective of this study was to describe the demographic, clinical, and drug use profiles of substance users admitted to the UP-PGH and referred to the NPMCC for drug testing.
METHODSThis is a cross-sectional study where participants included patients aged 10 years and above who were referred to the NPMCC for drug testing within three days of the ER consult. Once consent or assent from children was obtained, patients were interviewed and examined. Urine samples were collected for drug screening using drugs of abuse screening test kits. A split sample was sent to the UP Drugs of Abuse Research Laboratory (UP DARL) for analysis using the liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The data was encoded in the REDcap platform. The results were analyzed and summarized using descriptive statistics.
RESULTSThree hundred eighty-four (384) individuals participated in the study and submitted urine samples for testing from 1 January 2019 to 28 February 2020. One hundred thirty-four (134) samples were positive for substances of abuse detected by drug screening test kits for methamphetamine (MAP), delta-9-tetrahydrocannabinol (THC), cocaine, 3,4-methylenedioxymethamphetamine (MDMA), benzodiazepines, and opioids, and by LC-QTOF/ MS analysis. Majority of the patients were males with an average age of 34.54 ± 1.16 years old. Many complained of neurobehavioral changes necessitating consultation at the hospital emergency room. The neurologic and cardiovascular systems were frequently affected. By using the drugs of abuse test kit, methamphetamine was the most common substance of abuse detected and was seen in 40.3% of the samples. Amphetamine type stimulants were the most common group of drugs identified by LC-QTOF/ MS analysis and was seen in 103 instances. New psychoactive substances detected more frequently than others include paramethoxymethamphetamine (PMMA), 3,4- methylenedioxy methamphetamine (MDMA) and 3,4- methylenedioxyamphetamine (MDA). A few cathinones like butylone and cathinone were also detected.
CONCLUSIONMethamphetamine was the most common substance of abuse detected in urine samples of the participants. New psychoactive substances were also detected in urine samples when LC-QTOF/MS analysis was utilized. Most persons who use drugs are unemployed young- to mid-adult males. The participants often had neurobehavioral and cardiovascular signs and symptoms.
Human ; Methamphetamine
2.Proficiency testing program for screening drug testing laboratories in the Philippines, 2009-2019: Experience of the National Reference Laboratory of the East Avenue Medical Center
Augosto A. Misolas ; Maria Veronica C. Eulogio ; Marites D. Go ; Laura R. Magat ; Evangeline R. Castillo ; Jennifer C. Deoduco-Mercado
Philippine Journal of Pathology 2024;9(1):27-36
		                        		
		                        			Background:
		                        			According to the guidelines of the Department of Health (DOH)’s Health Facilities and Services Regulatory Bureau (HFSRB), accreditation of drug testing laboratories (DTLs) requires annual participation in a proficiency testing (PT) program. Since 2009, the National Reference Laboratory for Environmental and Occupational Health, Toxicology and Micronutrient Assay of the East Avenue Medical Center (NRL-EAMC) has conducted the PT program for DTLs.
		                        		
		                        			Objectives:
		                        			This article aims to provide a general overview of the PT program conducted for screening drug testing laboratories (SDTLs) and to examine data on laboratories’ participation and performance in the PT program.
		                        		
		                        			Methodology:
		                        			Laboratories registered for the PT program were given ten 3-mL synthetic urine specimens which may or may not contain drugs of abuse such as methamphetamine and tetrahydrocannabinol at or above the cut-off level. Laboratories analyzed the PT specimens using immunoassay test kits. The results of the analysis were reported back to NRL-EAMC. The performance of the laboratories in the PT depends on the number of incorrect responses.
		                        		
		                        			Results:
		                        			For ten years (2009-2019), 1102 ± 188 laboratories annually participated in the program. The mean passing rate was 96.6 ± 4.8%. The number of laboratories which initially failed the PT program significantly decreased from 2009 (15.1%) to 2012 (1.5%). From 2013 to 2019, only below 2.5% of the participating laboratories initially failed the PT. On average, 48.4 ± 18.4% of the laboratories achieved an excellent performance, 34.0 ± 13.6% had a highly satisfactory performance, and 14.3 ± 5.4% got an acceptable performance.
		                        		
		                        			Conclusion
		                        			The continued decreasing number of laboratories which failed the PT signifies the improvement of laboratories in urine drug testing. In general, some laboratories participating in the PT for the first time are the ones which initially fail the PT which could be due to a lack of experience in handling PT test items. The PT program highlights the effectiveness of quality control procedures being implemented in a drug testing laboratory.
		                        		
		                        		
		                        		
		                        			Laboratories
		                        			;
		                        		
		                        			 Quality Control
		                        			;
		                        		
		                        			 Accreditation
		                        			;
		                        		
		                        			 Methamphetamine 
		                        			
		                        		
		                        	
3.Methamphetamine: Mechanism of Action and Chinese Herbal Medicine Treatment for Its Addiction.
Rui ZENG ; Hong-Yu PU ; Xin-Yue ZHANG ; Meng-Lin YAO ; Qin SUN
Chinese journal of integrative medicine 2023;29(7):665-672
		                        		
		                        			
		                        			With the proliferation of synthetic drugs, research on the mechanism of action of addictive drugs and treatment methods is of great significance. Among them, methamphetamine (METH) is the most representative amphetamine synthetic drug, and the treatment of METH addiction has become an urgent medical and social problem. In recent years, the therapeutic effects of Chinese herbal medicines on METH addiction have gained widespread attention because of their non-addictiveness, multiple targets, low side effects, low cost, and other characteristics. Previous studies have identified a variety of Chinese herbal medicines with effects on METH addiction. Based on the research on METH in recent years, this article summarizes the mechanism of action of METH as the starting point and briefly reviews the Chinese herbal medicine-based treatment of METH.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methamphetamine/adverse effects*
		                        			;
		                        		
		                        			Drugs, Chinese Herbal/therapeutic use*
		                        			;
		                        		
		                        			Amphetamine/therapeutic use*
		                        			;
		                        		
		                        			Behavior, Addictive/drug therapy*
		                        			;
		                        		
		                        			Amphetamine-Related Disorders/drug therapy*
		                        			
		                        		
		                        	
4.Application Prospect of Integrative Omics in Forensic Identification of Methamphetamine-Associated Psychosis.
Long-Rui ZHAO ; Jian-Bo ZHANG ; Wei HAN ; Li ZHU ; Teng CHEN ; Fang-Lin GUAN
Journal of Forensic Medicine 2022;38(5):650-656
		                        		
		                        			
		                        			The clinical symptoms and signs of methamphetamine-associated psychosis (MAP) and schizophrenia are highly similar, but the situation is completely different when MAP and schizophrenia patients need to be assessed for criminal responsibility after they comitted a harmful behavior. Therefore, the distinction between the two psychoses is very important in forensic psychiatry. At present, the identification of these two psychoses is mainly dependent on the corresponding criteria such as the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Chinese Classification of Mental Disorders Version 3 (CCMD-3). It's challenging to diagnose and distinguish between the two in practical cases due to their similar clinical symptoms and the lack of effective objective indexes. Different from the limitations of single omics, integrative omics intergrates data from multiple dimensions and has been extensively studied in the field of schizophrenia and has achieved some preliminary results. In view of the correlation between MAP and schizophrenia and the potential application value of integrative omics, this paper proposes an integrative omics strategy for MAP pathogenesis and forensic identification, aiming to improve the further understanding of the relationship between the two psychoses and the corresponding pathogenesis. It also provides references for the future exploration of integrative omics in forensic precise identification and effective monitoring and early warning methods.
		                        		
		                        		
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methamphetamine/adverse effects*
		                        			;
		                        		
		                        			Psychoses, Substance-Induced/etiology*
		                        			;
		                        		
		                        			Psychotic Disorders/genetics*
		                        			;
		                        		
		                        			Schizophrenia/genetics*
		                        			;
		                        		
		                        			Diagnosis, Differential
		                        			
		                        		
		                        	
5.Structure Analysis of the Interfering Substance N-methyl-2-phenylpropan-1-amine of Methamphetamine in Wastewater.
Ting-Ting ZHANG ; Yu HUANG ; Xue-Jun ZHANG ; Jie CHEN ; Zhen-Dong HUA
Journal of Forensic Medicine 2022;38(6):726-732
		                        		
		                        			OBJECTIVES:
		                        			To analyze the chemical structure of the interfering substance that affects the result of methamphetamine analysis in wastewater.
		                        		
		                        			METHODS:
		                        			A combination of GC-MS and liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) was used to analyze the mass spectrum characteristics of the interfering substance that affects the result of methamphetamine analysis and to infer its possible structure. Liquid chromatography-triple quadrupole-mass spectrometry (LC-TQ-MS) was used to confirm the control material.
		                        		
		                        			RESULTS:
		                        			Using LC-QTOF-MS in positive electrospray ionization (ESI+) mode, the mass-to-charge ratio (m/z) of quasi-molecular ion in the MS1 mass spectrometry of interfering substance was identical to that of methamphetamine, indicating that the interfering substance was probably an isomer of methamphetamine. The MS2 mass spectra obtained at three collision energies of 15 V, 30 V and 45 V were highly similar to methamphetamine, suggesting that the interfering substance contained methylamino and benzyl groups. Further analysis using GC-MS in electron impact (EI) ionization mode showed that the base peak in the mass spectrum of the interfering substance was at m/z 44. The interfering substance was confirmed to be N-methyl-2-phenylpropan-1-amine by compared with the standard reference.
		                        		
		                        			CONCLUSIONS
		                        			The chemical structure of N-methyl-2-phenylpropan-1-amine is highly similar to methamphetamine, which is easy to cause interference for the detection of trace amounts of methamphetamine in wastewater using LC-TQ-MS. Therefore, in the actual analysis, the chromatographic retention time can be used to distinguish between N-methyl-2-phenylpropan-1-amine and methamphetamine.
		                        		
		                        		
		                        		
		                        			Methamphetamine
		                        			;
		                        		
		                        			Wastewater
		                        			;
		                        		
		                        			Amines
		                        			;
		                        		
		                        			Gas Chromatography-Mass Spectrometry/methods*
		                        			;
		                        		
		                        			Mass Spectrometry/methods*
		                        			;
		                        		
		                        			Spectrometry, Mass, Electrospray Ionization/methods*
		                        			
		                        		
		                        	
6.SUN's abdominal acupuncture for depression after methamphetamine withdrawal: a randomized controlled trial.
Yuan-Zheng SUN ; Yan-Lin LIU ; Xi-Tong ZHAO ; Chen ZHOU ; Yu HAN ; Xiu-Ge YANG ; Peng LI
Chinese Acupuncture & Moxibustion 2022;42(1):18-22
		                        		
		                        			OBJECTIVE:
		                        			To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.
		                        		
		                        			METHODS:
		                        			A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.
		                        		
		                        			RESULTS:
		                        			After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).
		                        		
		                        			CONCLUSION
		                        			SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.
		                        		
		                        		
		                        		
		                        			Abdomen
		                        			;
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			;
		                        		
		                        			Depression/therapy*
		                        			;
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methamphetamine/adverse effects*
		                        			;
		                        		
		                        			Sleep Quality
		                        			;
		                        		
		                        			Substance Withdrawal Syndrome/therapy*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			
		                        		
		                        	
7.Effect of Tiaoshen acupuncture on anxiety after methamphetamine withdrawal.
Yuan-Zheng SUN ; Yuan DING ; Tian-Yang YU ; Cun-Yang CHEN ; Peng LI ; Xiu-Ge YANG ; Ying-Zhe SUN
Chinese Acupuncture & Moxibustion 2022;42(3):277-280
		                        		
		                        			OBJECTIVE:
		                        			To compare the therapeutic effect between Tiaoshen acupuncture combined with psychotherapy and simple psychotherapy on anxiety after methamphetamine withdrawal.
		                        		
		                        			METHODS:
		                        			A total of 78 patients were randomized into an observation group (39 cases, 2 cases dropped off) and a control group (39 cases, 1 case dropped off). Psychotherapy was given in the control group. On the basis of the treatment in the control group, Tiaoshen acupuncture was applied at Baihui (GV 20), Shenting (GV 24), Benshen (GB 13), Neiguan (PC 6) and Shenmen (HT 7) in the observation group. The treatment was given once a day, 6 days were as one course and totally 4 courses were required in both groups. The scores of Hamilton anxiety scale (HAMA), quality of life for drug addicts (QOL-DA) and Pittsburgh sleep quality index (PSQI) before and after treatment were observed in both groups.
		                        		
		                        			RESULTS:
		                        			After treatment, the various scores and the total scores of HAMA, QOL-DA and PSQI were decreased compared before treatment in both groups (P<0.05), and the scores of somatic anxiety factor, the psychic anxiety factor and the total score of HAMA, each various score and the total score of QOL-DA as well as the scores of sleep quality, time to fall asleep, sleep time, daytime dysfunction and the total score of PSQI in the observation group were lower than those in the control group (P<0.05).
		                        		
		                        			CONCLUSION
		                        			Tiaoshen acupuncture combined with psychotherapy can relieve the anxiety in patients with anxiety after methamphetamine withdrawal, improve the quality of life and sleep, the therapeutic effect is superior to the simple psychotherapy.
		                        		
		                        		
		                        		
		                        			Acupuncture Points
		                        			;
		                        		
		                        			Acupuncture Therapy
		                        			;
		                        		
		                        			Anxiety/therapy*
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methamphetamine/adverse effects*
		                        			;
		                        		
		                        			Quality of Life
		                        			
		                        		
		                        	
8.Current Situation of Methamphetamine Abuse and Related Research Progress.
Shi-Jun HONG ; Bao-Yu SHEN ; Rong-Ji SUN ; Gen-Meng YANG ; Chun-Mei DUAN ; Qian-Yun NIE ; Cong-Bin ZHANG ; Wen-Juan DONG ; Hao YU ; Shang WANG ; Peng-Liang LIU ; Pin-Yuan WEN ; Li-Hua LI
Journal of Forensic Medicine 2021;37(6):763-775
		                        		
		                        			
		                        			Drug problem is a major social and public security problem in the world. Drug abuse poses a great threat to economic development, social stability and public health. In recent years, synthetic drugs represented by methamphetamine have surpassed traditional drugs such as morphine, heroin, ketamine and become one of the most abused drugs in the world. In order to solve the problem of drug abuse, it is of great theoretical value and practical significance to carry out all-round and multi-level scientific research on drug-related issues. Based on the current situation of drug abuse, this article reviews research progresses on the epidemiology of methamphetamine abuse, the monitoring technology, the basic researches on toxicity damage, the withdrawal drug screening, the related clinical comorbidity and the testing technologies, comprehensively presenting the development trend of methamphetamine abuse related issues.
		                        		
		                        		
		                        		
		                        			Amphetamine-Related Disorders/epidemiology*
		                        			;
		                        		
		                        			Heroin
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Illicit Drugs
		                        			;
		                        		
		                        			Methamphetamine/adverse effects*
		                        			;
		                        		
		                        			Substance Abuse Detection
		                        			
		                        		
		                        	
9.Research Progress on the Omics of Methamphetamine Toxic Damage and Addiction.
Cui ZHANG ; Xu ZHAO ; Hui-Jun WANG ; Xia YUE
Journal of Forensic Medicine 2021;37(6):776-787
		                        		
		                        			
		                        			The mechanism of methamphetamine toxicity and addiction is the key research direction of forensic toxicology, and the development of omics technology provides a new platform for further study of this direction. METH toxic damage and addiction are reflected differently in genes, ribonucleic acid (RNA) transcription, protein and metabolism. This article summarizes the achievements and shortcomings of multi-omics technologies such as genome, transcriptome, metabolome and proteome in the study of METH damage and addiction, and discusses the strategies and advantages of multi-omics combined analysis in the study of METH toxic damage and addiction mechanism, in order to provide more useful reference information for forensic toxicology of METH.
		                        		
		                        		
		                        		
		                        			Metabolome
		                        			;
		                        		
		                        			Metabolomics
		                        			;
		                        		
		                        			Methamphetamine/toxicity*
		                        			;
		                        		
		                        			Proteome
		                        			;
		                        		
		                        			Proteomics
		                        			
		                        		
		                        	
10.Inhibitory Effect of CCK-8 on Methamphetamine-Induced Apoptosis.
Wu-Hua ZHANG ; Ming-Long ZHANG ; Wei-Wei JING ; Bing XIE ; Hai-Tao BI ; Feng YU ; Bin CONG ; Chun-Ling MA ; Di WEN
Journal of Forensic Medicine 2021;37(6):796-805
		                        		
		                        			OBJECTIVES:
		                        			To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis.
		                        		
		                        			METHODS:
		                        			SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins.
		                        		
		                        			RESULTS:
		                        			The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells.
		                        		
		                        			CONCLUSIONS
		                        			CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.
		                        		
		                        		
		                        		
		                        			Apoptosis/physiology*
		                        			;
		                        		
		                        			Central Nervous System Stimulants/pharmacology*
		                        			;
		                        		
		                        			HEK293 Cells
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Methamphetamine/pharmacology*
		                        			;
		                        		
		                        			Sincalide/pharmacology*
		                        			
		                        		
		                        	
            

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