Metabolic Brain Disease

, Volume 33, Issue 5, pp 1585–1597 | Cite as

Effect of methamphetamine on the fasting blood glucose in methamphetamine abusers

  • Yanhong Zhang
  • Guofang Shu
  • Ying Bai
  • Jie Chao
  • Xufeng ChenEmail author
  • Honghong YaoEmail author
Original Article


Methamphetamine is a popular psychostimulant worldwide which causes neurotoxicity and neuroinflammation. Although previous studies have characterized potential associations between addictive drugs and fasting blood glucose, the influence of methamphetamine on the blood glucose is still largely unknown. The present study was designed to investigate the change of fasting blood glucose of methamphetamine abusers and to confirm the impairment of liver and kidney. Fasting blood glucose was significantly decreased in methamphetamine abusers and in a high-fat diet mouse model with methamphetamine treatment discontinuation. Serum level of ALT, creatine kinase and creatinine were increased in methamphetamine abusers. Serum level of ALT and AST were increased in a high-fat diet mouse model after methamphetamine injection, but there was no significant difference in the anatomy of the liver and kidney in high-fat diet treated mice with or without methamphetamine. The levels of ALT and creatinine were also increased in the methamphetamine abusers. This study demonstrated that the level of glucose was decreased in methamphetamine abusers and in high-fat diet-fed mice after methamphetamine treatment discontinuation. The effect of methamphetamine on the levels of blood glucose may provide the evidence that methamphetamine abusers should be keep energy balance due to the low blood glucose.


Methamphetamine Serum biochemical parameters Liver Kidney 



Alanine aminotransferase


Aspartate aminotransferase


Central nervous system


Creatinine phosphokinase


Alkaline phosphatase


Ethylenediaminetetraacetic acid


High fat diet




Total Cholesterol


Low density lipoproteins cholesterol


High density lipoproteins cholesterol


Creatine Kinase




Urea nitrogen



This work was supported by grants from the National Natural Science Foundation of China (No. 81322048 and No. 81473190).

Author contributions

Y.H. planned and designed the research, supervised and wrote the experiments; Y.H.Z carried out the experiments and wrote the manuscript; Y.B. participated in data acquisition and analysis; G.F.S and J.C participated in the design of study, drafted manuscript and coordinated the lab work; and X.F.C provided the comments on the manuscript, edited the writing, and involved in revising it critically for important intellectual content. All authors read and approved the final manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. Abdul Muneer PM, Alikunju S, Szlachetka AM, Haorah J (2011a) Methamphetamine inhibits the glucose uptake by human neurons and astrocytes: stabilization by acetyl-L-carnitine. PLoS One 6:e19258. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Abdul Muneer PM, Alikunju S, Szlachetka AM, Murrin LC, Haorah J (2011b) Impairment of brain endothelial glucose transporter by methamphetamine causes blood-brain barrier dysfunction. Mol Neurodegener 6:23. CrossRefPubMedPubMedCentralGoogle Scholar
  3. Bowyer JF, Hanig JP (2014) Amphetamine- and methamphetamine-induced hyperthermia: implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity. Temperature 1:172–182. CrossRefGoogle Scholar
  4. Bowyer JF, Tranter KM, Sarkar S, George NI, Hanig JP, Kelly KA, Michalovicz LT, Miller DB, O'Callaghan JP (2017) Corticosterone and exogenous glucose alter blood glucose levels, neurotoxicity, and vascular toxicity produced by methamphetamine. J Neurochem 143:198–213. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bressler R, Vargas-Cord M, Lebovitz HE (1968) Tranylcypromine: a potent insulin secretagogue and hypoglycemic agent. Diabetes 17:617–624CrossRefPubMedGoogle Scholar
  6. Caldwell J, Dring LG, Williams RT (1972) Metabolism of ( 14 C)methamphetamine in man, the Guinea pig and the rat. Biochem J 129:11–22CrossRefPubMedPubMedCentralGoogle Scholar
  7. Capela JP, Carmo H, Remiao F, Bastos ML, Meisel A, Carvalho F (2009) Molecular and cellular mechanisms of ecstasy-induced neurotoxicity: an overview. Mol Neurobiol 39:210–271. CrossRefPubMedGoogle Scholar
  8. Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, Carvalho F, Bastos ML (2012) Toxicity of amphetamines: an update. Arch Toxicol 86:1167–1231. CrossRefPubMedGoogle Scholar
  9. Cook CE, Jeffcoat AR, Hill JM, Pugh DE, Patetta PK, Sadler BM, White WR, Perez-Reyes M (1993) Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride. Drug Metab Dispos 21:717–723PubMedGoogle Scholar
  10. Courtney KE, Ray LA (2014) Methamphetamine: an update on epidemiology, pharmacology, clinical phenomenology, and treatment literature. Drug Alcohol Depend 143:11–21. CrossRefPubMedGoogle Scholar
  11. Cretzmeyer M, Sarrazin MV, Huber DL, Block RI, Hall JA (2003) Treatment of methamphetamine abuse: research findings and clinical directions. J Subst Abus Treat 24:267–277CrossRefGoogle Scholar
  12. Cruickshank CC, Dyer KR (2009) A review of the clinical pharmacology of methamphetamine. Addiction 104:1085–1099. CrossRefPubMedGoogle Scholar
  13. De La Garza R, Shoptaw S, Newton TF (2008) Evaluation of the cardiovascular and subjective effects of rivastigmine in combination with methamphetamine in methamphetamine-dependent human volunteers. Int J Neuropsychopharmacol 11:729–741. CrossRefGoogle Scholar
  14. Divsalar K, Meymandi MS, Afarinesh M, Zarandi MM, Haghpanah T, Keyhanfar F, Mahmoodi M, Kruszewski SP (2014) Serum biochemical parameters following heroin withdrawal: an exploratory study. Am J Addict 23:48–52. CrossRefPubMedGoogle Scholar
  15. Halpin LE, Gunning WT, Yamamoto BK (2013) Methamphetamine causes acute hyperthermia-dependent liver damage. Pharmacol Res Perspect 1:e00008. CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hassan SF, Wearne TA, Cornish JL, Goodchild AK (2016) Effects of acute and chronic systemic methamphetamine on respiratory, cardiovascular and metabolic function, and cardiorespiratory reflexes. J Physiol 594:763–780. CrossRefPubMedPubMedCentralGoogle Scholar
  17. Herring NR, Schaefer TL, Tang PH, Skelton MR, Lucot JP, Gudelsky GA, Vorhees CV, Williams MT (2008) Comparison of time-dependent effects of (+)-methamphetamine or forced swim on monoamines, corticosterone, glucose, creatine, and creatinine in rats. BMC Neurosci 9:49. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Homer BD, Solomon TM, Moeller RW, Mascia A, DeRaleau L, Halkitis PN (2008) Methamphetamine abuse and impairment of social functioning: a review of the underlying neurophysiological causes and behavioral implications. Psychol Bull 134:301–310. CrossRefPubMedGoogle Scholar
  19. Huang R, Zhang Y, Han B, Bai Y, Zhou R, Gan G, Chao J, Hu G, Yao H (2017) Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG. Autophagy 13:1722–1741. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ishigami A, Tokunaga I, Gotohda T, Kubo S (2003) Immunohistochemical study of myoglobin and oxidative injury-related markers in the kidney of methamphetamine abusers. Legal Med 5:42–48CrossRefPubMedGoogle Scholar
  21. Jumnongprakhon P, Govitrapong P, Tocharus C, Tocharus J (2016) Melatonin promotes blood-brain barrier integrity in methamphetamine-induced inflammation in primary rat brain microvascular endothelial cells. Brain Res 1646:182–192. CrossRefPubMedGoogle Scholar
  22. Kamijo Y, Soma K, Nishida M, Namera A, Ohwada T (2002) Acute liver failure following intravenous methamphetamine. Vet Hum Toxicol 44:216–217PubMedGoogle Scholar
  23. Kim I, Oyler JM, Moolchan ET, Cone EJ, Huestis MA (2004) Urinary pharmacokinetics of methamphetamine and its metabolite, amphetamine following controlled oral administration to humans. Ther Drug Monit 26:664–672CrossRefPubMedGoogle Scholar
  24. Kiyatkin EA, Brown PL, Sharma HS (2007) Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia. Eur J Neurosci 26:1242–1253. CrossRefPubMedGoogle Scholar
  25. Koriem KM, Soliman RE (2014) Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine. Journal of Toxicology 2014:583494. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Kouros D, Tahereh H, Mohammadreza A, Minoo MZ (2010) Opium and heroin alter biochemical parameters of human's serum. Am J Drug Alcohol Abuse 36:135–139. CrossRefPubMedGoogle Scholar
  27. Lala V, Minter DA (2018) Liver Function Tests. In: StatPearls. Treasure Island (FL),Google Scholar
  28. Langford D, Grigorian A, Hurford R, Adame A, Crews L, Masliah E (2004) The role of mitochondrial alterations in the combined toxic effects of human immunodeficiency virus tat protein and methamphetamine on calbindin positive-neurons. J Neurovirol 10:327–337. CrossRefPubMedGoogle Scholar
  29. Lee N, Pennay A, Hester R, McKetin R, Nielsen S, Ferris J (2013) A pilot randomised controlled trial of modafinil during acute methamphetamine withdrawal: feasibility, tolerability and clinical outcomes. Drug Alcohol Rev 32:88–95. CrossRefPubMedGoogle Scholar
  30. Lin SH, Yang YK, Lee SY, Hsieh PC, Chen PS, Lu RB, Chen KC (2012) Association between cholesterol plasma levels and craving among heroin users. J Addict Med 6:287–291. CrossRefPubMedGoogle Scholar
  31. Lv D, Zhang M, Jin X, Zhao J, Han B, Su H, Zhang J, Zhang X, Ren W, He J (2016) The body mass index, blood pressure, and fasting blood glucose in patients with methamphetamine dependence. Medicine 95:e3152. CrossRefPubMedPubMedCentralGoogle Scholar
  32. McKetin R, Baker AL, Dawe S, Voce A, Lubman DI (2017) Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders. Psychiatry Res 251:349–354. CrossRefPubMedGoogle Scholar
  33. McMahon EM, Andersen DK, Feldman JM, Schanberg SM (1971) Methamphetamine-induced insulin release. Science 174:66–68CrossRefPubMedGoogle Scholar
  34. McMahon EM, Feldman JM, Schanberg SM (1975) Further studies of methamphetamine-induced insulin release. Toxicol Appl Pharmacol 32:62–72CrossRefPubMedGoogle Scholar
  35. Moore KE, Sawdy LC, Shaul SR (1965) Effects of D-amphetamine on blood glucose and tissue glycogen levels of isolated and aggregated mice. Biochem Pharmacol 14:197–204CrossRefPubMedGoogle Scholar
  36. Northrop NA, Yamamoto BK (2015) Methamphetamine effects on blood-brain barrier structure and function. Front Neurosci 9:69. CrossRefPubMedPubMedCentralGoogle Scholar
  37. Pachmerhiwala R, Bhide N, Straiko M, Gudelsky GA (2010) Role of serotonin and/or norepinephrine in the MDMA-induced increase in extracellular glucose and glycogenolysis in the rat brain. Eur J Pharmacol 644:67–72. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Parikh NU, Aalinkeel R, Reynolds JL, Nair BB, Sykes DE, Mammen MJ, Schwartz SA, Mahajan SD (2015) Galectin-1 suppresses methamphetamine induced neuroinflammation in human brain microvascular endothelial cells: Neuroprotective role in maintaining blood brain barrier integrity. Brain Res 1624:175–187. CrossRefPubMedPubMedCentralGoogle Scholar
  39. Parrott AC (2007) The psychotherapeutic potential of MDMA (3,4-methylenedioxymethamphetamine): an evidence-based review. Psychopharmacology 191:181–193. CrossRefPubMedGoogle Scholar
  40. Peterfy G, Pinter EJ, Pattee CJ (1976) Psychosomatic aspects of catecholamine depletion: comparative studies of metabolic, Endocrine and Affective Changes. Psychoneuroendocrinology 1:243–253CrossRefPubMedGoogle Scholar
  41. Pinter EJ, Patee CJ (1968) Fat-mobilizing action of amphetamine. J Clin Invest 47:394–402. CrossRefPubMedPubMedCentralGoogle Scholar
  42. Rawson RA (2013) Current research on the epidemiology, medical and psychiatric effects, and treatment of methamphetamine use. J Food Drug Anal 21:S77–S81. CrossRefPubMedPubMedCentralGoogle Scholar
  43. Richards JR (2000) Rhabdomyolysis and drugs of abuse. J Emerg Med 19:51–56CrossRefPubMedGoogle Scholar
  44. Ros S, Zafra D, Valles-Ortega J, García-Rocha M, Forrow S, Domínguez J, Calbó J, Guinovart JJ (2010) Hepatic overexpression of a constitutively active form of liver glycogen synthase improves glucose homeostasis. J Biol Chem 285:37170–37177. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Ros S, Garcia-Rocha M, Calbo J, Guinovart JJ (2011) Restoration of hepatic glycogen deposition reduces hyperglycaemia, hyperphagia and gluconeogenic enzymes in a streptozotocin-induced model of diabetes in rats. Diabetologia 54:2639–2648. CrossRefPubMedGoogle Scholar
  46. Sadiko GN, Lavrinenko VI, Koloiarov PG (1990) The dynamics of visual analyzer sensitivity under industrial conditions in an arid zone. Fiziol Cheloveka 16:107–111PubMedGoogle Scholar
  47. Sajja RK, Rahman S, Cucullo L (2016) Drugs of abuse and blood-brain barrier endothelial dysfunction: a focus on the role of oxidative stress. J Cereb Blood Flow Metab 36:539–554. CrossRefPubMedGoogle Scholar
  48. Sekine Y, Minabe Y, Ouchi Y, Takei N, Iyo M, Nakamura K, Suzuki K, Tsukada H, Okada H, Yoshikawa E, Futatsubashi M, Mori N (2003) Association of dopamine transporter loss in the orbitofrontal and dorsolateral prefrontal cortices with methamphetamine-related psychiatric symptoms. Am J Psychiatry 160:1699–1701. CrossRefPubMedGoogle Scholar
  49. Shah A, Kumar S, Simon SD, Singh DP, Kumar A (2013) HIV gp120- and methamphetamine-mediated oxidative stress induces astrocyte apoptosis via cytochrome P450 2E1. Cell Death Dis 4:e850. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Shima N, Miyawaki I, Bando K, Horie H, Zaitsu K, Katagi M, Bamba T, Tsuchihashi H, Fukusaki E (2011) Influences of methamphetamine-induced acute intoxication on urinary and plasma metabolic profiles in the rat. Toxicology 287:29–37. CrossRefPubMedGoogle Scholar
  51. Shin EJ, Tran HQ, Nguyen PT, Jeong JH, Nah SY, Jang CG, Nabeshima T, Kim HC (2017) Role of mitochondria in methamphetamine-induced dopaminergic neurotoxicity: involvement in oxidative stress, Neuroinflammation, and pro-apoptosis-a review. Neurochem Res 43:57–69. CrossRefPubMedGoogle Scholar
  52. Song BJ, Moon KH, Upreti VV, Eddington ND, Lee IJ (2010) Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage. Curr Pharm Biotechnol 11:434–443CrossRefPubMedPubMedCentralGoogle Scholar
  53. Tian C, Murrin LC, Zheng JC (2009) Mitochondrial fragmentation is involved in methamphetamine-induced cell death in rat hippocampal neural progenitor cells. PLoS One 4:e5546. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Tokunaga I, Kubo S, Ishigami A, Gotohda T, Kitamura O (2006) Changes in renal function and oxidative damage in methamphetamine-treated rat. Legal Med 8:16–21. CrossRefPubMedGoogle Scholar
  55. Vearrier D, Greenberg MI, Miller SN, Okaneku JT, Haggerty DA (2012) Methamphetamine: history, pathophysiology, adverse health effects, current trends, and hazards associated with the clandestine manufacture of methamphetamine. Dis Mon 58:38–89. CrossRefPubMedGoogle Scholar
  56. Wakabayashi KT, Kiyatkin EA (2015) Central and peripheral contributions to dynamic changes in nucleus accumbens glucose induced by intravenous cocaine. Front Neurosci 9:42. CrossRefPubMedPubMedCentralGoogle Scholar
  57. Wan F, Zang S, Yu G, Xiao H, Wang J, Tang J (2017) Ginkgolide B suppresses methamphetamine-induced microglial activation through TLR4-NF-kappaB signaling pathway in BV2 cells. Neurochem Res 42:2881–2891. CrossRefPubMedGoogle Scholar
  58. Wang Q, Wei LW, Xiao HQ, Xue Y, Du SH, Liu YG, Xie XL (2017) Methamphetamine induces hepatotoxicity via inhibiting cell division, arresting cell cycle and activating apoptosis: in vivo and in vitro studies. Food Chem Toxicol 105:61–72. CrossRefPubMedGoogle Scholar
  59. Xu E, Liu J, Liu H, Wang X, Xiong H (2017) Role of microglia in methamphetamine-induced neurotoxicity. Int J Physiol Pathophysiol Pharmacol 9:84–100PubMedPubMedCentralGoogle Scholar
  60. Yang C, Liu Y, Yang JD, Li YH, Li X, Cheng JP (2016) Amination of 3-substituted Benzofuran-2(3H)-ones triggered by single-electron transfer. Org Lett 18:1036–1039. CrossRefPubMedGoogle Scholar
  61. Yang L, Han B, Zhang Y, Bai Y, Chao J, Hu G, Yao H (2018) Engagement of circular RNA HECW2 in the nonautophagic role of ATG5 implicated in the endothelial-mesenchymal transition. Autophagy 14:404–418. CrossRefPubMedGoogle Scholar
  62. Yeo KK, Wijetunga M, Ito H, Efird JT, Tay K, Seto TB, Alimineti K, Kimata C, Schatz IJ (2007) The association of methamphetamine use and cardiomyopathy in young patients. Am J Med 120:165–171. CrossRefPubMedGoogle Scholar
  63. Zhang Y, Zhu T, Zhang X, Chao J, Hu G, Yao H (2015) Role of high-mobility group box 1 in methamphetamine-induced activation and migration of astrocytes. J Neuroinflammation 12:156. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Zhang M, Lv D, Zhou W, Ji L, Zhou B, Chen H, Gu Y, Zhao J, He J (2017) The levels of triglyceride and total cholesterol in methamphetamine dependence. Medicine 96:e6631. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of PharmacologyMedical School of Southeast UniversityNanjingChina
  2. 2.Department of Clinical Laboratory, Zhongda HospitalSoutheast University School of MedicineNanjingChina
  3. 3.Department of PhysiologyMedical School of Southeast UniversityNanjingChina
  4. 4.Department of EmergencyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  5. 5.Institute of Life Sciences, Key Laboratory of Developmental Genes and Human DiseaseSoutheast UniversityNanjingChina

Personalised recommendations