Skip to main content

Advertisement

SpringerLink
Log in

A Potential Role for Creatine in Drug Abuse?

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Supplemental creatine has been promoted for its positive health effects and is best known for its use by athletes to increase muscle mass. In addition to its role in physical performance, creatine supplementation has protective effects on the brain in models of neuronal damage and also alters mood state and cognitive performance. Creatine is found in high protein foods, such as fish or meat, and is also produced endogenously from the biosynthesis of arginine, glycine, and methionine. Changes in brain creatine levels, as measured using magnetic resonance spectroscopy, are seen in individuals exposed to drugs of abuse and depressed individuals. These changes in brain creatine indicate that energy metabolism differs in these populations relative to healthy individuals. Recent work shows that creatine supplementation has the ability to function in a manner similar to antidepressant drugs and can offset negative consequences of stress. These observations are important in relation to addictive behaviors as addiction is influenced by psychological factors such as psychosocial stress and depression. The significance of altered brain levels of creatine in drug-exposed individuals and the role of creatine supplementation in models of drug abuse have yet to be explored and represent gaps in the current understanding of brain energetics and addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Andres RH et al (2008) Functions and effects of creatine in the central nervous system. Brain Res Bull 76(4):329–343

    Article  PubMed  CAS  Google Scholar 

  2. Gualano B et al (2010) Exploring the therapeutic role of creatine supplementation. Amino Acids 38(1):31–44

    Article  PubMed  CAS  Google Scholar 

  3. Allen PJ et al (2010) Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology 35(2):534–546

    Article  PubMed  CAS  Google Scholar 

  4. Amital D et al (2006) Open study of creatine monohydrate in treatment-resistant posttraumatic stress disorder. J Clin Psychiatry 67(5):836–837

    Article  PubMed  Google Scholar 

  5. Roitman S et al (2007) Creatine monohydrate in resistant depression: a preliminary study. Bipolar Disord 9(7):754–758

    Article  PubMed  CAS  Google Scholar 

  6. Beard E, Braissant O (2010) Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem 115(2):297–313

    Article  PubMed  CAS  Google Scholar 

  7. Wyss M, Kaddurah-Daouk R (2000) Creatine and creatinine metabolism. Physiol Rev 80(3):1107–1213

    PubMed  CAS  Google Scholar 

  8. Wyss M, Wallimann T (1994) Creatine metabolism and the consequences of creatine depletion in muscle. Mol Cell Biochem 133–134:51–66

    Article  PubMed  Google Scholar 

  9. Mudd SH et al (2007) Methyl balance and transmethylation fluxes in humans. Am J Clin Nutr 85(1):19–25

    PubMed  CAS  Google Scholar 

  10. Lyoo IK et al (2003) Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res 123(2):87–100

    Article  PubMed  CAS  Google Scholar 

  11. Brosnan JT, Brosnan ME (2007) Creatine: endogenous metabolite, dietary, and therapeutic supplement. Annu Rev Nutr 27:241–261

    Article  PubMed  CAS  Google Scholar 

  12. McLeish MJ, Kenyon GL (2005) Relating structure to mechanism in creatine kinase. Crit Rev Biochem Mol Biol 40(1):1–20

    Article  PubMed  CAS  Google Scholar 

  13. Wallimann T et al (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281(Pt 1):21–40

    PubMed  CAS  Google Scholar 

  14. Niklasson F, Agren H (1984) Brain energy metabolism and blood-brain barrier permeability in depressive patients: analyses of creatine, creatinine, urate, and albumin in CSF and blood. Biol Psychiatry 19(8):1183–1206

    PubMed  CAS  Google Scholar 

  15. Kuzhikandathil EV, Molloy GR (1994) Transcription of the brain creatine kinase gene in glial cells is modulated by cyclic AMP-dependent protein kinase. J Neurosci Res 39(1):70–82

    Article  PubMed  CAS  Google Scholar 

  16. Wilken B et al (1998) Creatine protects the central respiratory network of mammals under anoxic conditions. Pediatr Res 43(1):8–14

    Article  PubMed  CAS  Google Scholar 

  17. Andres RH et al (2005) Effects of creatine treatment on survival and differentiation of GABA-ergic neurons in cultured striatal tissue. J Neurochem 95(1):33–45

    Article  PubMed  CAS  Google Scholar 

  18. Andres RH et al (2005) Creatine supplementation improves dopaminergic cell survival and protects against MPP+ toxicity in an organotypic tissue culture system. Cell Transplant 14(8):537–550

    Article  PubMed  Google Scholar 

  19. Andres RH et al (2005) Effects of creatine treatment on the survival of dopaminergic neurons in cultured fetal ventral mesencephalic tissue. Neuroscience 133(3):701–713

    Article  PubMed  CAS  Google Scholar 

  20. Ducray AD et al (2007) Creatine treatment promotes differentiation of GABA-ergic neuronal precursors in cultured fetal rat spinal cord. J Neurosci Res 85(9):1863–1875

    Article  PubMed  CAS  Google Scholar 

  21. Renshaw PF et al (2001) Multinuclear magnetic resonance spectroscopy studies of brain purines in major depression. Am J Psychiatry 158(12):2048–2055

    Article  PubMed  CAS  Google Scholar 

  22. Rezin GT et al (2009) Mitochondrial dysfunction and psychiatric disorders. Neurochem Res 34(6):1021–1029

    Article  PubMed  CAS  Google Scholar 

  23. Shao L et al (2008) Mitochondrial involvement in psychiatric disorders. Ann Med 40(4):281–295

    Article  PubMed  CAS  Google Scholar 

  24. Brustovetsky N, Brustovetsky T, Dubinsky JM (2001) On the mechanisms of neuroprotection by creatine and phosphocreatine. J Neurochem 76(2):425–434

    Article  PubMed  CAS  Google Scholar 

  25. Matthews RT et al (1998) Neuroprotective effects of creatine and cyclocreatine in animal models of Huntington's disease. J Neurosci 18(1):156–163

    PubMed  CAS  Google Scholar 

  26. Matthews RT et al (1999) Creatine and cyclocreatine attenuate MPTP neurotoxicity. Exp Neurol 157(1):142–149

    Article  PubMed  CAS  Google Scholar 

  27. Roy BD et al (2002) Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats. Can J Physiol Pharmacol 80(10):1008–1014

    Article  PubMed  CAS  Google Scholar 

  28. Lyoo IK, Renshaw PF (2002) Magnetic resonance spectroscopy: current and future applications in psychiatric research. Biol Psychiatry 51(3):195–207

    Article  PubMed  Google Scholar 

  29. Agren H, Niklasson F (1988) Creatinine and creatine in CSF: indices of brain energy metabolism in depression. Short note. J Neural Transm 74(1):55–59

    Article  PubMed  CAS  Google Scholar 

  30. Czeh B et al (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98(22):12796–12801

    Article  PubMed  CAS  Google Scholar 

  31. Iosifescu DV et al (2008) Brain bioenergetics and response to triiodothyronine augmentation in major depressive disorder. Biol Psychiatry 63(12):1127–1134

    Article  PubMed  CAS  Google Scholar 

  32. Moore CM et al (1997) Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study. Am J Psychiatry 154(1):116–118

    PubMed  CAS  Google Scholar 

  33. Volz HP et al (1998) 31P magnetic resonance spectroscopy in the frontal lobe of major depressed patients. Eur Arch Psychiatry Clin Neurosci 248(6):289–295

    Article  PubMed  CAS  Google Scholar 

  34. Dager SR et al (2004) Brain metabolic alterations in medication-free patients with bipolar disorder. Arch Gen Psychiatry 61(5):450–458

    Article  PubMed  CAS  Google Scholar 

  35. Segal M et al (2007) Serum creatine kinase level in unmedicated nonpsychotic, psychotic, bipolar and schizoaffective depressed patients. Eur Neuropsychopharmacol 17(3):194–198

    Article  PubMed  CAS  Google Scholar 

  36. Kato T et al (1992) Brain phosphorous metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 26(4):223–230

    Article  PubMed  CAS  Google Scholar 

  37. Kato T et al (1994) Reduction of brain phosphocreatine in bipolar II disorder detected by phosphorus-31 magnetic resonance spectroscopy. J Affect Disord 31(2):125–133

    Article  PubMed  CAS  Google Scholar 

  38. Gold MS et al (2009) Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry 66(2):118–127

    Article  PubMed  CAS  Google Scholar 

  39. Licata SC, Renshaw PF (2010) Neurochemistry of drug action: insights from proton magnetic resonance spectroscopic imaging and their relevance to addiction. Ann N Y Acad Sci 1187:148–171

    Article  PubMed  CAS  Google Scholar 

  40. Sakellaris G et al (2006) Prevention of complications related to traumatic brain injury in children and adolescents with creatine administration: an open label randomized pilot study. J Trauma 61(2):322–329

    Article  PubMed  CAS  Google Scholar 

  41. Sakellaris G et al (2008) Prevention of traumatic headache, dizziness and fatigue with creatine administration. A pilot study. Acta Paediatr 97(1):31–34

    Article  PubMed  CAS  Google Scholar 

  42. Sullivan PG et al (2000) Dietary supplement creatine protects against traumatic brain injury. Ann Neurol 48(5):723–729

    Article  PubMed  CAS  Google Scholar 

  43. Scheff SW, Dhillon HS (2004) Creatine-enhanced diet alters levels of lactate and free fatty acids after experimental brain injury. Neurochem Res 29(2):469–479

    Article  PubMed  CAS  Google Scholar 

  44. Zhu S et al (2004) Prophylactic creatine administration mediates neuroprotection in cerebral ischemia in mice. J Neurosci 24(26):5909–5912

    Article  PubMed  CAS  Google Scholar 

  45. Daumann J et al (2004) Proton magnetic resonance spectroscopy in ecstasy (MDMA) users. Neurosci Lett 362(2):113–116

    Article  PubMed  CAS  Google Scholar 

  46. Reneman L et al (2001) Prefrontal N-acetylaspartate is strongly associated with memory performance in (abstinent) ecstasy users: preliminary report. Biol Psychiatry 50(7):550–554

    Article  PubMed  CAS  Google Scholar 

  47. Salo R et al (2007) Attentional control and brain metabolite levels in methamphetamine abusers. Biol Psychiatry 61(11):1272–1280

    Article  PubMed  CAS  Google Scholar 

  48. Hermann D et al (2007) Dorsolateral prefrontal cortex N-acetylaspartate/total creatine (NAA/tCr) loss in male recreational cannabis users. Biol Psychiatry 61(11):1281–1289

    Article  PubMed  CAS  Google Scholar 

  49. O’Neill J, Cardenas VA, Meyerhoff DJ (2001) Separate and interactive effects of cocaine and alcohol dependence on brain structures and metabolites: quantitative MRI and proton MR spectroscopic imaging. Addict Biol 6(4):347–361

    Article  PubMed  Google Scholar 

  50. O’Neill J, Cardenas VA, Meyerhoff DJ (2001) Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcohol Clin Exp Res 25(11):1673–1682

    Article  PubMed  Google Scholar 

  51. Yang S et al (2009) Lower glutamate levels in rostral anterior cingulate of chronic cocaine users—a (1)H-MRS study using TE-averaged PRESS at 3 T with an optimized quantification strategy. Psychiatry Res 174(3):171–176

    Article  PubMed  CAS  Google Scholar 

  52. Adriani W et al (2007) 1 H MRS-detectable metabolic brain changes and reduced impulsive behavior in adult rats exposed to methylphenidate during adolescence. Neurotoxicol Teratol 29(1):116–125

    Article  PubMed  CAS  Google Scholar 

  53. Ernst T et al (2000) Evidence for long-term neurotoxicity associated with methamphetamine abuse: a 1 H MRS study. Neurology 54(6):1344–1349

    PubMed  CAS  Google Scholar 

  54. Chang L et al (1999) Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users. Am J Psychiatry 156(5):716–722

    PubMed  CAS  Google Scholar 

  55. Smith LM et al (2001) Brain proton magnetic resonance spectroscopy and imaging in children exposed to cocaine in utero. Pediatrics 107(2):227–231

    Article  PubMed  CAS  Google Scholar 

  56. Buttner A (2011) Review: the neuropathology of drug abuse. Neuropathol Appl Neurobiol 37(2):118–134

    Article  PubMed  CAS  Google Scholar 

  57. Silva AP et al (2010) Brain injury associated with widely abused amphetamines: neuroinflammation, neurogenesis and blood–brain barrier. Curr Drug Abuse Rev 3(4):239–254

    Article  PubMed  CAS  Google Scholar 

  58. Dechent P et al (1999) Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 277(3 Pt 2):R698–R704

    PubMed  CAS  Google Scholar 

  59. Nash SR et al (1994) Cloning, pharmacological characterization, and genomic localization of the human creatine transporter. Recept Channels 2(2):165–174

    PubMed  CAS  Google Scholar 

  60. Ohtsuki S et al (2002) The blood–brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab 22(11):1327–1335

    Article  PubMed  CAS  Google Scholar 

  61. Pan JW, Takahashi K (2007) Cerebral energetic effects of creatine supplementation in humans. Am J Physiol Regul Integr Comp Physiol 292(4):R1745–R1750

    Article  PubMed  CAS  Google Scholar 

  62. Sestili P et al (2006) Creatine supplementation affords cytoprotection in oxidatively injured cultured mammalian cells via direct antioxidant activity. Free Radic Biol Med 40(5):837–849

    Article  PubMed  CAS  Google Scholar 

  63. Abou-Sleiman PM, Muqit MM, Wood NW (2006) Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci 7(3):207–219

    Article  PubMed  CAS  Google Scholar 

  64. Kim J et al (2010) Reduced creatine kinase as a central and peripheral biomarker in Huntington's disease. Biochim Biophys Acta 1802(7–8):673–681

    PubMed  CAS  Google Scholar 

  65. Stack EC, Matson WR, Ferrante RJ (2008) Evidence of oxidant damage in Huntington's disease: translational strategies using antioxidants. Ann NY Acad Sci 1147:79–92

    Article  PubMed  CAS  Google Scholar 

  66. Zhang, S.F., et al. (2011) Impaired brain creatine kinase activity in Huntington's disease. Neurodegener Dis. doi:10.1159/000321681

  67. Bender A et al (2005) Creatine supplementation lowers brain glutamate levels in Huntington's disease. J Neurol 252(1):36–41

    Article  PubMed  CAS  Google Scholar 

  68. Hersch SM et al (2006) Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2’dG. Neurology 66(2):250–252

    Article  PubMed  CAS  Google Scholar 

  69. Bender A et al (2006) Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Neurology 67(7):1262–1264

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, Tufts University, 490 Boston Ave, Medford, MA, 02155, USA

    Kristen E. D’Anci, Patricia J. Allen & Robin B. Kanarek

Authors
  1. Kristen E. D’Anci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patricia J. Allen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robin B. Kanarek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kristen E. D’Anci.

Rights and permissions

Reprints and permissions

About this article

Cite this article

D’Anci, K.E., Allen, P.J. & Kanarek, R.B. A Potential Role for Creatine in Drug Abuse?. Mol Neurobiol 44, 136–141 (2011). https://doi.org/10.1007/s12035-011-8176-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-011-8176-2

Keywords

Search

Navigation