Journal of Neural Transmission

, Volume 125, Issue 4, pp 651–672 | Cite as

The role of sphingolipids in psychoactive drug use and addiction

  • Liubov S. Kalinichenko
  • Erich Gulbins
  • Johannes Kornhuber
  • Christian P. Müller
High Impact Review in Neuroscience, Neurology or Psychiatry - Review Article


Psychoactive drug use is a common behavior in many societies worldwide, frequently associated with drug instrumentalization. Regular use may develop into drug addiction, which is a severe psychiatric disorder with multiple pathological effects to virtually all organ systems. Treatment strategies for addiction are often insufficient with no broadly working pharmaco-treatment available. Recently, lipids, and particularly sphingolipids, have been considered as new mediators in the pathogenic pathways and as possible therapeutic targets for the treatment of addictive states. In our review, we discuss the contribution of sphingolipids in the development of addictive states including alcohol consumption, nicotine, amphetamine, morphine, and cocaine dependencies. Recent data show that the involvement of various classes of sphingolipids, such as sphingomyelins, ceramides, globosides, sulfatides, and cerebrosides, might explain the development of some specific features of addictive states, for example, apoptotic neurodegeneration induced by psychoactive substances. On the other hand, protective effects of sphingolipids are discussed. Sphingolipids might be a key mechanism in the development of beneficial effects of moderate alcohol consumption. Therefore, sphingolipid systems emerge as possible new pathways involved in the development of addiction and its pathophysiological consequences. However, further analysis is still needed to investigate the exact mechanisms of sphingolipid contribution and possibility of using of sphingolipids as new therapeutic targets.


Addiction Lipids Sphingolipids Neuroapoptosis Protective properties 



Alkaline sphingomyelinase


AMP-activated protein kinase


Acid sphingomyelinase


ASM knockout mice


Brain-derived neurotrophic factor




Cyclic adenosine monophosphate






Ceramide synthases


Cerebroside sulfotransferase


Endoplasmic reticulum


Functional inhibitor of ASM










Nicotinamide adenine dinucleotide phosphate




Nicotine-derived nitrosamine ketone


Neutral sphingomyelinase




Stearoyl-CoA desaturase-1


Sphingosine kinase






Sphingomyelin phosphodiesterase


Sphingomyelin synthase


Sphingosine-1-phosphate lyase


Sphingosine-1-phosphate phosphatase


Serine palmitoyltransferase




Transgenic mice with ASM hyperactivity


Tumor necrosis factor α



This work was supported by funding from DFG Grants MU 2789/8-1 (C.P.M.), KO 947/15-1, KO 947/13-1 (J.K.), and GU 335/29-1 (E.G.) and by funding from the Interdisciplinary Center for Clinical Research (IZKF) Erlangen, Project E13 (L.S.K., C.P.M., J.K.).

Compliance with ethical standards

Conflict of interest

The authors declare no competing financial interests.


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  • Liubov S. Kalinichenko
    • 1
  • Erich Gulbins
    • 2
    • 3
  • Johannes Kornhuber
    • 1
  • Christian P. Müller
    • 1
  1. 1.Section of Addiction Medicine, Department of Psychiatry and Psychotherapy, University ClinicFriedrich-Alexander-University of Erlangen-NurembergErlangenGermany
  2. 2.Department of Molecular BiologyUniversity of Duisburg-EssenEssenGermany
  3. 3.Department of SurgeryUniversity of Cincinnati, College of MedicineCincinnatiUSA

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