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Increased CB2 mRNA and anandamide in human blood after cessation of cannabis abuse

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Abstract

In previous studies, long-term cannabis use led to alterations of the endocannabinoid system including an increase in CB1 and/or CB2 receptor messenger RNA (mRNA) in blood cells and an increase in the serum level of the endocannabinoid 2-arachidonoyl glycerol. However, in those studies, cannabis use was stopped only few days before testing or not interrupted at all. Therefore, one cannot decide whether the alterations are due to long-term cannabis abuse or are confounded by acute effects of cannabis. Blood was sampled from donors that had smoked marijuana ≥20 times in their lives but had abstained from cannabis for ≥6 months (high-frequency users, HFU) and from controls (cannabis use ≤5 times lifetime). CB1 and CB2 mRNA was determined in peripheral mononuclear blood cells using the reverse transcriptase polymerase chain reaction. Serum anandamide level was assayed using electrospray tandem mass spectrometry. CB2 mRNA was increased by 45 % in HFU when compared to controls, whereas CB1 mRNA did not differ. The anandamide level in HFU exceeded that in controls by 90 %. Tobacco smoking could be excluded as a confounding factor. In conclusion, marijuana users that had smoked marijuana ≥20 times in their lives and stopped cannabis use at least 6 months before the study show an increase in CB2 receptor mRNA in the blood and in serum anandamide level. These alterations resemble those obtained for marijuana smokers that had stopped cannabis use only few days before testing and may be implicated in the pathogenesis of disorders associated with long-term cannabis use.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft to E.S. and the Stanley Medical Research Institute to F.M.L. The skilled technical assistance of Mrs. Petra Spitzlei and valued study assistance of Mr. Torsten Noack-Schönborn are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Cologne, 50924, Cologne, Germany

    Daniela Muhl, Christoph W. Gerth, Johannes Faulhaber & F. Markus Leweke

  2. Department of Pharmacology and Toxicology, University of Bonn, 53105, Bonn, Germany

    Markus Kathmann & Eberhard Schlicker

  3. Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159, Mannheim, Germany

    Carolin Hoyer, Laura Kranaster & F. Markus Leweke

  4. Department of Medical Statistics, Informatics and Epidemiology, University of Cologne, 50924, Cologne, Germany

    Martin Hellmich

Authors
  1. Daniela Muhl
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  2. Markus Kathmann
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  3. Carolin Hoyer
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  4. Laura Kranaster
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  5. Martin Hellmich
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  6. Christoph W. Gerth
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  7. Johannes Faulhaber
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  8. Eberhard Schlicker
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  9. F. Markus Leweke
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Corresponding author

Correspondence to Eberhard Schlicker.

Additional information

Daniela Muhl, Markus Kathmann, and Carolin Hoyer contributed equally to this paper. E. Schlicker and F.M. Leweke share senior authorship.

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Muhl, D., Kathmann, M., Hoyer, C. et al. Increased CB2 mRNA and anandamide in human blood after cessation of cannabis abuse. Naunyn-Schmiedeberg's Arch Pharmacol 387, 691–695 (2014). https://doi.org/10.1007/s00210-014-0984-2

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  • DOI: https://doi.org/10.1007/s00210-014-0984-2

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