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An endocannabinoid signal associated with desire for alcohol is suppressed in recently abstinent alcoholics

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Abstract

Background

Alcoholics report persistent alcohol craving that is heightened by cognitive cues, stressful situations, and abstinence. The role of endogenous cannabinoids in human alcohol craving—though long suspected—remains elusive.

Materials and methods

We employed laboratory exposure to stress, alcohol cue, and neutral relaxed situations through guided imagery procedures to evoke alcohol desire and craving in healthy social drinkers (n = 11) and in treatment-engaged, recently abstinent alcoholic subjects (n = 12) and assessed alcohol craving, heart rate, and changes in circulating endocannabinoid levels. Subjective anxiety was also measured as a manipulation check for the procedures.

Results

In healthy social drinkers, alcohol cue imagery increased circulating levels of the endocannabinoid anandamide, whereas neutral and stress-related imagery had no such effect. Notably, baseline and response anandamide levels in these subjects were negatively and positively correlated with self-reported alcohol craving scores, respectively. Cue-induced increases in heart rate were also correlated with anandamide responses. By contrast, no imagery-induced anandamide mobilization was observed in alcoholics, whose baseline anandamide levels were markedly reduced compared to healthy drinkers and were uncorrelated to either alcohol craving or heart rate.

Conclusions

The results suggest that plasma anandamide levels provide a marker of the desire for alcohol in social drinkers, which is suppressed in recently abstinent alcoholics.

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Acknowledgments

The present study was partially supported by NIH grants R01-AA113892 and K02-DA17232 (to R.S.) and DA-012413 and DA-022702 (to D.P.) and by the NIH Roadmap Interdisciplinary Research Consortium grant on Stress, Self Control and Addiction (UL1-DE019586) and the NIH/NCRR/CTSA Program Grant (UL1 RR024139). Support was also provided by the Department of Mental Health and Addiction Services of the State of Connecticut. We wish to thank Giuseppe Astarita, Lauren Burgeno, Saurabh Sharma, Ronak Kedia, Monica Arnold, Keri Bergquist, Kristen Siedlarz, and Helen Fox for their assistance.

Disclosure

DP is an inventor in a patent disclosing FAAH inhibitors, owned by the University of California, Irvine and licensed to Organon Biosciences, a unit of Schering-Plough.

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Authors and Affiliations

  1. Department of Pharmacology, University of California, Irvine, 3101 Gillespie NRF, Irvine, CA, 92697, USA

    Regina A. Mangieri & Daniele Piomelli

  2. Department of Psychiatry, Yale University School of Medicine, 34 Park Street, Room S110, New Haven, CT, 06519, USA

    Kwang-Ik A. Hong & Rajita Sinha

  3. Unit of Drug Discovery and Development, Italian Institute of Technology, Genoa, 16136, Italy

    Daniele Piomelli

Authors
  1. Regina A. Mangieri
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  2. Kwang-Ik A. Hong
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  3. Daniele Piomelli
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  4. Rajita Sinha
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Correspondence to Daniele Piomelli or Rajita Sinha.

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Mangieri, R.A., Hong, KI.A., Piomelli, D. et al. An endocannabinoid signal associated with desire for alcohol is suppressed in recently abstinent alcoholics. Psychopharmacology 205, 63–72 (2009). https://doi.org/10.1007/s00213-009-1518-3

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