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Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use

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Abstract

Rationale

Upregulation of α4β2* nicotinic acetylcholine receptors (nAChRs) is one of the most well-established effects of chronic cigarette smoking on the brain. Prior research by our group gave a preliminary indication that cigarette smokers with concomitant use of caffeine or marijuana have altered nAChR availability.

Objective

We sought to determine if smokers with heavy caffeine or marijuana use have different levels of α4β2* nAChRs than smokers without these drug usages.

Methods

One hundred and one positron emission tomography (PET) scans, using the radiotracer 2-FA (a ligand for β2*-containing nAChRs), were obtained from four groups of males: non-smokers without heavy caffeine or marijuana use, smokers without heavy caffeine or marijuana use, smokers with heavy caffeine use (mean four coffee cups per day), and smokers with heavy marijuana use (mean 22 days of use per month). Total distribution volume (Vt/fp) was determined for the brainstem, prefrontal cortex, and thalamus, as a measure of nAChR availability.

Results

A significant between-group effect was found, resulting from the heavy caffeine and marijuana groups having the highest Vt/fp values (especially for the brainstem and prefrontal cortex), followed by smokers without such use, followed by non-smokers. Direct between-group comparisons revealed significant differences for Vt/fp values between the smoker groups with and without heavy caffeine or marijuana use.

Conclusions

Smokers with heavy caffeine or marijuana use have higher α4β2* nAChR availability than smokers without these drug usages. These findings are likely due to increased nicotine exposure but could also be due to an interaction on a cellular/molecular level.

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Acknowledgments

The authors thank the PET and MRI technicians at the VA Greater Los Angeles Healthcare System for assistance in acquiring brain images for this study. The authors also thank the laboratory of Payton Jacob III at the University of California at San Francisco for determining plasma nicotine levels from study samples.

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Authors and Affiliations

  1. Departments of Psychiatry and Research, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Arthur L. Brody, Robert Hubert, Michael S. Mamoun, Ryutaro Enoki, Lizette Y. Garcia, Paul Abraham, Paulina Young & Mark A. Mandelkern

  2. Department of Psychiatry, University of California at Los Angeles, Los Angeles, CA, USA

    Arthur L. Brody

  3. Department of Physics, University of California at Irvine, Irvine, CA, USA

    Mark A. Mandelkern

  4. 300 UCLA Medical Plaza, Suite 2200, Los Angeles, CA, 90095, USA

    Arthur L. Brody

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  1. Arthur L. Brody
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  2. Robert Hubert
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  3. Michael S. Mamoun
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  5. Lizette Y. Garcia
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  8. Mark A. Mandelkern
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Corresponding author

Correspondence to Arthur L. Brody.

Ethics declarations

Participants gave written informed consent, using a form approved by the Institutional Review Board at the VA Greater Los Angeles Healthcare System.

Funding

This work was supported by the National Institute on Drug Abuse (R01 DA20872), the Department of Veterans Affairs, Office of Research and Development (CSR&D Merit Review Award I01 CX000412), and the Tobacco-Related Disease Research Program (#23XT-0002) to ALB. The authors report no biomedical financial interests or potential conflicts of interest.

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Brody, A.L., Hubert, R., Mamoun, M.S. et al. Nicotinic acetylcholine receptor availability in cigarette smokers: effect of heavy caffeine or marijuana use. Psychopharmacology 233, 3249–3257 (2016). https://doi.org/10.1007/s00213-016-4367-x

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