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Published Online: 4 December 2023

The Relationship Between Circulating Endogenous Cannabinoids and the Effects of Smoked Cannabis

Publication: Cannabis and Cannabinoid Research
Volume 8, Issue Number 6

Abstract

Background: The endogenous cannabinoid system (ECS), including the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), plays an integral role in psychophysiological functions. Although frequent cannabis use is associated with adaptations in the ECS, the impact of acute smoked cannabis administration on circulating eCBs, and the relationship between cannabis effects and circulating eCBs are poorly understood.
Methods: This study measured the plasma levels of AEA, 2-AG, and Δ-9-tetrahydrocannabinol (THC), subjective drug-effects ratings, and cardiovascular measures at baseline and 15–180 min after cannabis users (n=26) smoked 70% of a cannabis cigarette (5.6% THC).
Results: Cannabis administration increased the ratings of intoxication, heart rate, and plasma THC levels relative to baseline. Although cannabis administration did not affect eCB levels relative to baseline, there was a significant positive correlation between baseline AEA levels and peak ratings of “High” and “Good Drug Effect.” Further, baseline 2-AG levels negatively correlated with frequency of cannabis use (mean days/week) and with baseline THC metabolite levels.
Conclusions: In a subset of heavy cannabis smokers: (1) more frequent cannabis use was associated with lower baseline 2-AG, and (2) those with lower AEA got less intoxicated after smoking cannabis. These findings contribute to a sparse literature on the interaction between endo- and phyto-cannabinoids. Future studies in participants with varied cannabis use patterns are needed to clarify the association between circulating eCBs and the abuse-related effects of cannabis, and to test whether baseline eCBs predict the intoxicating effects of cannabis and are a potential biomarker of cannabis tolerance.

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Cite this article as: Kearney-Ramos T, Herrmann ES, Belluomo I, Matias I, Vallee M, Monlezun S, Piazza PV, Haney M (2023) The relationship between circulating endogenous cannabinoids and the effects of smoked cannabis, Cannabis and Cannabinoid Research 8:6, 1069–1078, DOI: 10.1089/can.2021.0185.

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cover image Cannabis and Cannabinoid Research
Cannabis and Cannabinoid Research
Volume 8Issue Number 6December 2023
Pages: 1069 - 1078
PubMed: 35486827

History

Published online: 4 December 2023
Published in print: December 2023
Published ahead of print: 29 April 2022

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Authors

Affiliations

Division on Substance Use Disorders, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, New York, USA.
Evan S. Herrmann
Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, Maryland, USA.
Ilaria Belluomo
Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux, France.
Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
Isabel Matias
Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux, France.
Monique Vallée
Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux, France.
Stéphanie Monlezun
Aelis Farma, Bordeaux, France.
Pier Vincenzo Piazza
Aelis Farma, Bordeaux, France.
Margaret Haney* [email protected]
Division on Substance Use Disorders, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, New York, USA.

Notes

*
Address correspondence to: Margaret Haney, PhD, Division on Substance Use Disorders, New York State Psychiatric Institute, Columbia University Irving Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA, [email protected]

Authors' Contributions

M.H. and P.V.P. were responsible for the concept and design of the overall research study. M.H. and E.S.H. screened participants and oversaw cannabis sessions. I.B., I.M., M.V., and S.M. conducted the extraction, derivatization, and gas chromatography-tandem mass spectrometry of the plasma samples. T.K.-R. conducted data analyses and drafted the article. M.H. provided critical revision of the article for intellectual content. All authors reviewed and approved the final version for publication.

Author Disclosure Statement

During the past three years, M.H. has been serving on the scientific advisory board of Pleo Pharma and has received cannabis capsules from Tilray, Inc., to conduct a research study on cannabis and neuropathy (NCT03782402). All other authors declare no conflicts of interest.

Funding Information

The study was funded by a gift account from the Institut National de la Santé et de la Recherche Médical.

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