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

Tonisha Kearney-Ramos, Evan S. Herrmann, Ilaria Belluomo, Isabel Matias, Monique Vallée, Stéphanie Monlezun, Pier Vincenzo Piazza, Margaret Haney
Cannabis and Cannabinoid Research. 2022-04-29; :
DOI: 10.1089/can.2021.0185

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Kearney-Ramos T(1), Herrmann ES(2), Belluomo I(3)(4), Matias I(3), Vallée M(3), Monlezun S(5), Piazza PV(5), Haney M(1).

Author information:
(1)Division on Substance Use Disorders, New York State Psychiatric Institute,
Columbia University Irving Medical Center, New York, New York, USA.
(2)Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, Maryland, USA.
(3)Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux, France.
(4)Department of Surgery and Cancer, Imperial College London, London, United Kingdom.
(5)Aelis Farma, Bordeaux, France.

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

DOI: 10.1089/can.2021.0185
PMID: 35486827

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