Serum lipid analysis and isotopic enrichment is suggestive of greater lipogenesis in young long‐term cannabis users: A secondary analysis of a case–control study

Abstract

Cannabis is now legal in many countries and while numerous studies have reported on its impact on cognition and appetite regulation, none have examined fatty acid metabolism in young cannabis users. We conducted an exploratory analysis to evaluate cannabis impact on fatty acid metabolism in cannabis users (n = 21) and non‐cannabis users (n = 16). Serum levels of some saturated and monounsaturated fatty acids, including palmitic, palmitoleic, and oleic acids were higher in cannabis users compared to nonusers. As palmitic acid can be derived from diet or lipogenesis from sugars, we evaluated lipogenesis using a de novo lipogenesis index (palmitate/linoleic acid) and carbon‐specific isotope analysis, which allows for the determination of fatty acid 13C signature. The significantly higher de novo lipogenesis index in the cannabis users group along with a more enriched 13C signature of palmitic acid suggested an increase in lipogenesis. In addition, while serum glucose concentration did not differ between groups, pyruvate and lactate were lower in the cannabis user group, with pyruvate negatively correlating with palmitic acid. Furthermore, the endocannabinoid 2‐arachidonoylglycerol was elevated in cannabis users and could contribute to lipogenesis by activating the cannabinoid receptor 1. Because palmitic acid has been suggested to increase inflammation, we measured peripheral cytokines and observed no changes in inflammatory cytokines. Finally, an anti‐inflammatory metabolite of palmitic acid, palmitoylethanolamide was elevated in cannabis users. Our results suggest that lipogenic activity is increased in cannabis users; however, future studies, including prospective studies that control dietary intake are required.

Prior acute exercise restores postprandial fat oxidation in active cannabis users

“…It has been speculated that cannabis users may have increased metabolic rates, but this data are purely speculative, and we observed no indication of this in this study (Clark et al., 2018 ). Another secondary analysis of a larger trial reported higher levels of palmitic, palmitoleic, and oleic acids in the serum of cannabis users compared to nonusers; in addition, the authors estimated de novo lipogenesis (DNL) from the ratio of palmitic acid to linoleic acid and reported higher DNL levels in cannabis users (Cisbani et al., 2022 ). The authors speculated that elevated serum glucose could have influenced palmitic acid production, though there was no difference between cannabis users and nonusers (Cisbani et al., 2022 ).…”

“…Another secondary analysis of a larger trial reported higher levels of palmitic, palmitoleic, and oleic acids in the serum of cannabis users compared to nonusers; in addition, the authors estimated de novo lipogenesis (DNL) from the ratio of palmitic acid to linoleic acid and reported higher DNL levels in cannabis users (Cisbani et al., 2022 ). The authors speculated that elevated serum glucose could have influenced palmitic acid production, though there was no difference between cannabis users and nonusers (Cisbani et al., 2022 ). Furthermore, pyruvate and lactate—the end products of glycolysis—were downregulated, which suggests the possibility that they were more rapidly converted into palmitic acid in cannabis users (Cisbani et al., 2022 ).…”

“…The authors speculated that elevated serum glucose could have influenced palmitic acid production, though there was no difference between cannabis users and nonusers (Cisbani et al., 2022 ). Furthermore, pyruvate and lactate—the end products of glycolysis—were downregulated, which suggests the possibility that they were more rapidly converted into palmitic acid in cannabis users (Cisbani et al., 2022 ). However, this study did not control for habitual dietary intake or physical activity before blood collection nor were participants fasted for their blood draw (Cisbani et al., 2022 ).…”

Plasma and Liver Lipids are Differentially Regulated After Cannabinoid Treatments in Male and Female Mice

“…Already, we have shown sex differences in endolipids in plasma of patients with gastroparesis 22 . Likewise, serum collected from cannabis users shows increased palmitic acid, oleic acid, 2-AG, and PEA, but not AEA or OEA compared to non-cannabis users 23 , which illustrates that plasma endolipids are responsive to changes in systemic CB pharmacology. It will be informative to compare plasma levels of endolipids with CB treatments to other tissues in order to determine how translatable these values are to other parts of the body.…”

Recent Applications of Gas Chromatography in Bioanalysis

“…The method requires a very small volume of plasma (50 μL) and has a detection limit of 0.1 ng/mL. The relationships between fatty acid imbalances and the investigated diseases [44], or the influence of the use of drugs [49] have been recently reviewed.…”