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.