Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine‐induced gut microbiota dysbiosis

Abstract Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum , has potential health‐promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA‐induced CPP and hyperactivity. Interestingly, LBP improved MA‐induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum , Gordonibacter , and Ileibacterium . MA exposure induced the co‐occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short‐chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA‐induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.