Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut–Immune–Brain Axis

Abstract

Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and finding effective treatments. This study aims to understand the complex interactions of the gastrointestinal–immune–nervous systems following an acute METH dose administration as one of the potential underlying molecular mechanisms concentrating on the impact of METH abuse on gut permeability. Findings showed a decreased expression of tight junction proteins ZO-1 and EpCAm in intestinal tissue and the presence of FABP-1 in sera of METH treated mice suggests intestinal wall disruption. The increased presence of CD45+ immune cells in the intestinal wall further confirms gut wall inflammation/disruption. In the brain, the expression of inflammatory markers Ccl2, Cxcl1, IL-1β, TMEM119, and the presence of albumin were higher in METH mice compared to shams, suggesting METH-induced blood–brain barrier disruption. In the spleen, cellular and gene changes are also noted. In addition, mice treated with an acute dose of METH showed anxious behavior in dark and light, open field, and elevated maze tests compared to sham controls. The findings on METH-induced inflammation and anxiety may provide opportunities to develop effective treatments for METH addiction in the future.

The gut microbiota as a potential biomarker for methamphetamine use disorder: evidence from two independent datasets

“…An unbalanced Firmicutes / Bacteroidetes ratio is indicative of gut dysbiosis and is associated with various chronic diseases, such as obesity ( Magne et al., 2020 ), inflammation ( Stojanov et al., 2020 ), and hypertension ( Yang et al., 2015 ). Interestingly, MUD patients are also a high-risk population for these diseases ( Kaye et al., 2007 ; J Edge and Gold, 2011 ; Davidson et al., 2022 ). Even though it is challenging to determine a causal relationship, future studies should consider the potential role of the gut microbiota in the increased susceptibility to chronic illnesses among MUD patients.…”

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions

“…This approach has garnered attention due to its versatility and potential to bring about structural modifications in a range of compounds that can target various drugs or even combinations of drugs [ 34 , 35 , 36 ]. The primary objective of these adjustments is to encourage the generation of potent antibody responses, a key element in the effectiveness of vaccination initiatives [ 37 , 38 ]. Conjugate vaccines have shown great promise as an immunotherapeutic intervention strategy for SUDs.…”

Tryptophan and Substance Abuse: Mechanisms and Impact

“…METH is an amine drug that is abused due to its sympathomimetic effects and is taken via inhalation, ingestion, injection, or smoking [49,50]. METH is a weak lipophilic base that diffuses across the plasmalemma of the presynaptic neurons and vesicular membranes [51].…”