To explore the neuronal circuits underlying addiction and the Traditional Chinese Medicine (TCM) therapy, chronic methamphetamine (METH) exposed models and adolescent cocaine exposed(ACE) models are established in mice. With the methods of virus tracing, fiber photometry, DDREADs, patch clamp and conditioned place preference (CPP), we found that eLPBChAT-lCeA pathway is implicated in METH withdrawal anxiety, while eLPBChAT-ovBNST pathway is involved in METH-primed reinstatement of CPP. In addiction, the Gegen-Qinlian-Decoction alleviate the METH relapse by targeting eLPBChAT neuronal ensembles. When growing into adulthood, ACE mice exhibit anxiety-like behaviors and susceptibility to drug, recruiting distinct sub-regions of claustrum, which are cured by acupuncture.