Tobacco use is a significant hurdle to development gains worldwide and the leading cause of preventable morbidity and mortality in the world. According to WHO report on the global tobacco epidemic in 2015, smoking-related illness costs billions of dollars and over 6 million deaths each year, imposing a heavy economic toll on countries, both in terms of direct medical care for adults and lost productivity. It is thus a pressing need for innovation in the smoking cessation field to reduce the enormous personal, social, and health care costs associated with smoking related diseases.

Nicotine addiction is characterized by high relapse rates and persistent memories of both nicotine reward and nicotine-associated conditioned stimuli. Chronic use of nicotine will cause permanent maladaptive alterations in our brain, varying from molecular signature to neural circuitry. They will usurp our normal memory systems and result in long-lasting pathological memories that are more refractory to commonly used therapies. Targeting these maladaptive memory systems is thought to underlie the successful treatment to nicotine craving and relapse clinically.

Recently Professor Lu L, the senior investigator of IDG/McGovern Institute for Brain Research, published a research article entitled ‘Effect of selective inhibition of reactivated nicotine-associated memories with propranolol on nicotine craving’ in JAMA Psychiatry. This work tackles treatment of nicotine addiction using a novel strategy for successfully modifying these maladaptive reward memories during reconsolidation, the process by which long-term memories are updated, strengthened, or both. The authors carried out a rat-to-human translational study to coincide administration of the beta-adrenoceptor antagonist propranolol with the time window of reconsolidation after nicotine exposure (unconditioned stimulus, UCS). In animal models, they observed propranolol injections immediately after nicotine UCS-induced memory retrieval successfully suppressed relapse to nicotine conditioned place preference (CPP) and operant nicotine seeking in rats simultaneously. They further validated the inhibitory effect of this pharmacological intervention on conditioned preference to nicotine-associated cues and nicotine craving induced by the pre-existing nicotine-related cues in human smokers. This innovative procedure has great translational potential for preventing nicotine craving and relapse to nicotine addiction.

It is noticeable that they previously introduced a conditioned stimulus (CS)-based retrieval extinction and UCS-based retrieval extinction to inhibit drug craving and relapse in animal models and humans in Science, 2012 and Nature Communication, 2015, respectively. These innovative procedures have received a world-wide attention and are validated by others in both animal models and humans. The same issue of JAMA Psychiatry also reported American researchers successfully inhibited nicotine craving and relapse in humans using CS-based retrieval extinction procedure introduced by Professor Lu’s group in 2012. Sunjeev K. Kamboj, Kamboj SK and Das RK from University College London also wrote a comment article on JAMA Psychiatry entitled ‘Behavioral and Pharmacological Strategies for Weakening Maladaptive Reward Memories: A New Approach to Treating a Core Disease Mechanism in Tobacco Use Disorder’ and suggested the minimally invasive reconsolidation-based treatments mark a step changein treatment of tobacco use and substance use more generally.

Xue YX and Deng JH from National Institute of Drug Dependence, PKU and Peking University Sixth Hospital, respectively are the co-first authors of this article, and Professor Lu L is the corresponding author. This work is partially supported by NSFC and National key basic research program of Ministry of science and Technology (973).