Addiction to cigarette smoking is a stubborn and persistent condition whereby intense craving, dysphoria and relapse are all too common. Maladaptive memories are formed when the brain’s reward-learning system is usurped by addictive drugs, which produce a level of salience beyond the normal human emotional experience, thus biasing neural processing and memory toward hyper salience. The resulting maladaptive memories help us understand the chronicity and persistence of addictive driven behavior.
Accordingly, the efficacy of most smoking cessation treatment strategies is poor. The reasons for treatment failure are complicated. Most fail in addressing the psychobiological processes that drive craving and relapse. Smokers who attempt cessation, experience intense urges to smoke, even after months of non smoking. These cravings are biological and many are triggered unexpectedly by specific cues that predispose craving and relapse. This research underscores the importance of addressing the conditioned maladaptive reward memories that underlie relapse susceptibility in addicted smokers.
Smoking and the Pavlovian Conditioning Theory
Conditioned stimulus is the psychobiological process in which reward cues are paired with smoking reward. In addictive disease, we have learned that the levels of reward and craving can vary among individuals and among the differing mechanism in which a particular psychoactive substance produces reward.
It has been well established that conditioned stimuli reliably predict smoking reward through Pavlovian conditioning, whereby conditioned paired responses such as cues and craving are generated. Brief exposure to a conditioned stimulus such as the smell of a cigarette, or exposure to an unconditioned stimulus such as taking a drag off a friend’s cigarette provoke the recall of previously established reward associations. On the other side of the same coin, newly learned, and persistently reinforced conditioned stimulus that is paired with a no smoking reward can be established and encoded as a new conditioned stimulus that is predictive of the absence of smoking reward.
There are also pharmacological treatments with amnestic agents such as propranolol that disrupt restabilization of Pavlovian reward by inhibiting the storage process of robust conditioned associations that induce smoking reward, and thus relapse.
When given to rats, in combination with memory reactivation modalities, Propranolol reduced the Pavlovian response to nicotine. Among human smokers, research by Xue, et al, found that subjective liking of both recently trained, natural or preexisting smoking cues decreased among those who ingested 40 mg of propranolol one hour prior to smoking reward memory reactivation. This effect was not found in control groups who were given placebo. The effect on the propranolol group was observed for 48 hours after ingesting the drug. Evaluations of the effect did not exceed 48 hours.
Why Does This Matter?
Smoking addiction is the leading cause of preventable morbidity and mortality globally. The enormous personal burden, social, and health care costs associated with smoking-related diseases is overwhelming. There is a pressing need for treatment innovation in order to save lives.
This excellent study has shed light on a novel multimodal approach. Going forward, there are numerous issues to be considered and resolved in providing a clinically based, smoking cessation using this approach. For example, reliable, repeatable and predictable procedures for establishing indices of memory reactivation is a huge challenge and a critical step toward a viable, multimodal treatment approach for chronically addicted smokers. More research is needed, but it is clearly worth doing.
Kamboj SK, Das RK. Behavioral and Pharmacological Strategies for Weakening Maladaptive Reward Memories: A New Approach to Treating a Core Disease Mechanism in Tobacco Use Disorder. JAMA Psychiatry. 2017 Mar 1;74(3):209- 211.