Effects of nicotine withdrawal on cognition in a clinical trial setting.

Rationale: Smoking withdrawal has been widely established to produce a range of impairments to the quality of several major domains of cognitive function including attention, working memory and episodic memory.

Objectives: This study was conducted to determine the degree to which smoking withdrawal will produce impairments in cognitive function in phase I clinical trials.

Methods: Healthy male volunteers who were housed in a clinical trial facility for 16 days underwent periods of ad libitum smoking and smoking withdrawal.

Results: Smoking withdrawal disrupted aspects of attention and episodic verbal recall and recognition.

Conclusions: This study confirms previous work showing cognitive declines in smoking withdrawal and illustrates that such effects occur in ongoing safety and tolerability studies of new medicines and thus require careful consideration for the assessment of cognitive function in such trials as well as the accurate attribution of adverse events to the safety profiles of the medicines.