Objective Preclinical studies have shown that low-dose USP methylene blue increases mitochondrial cytochrome oxidase activity in the brain and improves memory retention after learning tasks, including fear extinction. We report on the first controlled experiment to examine the memory-enhancing effects of post-training methylene blue administration on retention of fear extinction and contextual memory following fear extinction training. Method Adults (N = 42) displaying marked claustrophobic fear were randomized to double-blind administration of 260 mg of methylene blue versus placebo immediately following six five-minute extinction trials to an enclosed chamber. Retesting occurred one month later to assess fear renewal as indexed by peak fear during exposure to a non-trained enclosed chamber with the prediction that methylene blue's effects would vary as a function of fear reduction achieved during extinction training. Incidental contextual memory was assessed 1 and 30 days after training to assess the cognitive enhancing effects of methylene blue independent of its effects on fear attenuation. Results Consistent with predictions, participants displaying low end fear at post-training showed significantly less fear at follow-up if they received methylene blue post-training relative to placebo. In contrast, participants displaying moderate to high levels of post-training fear tended to fare worse at follow-up relative to placebo. Methylene blue's enhancement of contextual memory was unrelated to initial or post-training claustrophobic fear. Conclusions Methylene blue enhances memory and the retention of fear extinction when administered after a successful exposure session, but may have a deleterious effect on extinction when administered after an unsuccessful exposure session.

ClinicalTrials.gov identifier: NCT01188694.

Results highlight the important role of threat perception as a risk marker for the acute experience of depression and PTSD symptoms during deployment. (PsycINFO Database Record

Despite significant research demonstrating the deleterious effects of tobacco abstinence on memory, and research showing substantial sex differences in nicotine withdrawal and memory processes, there has been scant work on how males and females might differ in the effects of tobacco abstinence on memory and cognition. Using a standard recognition memory task, we conducted a pilot study to examine how 24 hours of tobacco abstinence in moderate to heavy smokers would affect memory in males and females. Twenty-five moderate to heavy smokers were tested following a period of smoking normally and following 24 hours of tobacco abstinence. At each session, participants completed a recognition memory task in which items were studied under full- and divided-attention conditions (a standard manipulation of memory encoding) as well as tests of passive short-term and working memory (forward and backward digit span). Tobacco abstinence significantly reduced memory performance under full attention conditions for males but not for females. A significant main effect of smoking status in which abstinence significantly reduced performance, as well as a main effect of encoding condition (divided attention < full attention), were found. Our results demonstrate that there may be substantial sex differences in the cognitive effects of tobacco abstinence. While preliminary, the data suggest the need for further, more extensive study of how males and females differ during tobacco abstinence. Such information will inform the best strategies for tobacco cessation efforts.

Previous studies have demonstrated reductions in episodic memory during nicotine withdrawal. However, these studies have been unable to dissociate memory reductions from losses in attention associated with tobacco abstinence. In the present study, the authors sought to determine whether episodic memory reduction is a primary effect of nicotine withdrawal during tobacco abstinence. Heavy smokers were tested when smoking normally and following 24 hrs of abstinence. Participants were tested with a recognition memory task in which items were studied under full and divided attention conditions. Forward digit span and backward digit span were also included as control measures. Withdrawal was associated with a reduction in memory performance that was independent of attention at encoding. The authors conclude that impairment of episodic memory is a primary effect of nicotine withdrawal during tobacco abstinence. Further research is required to determine if this is associated with continued use of tobacco and cessation failures.