Int. J. Environ. Res. Public Health 2012, 9 207 in addictions to different substances, and apparently found it. Before accepting such a result at face value, it is necessary to explore how robust it is. By concentrating on data from systematic reviews and meta-analyses of randomised trials reporting abstinence at six months or longer it relied on studies least open to bias. Most information came from reviews of smoking cessation in over 127,000 participants, though reviews for treatments of other addictions covered a few thousand participants. Most of the reviews included had a preponderance of longer-term studies, with determination of abstinence using objective measures. As much as possible, therefore, comparisons were of like for like. The example of nicotine replacement therapy, with over 43,000 participants in trials of six months or longer, showed that vagaries of trial design made little difference to placebo response rates, though trials lasting 12 months were less effective than those lasting only six months. Together, these approaches support the contention that between-addiction comparisons of quit rates with placebo are justified. Unresolved issues include how missing data are treated in clinical trials; missing data should probably be counted as failure, but this may not be uniformly applied, and is not generally discussed. Trials with cocaine addicts had shorter durations than with other substances. As the abstinence rate tends to decrease with time, this bias is of concern. The use of a no-treatment control rather than actual placebo might be important in both non-drug and drug interventions. Placebo has been shown to produce genuine effects through psychological mechanism (involving expectations, conditioning learning, memory, motivation somatic focus, reward, anxiety reduction, and meaning), as well as changes of metabolic activity in different brain regions in cocaine abusers [39]. Context effects could also be a source of variation in placebo response rates [40,41]. However, placebo response rates tend to be consistent in particular randomised trial models, using the same outcomes, over the same period of time [42], differing only when the outcome differs [43-45]. In the case of addiction, the same outcome was being sought over the same time. We have shown a high variability of success rates in smoking cessation trials where the group size is below 200 subjects. Trials with fewer than 200 participants were over-represented in opiate and cocaine studies. Finally, studies included in the systematic reviews were sensitive in that interventions caused change in response, with statistically significant relative benefit. This should give comfort that placebo response measured were meaningful. Few interventions were shown to be highly effective, and low NNTs were rare, except for buprenorphine treatment for opioid addiction, where one opioid replaces another (Table 5). The conclusion, then, is that in the circumstances chosen, placebo quit rates are a useful proxy marker for the strength of different addictions. The results point to tobacco being by far the strongest, as has already suggested the findings from epidemiological data [1,2]. Tobacco addiction is far more widespread than other addictions. Many smokers are not alcohol or drug addicts, though most alcohol or drug addicts are also smokers. One can hypothesize on individual vulnerability to addictive behaviours, this vulnerability being highest in alcohol and drug addicts. One other approach could be to look at differential outcomes in tobacco and other substance cessation in subjects having a dual addiction. In this respect, it has been shown that alcohol outcome was far better than tobacco outcome in alcoholic smokers undergoing an alcohol and tobacco concurrent