Wallace MS, Marcotte TD, Atkinson JH, et al. - Via performing a secondary analysis of data from a recent diabetic neuropathy study that demonstrated a dose-dependent reduction in spontaneous and elicited pain at specific time points researchers sought to report on the association between tetrahydrocannabinol (THC) plasma levels and pain response. In the randomized, double-blinded, placebo-controlled crossover study, 16 patients with painful diabetic peripheral neuropathy participated in four sessions, separated by 2 weeks, during each of which exposure to one of four conditions was done: placebo, or 1%, 4%, or 7% THC dose of cannabis. Aerosolized cannabis or placebo was then administered to the participants and pain intensity and cognitive testing were done at specific time points for 4 hours. Plasma assay of total THC was done on blood sample drawn from the left antecubital vein at 0, 15, 30, 45, 60, 150, and 240 minutes. A U-shaped relation was indicated by the results whereby pain ratings are greatest at extreme (low and high) levels of THC. The analysis correlating plasma THC levels with pain reduction in diabetic neuropathy indicate a therapeutic window. A negative association (no reduction) was observed of low and high THC levels and a positive association (reduction) was noted of THC levels within the window. THC showed a minor negative linear effect on cognitive function.