Insights into the effects of crack abuse on the human metabolome using a nmr approach

Approximately 255 million people consume illicit drugs every year, among which 18 million use cocaine. A portion of this drug is represented by crack, but it is difficult to estimate the number of users since most are marginalized. However, there are no recognized efficacious pharmacotherapies for crack-cocaine dependence. Inflammation and infection in cocaine users may be due to behavior adopted in conjunction with drug-related changes in the brain. To understand the metabolic changes associated with the drug abuse disorder and identify biomarkers, we performed a 1H NMR-based metabonomic analysis of 44 crack users’ and 44 healthy volunteers’ blood serum. The LDA model achieved 98% of accuracy. From the water suppressed 1H NMR spectra analyses, it was observed that the relative concentration of lactate was higher in the crack group, while long chain fatty acid acylated carnitines were decreased, which was associated with their nutritional behavior. Analyses of the aromatic region of CPMG 1H NMR spectra demonstrated histidine and tyrosine levels increased in the blood serum of crack users. The reduction of carnitine and acylcarnitines and the accumulation of histidine in the serum of the crack users suggest that histamine biosynthesis is compromised. The tyrosine level points to altered dopamine concentration181341348CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ305134/2014-0; 454234/2014–7; 465389/2014–72014/18938–8; 2014/50867–3We kindly acknowledge the assistance of Danijela Stanisic and Dr. Banny Barbosa for their help with the NMR experiments. T.B.B.C.C. thanks INCTBio and CAPES for a PhD grant. L.T. thanks the Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq for Grant No. 305134/2014-0. The authors acknowledge the Emeritus Professor Carol Hollingworth Collins for the great contribution in revising the manuscript. This research received research support from the following Brazilian agencies: Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP (Sao Paulo Research Foundation) Grant Nos. 2014/18938–8 and 2014/50867–3 and Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (National Council of Technological and Scientific Development) Grant Nos. 454234/2014–7 and 465389/2014–