Abstract

In patients suffering from treatment-resistant bipolar depression (BP) and with unresponsive chronic pain that is diagnosed as Complex Regional Pain Syndrome (CRPS)have responded to treatment with ketamine. The CRPS patients were treated with a five-day infusion of the drug produced pain relief in 75% of the patients and 67% of the BP responded after a single dose. The objective of the ongoing study is to identify the reasons why some patients respond and other do not, to be able to identify the responders before treatment begins and to individualize treatment to increase response. These initial pharmacokinetic and pharmacodynamic studies of ketamine in CRPS and BP patients are completed. The data indicates that the therapeutic activity of ketamine is due, in part, to hydroxynorketamine and dehydronorketamine and the pharmacological activities of the compounds have been investigated. In addition, metabolomic studies have determined that response and non-response to treatment with ketamine in BP patients is related to mitochodrial function. This relationship is under investigation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000297-15
Application #
9341855
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
2016
Total Cost
Indirect Cost

  Institution

Name
Aging
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Gonzalez-Freire, Marta; Moaddel, Ruin; Sun, Kai et al. (2018) Targeted Metabolomics Shows Low Plasma Lysophosphatidylcholine 18:2 Predicts Greater Decline of Gait Speed in Older Adults: The Baltimore Longitudinal Study of Aging. J Gerontol A Biol Sci Med Sci :
Moaddel, Ruin; Shardell, Michelle; Khadeer, Mohammed et al. (2018) Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects. Psychopharmacology (Berl) 235:3017-3030
Pollack, Rena M; Barzilai, Nir; Anghel, Valentin et al. (2017) Resveratrol Improves Vascular Function and Mitochondrial Number but Not Glucose Metabolism in Older Adults. J Gerontol A Biol Sci Med Sci 72:1703-1709
Ghosh, Soumita; González-Mariscal, Isabel; Egan, Josephine M et al. (2017) Targeted proteomics of cannabinoid receptor CB1 and the CB1b isoform. J Pharm Biomed Anal 144:154-158
Asher, Gary N; Xie, Ying; Moaddel, Ruin et al. (2017) Randomized Pharmacokinetic Crossover Study Comparing 2 Curcumin Preparations in Plasma and Rectal Tissue of Healthy Human Volunteers. J Clin Pharmacol 57:185-193
Semba, Richard D; Trehan, Indi; Li, Ximin et al. (2017) Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation. EBioMedicine 17:57-66
Semba, Richard D; Gonzalez-Freire, Marta; Moaddel, Ruin et al. (2017) Environmental Enteric Dysfunction Is Associated With Altered Bile Acid Metabolism. J Pediatr Gastroenterol Nutr 64:536-540
Semba, Richard D; Trehan, Indi; Li, Ximin et al. (2017) Low serum ?-3 and ?-6 polyunsaturated fatty acids and other metabolites are associated with poor linear growth in young children from rural Malawi. Am J Clin Nutr 106:1490-1499
Zanos, Panos; Moaddel, Ruin; Morris, Patrick J et al. (2017) Zanos et al. reply. Nature 546:E4-E5
Leinwand, Kristina L; Jones, Ashleigh A; Huang, Rick H et al. (2017) Cannabinoid Receptor-2 Ameliorates Inflammation in Murine Model of Crohn's Disease. J Crohns Colitis 11:1369-1380

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