Ming-Chyi Huang1,2,3, Chun-Hsin Chen3,4, Lian-Yu Chen1,5, Hu-Ming Chang1, Chih-Ken Chen6,7, Shih-Ku Lin8,9, Ke Xu10. 1. Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, 309, Song-De Road, Xinyi District, Taipei City, 110, Taiwan. 2. Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Xing St., Taipei, 110, Taiwan. 3. Psychiatric Research Center, Taipei Medical University Hospital, Taipei, Taiwan. 4. Department of Psychiatry, Wan-Fang Hospital, Taipei Medical University, 111, Sec. 3, Hsing-Long Rd, Taipei, 116, Taiwan. 5. Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan. 6. Department of Psychiatry & Community Medicine Research Center, Chang Gung Memorial Hospital, 200, Ln 208, Ji-Jing 1st Rd, Keelung, Taiwan. kenchen@cgmh.org.tw. 7. Chang Gung University School of Medicine, 5, Fu-Hsing Rd, Gue-Shan District Taoyuan City, 333, Taiwan. kenchen@cgmh.org.tw. 8. Department of Psychiatry, Taipei City Psychiatric Center, Taipei City Hospital, 309, Song-De Road, Xinyi District, Taipei City, 110, Taiwan. sklin@tpech.gov.tw. 9. Department of Psychiatry, School of Medicine, College of Medicine, Taipei Medical University, 250 Wu-Xing St., Taipei, 110, Taiwan. sklin@tpech.gov.tw. 10. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Abstract
BACKGROUND: Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic-pituitary-adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse. METHODS: We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1 week, and 2 weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline. RESULTS: Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10 ng/mL, p < 0.001) and increased ACTH (32.3 ± 16.3 vs. 22.3 ± 11.0 pg/mL, p = 0.008) levels at baseline, whereas cortisol levels were similar between two groups. Levels of the three markers did not correlate with ketamine use variables, craving, depression, or anxiety symptoms. The levels did not alter after 1 or 2 weeks of ketamine discontinuation. Notably, those with higher anxiety had lower orexin-A but increased cortisol levels than did those with lower anxiety. CONCLUSIONS: This study showed that KD patients had persistent orexin-A reduction and stress hormone dysregulation in early abstinence. The anxious phenotype of KD might be associated with a lower orexin-A expression. These results point to a promising pathway to investigate the neurochemical mechanisms of ketamine addiction.
BACKGROUND: Ketamine has emerged as a major substance of abuse worldwide. Evidence suggests a role of orexin system in reward processing, withdrawal, and stress response. It also interacts with the stress mechanisms of hypothalamic-pituitary-adrenal (HPA) axis to regulate drug-taking behavior. The study aimed to explore the relevance of orexin and stress hormones to chronic ketamine abuse. METHODS: We enrolled 67 ketamine-dependent (KD) patients and 64 controls. The levels of orexin-A, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline, 1 week, and 2 weeks after ketamine discontinuation. KD patients were assessed by Beck Depression Inventory, Beck Anxiety Inventory, and Visual Analogue Scale for ketamine craving at baseline. RESULTS: Compared with the controls, KD patients had significantly lower orexin-A (0.65 ± 0.12 vs. 0.74 ± 0.10 ng/mL, p < 0.001) and increased ACTH (32.3 ± 16.3 vs. 22.3 ± 11.0 pg/mL, p = 0.008) levels at baseline, whereas cortisol levels were similar between two groups. Levels of the three markers did not correlate with ketamine use variables, craving, depression, or anxiety symptoms. The levels did not alter after 1 or 2 weeks of ketamine discontinuation. Notably, those with higher anxiety had lower orexin-A but increased cortisol levels than did those with lower anxiety. CONCLUSIONS: This study showed that KD patients had persistent orexin-A reduction and stress hormone dysregulation in early abstinence. The anxious phenotype of KD might be associated with a lower orexin-A expression. These results point to a promising pathway to investigate the neurochemical mechanisms of ketamine addiction.
Authors: Christoph von der Goltz; Anne Koopmann; Christina Dinter; Anne Richter; Christine Rockenbach; Martin Grosshans; Helmut Nakovics; Klaus Wiedemann; Karl Mann; Georg Winterer; Falk Kiefer Journal: Psychoneuroendocrinology Date: 2009-10-13 Impact factor: 4.905
Authors: Jiann Wei Yeoh; Erin J Campbell; Morgan H James; Brett A Graham; Christopher V Dayas Journal: Front Neurosci Date: 2014-02-25 Impact factor: 4.677