Abstract
Background: Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is a common drug of abuse worldwide. Existing evidence suggest a disruption of oxytocin system involves in the development of addiction. In this study, we aimed to investigate the role of oxytocin in ketamine addiction by measuring the blood oxytocin levels in ketamine-dependent (KD) patients.Methods: Sixty-five KD patients and 65 controls were enrolled. Fasting plasma levels of oxytocin were determined at baseline and 1 and 2 weeks after ketamine withdrawal. Ketamine use variables, Beck Depression Inventory, Beck Anxiety Inventory (BAI), Visual Analog Scale for craving, and Childhood Trauma Questionnaire-short form were assessed in KD patients.Results: KD patients had significantly lower levels of oxytocin at baseline compared to controls (5.89 ± 2.13 vs. 9.53 ± 4.17 ng/mL, P < 0.001). Oxytocin levels increased after one (6.74 ± 2.63, P < 0.002) and 2 weeks (6.89 ± 2.69, P = 0.01) of withdrawal in KD patient despite the levels were still lower than controls (P = 0.001 and 0.002, respectively). The clinical variables did not correlate with baseline oxytocin levels except BAI scores, which showed a negative correlation with the levels (r = −0.263; P = 0.039).Conclusion: We found a distinctively reduced oxytocin level in KD patients and the level did not normalize after early abstinence. Lower oxytocin might be associated with anxious phenotype of ketamine dependence. These results suggest that oxytocin system dysregulated following chronic ketamine abuse and might provide insight in evaluating the potential therapeutic use of oxytocin for treating ketamine dependence.
Highlights
Ketamine hydrochloride, a non-competitive antagonist of Nmethyl-D-aspartate (NMDA) receptor, has long been used as a short-acting anesthetic agent in humans and veterinary medicine
This study aimed to explore the difference of oxytocin plasma levels between treatment-seeking ketamine-dependent (KD) patients with the most recent ketamine use in the preceding 24 h and healthy controls
In pairwise t-tests, we found that KD patients had significantly lower levels of oxytocin at baseline compared to controls (5.89 ± 2.13 vs. 9.53 ± 4.17 ng/mL, P < 0.001)
Summary
A non-competitive antagonist of Nmethyl-D-aspartate (NMDA) receptor, has long been used as a short-acting anesthetic agent in humans and veterinary medicine. Emerging evidence suggests that oxytocin is involved in the neuroadaptive processes associated with the development of addiction [7]. Animal studies have demonstrated that oxytocin interferes the development of tolerance to morphine [9] and alcohol [10]. It may have the effects of reducing self-administrative behavior of heroin [9], alcohol [11], methamphetamine [12], and cocaine [13]. Further evidence supporting the role of oxytocin in the involvement of addiction is that a negative association of plasma oxytocin levels with novelty-seeking, one of the indicators of addiction, was observed in heroin users [17]. An N-methyl-D-aspartate (NMDA) receptor antagonist, is a common drug of abuse worldwide. We aimed to investigate the role of oxytocin in ketamine addiction by measuring the blood oxytocin levels in ketamine-dependent (KD) patients
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