ArticlePsychopharmacology2020
Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation.
Article in Psychopharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 16 citations in OpenAlex.
- Cognitive and physiological impacts of psychotherapy incorporating human-equine interactions during substance withdrawal: A scoping review.Journal of equine rehabilitation · 2025Article
- Reduction of Orexin-A Is Associated With Anxiety and the Level of Depression of Male Methamphetamine Users During the Initial Withdrawal Period.Frontiers in psychiatry · 2022Article
- Changes of adrenocorticotropic hormone rhythm and cortisol circadian rhythm in patients with depression complicated with anxiety and their effects on the psychological state of patients.Frontiers in psychiatry · 2022Article
- Enhancement of Oxytocin in the Medial Prefrontal Cortex Reverses Behavioral Deficits Induced by Repeated Ketamine Administration in Mice.Frontiers in neuroscience · 2021Article
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundKetamine 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.
methodsWe 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.
resultsCompared 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.
conclusionsThis 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.
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