Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation
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 st...
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| Veröffentlicht in: | Psychopharmacology 2020, Vol.237 (1), p.45-53 |
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| creator | Huang, Ming-Chyi Chen, Chun-Hsin Chen, Lian-Yu Chang, Hu-Ming Chen, Chih-Ken Lin, Shih-Ku Xu, Ke |
| description | 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
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| doi_str_mv | 10.1007/s00213-019-05342-9 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_journals_2268108192</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A610971600</galeid><sourcerecordid>A610971600</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-8d6b6b90bba900e6ae83cc8d2f5491a451d4c4e2b78cb7208e532af31e29e9a53</originalsourceid><addsrcrecordid>eNp9kU1P3DAQhq2Kqmy3_QMckCXOpuOPJPZxtaKlEhIXerYcZwKmGxvsBOi_r-nSokpVx4eRZt537PFDyBGHUw7QfSoAgksG3DBopBLMvCErrqRgAjpxQFYAUjLJG31I3pdyCzWUVu_IoeSy67RuV-Rye5NTDJ5-x9lNISJ1_VKQhkJdKckHN-NAH8N8Q1PGpxDZhmYcFj-HFKmLA91sr84p7vDBPZc-kLej2xX8-JLX5Nvns6vtObu4_PJ1u7lgXikxMz20fdsb6HtnALB1qKX3ehBjowx3quGD8gpF32nfdwI0NlK4UXIUBo1r5Jqc7Ofe5XS_YJntbVpyrFdaIVrNQXMjXlXXboc2xDHN2fkpFG83LQfT8bb-0Zqc_kNVz4BT8CniGGr9L4PYG3xOpWQc7V0Ok8s_LAf7jMbu0diKxv5CY001Hb-8eOknHP5YfrOoArkXlNqK15hfV_rP2J-tb5bi</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2268108192</pqid></control><display><type>article</type><title>Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation</title><source>MEDLINE</source><source>SpringerNature Journals</source><creator>Huang, Ming-Chyi ; Chen, Chun-Hsin ; Chen, Lian-Yu ; Chang, Hu-Ming ; Chen, Chih-Ken ; Lin, Shih-Ku ; Xu, Ke</creator><creatorcontrib>Huang, Ming-Chyi ; Chen, Chun-Hsin ; Chen, Lian-Yu ; Chang, Hu-Ming ; Chen, Chih-Ken ; Lin, Shih-Ku ; Xu, Ke</creatorcontrib><description>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.</description><identifier>ISSN: 0033-3158</identifier><identifier>EISSN: 1432-2072</identifier><identifier>DOI: 10.1007/s00213-019-05342-9</identifier><identifier>PMID: 31377886</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Abstinence ; ACTH ; Addictions ; Adrenal glands ; Adrenocorticotropic hormone ; Adrenocorticotropic Hormone - metabolism ; Adult ; Anxiety ; Anxiety - metabolism ; Biomedical and Life Sciences ; Biomedicine ; Case-Control Studies ; Corticosteroids ; Cortisol ; Craving - physiology ; Depression, Mental ; Depressive Disorder - metabolism ; Drug abuse ; Female ; Hormones ; Humans ; Hydrocortisone - metabolism ; Hypothalamo-Hypophyseal System - metabolism ; Hypothalamus ; Ketamine ; Ketamine - adverse effects ; Male ; Medical colleges ; Medical research ; Medicine, Experimental ; Mental depression ; Middle Aged ; Neurosciences ; Orexins ; Orexins - metabolism ; Original Investigation ; Pharmacology/Toxicology ; Phenotypes ; Pituitary ; Pituitary-Adrenal System - metabolism ; Psychiatric Status Rating Scales ; Psychiatry ; Reinforcement ; Stress ; Stress response ; Substance Withdrawal Syndrome - metabolism ; Substance-Related Disorders - metabolism ; Substance-Related Disorders - psychology ; Withdrawal</subject><ispartof>Psychopharmacology, 2020, Vol.237 (1), p.45-53</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2019</rights><rights>COPYRIGHT 2020 Springer</rights><rights>Psychopharmacology is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-8d6b6b90bba900e6ae83cc8d2f5491a451d4c4e2b78cb7208e532af31e29e9a53</citedby><cites>FETCH-LOGICAL-c442t-8d6b6b90bba900e6ae83cc8d2f5491a451d4c4e2b78cb7208e532af31e29e9a53</cites><orcidid>0000-0002-5123-0389</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00213-019-05342-9$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00213-019-05342-9$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31377886$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Ming-Chyi</creatorcontrib><creatorcontrib>Chen, Chun-Hsin</creatorcontrib><creatorcontrib>Chen, Lian-Yu</creatorcontrib><creatorcontrib>Chang, Hu-Ming</creatorcontrib><creatorcontrib>Chen, Chih-Ken</creatorcontrib><creatorcontrib>Lin, Shih-Ku</creatorcontrib><creatorcontrib>Xu, Ke</creatorcontrib><title>Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation</title><title>Psychopharmacology</title><addtitle>Psychopharmacology</addtitle><addtitle>Psychopharmacology (Berl)</addtitle><description>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.</description><subject>Abstinence</subject><subject>ACTH</subject><subject>Addictions</subject><subject>Adrenal glands</subject><subject>Adrenocorticotropic hormone</subject><subject>Adrenocorticotropic Hormone - metabolism</subject><subject>Adult</subject><subject>Anxiety</subject><subject>Anxiety - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Case-Control Studies</subject><subject>Corticosteroids</subject><subject>Cortisol</subject><subject>Craving - physiology</subject><subject>Depression, Mental</subject><subject>Depressive Disorder - metabolism</subject><subject>Drug abuse</subject><subject>Female</subject><subject>Hormones</subject><subject>Humans</subject><subject>Hydrocortisone - metabolism</subject><subject>Hypothalamo-Hypophyseal System - metabolism</subject><subject>Hypothalamus</subject><subject>Ketamine</subject><subject>Ketamine - adverse effects</subject><subject>Male</subject><subject>Medical colleges</subject><subject>Medical research</subject><subject>Medicine, Experimental</subject><subject>Mental depression</subject><subject>Middle Aged</subject><subject>Neurosciences</subject><subject>Orexins</subject><subject>Orexins - metabolism</subject><subject>Original Investigation</subject><subject>Pharmacology/Toxicology</subject><subject>Phenotypes</subject><subject>Pituitary</subject><subject>Pituitary-Adrenal System - metabolism</subject><subject>Psychiatric Status Rating Scales</subject><subject>Psychiatry</subject><subject>Reinforcement</subject><subject>Stress</subject><subject>Stress response</subject><subject>Substance Withdrawal Syndrome - metabolism</subject><subject>Substance-Related Disorders - metabolism</subject><subject>Substance-Related Disorders - psychology</subject><subject>Withdrawal</subject><issn>0033-3158</issn><issn>1432-2072</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1P3DAQhq2Kqmy3_QMckCXOpuOPJPZxtaKlEhIXerYcZwKmGxvsBOi_r-nSokpVx4eRZt537PFDyBGHUw7QfSoAgksG3DBopBLMvCErrqRgAjpxQFYAUjLJG31I3pdyCzWUVu_IoeSy67RuV-Rye5NTDJ5-x9lNISJ1_VKQhkJdKckHN-NAH8N8Q1PGpxDZhmYcFj-HFKmLA91sr84p7vDBPZc-kLej2xX8-JLX5Nvns6vtObu4_PJ1u7lgXikxMz20fdsb6HtnALB1qKX3ehBjowx3quGD8gpF32nfdwI0NlK4UXIUBo1r5Jqc7Ofe5XS_YJntbVpyrFdaIVrNQXMjXlXXboc2xDHN2fkpFG83LQfT8bb-0Zqc_kNVz4BT8CniGGr9L4PYG3xOpWQc7V0Ok8s_LAf7jMbu0diKxv5CY001Hb-8eOknHP5YfrOoArkXlNqK15hfV_rP2J-tb5bi</recordid><startdate>2020</startdate><enddate>2020</enddate><creator>Huang, Ming-Chyi</creator><creator>Chen, Chun-Hsin</creator><creator>Chen, Lian-Yu</creator><creator>Chang, Hu-Ming</creator><creator>Chen, Chih-Ken</creator><creator>Lin, Shih-Ku</creator><creator>Xu, Ke</creator><general>Springer Berlin Heidelberg</general><general>Springer</general><general>Springer Nature B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QR</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>Q9U</scope><orcidid>https://orcid.org/0000-0002-5123-0389</orcidid></search><sort><creationdate>2020</creationdate><title>Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation</title><author>Huang, Ming-Chyi ; Chen, Chun-Hsin ; Chen, Lian-Yu ; Chang, Hu-Ming ; Chen, Chih-Ken ; Lin, Shih-Ku ; Xu, Ke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-8d6b6b90bba900e6ae83cc8d2f5491a451d4c4e2b78cb7208e532af31e29e9a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abstinence</topic><topic>ACTH</topic><topic>Addictions</topic><topic>Adrenal glands</topic><topic>Adrenocorticotropic hormone</topic><topic>Adrenocorticotropic Hormone - metabolism</topic><topic>Adult</topic><topic>Anxiety</topic><topic>Anxiety - metabolism</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Case-Control Studies</topic><topic>Corticosteroids</topic><topic>Cortisol</topic><topic>Craving - physiology</topic><topic>Depression, Mental</topic><topic>Depressive Disorder - metabolism</topic><topic>Drug abuse</topic><topic>Female</topic><topic>Hormones</topic><topic>Humans</topic><topic>Hydrocortisone - metabolism</topic><topic>Hypothalamo-Hypophyseal System - metabolism</topic><topic>Hypothalamus</topic><topic>Ketamine</topic><topic>Ketamine - adverse effects</topic><topic>Male</topic><topic>Medical colleges</topic><topic>Medical research</topic><topic>Medicine, Experimental</topic><topic>Mental depression</topic><topic>Middle Aged</topic><topic>Neurosciences</topic><topic>Orexins</topic><topic>Orexins - metabolism</topic><topic>Original Investigation</topic><topic>Pharmacology/Toxicology</topic><topic>Phenotypes</topic><topic>Pituitary</topic><topic>Pituitary-Adrenal System - metabolism</topic><topic>Psychiatric Status Rating Scales</topic><topic>Psychiatry</topic><topic>Reinforcement</topic><topic>Stress</topic><topic>Stress response</topic><topic>Substance Withdrawal Syndrome - metabolism</topic><topic>Substance-Related Disorders - metabolism</topic><topic>Substance-Related Disorders - psychology</topic><topic>Withdrawal</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Ming-Chyi</creatorcontrib><creatorcontrib>Chen, Chun-Hsin</creatorcontrib><creatorcontrib>Chen, Lian-Yu</creatorcontrib><creatorcontrib>Chang, Hu-Ming</creatorcontrib><creatorcontrib>Chen, Chih-Ken</creatorcontrib><creatorcontrib>Lin, Shih-Ku</creatorcontrib><creatorcontrib>Xu, Ke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Psychology Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><jtitle>Psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Ming-Chyi</au><au>Chen, Chun-Hsin</au><au>Chen, Lian-Yu</au><au>Chang, Hu-Ming</au><au>Chen, Chih-Ken</au><au>Lin, Shih-Ku</au><au>Xu, Ke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation</atitle><jtitle>Psychopharmacology</jtitle><stitle>Psychopharmacology</stitle><addtitle>Psychopharmacology (Berl)</addtitle><date>2020</date><risdate>2020</risdate><volume>237</volume><issue>1</issue><spage>45</spage><epage>53</epage><pages>45-53</pages><issn>0033-3158</issn><eissn>1432-2072</eissn><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.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31377886</pmid><doi>10.1007/s00213-019-05342-9</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5123-0389</orcidid></addata></record> |
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| ispartof | Psychopharmacology, 2020, Vol.237 (1), p.45-53 |
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| language | eng |
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| subjects | Abstinence ACTH Addictions Adrenal glands Adrenocorticotropic hormone Adrenocorticotropic Hormone - metabolism Adult Anxiety Anxiety - metabolism Biomedical and Life Sciences Biomedicine Case-Control Studies Corticosteroids Cortisol Craving - physiology Depression, Mental Depressive Disorder - metabolism Drug abuse Female Hormones Humans Hydrocortisone - metabolism Hypothalamo-Hypophyseal System - metabolism Hypothalamus Ketamine Ketamine - adverse effects Male Medical colleges Medical research Medicine, Experimental Mental depression Middle Aged Neurosciences Orexins Orexins - metabolism Original Investigation Pharmacology/Toxicology Phenotypes Pituitary Pituitary-Adrenal System - metabolism Psychiatric Status Rating Scales Psychiatry Reinforcement Stress Stress response Substance Withdrawal Syndrome - metabolism Substance-Related Disorders - metabolism Substance-Related Disorders - psychology Withdrawal |
| title | Chronic ketamine abuse is associated with orexin-A reduction and ACTH elevation |
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