Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances
There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter...
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| Veröffentlicht in: | The Journal of neuroscience 2009-11, Vol.29 (47), p.14764-14769 |
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| creator | Ren, Yanhua Whittard, John Higuera-Matas, Alejandro Morris, Claudia V Hurd, Yasmin L |
| description | There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse. |
| doi_str_mv | 10.1523/JNEUROSCI.4291-09.2009 |
| format | Article |
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Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.</description><identifier>ISSN: 0270-6474</identifier><identifier>ISSN: 1529-2401</identifier><identifier>EISSN: 1529-2401</identifier><identifier>DOI: 10.1523/JNEUROSCI.4291-09.2009</identifier><identifier>PMID: 19940171</identifier><language>eng</language><publisher>United States: Soc Neuroscience</publisher><subject>Animals ; Brief Communications ; Cannabidiol - pharmacology ; Cannabidiol - therapeutic use ; Cannabinoid Receptor Modulators - metabolism ; Conditioning, Psychological - drug effects ; Conditioning, Psychological - physiology ; Cues ; Disease Models, Animal ; Glutamic Acid - metabolism ; Heroin - adverse effects ; Heroin Dependence - drug therapy ; Heroin Dependence - metabolism ; Heroin Dependence - physiopathology ; Limbic System - drug effects ; Limbic System - metabolism ; Limbic System - physiopathology ; Male ; Narcotic Antagonists - pharmacology ; Narcotics - adverse effects ; Neural Pathways - drug effects ; Neural Pathways - metabolism ; Neural Pathways - physiopathology ; Nucleus Accumbens - drug effects ; Nucleus Accumbens - metabolism ; Nucleus Accumbens - physiopathology ; Rats ; Rats, Long-Evans ; Receptor, Cannabinoid, CB1 - drug effects ; Receptor, Cannabinoid, CB1 - metabolism ; Receptors, AMPA - drug effects ; Receptors, AMPA - metabolism ; Treatment Outcome ; Ventral Tegmental Area - drug effects ; Ventral Tegmental Area - metabolism ; Ventral Tegmental Area - physiopathology</subject><ispartof>The Journal of neuroscience, 2009-11, Vol.29 (47), p.14764-14769</ispartof><rights>Copyright © 2009 Society for Neuroscience 0270-6474/09/2914764-06$15.00/0 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-a0de6436a6c143f6814de9fc0ec8ab936fbe125c8e30d9cabfb4b4505da1a51d3</citedby><cites>FETCH-LOGICAL-c499t-a0de6436a6c143f6814de9fc0ec8ab936fbe125c8e30d9cabfb4b4505da1a51d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829756/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829756/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19940171$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ren, Yanhua</creatorcontrib><creatorcontrib>Whittard, John</creatorcontrib><creatorcontrib>Higuera-Matas, Alejandro</creatorcontrib><creatorcontrib>Morris, Claudia V</creatorcontrib><creatorcontrib>Hurd, Yasmin L</creatorcontrib><title>Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances</title><title>The Journal of neuroscience</title><addtitle>J Neurosci</addtitle><description>There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. The findings highlight the unique contributions of distinct cannabis constituents to addiction vulnerability and suggest that CBD may be a potential treatment for heroin craving and relapse.</description><subject>Animals</subject><subject>Brief Communications</subject><subject>Cannabidiol - pharmacology</subject><subject>Cannabidiol - therapeutic use</subject><subject>Cannabinoid Receptor Modulators - metabolism</subject><subject>Conditioning, Psychological - drug effects</subject><subject>Conditioning, Psychological - physiology</subject><subject>Cues</subject><subject>Disease Models, Animal</subject><subject>Glutamic Acid - metabolism</subject><subject>Heroin - adverse effects</subject><subject>Heroin Dependence - drug therapy</subject><subject>Heroin Dependence - metabolism</subject><subject>Heroin Dependence - physiopathology</subject><subject>Limbic System - drug effects</subject><subject>Limbic System - metabolism</subject><subject>Limbic System - physiopathology</subject><subject>Male</subject><subject>Narcotic Antagonists - pharmacology</subject><subject>Narcotics - adverse effects</subject><subject>Neural Pathways - drug effects</subject><subject>Neural Pathways - metabolism</subject><subject>Neural Pathways - physiopathology</subject><subject>Nucleus Accumbens - drug effects</subject><subject>Nucleus Accumbens - metabolism</subject><subject>Nucleus Accumbens - physiopathology</subject><subject>Rats</subject><subject>Rats, Long-Evans</subject><subject>Receptor, Cannabinoid, CB1 - drug effects</subject><subject>Receptor, Cannabinoid, CB1 - metabolism</subject><subject>Receptors, AMPA - drug effects</subject><subject>Receptors, AMPA - metabolism</subject><subject>Treatment Outcome</subject><subject>Ventral Tegmental Area - drug effects</subject><subject>Ventral Tegmental Area - metabolism</subject><subject>Ventral Tegmental Area - physiopathology</subject><issn>0270-6474</issn><issn>1529-2401</issn><issn>1529-2401</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1u1DAUhS0EokPhFSrvYNEMduLE8QYJhdIOKlOJ0rXl2DczhsRO7YRR-xg8MR7NqMDqLs53z_05CJ1RsqRlXrz_sr64-3Zz26yWLBc0I2KZEyKeoUVSRZYzQp-jBck5ySrG2Ql6FeMPQggnlL9EJ1SIRHC6QL8b5ZxqrbG-P8cKr70b44Pe-in40Wrc-GH0DtyEfYePbDzHK7e1rZ0ibmbIVs7MGgy-guCtw7cAP63bYOVMsguD6u0jRPzJRh1gAvwVou_t0Cb3NczBO9XvxWkOrXIa4mv0olN9hDfHeoruPl98b66y65vLVfPxOtNMiClTxEDFikpVmrKiq2rKDIhOE9C1akVRdS3QvNQ1FMQIrdquZS0rSWkUVSU1xSn6cPAd53YAo9ORQfVyDHZQ4UF6ZeX_irNbufG_ZF7ngpdVMnh7NAj-foY4ySHdCH2vHPg5Sl4UpC7LmieyOpA6-BgDdE9TKJH7POVTnnKfpyRC7vNMjWf_7vi37RhgAt4dgK3dbHc2gIzp4X3CqdztdrmQjEvKePrUH9Lkr7U</recordid><startdate>20091125</startdate><enddate>20091125</enddate><creator>Ren, Yanhua</creator><creator>Whittard, John</creator><creator>Higuera-Matas, Alejandro</creator><creator>Morris, Claudia V</creator><creator>Hurd, Yasmin L</creator><general>Soc Neuroscience</general><general>Society for Neuroscience</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091125</creationdate><title>Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances</title><author>Ren, Yanhua ; Whittard, John ; Higuera-Matas, Alejandro ; Morris, Claudia V ; Hurd, Yasmin L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-a0de6436a6c143f6814de9fc0ec8ab936fbe125c8e30d9cabfb4b4505da1a51d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Brief Communications</topic><topic>Cannabidiol - pharmacology</topic><topic>Cannabidiol - therapeutic use</topic><topic>Cannabinoid Receptor Modulators - metabolism</topic><topic>Conditioning, Psychological - drug effects</topic><topic>Conditioning, Psychological - physiology</topic><topic>Cues</topic><topic>Disease Models, Animal</topic><topic>Glutamic Acid - metabolism</topic><topic>Heroin - adverse effects</topic><topic>Heroin Dependence - drug therapy</topic><topic>Heroin Dependence - metabolism</topic><topic>Heroin Dependence - physiopathology</topic><topic>Limbic System - drug effects</topic><topic>Limbic System - metabolism</topic><topic>Limbic System - physiopathology</topic><topic>Male</topic><topic>Narcotic Antagonists - pharmacology</topic><topic>Narcotics - adverse effects</topic><topic>Neural Pathways - drug effects</topic><topic>Neural Pathways - metabolism</topic><topic>Neural Pathways - physiopathology</topic><topic>Nucleus Accumbens - drug effects</topic><topic>Nucleus Accumbens - metabolism</topic><topic>Nucleus Accumbens - physiopathology</topic><topic>Rats</topic><topic>Rats, Long-Evans</topic><topic>Receptor, Cannabinoid, CB1 - drug effects</topic><topic>Receptor, Cannabinoid, CB1 - metabolism</topic><topic>Receptors, AMPA - drug effects</topic><topic>Receptors, AMPA - metabolism</topic><topic>Treatment Outcome</topic><topic>Ventral Tegmental Area - drug effects</topic><topic>Ventral Tegmental Area - metabolism</topic><topic>Ventral Tegmental Area - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ren, Yanhua</creatorcontrib><creatorcontrib>Whittard, John</creatorcontrib><creatorcontrib>Higuera-Matas, Alejandro</creatorcontrib><creatorcontrib>Morris, Claudia V</creatorcontrib><creatorcontrib>Hurd, Yasmin L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ren, Yanhua</au><au>Whittard, John</au><au>Higuera-Matas, Alejandro</au><au>Morris, Claudia V</au><au>Hurd, Yasmin L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances</atitle><jtitle>The Journal of neuroscience</jtitle><addtitle>J Neurosci</addtitle><date>2009-11-25</date><risdate>2009</risdate><volume>29</volume><issue>47</issue><spage>14764</spage><epage>14769</epage><pages>14764-14769</pages><issn>0270-6474</issn><issn>1529-2401</issn><eissn>1529-2401</eissn><abstract>There remains debate regarding the impact of cannabis on neuropsychiatric disorders. Here, we examined the effects of cannabidiol (CBD), a nonpsychoactive constituent of cannabis, on heroin self-administration and drug-seeking behavior using an experimental rat model. CBD (5-20 mg/kg) did not alter stable intake of heroin self-administration, extinction behavior, or drug seeking induced by a heroin prime injection. Instead, it specifically attenuated heroin-seeking behavior reinstated by exposure to a conditioned stimulus cue. CBD had a protracted effect with significance evident after 24 h and even 2 weeks after administration. The behavioral effects were paralleled by neurobiological alterations in the glutamatergic and endocannabinoid systems. Discrete disturbances of AMPA GluR1 and cannabinoid type-1 receptor expression observed in the nucleus accumbens associated with stimulus cue-induced heroin seeking were normalized by CBD treatment. 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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Brief Communications Cannabidiol - pharmacology Cannabidiol - therapeutic use Cannabinoid Receptor Modulators - metabolism Conditioning, Psychological - drug effects Conditioning, Psychological - physiology Cues Disease Models, Animal Glutamic Acid - metabolism Heroin - adverse effects Heroin Dependence - drug therapy Heroin Dependence - metabolism Heroin Dependence - physiopathology Limbic System - drug effects Limbic System - metabolism Limbic System - physiopathology Male Narcotic Antagonists - pharmacology Narcotics - adverse effects Neural Pathways - drug effects Neural Pathways - metabolism Neural Pathways - physiopathology Nucleus Accumbens - drug effects Nucleus Accumbens - metabolism Nucleus Accumbens - physiopathology Rats Rats, Long-Evans Receptor, Cannabinoid, CB1 - drug effects Receptor, Cannabinoid, CB1 - metabolism Receptors, AMPA - drug effects Receptors, AMPA - metabolism Treatment Outcome Ventral Tegmental Area - drug effects Ventral Tegmental Area - metabolism Ventral Tegmental Area - physiopathology |
| title | Cannabidiol, a Nonpsychotropic Component of Cannabis, Inhibits Cue-Induced Heroin Seeking and Normalizes Discrete Mesolimbic Neuronal Disturbances |
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