Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review
<b>Background/Objectives</b>: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pat...
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2024-11-01
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| Series: | Metabolites |
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| author | Lindsey Contella Christopher L. Farrell Luigi Boccuto Alain H. Litwin Marion L. Snyder |
| author_facet | Lindsey Contella Christopher L. Farrell Luigi Boccuto Alain H. Litwin Marion L. Snyder |
| author_sort | Lindsey Contella |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pathways. The metabolites of these pathways play a role in the biological reward system. Addictive substances have been shown to cause imbalances in the ratios of these metabolites. With current treatment and therapeutic options being suboptimal, identifying biochemical mechanisms that are impacted during the use of addictive substances can provide alternative options for treatment or drug discovery. <b>Methods</b>: A systematic literature search was conducted to identify studies evaluating the relationship between substance use disorder and tryptophan metabolism through the kynurenine pathway. A total of 32 articles meeting eligibility criteria were used to review the relationship between the kynurenine pathway, tryptophan breakdown, and addictive substances. <b>Results:</b> The use of addictive substances dysregulates tryptophan metabolism and kynurenine metabolite concentrations. This imbalance directly affects the dopamine reward system and is thought to promote continued substance use. <b>Conclusions:</b> Further studies are needed to fully evaluate the metabolites of the kynurenine pathway, along with other options for treatment to repair the metabolite imbalance. Several possible therapeutics have been identified; drugs that restore homeostasis, such as Ro 61-8048 and natural products like <i>Tinospora cordifolia</i> or <i>Decaisnea insignis</i>, are promising options for the treatment of substance use disorder. |
| format | Article |
| id | doaj-art-d24943a1e23a4c5ca1b6b6eeb8b38336 |
| institution | DOAJ |
| issn | 2218-1989 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Metabolites |
| spelling | doaj-art-d24943a1e23a4c5ca1b6b6eeb8b383362025-08-20T02:48:06ZengMDPI AGMetabolites2218-19892024-11-01141161110.3390/metabo14110611Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative ReviewLindsey Contella0Christopher L. Farrell1Luigi Boccuto2Alain H. Litwin3Marion L. Snyder4Healthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USAHealthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USAHealthcare Genetics and Genomics, School of Nursing, Clemson University, 605 Grove Rd., Greenville, SC 29605, USASchool of Health Research, Clemson University, Clemson, SC 29631, USALuxor Scientific, LLC, 1327 Miller Rd., Greenville, SC 29607, USA<b>Background/Objectives</b>: Substance use disorder is a crisis impacting many people in the United States. This review aimed to identify the effect addictive substances have on the kynurenine pathway. Tryptophan is an essential amino acid metabolized by the serotonin and kynurenine pathways. The metabolites of these pathways play a role in the biological reward system. Addictive substances have been shown to cause imbalances in the ratios of these metabolites. With current treatment and therapeutic options being suboptimal, identifying biochemical mechanisms that are impacted during the use of addictive substances can provide alternative options for treatment or drug discovery. <b>Methods</b>: A systematic literature search was conducted to identify studies evaluating the relationship between substance use disorder and tryptophan metabolism through the kynurenine pathway. A total of 32 articles meeting eligibility criteria were used to review the relationship between the kynurenine pathway, tryptophan breakdown, and addictive substances. <b>Results:</b> The use of addictive substances dysregulates tryptophan metabolism and kynurenine metabolite concentrations. This imbalance directly affects the dopamine reward system and is thought to promote continued substance use. <b>Conclusions:</b> Further studies are needed to fully evaluate the metabolites of the kynurenine pathway, along with other options for treatment to repair the metabolite imbalance. Several possible therapeutics have been identified; drugs that restore homeostasis, such as Ro 61-8048 and natural products like <i>Tinospora cordifolia</i> or <i>Decaisnea insignis</i>, are promising options for the treatment of substance use disorder.https://www.mdpi.com/2218-1989/14/11/611kynurenine pathwaytryptophansubstance use disorder |
| spellingShingle | Lindsey Contella Christopher L. Farrell Luigi Boccuto Alain H. Litwin Marion L. Snyder Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review Metabolites kynurenine pathway tryptophan substance use disorder |
| title | Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review |
| title_full | Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review |
| title_fullStr | Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review |
| title_full_unstemmed | Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review |
| title_short | Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review |
| title_sort | impact of substance use disorder on tryptophan metabolism through the kynurenine pathway a narrative review |
| topic | kynurenine pathway tryptophan substance use disorder |
| url | https://www.mdpi.com/2218-1989/14/11/611 |
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