Warning: file_put_contents(/opt/frankenphp/design.onmedianet.com/storage/proxy/cache/886e79fb8ac6f091b48d3aec3ec46f6c.html): Failed to open stream: No space left on device in /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php on line 36

Warning: http_response_code(): Cannot set response code - headers already sent (output started at /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php:36) in /opt/frankenphp/design.onmedianet.com/app/src/Models/Response.php on line 17

Warning: Cannot modify header information - headers already sent by (output started at /opt/frankenphp/design.onmedianet.com/app/src/Arsae/CacheManager.php:36) in /opt/frankenphp/design.onmedianet.com/app/src/Models/Response.php on line 20
DARK Classics in Chemical Neuroscience: Cocaine | ACS Chemical Neuroscience
    Review

    DARK Classics in Chemical Neuroscience: Cocaine
    Click to copy article linkArticle link copied!

    • Lindsey R. Drake
      Lindsey R. Drake
      Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States
      Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48105, United States
    • Peter J. H. Scott*
      Peter J. H. Scott
      Department of Radiology, University of Michigan Medical School, Ann Arbor, Michigan 48109, United States
      Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan 48105, United States
      *E-mail: [email protected]
    Other Access Options

    ACS Chemical Neuroscience

    Cite this: ACS Chem. Neurosci. 2018, 9, 10, 2358–2372
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschemneuro.8b00117
    Published April 9, 2018
    Copyright © 2018 American Chemical Society

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    In this Review, we consider the story of cocaine from its humble origins in South America to its status as one of the most abused substances in 21st century society. The synthesis and biosynthesis of cocaine are discussed, as well as its pharmacokinetics, metabolism, pharmacology, and importance in modern neuroscience and molecular imaging.

    Copyright © 2018 American Chemical Society

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 61 publications.

    1. Sofiane Hocine, Edouard Duchamp, Akash Mishra, Jean-Marie Fourquez, Stephen Hanessian. Synthesis of Aza-Bridged Perhydroazulene Chimeras of Tropanes and Hederacine A. The Journal of Organic Chemistry 2023, 88 (7) , 4675-4686. https://doi.org/10.1021/acs.joc.3c00169
    2. Robert J. Tombari, Paige C. Mundy, Kelly M. Morales, Lee E. Dunlap, David E. Olson, Pamela J. Lein. Developmental Neurotoxicity Screen of Psychedelics and Other Drugs of Abuse in Larval Zebrafish (Danio rerio). ACS Chemical Neuroscience 2023, 14 (5) , 875-884. https://doi.org/10.1021/acschemneuro.2c00642
    3. Chencheng Fu, Wanna Sungnoi, Jianzhuo Tu, Steven P. Kelley, Michael Harmata. Tropane Skeleta from the Intramolecular Photocycloaddition of (4+3) Cycloadducts of Oxidopyridinium Ions and Dienes. Organic Letters 2022, 24 (19) , 3521-3525. https://doi.org/10.1021/acs.orglett.2c01228
    4. Merel Dagher, Katie A. Perrotta, Sara A. Erwin, Ayaka Hachisuka, Rahul Iyer, Sotiris C. Masmanidis, Hongyan Yang, Anne M. Andrews. Optogenetic Stimulation of Midbrain Dopamine Neurons Produces Striatal Serotonin Release. ACS Chemical Neuroscience 2022, 13 (7) , 946-958. https://doi.org/10.1021/acschemneuro.1c00715
    5. Trevor A. Trombley, Rory A. Capstick, Craig W. Lindsley. DARK Classics in Chemical Neuroscience: Gamma-Hydroxybutyrate (GHB). ACS Chemical Neuroscience 2020, 11 (23) , 3850-3859. https://doi.org/10.1021/acschemneuro.9b00336
    6. Nicolas Garel, Kyle T. Greenway, Paola Lavin, C. William Pike, Rebecca Hyde, Didier Jutras-Aswad, Steven D. Tate, Anna Lembke. Increased Risks of Major Cardiac Adverse Events in Stimulant Use Disorder as Compared With Other Substance Use Disorders: A Propensity-score Matching Cohort Study. Journal of Addiction Medicine 2025, 19 (5) , 599-604. https://doi.org/10.1097/ADM.0000000000001461
    7. Candela R. González, Betina González. Paternal Cocaine Exposure and Its Testicular Legacy: Epigenetic, Physiological, and Intergenerational Consequences. Biology 2025, 14 (8) , 1072. https://doi.org/10.3390/biology14081072
    8. Beimnet B. Kassaye, Alexis N. Jameson, Katherine Moore, Douglas G. McMahon, Brad A. Grueter. Identification of photoperiod as a regulator of dopamine-mediated behavior in female mice. Neurobiology of Sleep and Circadian Rhythms 2025, 28 , 100135. https://doi.org/10.1016/j.nbscr.2025.100135
    9. Khalid Seedahmed, Malaz Kamaleldin Omer, Mohammed Osman. Midline Destructive Lesions: Differentiating Granulomatosis With Polyangiitis From Cocaine-Induced Perforations. Cureus 2025, 2 https://doi.org/10.7759/cureus.83425
    10. A. Fleming, P. Wescombe, P. Gregorini. Review: A vade-mecum for ruminant grazing and health. animal 2025, 73 , 101548. https://doi.org/10.1016/j.animal.2025.101548
    11. Maria Hrickova, Jana Ruda-Kucerova. Do AMPA/kainate antagonists possess potential in the treatment of addiction? Evidence from animal behavioural studies. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2025, 138 , 111355. https://doi.org/10.1016/j.pnpbp.2025.111355
    12. Oleg Lukin, Alexander Shivanyuk, Grygoriy Dolgonos, Andrii Gerasov, Aleksandr Mandzhulo, Volodymyr Fetyukhin. Spirocyclizations of Nortropanes. Synthesis 2025, 57 (08) , 1375-1401. https://doi.org/10.1055/a-2503-2459
    13. Luciano Chaves Arantes, Dâmaris Silveira, Gabriel Magno Sousa de Azerêdo, Omar Enrique Estrada Semprun, Aline Lima de Oliveira, Luiz Eduardo Celino Benedito, Luciano Morais Lião, Gerlon de Almeida Ribeiro Oliveira. Enhancing Forensic Laboratories Through University Collaboration: Obtaining Conclusive Reports and Reference Materials via NMR. Magnetic Resonance in Chemistry 2025, 63 (2) , 155-166. https://doi.org/10.1002/mrc.5497
    14. Priya Koley, Poojitha Jain, Kiran S. Mawale, Parvatam Giridhar. Cocaine: A Stimulant Tropane Alkaloid Drug and Its Regulation. 2025, 267-283. https://doi.org/10.1007/978-981-96-5805-3_13
    15. Seetal Dodd, Laura Ospina-Pinillos, John S. Markowitz. Central nervous system stimulants in recreational and medical use. CNS Spectrums 2025, 30 (1) https://doi.org/10.1017/S1092852925100357
    16. Pingyang Liu, Zhanfang Liu, Hong Zhou, Jun Zhu, Zhenwen Sun, Guannan Zhang, Yao Liu. Lipidomics in forensic science: a comprehensive review of applications in drugs, alcohol, latent fingermarks, fire debris, and seafood authentication. Molecular Omics 2024, 20 (10) , 618-629. https://doi.org/10.1039/D4MO00124A
    17. Marta Armentano, Ludovico Alisi, Giacomo Visioli, Maria Carmela Saturno, Arianna Barba, Alessio Speranzini, Giuseppe Maria Albanese, Magda Gharbiya, Ludovico Iannetti. Retinal Vascular Complications in Cocaine Abuse: A Case Report and a Literature Review. Journal of Clinical Medicine 2024, 13 (24) , 7838. https://doi.org/10.3390/jcm13247838
    18. Jia‐Yi Wei, Hui Liu, Yuan Li, Dan Zhao, Bo Wang, Hui‐Jie Wang, Li Wang, Kang‐Ji Wang, Jin‐Li Yue, Hong‐Yan Zhang, Tian‐Yue Li, Yi‐Jue Miao, Kai‐Li Wang, Pai‐Ge Tong, Zhuo Zhang, Ze‐Ye Li, Zheng Shi, Jia‐Yuan Yao, Dong‐Xin Liu, Wen‐Gang Fang, Bo Li, De‐Shu Shang, Yuan Lyu, Hong‐Zan Sun, Wei‐Dong Zhao, Yu‐Hua Chen. Melatonin Protects Against Cocaine‐Induced Blood−Brain Barrier Dysfunction and Cognitive Impairment by Regulating miR‐320a‐Dependent GLUT1 Expression. Journal of Pineal Research 2024, 76 (8) https://doi.org/10.1111/jpi.70002
    19. Crist N. Filer. A synthesis of [3H] cocaine at high specific activity. Journal of Radioanalytical and Nuclear Chemistry 2024, 333 (10) , 4869-4872. https://doi.org/10.1007/s10967-024-09589-1
    20. Killian C. O'Connell, Mariana B. Almeida, Renna L. Nouwairi, Emmet T. Costen, Nicola K. Lawless, Maura E. Charette, Brennan M. Stewart, Suzana L. Nixdorf, James P. Landers. Microwave-assisted extraction, separation, and chromogenic detection of laced marijuana for presumptive point-of-interdiction testing. Lab on a Chip 2024, 24 (18) , 4403-4421. https://doi.org/10.1039/D4LC00223G
    21. Erin Lange, Felicity Carlysle-Davies. Presumptive drug identification by ninhydrin fingerprint analysis. Forensic Chemistry 2024, 40 , 100597. https://doi.org/10.1016/j.forc.2024.100597
    22. Marko Milojević, Tina Maver, Uroš Maver. Farmakodinamika psihoaktivnih učinkovin in mehanizmi odvisnosti. 2024, 37-48. https://doi.org/10.18690/um.mf.4.2024.5
    23. Francisco J. Appiani, Stanley N. Caroff. The cyclical revival of psychedelics in psychiatric treatment. Current Medical Research and Opinion 2024, 40 (8) , 1389-1396. https://doi.org/10.1080/03007995.2024.2368725
    24. Reece M. Hass, Derek Stitt. Neurological Effects of Stimulants and Hallucinogens. Seminars in Neurology 2024, 44 (04) , 459-470. https://doi.org/10.1055/s-0044-1787572
    25. Manuel Glauco Carbone, Icro Maremmani. Chronic Cocaine Use and Parkinson’s Disease: An Interpretative Model. International Journal of Environmental Research and Public Health 2024, 21 (8) , 1105. https://doi.org/10.3390/ijerph21081105
    26. Andres Angel Calderon-Garcia, Mercedes Sánchez-Barba, Veronica Gonzalez-Nunez. Exposure of Zebrafish Embryos to Morphine and Cocaine Induces Changes in the Levels of Dopamine and of Proteins Related to the Reward Pathway. Fishes 2024, 9 (7) , 268. https://doi.org/10.3390/fishes9070268
    27. Consuelo Castillo-Toledo, Oscar Fraile-Martínez, Carolina Donat-Vargas, F. J. Lara-Abelenda, Miguel Angel Ortega, Cielo Garcia-Montero, Fernando Mora, Melchor Alvarez-Mon, Javier Quintero, Miguel Angel Alvarez-Mon. Insights from the Twittersphere: a cross-sectional study of public perceptions, usage patterns, and geographical differences of tweets discussing cocaine. Frontiers in Psychiatry 2024, 15 https://doi.org/10.3389/fpsyt.2024.1282026
    28. John P. Gallagher, Patrick A. Twohig, Agnes Crnic, Fedja A. Rochling. Illicit Drugs and Candidates for Endoscopy and Surgery. 2024, 127-144. https://doi.org/10.1007/978-3-031-56270-9_8
    29. Luan Luong Chu, Linh Quyen My, Huy Nguyen Quang. Microbial alkaloids and their pharmaceutical and agricultural application. 2024, 73-90. https://doi.org/10.1016/B978-0-323-95241-5.00018-6
    30. Vishnu Vardhan Byroju, Jamir Pitton Rissardo, Ícaro Durante, Ana Letícia Fornari Caprara. Cocaine-induced Movement Disorder: A Literature Review. Prague Medical Report 2024, 125 (3) , 195-219. https://doi.org/10.14712/23362936.2024.19
    31. Lindsay Glicksberg, Brittany K. Casey, Sara K. Dempsey. Classical stimulants in Dallas County: A retrospective review of toxicological, seized drug, and demographical data from 2017 to 2022. Journal of Forensic Sciences 2023, 68 (6) , 2093-2102. https://doi.org/10.1111/1556-4029.15373
    32. James Chmiel, Justyna Chojdak-Łukasiewicz, Jerzy Leszek. The Effect of Transcranial Direct Current Stimulation (tDCS) on Cocaine Addiction: A Narrative Review. Journal of Clinical Medicine 2023, 12 (20) , 6511. https://doi.org/10.3390/jcm12206511
    33. Ryoichi Fujiwara, Megan Journey, Fatimah Al-Doori, Paris Bell, Brahmjot Judge, Kamille Miracle, Kousei Ito, Sabrina Jones. Potential neonatal toxicity of new psychoactive substances. Pharmacology & Therapeutics 2023, 248 , 108468. https://doi.org/10.1016/j.pharmthera.2023.108468
    34. Andrew T. Hodge, Robert Strayhan, Suporn Sukpraprut-Braaten. Systematic Review: Is There a Medicinal Use of Cocaine in Psychiatry?. Current Treatment Options in Psychiatry 2023, 10 (1) , 50-58. https://doi.org/10.1007/s40501-023-00285-7
    35. Gabriela de Paula Meirelles, André Luis Fabris, Karina Ferreira dos Santos, José Luiz Costa, Mauricio Yonamine. Green Analytical Toxicology for the Determination of Cocaine Metabolites. Journal of Analytical Toxicology 2023, 46 (9) , 965-978. https://doi.org/10.1093/jat/bkac005
    36. Radomir Juza, Kamil Musilek, Eva Mezeiova, Ondrej Soukup, Jan Korabecny. Recent advances in dopamine D 2 receptor ligands in the treatment of neuropsychiatric disorders. Medicinal Research Reviews 2023, 43 (1) , 55-211. https://doi.org/10.1002/med.21923
    37. John P. Gallagher, Patrick A. Twohig, Agnes Crnic, Fedja A. Rochling. Illicit Drug Use and Endoscopy: When Do We Say No?. Digestive Diseases and Sciences 2022, 67 (12) , 5371-5381. https://doi.org/10.1007/s10620-022-07619-0
    38. Yulian Lv, Tian Tian, Yong-Jiang Wang, Jian-Ping Huang, Sheng-Xiong Huang. Advances in chemistry and bioactivity of the genus Erythroxylum. Natural Products and Bioprospecting 2022, 12 (1) https://doi.org/10.1007/s13659-022-00338-z
    39. Kathryn Burton, Niamh Nic Daeid, Oluwasesan Adegoke. Surface plasmon-enhanced aptamer-based fluorescence detection of cocaine using hybrid nanostructure of cadmium-free ZnSe/In2S3 core/shell quantum dots and gold nanoparticles. Journal of Photochemistry and Photobiology A: Chemistry 2022, 433 , 114131. https://doi.org/10.1016/j.jphotochem.2022.114131
    40. Andrés Angel Calderon-Garcia, Maria Perez-Fernandez, Daniel Curto-Aguilera, Ivan Rodriguez-Martin, Mercedes Sánchez-Barba, Veronica Gonzalez-Nunez. Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos. Neuroscience 2022, 507 , 14-27. https://doi.org/10.1016/j.neuroscience.2022.10.017
    41. Zhiwen Shi, Wenjin Zou, Zhiming Zhu, Ziwen Xiong, Shanying Li, Pan Dong, Zhenglin Zhu. Tropane alkaloids (hyoscyamine, scopolamine and atropine) from genus Datura: extractions, contents, syntheses and effects. Industrial Crops and Products 2022, 186 , 115283. https://doi.org/10.1016/j.indcrop.2022.115283
    42. Luke R. Gagnon, Chandu Sadasivan, Kevin Perera, Gavin Y. Oudit. Cardiac Complications of Common Drugs of Abuse: Pharmacology, Toxicology, and Management. Canadian Journal of Cardiology 2022, 38 (9) , 1331-1341. https://doi.org/10.1016/j.cjca.2021.10.008
    43. Flávia Sirotheau Corrêa Pontes, Rosa Hiolanda Abreu de Souza, Franciely Araujo Moura, Glauce Guimarães Pereira, Diogo de Vasconcelos Macedo, Gabrielle Bastos Machado Ferreira, Vitória Lacerda Santos, Carolina Cavalieri Gomes, Hélder Antônio Rebelo Pontes. Necrotic lesion in the palate. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 2022, 134 (2) , 120-123. https://doi.org/10.1016/j.oooo.2021.09.013
    44. Olga Lucía Murillo-García, Marie Claire Berrouet-Mejía. La N-acetilcisteína como coadyuvante en el manejo del craving por cocaína y tabaco. Revisión narrativa. Revista de la Facultad de Ciencias de la Salud Universidad del Cauca 2022, 24 (2) , 24-31. https://doi.org/10.47373/rfcs.2022.v24.2119
    45. Jinghan Dang, Qiuying Tao, Xiaoyu Niu, Mengzhe Zhang, Xinyu Gao, Zhengui Yang, Miaomiao Yu, Weijian Wang, Shaoqiang Han, Jingliang Cheng, Yong Zhang. Meta-Analysis of Structural and Functional Brain Abnormalities in Cocaine Addiction. Frontiers in Psychiatry 2022, 13 https://doi.org/10.3389/fpsyt.2022.927075
    46. Qinghui Lan, Peiqing Guan, Chunzheng Huang, Shile Huang, Peiling Zhou, Changzheng Zhang. Arecoline Induces an Excitatory Response in Ventral Tegmental Area Dopaminergic Neurons in Anesthetized Rats. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.872212
    47. Rita Roque Bravo, Ana Carolina Faria, Andreia Machado Brito-da-Costa, Helena Carmo, Přemysl Mladěnka, Diana Dias da Silva, Fernando Remião, . Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern. Toxins 2022, 14 (4) , 278. https://doi.org/10.3390/toxins14040278
    48. Georg Niggemeyer, Anastasia Knyazeva, Raphael Gasper, Dale Corkery, Pia Bodenbinder, Julian J. Holstein, Sonja Sievers, Yao‐Wen Wu, Herbert Waldmann. Synthesis of 20‐Membered Macrocyclic Pseudo‐Natural Products Yields Inducers of LC3 Lipidation. Angewandte Chemie 2022, 134 (11) https://doi.org/10.1002/ange.202114328
    49. Georg Niggemeyer, Anastasia Knyazeva, Raphael Gasper, Dale Corkery, Pia Bodenbinder, Julian J. Holstein, Sonja Sievers, Yao‐Wen Wu, Herbert Waldmann. Synthesis of 20‐Membered Macrocyclic Pseudo‐Natural Products Yields Inducers of LC3 Lipidation. Angewandte Chemie International Edition 2022, 61 (11) https://doi.org/10.1002/anie.202114328
    50. Andrii Gerasov, Rodion Boiko, Grygoriy Dolgonos, Aleksandr Mandzhulo, Alexander Shivanyuk, Volodymyr Fetyukhin, Oleg Lukin. Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones. Synthesis 2022, 54 (03) , 723-731. https://doi.org/10.1055/s-0040-1719848
    51. Davide Cenci, Manuel Glauco Carbone, Camilla Callegari, Icro Maremmani. Psychomotor Symptoms in Chronic Cocaine Users: An Interpretative Model. International Journal of Environmental Research and Public Health 2022, 19 (3) , 1897. https://doi.org/10.3390/ijerph19031897
    52. Andreas Büttner. Grundlegende Substanzmerkmale und neuropathologische Befunde bei Drogenkonsumenten. 2022, 23-90. https://doi.org/10.1007/978-3-031-13619-1_4
    53. Zaheer Ahmad Qureshi, Elina Shrestha, Pravash Budhathoki, Haider Ghazanfar, Arundhati Dileep, Muhammad S Akhter. Drug-Induced Deafness: A Rare Case of Bilateral Sensorineural Hearing Loss Following Speedballing. Cureus 2021, 1141 https://doi.org/10.7759/cureus.20686
    54. Andreas Büttner. Basic Substance Characteristics and Neuropathological Findings in Drug Abusers. 2021, 23-87. https://doi.org/10.1007/978-3-030-60531-5_4
    55. Flávia Zacouteguy Boos, Núbia Broetto, Roberta Bristot Silvestrin. Psychopharmacology of Drugs of Abuse. 2021, 3-21. https://doi.org/10.1007/978-3-030-62106-3_1
    56. Ying Song, Rong Li. Effects of Environment and Lifestyle Factors on Anovulatory Disorder. 2021, 113-136. https://doi.org/10.1007/978-981-33-4187-6_5
    57. Danuta Kowalczyk-Pachel, Małgorzata Iciek, Anna Bilska-Wilkosz, Magdalena Górny, Joanna Jastrzębska, Kinga Kamińska, Paulina Dudzik, Małgorzata Filip, Elżbieta Lorenc-Koci. Evaluation of Cysteine Metabolism in the Rat Liver and Kidney Following Intravenous Cocaine Administration and Abstinence. Antioxidants 2021, 10 (1) , 74. https://doi.org/10.3390/antiox10010074
    58. Harald Sontheimer. Drug Addiction. 2021, 357-381. https://doi.org/10.1016/B978-0-12-821228-8.00012-3
    59. Hiroyuki Suga, Yasunori Toda. Catalytic Asymmetric 1,3-Dipolar Cycloaddition Reactions Based on Ylide Formation Reactions. Journal of Synthetic Organic Chemistry, Japan 2019, 77 (10) , 1014-1022. https://doi.org/10.5059/yukigoseikyokaishi.77.1014
    60. Hiroyuki Suga, Masahiro Yoshiwara, Takaaki Yamaguchi, Takashi Bando, Mizuki Taguchi, Ayano Inaba, Yuichi Goto, Ayaka Kikuchi, Kennosuke Itoh, Yasunori Toda. Enantioselective synthesis of 8-azabicyclo[3.2.1]octanes via asymmetric 1,3-dipolar cycloadditions of cyclic azomethine ylides using a dual catalytic system. Chemical Communications 2019, 55 (11) , 1552-1555. https://doi.org/10.1039/C8CC09224A
    61. Roland Seifert. Rethinking Pharmacological Nomenclature. Trends in Pharmacological Sciences 2018, 39 (9) , 785-797. https://doi.org/10.1016/j.tips.2018.06.006

    ACS Chemical Neuroscience

    Cite this: ACS Chem. Neurosci. 2018, 9, 10, 2358–2372
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acschemneuro.8b00117
    Published April 9, 2018
    Copyright © 2018 American Chemical Society

    Article Views

    6050

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.