Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (763 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Cocaine Hydrochloride; Hydrochloride, Cocaine; Cocaine HCl; HCl, Cocaine.
Where it fits in the MeSH classification
- Broader topics
- Tropanes
- Narrower topics
- Crack Cocaine
Research landscape
PubMed indexes 28,254 records tagged with the MeSH heading “Cocaine” (counts retrieved 2026-10-31). 2,863 of them (10.1%) were published from 2020 onward, and the busiest period so far is through 1999 with 13,253 records.
Reviews account for 2,075 records (7.3%) and meta-analyses for 61. Randomized controlled trials number 600 (2.1%) as a share of all records on the topic.
Show the data
| Period | Records |
|---|---|
| through 1999 | 13,253 |
| 2000-2009 | 6,078 |
| 2010-2019 | 6,060 |
| 2020 onward | 2,863 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 2,075 | 7.3% |
| Meta-analyses | 61 | 0.2% |
| Randomized controlled trials | 600 | 2.1% |
Method: PubMed query "Cocaine"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in drugs and chemicals
Studies of a chemical or drug can answer very different questions: what it is and how it behaves in cells and animals, how the body handles it, and whether it changes outcomes in people. Laboratory and animal findings often do not carry over to patients, and observational studies of exposures are confounded by who uses a substance and why. Nothing on this page is a recommendation to use, avoid, start or stop any substance or medicine; talk to a qualified clinician or pharmacist about your own situation. Check the dose, the species, the comparison group and whether a patient-relevant outcome was measured.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor [1]
Abstract reading summary — source excerpts
- Opening excerpt
- The development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult.
- Closing excerpt
- Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (153 words)
The development of genetically encoded dopamine sensors such as dLight has provided a new approach to measuring slow and fast dopamine dynamics both in brain slices and in vivo, possibly enabling dopamine measurements in areas like the dorsolateral striatum (DLS) where previously such recordings with fast-scan cyclic voltammetry (FSCV) were difficult. To test this, we first evaluated dLight photometry in mouse brain slices with simultaneous FSCV and found that both techniques yielded comparable results, but notable differences in responses to dopamine transporter inhibitors, including cocaine. We then used in vivo fiber photometry with dLight in mice to examine responses to cocaine in DLS. We also compared dopamine responses during Pavlovian conditioning across the striatum. We show that dopamine increases were readily detectable in DLS and describe transient dopamine kinetics, as well as slowly developing signals during conditioning. Overall, our findings indicate that dLight photometry is well suited to measuring dopamine dynamics in DLS.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37739964 · DOI · PMC10517008
An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate cocaine seeking.
- Closing excerpt
- Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (158 words)
Recent studies show that systemic administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist is sufficient to attenuate cocaine seeking. However, the neural mechanisms mediating these effects and the role of endogenous central GLP-1 signaling in cocaine seeking remain unknown. Here, we show that voluntary cocaine taking decreased plasma GLP-1 levels in rats and that chemogenetic activation of GLP-1-producing neurons in the nucleus tractus solitarius that project to the ventral tegmental area (VTA) decreased cocaine seeking. Single-nuclei transcriptomics and FISH studies revealed that GLP-1Rs are expressed primarily on GABA neurons in the VTA. Using in vivo fiber photometry, we found that the efficacy of a systemic GLP-1R agonist to attenuate cocaine seeking was associated with increased activity of VTA GABA neurons and decreased activity of VTA dopamine neurons. Together, these findings suggest that targeting central GLP-1 circuits may be an effective strategy toward reducing cocaine relapse and highlight a functional role of GABAergic GLP-1R-expressing midbrain neurons in drug seeking.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40009667 · DOI · PMC11864183
Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences.
- Closing excerpt
- Furthermore, our results highlight sex differences in resilience to addiction-like behaviors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (224 words)
Addiction is commonly characterized by escalation of drug intake, compulsive drug seeking, and continued use despite harmful consequences. However, the factors contributing to the transition from moderate drug use to these problematic patterns remain unclear, particularly regarding the role of sex. Many preclinical studies have been limited by small sample sizes, low genetic diversity, and restricted drug access, making it challenging to model significant levels of intoxication or dependence and translate findings to humans. To address these limitations, we characterized addiction-like behaviors in a large sample of >500 outbred heterogeneous stock (HS) rats using an extended cocaine self-administration paradigm (6 hr/daily). We analyzed individual differences in escalation of intake, progressive ratio (PR) responding, continued use despite adverse consequences (contingent foot shocks), and irritability-like behavior during withdrawal. Principal component analysis showed that escalation of intake, progressive ratio responding, and continued use despite adverse consequences loaded onto a single factor that was distinct from irritability-like behaviors. Categorizing rats into resilient, mild, moderate, and severe addiction-like phenotypes showed that females exhibited higher addiction-like behaviors, with a lower proportion of resilient individuals compared to males. These findings suggest that, in genetically diverse rats with extended drug access, escalation of intake, continued use despite adverse consequences, and PR responding are highly correlated measures of a shared underlying construct. Furthermore, our results highlight sex differences in resilience to addiction-like behaviors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 39484794 · DOI · PMC11530236
Tirzepatide attenuates mesolimbic cocaine-evoked dopamine levels and reduces cocaine taking, motivation and seeking behaviours in male rodents [4]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundCocaine use disorder (CUD) remains among the most treatment-resistant addictions, characterised by high relapse rates even following extended abstinence periods.
- Closing excerpt
- ) Thaynnam A Emous held an international internship scholarship from the São Paulo Research Foundation (FAPESP), Process Number #2023/18470-5, while conducting research at the University of Gothenburg.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (228 words)
BackgroundCocaine use disorder (CUD) remains among the most treatment-resistant addictions, characterised by high relapse rates even following extended abstinence periods. Dopamine signalling in mesocorticolimbic circuits contributes to cocaine's reinforcing effects and remains an important target for therapeutic intervention. Growing evidence suggests appetite-regulating peptides may influence central dopamine transmission. Whether recently approved incretin polyagonists can modulate cocaine-related behaviours through their capacity to simultaneously engage multiple appetite-regulating peptide receptor pathways remains unexplored.MethodsHere we investigated whether tirzepatide, a clinically approved long-acting dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) receptor agonist, alters cocaine-related behavioural and neurochemical responses in male rodents.FindingsWe found that tirzepatide produced dose-dependent reductions in cocaine self-administration (P InterpretationWhen considering our findings alongside tirzepatide's clinical availability, the evidence suggests this incretin polyagonist merits investigation as a potential treatment approach for CUD.FundingThe study is supported by grants (EJ) from the Swedish Research Council (2023-2600 and 2025-07154), LUA/ALF (grant no. 723941) from the Sahlgrenska University Hospital, Alcohol Research Council of the Swedish Alcohol Retailing Monopoly (FO2024-0048), Adlerbertska Research Foundation (2024-791), Wilhelm & Martina Lundgren's Research Foundation (2024-SA-4698) and Mary von Sydow Foundation (2024-36). This work was also supported by the following grants from the National Institutes of Health (NIH): R01 DA037897 and R01 DA061799 (H.D.S.) Thaynnam A Emous held an international internship scholarship from the São Paulo Research Foundation (FAPESP), Process Number #2023/18470-5, while conducting research at the University of Gothenburg.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41875498 · DOI · PMC13049583
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Responding to global stimulant use: challenges and opportunities [5]
- Research article The treatment of cocaine use disorder [6]
- Research article Crack cocaine and cocaine hydrochloride. Are the differences myth or reality? [7]
- Research article Sex Differences in Opioid and Psychostimulant Craving and Relapse: A Critical Review [8]
- Research article How fast and how often: The pharmacokinetics of drug use are decisive in addiction [9]
- Research article Cocaine and cognition: a systematic quantitative review [10]
References
- Salinas AG, Lee JO, Augustin SM, Zhang S, Patriarchi T, Tian L, et al.. Distinct sub-second dopamine signaling in dorsolateral striatum measured by a genetically-encoded fluorescent sensor. . 2023. PMID 37739964 · DOI · PMC10517008
- Merkel R, Hernandez NS, Weir V, Zhang Y, Caffrey A, Rich MT, et al.. An endogenous GLP-1 circuit engages VTA GABA neurons to regulate mesolimbic dopamine neurons and attenuate cocaine seeking. . 2025. PMID 40009667 · DOI · PMC11864183
- de Guglielmo G, Carrette L, Kallupi M, Brennan M, Boomhower B, Maturin L, et al.. Large-scale characterization of cocaine addiction-like behaviors reveals that escalation of intake, aversion-resistant responding, and breaking-points are highly correlated measures of the same construct. . 2024. PMID 39484794 · DOI · PMC11530236
- Edvardsson CE, Zhang X, Emous TA, Adermark L, Witley S, Ericson M, et al.. Tirzepatide attenuates mesolimbic cocaine-evoked dopamine levels and reduces cocaine taking, motivation and seeking behaviours in male rodents. . 2026. PMID 41875498 · DOI · PMC13049583
- Farrell M, Martin NK, Stockings E, Bórquez A, Cepeda JA, Degenhardt L, et al.. Responding to global stimulant use: challenges and opportunities. Lancet. 2019. PMID 31668409 · DOI · PMC6924572
- Kampman KM. The treatment of cocaine use disorder. Sci Adv. 2019. PMID 31663022 · DOI · PMC6795516
- Hatsukami DK, Fischman MW. Crack cocaine and cocaine hydrochloride. Are the differences myth or reality?. JAMA. 1996. PMID 8918856 · DOI
- Nicolas C, Zlebnik NE, Farokhnia M, Leggio L, Ikemoto S, Shaham Y. Sex Differences in Opioid and Psychostimulant Craving and Relapse: A Critical Review. Pharmacol Rev. 2022. PMID 34987089 · DOI · PMC11060335
- Allain F, Minogianis EA, Roberts DC, Samaha AN. How fast and how often: The pharmacokinetics of drug use are decisive in addiction. Neurosci Biobehav Rev. 2015. PMID 26116543 · DOI
- Potvin S, Stavro K, Rizkallah E, Pelletier J. Cocaine and cognition: a systematic quantitative review. J Addict Med. 2014. PMID 25187977 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.