Editing Cocaine (section)

==== Addiction ====
{{For|harm caused by the freebase form|Crack cocaine#Addiction}}
{{See also|Cocaine Anonymous|Epigenetics of cocaine addiction}}

In humans, cocaine abuse may cause [[addiction-related structural neuroplasticity]], though it is unclear to what extent these changes are permanent.<ref name=Hamp2019>{{cite journal | vauthors = Hampton WH, Hanik I, Olson IR | title = [Substance Abuse and White Matter: Findings, Limitations, and Future of Diffusion Tensor Imaging Research] | journal = Drug and Alcohol Dependence | volume = 197 | issue = 4 | pages = 288–298 | year = 2019 | pmid = 30875650 | pmc = 6440853 | doi = 10.1016/j.drugalcdep.2019.02.005}}</ref>

Relatives of persons with cocaine addiction have an increased risk of cocaine addiction.<ref>{{Cite journal | vauthors = Fernàndez-Castillo N, Cabana-Domínguez J, Corominas R, Cormand B | title = Molecular genetics of cocaine use disorders in humans | journal = Molecular Psychiatry | volume = 27 | issue = 1 | pages = 624–639 | date = January 2022 | pmid = 34453125 | doi = 10.1038/s41380-021-01256-1 | pmc = 8960411 }}</ref> [[Cocaine addiction]] occurs through [[ΔFosB]] overexpression in the [[nucleus accumbens]], which results in altered [[transcriptional regulation]] in neurons within the [[nucleus accumbens]]. ΔFosB levels have been found to increase upon the use of cocaine.<ref name="pmid9668659">{{Cite journal | vauthors = Hope BT | title = Cocaine and the AP-1 transcription factor complex | journal = Annals of the New York Academy of Sciences | volume = 844 | issue = 1 | pages = 1–6 | date = May 1998 | pmid = 9668659 | doi = 10.1111/j.1749-6632.1998.tb08216.x | s2cid = 11683570 | bibcode = 1998NYASA.844....1H | url = https://zenodo.org/record/1230756 | access-date = 30 June 2019 | archive-date = 28 July 2020 | archive-url = https://web.archive.org/web/20200728160757/https://zenodo.org/record/1230756 | url-status = live }}</ref> Each subsequent dose of cocaine continues to increase ΔFosB levels with no ceiling of tolerance. Elevated levels of ΔFosB leads to increases in brain-derived neurotrophic factor ([[BDNF]]) levels, which in turn increases the number of [[dendrite|dendritic]] branches and [[dendritic spine|spines]] present on neurons involved with the nucleus accumbens and [[prefrontal cortex]] areas of the brain. This change can be identified rather quickly, and may be sustained weeks after the last dose of the drug.

[[Genetically modified mouse|Genetically modified mice]] exhibiting inducible expression of ΔFosB primarily in the nucleus accumbens and [[dorsal striatum]] exhibit [[drug sensitization|sensitized]] behavioural responses to cocaine.<ref name="pmid10499584">{{Cite journal |author-link13=D. James Surmeier | vauthors = Kelz MB, Chen J, Carlezon WA, Whisler K, Gilden L, Beckmann AM, Steffen C, Zhang YJ, Marotti L, Self DW, Tkatch T, Baranauskas G, Surmeier DJ, Neve RL, Duman RS, Picciotto MR, Nestler EJ | title = Expression of the transcription factor deltaFosB in the brain controls sensitivity to cocaine | journal = Nature | volume = 401 | issue = 6750 | pages = 272–6 | date = September 1999 | pmid = 10499584 | doi = 10.1038/45790 | bibcode = 1999Natur.401..272K | s2cid = 4390717 }}</ref> They self-administer cocaine at lower doses than control,<ref name="pmid12657709">{{Cite journal | vauthors = Colby CR, Whisler K, Steffen C, Nestler EJ, Self DW | title = Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine | journal = The Journal of Neuroscience | volume = 23 | issue = 6 | pages = 2488–93 | date = March 2003 | pmid = 12657709 | doi =  10.1523/JNEUROSCI.23-06-02488.2003| pmc = 6742034 }}</ref> but have a greater likelihood of [[relapse]] when the drug is withheld.<ref name="pmid12657709" /><ref name="pmid11572966">{{Cite journal | vauthors = Nestler EJ, Barrot M, Self DW | title = DeltaFosB: a sustained molecular switch for addiction | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 20 | pages = 11042–6 | date = September 2001 | pmid = 11572966 | pmc = 58680 | doi = 10.1073/pnas.191352698 | quote = <!-- Although the ΔFosB signal is relatively long-lived, it is not permanent. ΔFosB degrades gradually and can no longer be detected in brain after 1–2 months of drug withdrawal&nbsp;... Indeed, ΔFosB is the longest-lived adaptation known to occur in adult brain, not only in response to drugs of abuse, but to any other perturbation (that doesn't involve lesions) as well. --> | bibcode = 2001PNAS...9811042N | doi-access = free }}</ref> ΔFosB increases the expression of [[AMPA receptor]] subunit GluR2<ref name="pmid10499584" /> and also decreases expression of [[dynorphin]], thereby enhancing sensitivity to reward.<ref name="pmid11572966" />

[[DNA damage (naturally occurring)|DNA damage]] is increased in the brain of rodents by administration of cocaine.<ref name="pmid24552452">{{Cite journal | vauthors = de Souza MF, Gonçales TA, Steinmetz A, Moura DJ, Saffi J, Gomez R, Barros HM | title = Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions | journal = Clinical and Experimental Pharmacology & Physiology | volume = 41 | issue = 4 | pages = 265–9 | date = April 2014 | pmid = 24552452 | doi = 10.1111/1440-1681.12218 | s2cid = 20849951 }}</ref><ref name="pmid19878142">{{Cite journal | vauthors = Alvarenga TA, Andersen ML, Ribeiro DA, Araujo P, Hirotsu C, Costa JL, Battisti MC, Tufik S | title = Single exposure to cocaine or ecstasy induces DNA damage in brain and other organs of mice | journal = Addiction Biology | volume = 15 | issue = 1 | pages = 96–9 | date = January 2010 | pmid = 19878142 | doi = 10.1111/j.1369-1600.2009.00179.x | s2cid = 21347765 }}</ref> During [[DNA repair]] of such damages, persistent [[chromatin]] alterations may occur such as [[DNA methylation|methylation of DNA]] or the acetylation or [[histone methylation|methylation of histones]] at the sites of repair.<ref name="pmid27259203">{{Cite journal | vauthors = Dabin J, Fortuny A, Polo SE | title = Epigenome Maintenance in Response to DNA Damage | journal = Molecular Cell | volume = 62 | issue = 5 | pages = 712–27 | date = June 2016 | pmid = 27259203 | pmc = 5476208 | doi = 10.1016/j.molcel.2016.04.006 }}</ref>  These alterations can be [[epigenetics|epigenetic]] {{Clarify|date=March 2025|reason= epigenetics article doesn't mention 'scars'|text= scars}} in the chromatin that contribute to the persistent [[Epigenetics of cocaine addiction|epigenetic changes found in cocaine addiction]].