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Cocaine Addiction: Rebalancing the Brain


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Cocaine use and addiction are now widespread throughout the world. Cocaine is a drug derived from the leaves of the Coca plant, which is native to Central and South America.[1] Humans have chewed coca leaves for increased energy and productivity for thousands of years.[2] The chemist Albert Niemann isolated cocaine in the mid-1800’s after coca leaves were brought to Europe.[3]

In the United States, there are an estimated 1.5 million current cocaine users as of 2014.[4] In 2014 there were also around 5,000 deaths due to cocaine overdose. Cocaine use can have other serious health consequences, including toxicity in heart tissues and vascular tissues, increased risk of liver damage, and addiction.[5],[6]

Historically addiction has been characterized by “weak personality” or moral shortcoming.[7] However, addictions today are commonly understood as chronic, multifactorial diseases of the brain.[8] When someone suffers from an addiction, their neurochemistry is imbalanced from drug use itself, poor nutrition, environmental factors, or genetic factors.

Cocaine: a Powerful Motivator

Cocaine, and other drugs of abuse, cause both short-term and long-term neuronal changes which may lead to addiction in some individuals.[9],[10],[11] The mesolimbic dopamine system of the brain influences feelings of pleasure, as well as learning and motivation. This system includes the ventral tegmental area (VTA), nucleus accumbens (NAcc), and amygdala. Changes within these brain regions are central to the maintenance of addiction cycles.

When it comes to complex, motivated behavior, (such as seeking out drugs) the amygdala and NAcc, as well as the prefrontal cortex (PFC), are of great importance. The amygdala is involved in fear-motivated behaviors and the NAcc mediates reward-motivated behaviors.[12] The prefrontal cortex determines the salience, or relative importance, of a behavior.[13] Both dopaminergic and glutaminergic neurons facilitate connections between these regions.[14]

Cocaine inhibits the reuptake of dopamine, norepinephrine, and serotonin, thereby increasing the amount of extracellular levels of these neurotransmitters.[15] When greater neurotransmitter levels are available in the synapse, more neurotransmitters can bind to post-synaptic receptors. Thus, the physical or behavioral effects of a neurotransmitter are increased. Dopamine in the PFC modulates salience and increased dopamine in the NAcc increases feelings of reward, causing a “high”. Therefore, altered dopaminergic neurotransmission is thought to be primarily responsible for cocaine’s rewarding effects and addictive potential.[16],[17] When a person uses cocaine, the immediate effect is an elevated dopamine level. However, addiction to cocaine is related to reduced dopamine function, especially in the NAcc.[18]

Both dopaminergic neurons and glutaminergic neuronal connections from the PFC to the NAcc are responsible for expressing behavior based on ascribed salience.[19] These glutaminergic projections are thought to be involved in drug-seeking behavior that occurs following a drug high.[20] Studies show a reduction in basal glutamate levels in the NAcc after cocaine withdrawal.[21],[22] Additionally, Ferraro et. al. found that even very small doses of cocaine can increase binding at the dopamine D2 receptor.[23] These D2 receptors alter glutaminergic neurotransmission in the NAcc; therefore, cocaine consumption may directly affect drug-seeking behaviors, as well as inducing acute highs.

Cocaine and Serotonin

Stress also increases drug craving. In fact, up-regulated HPA activity in response to stress is a good predictor of whether a person will relapse.[24],[25] In addition to releasing adrenal hormones, social stress has also been shown to increase extracellular dopamine.[26] This may lead to neurological adaptations, such as decreased sensitivity to dopamine, that could affect susceptibility to addiction.[27] Han et. al. demonstrated that social stress causes increased self-administration of cocaine in rats.[28] Animal models show that increased CRF (corticotropin-releasing factor) activity in the amygdala caused by stress may be linked to the anxiety and nervousness associated with drug withdrawal.[29] These findings may help explain why stressful situations may drive drug use.

There are no pharmaceuticals approved for the treatment of cocaine addiction.[30] However, animal models show serotonin reuptake inhibition reduces the increase in extracellular dopamine following cocaine administration, as well as drug seeking behaviors.[31],[32] These effects are most likely due to activation of the serotonin2C receptor, as it plays an important role in modulating the mesolimbic dopamine system.[33],[34] Therefore, increasing serotonin levels may be helpful in the treatment of cocaine addiction. L-tryptophan or 5-HTP may be used to boost serotonin and potentially help attenuate the effects of cocaine use.

Addiction is an extremely complex disorder. However, monitoring neurotransmitter and adrenal hormone levels, maintaining a healthy diet, and implementing appropriate supplements may help rebalance the chemistry of an addicted brain.

[1] Mulé SJ. (1984) The Pharmacodynamics of Cocaine Abuse. Psychiatric Annals, 14:10.
[2] Ibid.
[3] Ibid.
[4] National Institute on Drug Abuse. “What Is the Scope of Cocaine Use in the United States?” (2016). NIDA, NIH Web.
[5] Agrawal PR, Scarabelli TM, Saravolatz L, et al. (2015). Current Strategies in the Evaluation and Management of Cocaine-Induced Chest Pain. Cardiol Rev. Jan 9. [Epub ahead of print]
[6] NIDA op. cit.
[7] Kreek MJ, Levran O, Reed B, et. al. (2012). Opiate addiction and cocaine addiction: underlying molecular neurobiology and genetics. Journal of Clinical Investigation; 122, 10.
[8] Kreek et. al. op. cit.
[9] Han X, Albrechet-Souza L, Doyle MR, et. al. (2015). Social Stress and Escalated Drug Self-administration in Mice II. Cocaine and Dopamine in Nucleus Accumbens. Psychopharmacology (Berl); 232(6): 1003–1010.
[10] Kreek et. al. op. cit.
[11] Puig S, Noble F, and Benturquia N. (2012). Short- and long-lasting behavioral and neurochemical adaptations: relationship with patterns of cocaine administration and expectation of drug effects in rats. Translational Psychiatry 2, e175; doi:10.1038/tp.2012.103
[12] Kalivas PW & Volkow ND. (2005). The Neural Basis of Addiction: A Pathology of Motivation and Choice. The American Journal of Psychiatry; 162, 8;
[13] Ibid.
[14] Ibid.
[15] Mulé op. cit.
[16]Kreek et. al. op. cit.
[17] Han et. al. op. cit.
[18] Martinez D, Narendran R, Foltin RW, et al. (2007). Amphetamine-induced dopamine release: markedly blunted in cocaine dependence and predictive of the choice to self-administer cocaine. Am J Psychiatry. Apr;164(4):622-9.
[19] Kalivas & Volkow op. cit.
[20] Kalivas & Volkow op. cit.
[21] Kalivas & Volkow op. cit.
[22] Ferraro L, Frankowska M, Marcellino D, et. al. (2012). A Novel Mechanism of Cocaine to Enhance Dopamine D2-Like Receptor Mediated Neurochemical and Behavioral Effects. An In Vivo and In Vitro Study. Neuropsychopharmacology 37, 1856–1866.
[23]Ferraro et. al. op. cit.
[24] Kreek et. al. op. cit.
[25] Han et. al. op. cit.
[26] Han et. al. op. cit.
[27] Han et. al. op. cit.
[28] Han et. al. op. cit.
[29] Kreek et. al. op. cit.
[30] Kreek et. al. op. cit.
[31] Rüedi-Bettschen, Spealman, & op. cit.
[32] Devroye et. al. op. cit.
[33] Rüedi-Bettschen D, Spealman RD, & Platt DM. (2015). Attenuation of cocaine-induced reinstatement of drug seeking in squirrel monkeys by direct and indirect activation of 5-HT2C receptors. Psychopharmacology, 232:2959–2968.
[34] Devroye C, Filip M, Przegalin´ski E, et. al. (2013). Serotonin2C receptors and drug addiction: focus on cocaine. Exp Brain Res, 230:537–545

Clinical Contributor

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Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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