Many drastic actions are taken by cocaine users for the sake of experiencing high dopamine levels, which depends on iron for its synthesis. Dopamine depletion and iron deficiency are also involved in the symptoms of restless leg syndrome (RLS). The intersecting biochemical pathways of cocaine use, iron deficiency, and RLS have not been adequately investigated. This case report reveals the successful treatment of a patient with these conditions. A 63-year-old male with a history of cocaine use disorder, insomnia, and RLS sought emergency care for suicidality. Upon admission, he was also found to be iron-deficient. He revealed that his RLS worsened when he attempted to abstain from cocaine. He also used alcohol to sustain the effects of cocaine when the cost of cocaine was too high. During hospitalization, his mood, cravings, and RLS were resolved with adjunctive iron supplementation as well as 300 mg of Wellbutrin. If iron-deficient, replenishment of adequate dopaminergic receptor density and function via supplementation may play an essential role in the prevention of cocaine use and cessation of cocaine withdrawal. Further research is warranted to validate these findings and understand the implications of iron supplementation in addiction medicine.

Repeated cocaine produces an enhanced locomotor response (sensitization) paralleled by biological adaptations in the brain. Previous studies demonstrated region-specific responsiv-ity of adenosine monophosphate-activated protein kinase (AMPK) to repeated cocaine. AMPK maintains cellular energy homeostasis at the organismal and cellular level. Here we first quanti-fied changes in phosphorylated (active) and total AMPK in the cytosol and synaptosome of the medial prefrontal cortex, nucleus accumbens, and dorsal striatum following acute or sensitizing cocaine injections. Rats were given cocaine (15 mg/kg, IP) or saline for six days with a challenge injection on day seven resulting in four groups: saline-saline, saline-cocaine, cocaine-saline, and cocaine-cocaine. Brain region and cellular compartment selective changes in AMPK and pAMPK were found with some differences associated with acute withdrawal versus ongoing cocaine treatment. Other rats were pretreated with the indirect AMPK activator metformin. Metformin potentiated the locomotor activating effects of acute cocaine but blocked the development of sensi-tization. Sex differences largely obscured protein level treatment group effects, although pAMPK in the NAc shell cytosol was surprisingly reduced by metformin in rats receiving repeated co-caine. These data inform our understanding of AMPK activation dynamics in subcellular com-partments and provide additional support for repurposing metformin for cocaine use disorder.

Background: Different drugs damage the frontal cortices, particularly the prefrontal areas involved in both emotional and cognitive functions, with a consequence of decoding emotion deficits for people with substance abuse. The present study aims to explore the cognitive impairments in drug abusers through facial, body and disgust emotion recognition, expanding the investigation of emotions, processing, measuring accuracy and response velocity. Method: We enrolled 13 addicted to cocaine and 12 alcohol patients attending treatment services in Italy, comparing them with 33 matched controls. Facial emotion and body posture recognition tasks, a disgust rating task, and the Barrat Impulsivity Scale were included in the experimental assessment. Results: We found that emotional processes are differently influenced by cocaine and alcohol, suggesting that these substances impact diverse cerebral systems. Conclusion: The contribution made by the duration of consumption on emotional processing seems far less important than for cognitive processes. Drug abusers seem to be slower on elaboration of emotions and, in particular, of disgust emotion. Considering that the participants were not impaired in cognition, our data support the hypothesis that emotional impairments emerge independently from damage to cognitive functions.

Cocaine addiction is a global health problem that causes substantial damage to the health of addicted individuals around the world. Dopamine synthesizing neurons in the brain play a vital role in the addiction to cocaine. But the underlying molecular mechanisms that help cocaine exert its addictive effect have not been very well understood. Bioinformatics can be a useful tool in the attempt to broaden our understanding in this area. In the present study, Gene Set Enrichment Analysis (GSEA) was carried out on the upregulated genes from a dataset of Dopamine synthesizing neurons of post-mortem human brain of cocaine addicts. As a result of this analysis, 3 miRNAs have been identified as having significant influence on transcription of the upregulated genes. These 3 miRNAs hold therapeutic potential for the treatment of cocaine addiction.

Due to similarities in genetics, cellular response, and behavior, Drosophila is used as a model organism in addiction research. A well described behavioral response examined in flies is the induced increase in locomotor activity after a single dose of volatilized cocaine (vCOC) and volatilized methamphetamine (vMETH) known as sensitivity, and the escalation of the locomotor response after the repeated dose, known as the locomotor sensitization. However, knowledge about how vCOC and vMETH affect different neurotransmitter systems over time is scarce. We used LC-MS/MS to systematically examine changes in the concentration of neurotransmitters, metabolites and non-metabolized COC and METH in the whole head homogenates of male flies one to seven hours after single and double vCOC or vMETH administrations. vMETH leads to complex changes in the levels of examined substances over time, while vCOC strongly and briefly increases concentrations of dopamine, tyramine and octopamine followed by a delayed degradation into N-acetyl dopamine and N-acetyl tyramine. The first exposure to psychostimulants leads to significant and dynamic changes in the concentrations relative to the second administration when they are more stable over several hours. Further investigations are needed to understand neurochemical and molecular changes post-psychostimulant administration.