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However, many investigations have found additional effects of opioids, including regulation of the immune system. As such, chronic opioid abuse has been shown to promote HIV\u20101 pathogenesis and facilitate HIV\u20101\u2010associated neurocognitive dysfunction. Clinical opioids, such as morphine and methadone, as well as illicit opioids, such as heroin, exert their effects primarily through interactions with the \u00b5\u2010opioid receptor (MOR). However, the mechanisms by which opioids enhance neurocognitive dysfunction through MOR\u2010mediated signaling pathways are not completely understood. New findings in the regulation of MOR expression, particularly epigenetic and transcriptional regulation as well as alternative splicing, sheds new insights into possible mechanisms of HIV\u20101 and opiate synergy. In this review, we identify mechanisms regulating MOR expression and propose novel mechanisms by which opioids and HIV\u20101 may modulate this regulation. 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