From the Research
Naltrexone typically causes an initial increase in cortisol levels, followed by normalization with continued treatment, as it blocks endogenous opioid activity that normally suppresses the hypothalamic-pituitary-adrenal (HPA) axis. When first administered, naltrexone often elevates cortisol levels acutely, and this initial increase is most pronounced in the first few hours after administration, as seen in a study where naltrexone administration resulted in a significant ACTH response in patients, while cortisol and ACTH responses were found to be significant in controls 1. However, with continued naltrexone treatment, cortisol levels tend to normalize or even decrease over time as the HPA axis adapts. This effect varies between individuals, with more pronounced cortisol increases observed in patients with alcohol use disorder, opioid dependence, or dysregulated stress responses, as noted in a study that found individuals with a family history of alcoholism had a different pattern of response to naltrexone, with heightened ACTH and cortisol levels 2.
The cortisol-modulating effects of naltrexone may contribute to its therapeutic benefits in addiction treatment by helping normalize stress responses that drive substance cravings. Patients should be aware that they might experience temporary symptoms of increased stress or anxiety when starting naltrexone treatment, but these effects typically diminish with continued use as the body adjusts to the medication. It's also important to consider that long-term opioid use can lead to opioid-induced adrenal insufficiency, which may be challenging to diagnose, as reported in a study that found opioid-induced adrenal insufficiency occurs in 9% to 29% of patients receiving long-term opiate therapy 3.
Some key points to consider when evaluating the effect of naltrexone on cortisol levels include:
- The initial increase in cortisol levels after naltrexone administration
- The variation in response between individuals, particularly those with a family history of alcoholism
- The potential for cortisol levels to normalize or decrease with continued treatment
- The importance of monitoring for opioid-induced adrenal insufficiency in patients with a history of long-term opioid use
- The therapeutic benefits of naltrexone in addiction treatment, including its ability to help normalize stress responses that drive substance cravings, as supported by studies on the efficacy and tolerability of naltrexone in the management of alcohol dependence 4, 5.