The role of estrogen in developing various addictions is well-known in animal research, with a lot of work already performed to demonstrate the crucial role of estrogen in developing opioid addiction. Estrogen itself is an activator of the mu-opioid receptor, so it has direct opioid-like effects, but it has also been shown to accelerate the development of physical addiction to opioids, increase drug seeking and worsen withdrawal symptoms. The new study below demonstrates that estrogen is required for the development of “addiction” to psychologically-addictive drugs such as cocaine. Non-aromatizable androgens such as DHT did not promote “addiction” development and pure estrogen antagonists completely prevented the “addiction” development. These findings suggest that progesterone and/or aspirin, vitamin E/D/A/K, non-aromatizable androgens, caffeine, etc could be viable options for preventing cocaine “addiction”, and based on other research the study cites those remedies may even reverse already developed “addiction”.
https://pubmed.ncbi.nlm.nih.gov/38370714/
“…It must be emphasized that pharmacokinetics studies are complex, and multiple factors, such as age, dose, individual differences in metabolism among others can affect the results obtained. One factor that has received more attention is the role of gonadal steroids in mediating these different behavioral responses. For example, in females estradiol enhances cocaine-induced sensitization (Segarra et al., 2014; Souza et al., 2014), conditioned place preference (Segarra et al., 2014) cocaine self-administration (Hu and Becker, 2008; Lynch et al., 2002; Perry et al., 2013; Ramôa et al., 2013) and the motivation to seek drugs.”
“…We had previously demonstrated that gonadectomy increased the acute locomotor response to cocaine but prevented the progressive increase in locomotion over time observed after repeated injections, i.e. cocaine-induced behavioral sensitization (Menéndez-Delmestre and Segarra, 2011). We had also reported that testosterone administration to GDX rats restored sensitization in male rats and decreased the acute locomotor response to cocaine (Menéndez-Delmestre and Segarra, 2011). The present study extends these findings and reports that estradiol, but not DHT, enhances the locomotor response to repeated cocaine administration. These results suggest that in male rats, androgen receptors do not participate in mediating neuroadaptations resulting from long-term drug administration. Furthermore, we report that intracellular ERs mediate the enhancement of cocaine-induced locomotor activity over time. This study found that blocking central ERs eliminates cocaine-induced behavioral sensitization. To our knowledge, this is the first study that illustrates the pivotal role of ERs in cocaine sensitization in males, suggesting that estrogen receptors play a key role in cocaine-induced neuroadaptations. Moreover, this study indicates that estrogen signaling participates in mediating drug-related behaviors in males and is also a key signal of cocaine-induced neuroplasticity in the rodent brain.’
