What is the kappa opioid receptor?


The kappa opioid receptor plays a critical role in the body's response to certain stimuli, particularly those associated with stress and discomfort. According to , it is involved in a feedback loop where agonism (activation) of the kappa opioid receptor actually sensitizes mu opioid receptors. These mu opioid receptors bind to beta endorphins, which are the body's natural "feel-good" molecules. This sensitization makes the mu receptors more responsive to beta endorphins, leading to longer-lasting feeling of well-being 1.

Rhonda Patrick has also mentioned that the kappa opioid receptor is involved in the body's thermoregulatory response. For example, dinorphin, which binds to the kappa opioid receptor, is released in response to heat stress (e.g., from sauna use or vigorous exercise) and can generate a dysphoric feeling. However, this activation of the kappa opioid receptor can lead to heightened sensitivity of the mu opioid receptors, potentially explaining the longer-lasting positive effects experienced after such activities 2.

In a discussion with , it was highlighted that interest exists in kappa opioid receptor agonists, such as Salvinorin A, for therapeutic purposes, including possible antidepressant effects at lower doses. This complexity shows that manipulating the kappa opioid pathway can have versatile and sometimes opposing outcomes, depending on the context and specific treatments used 3.

Opioid Receptor Pathway

Rhonda discusses the feedback loop effect of agonism of the kappa opioid receptor and how it causes mu opioid receptors to become sensitized to endorphins. She also talks about the dinorphin pathway and how it cools the body down by binding to the kappa opioid receptor, which then sensitizes the mu opioid receptor.

Found My Fitness

Roland Griffiths, Ph.D. on Psilocybin, Psychedelic Therapies & Mystical Experiences