Deletion of kappa receptors ablates THC place aversion and furthermore unmasks THC place preference. Thus, an opposing activity of mu- and kappa-opioid receptors in modulating reward pathways forms the basis for the dual euphoric-dysphoric activity of THC.
https://pubmed.ncbi.nlm.nih.gov/11826143/
Repeated THC administration produces motivational and somatic adaptive changes leading to dependence in rodents.
https://www.reddit.com/r/IAmA/comments/5jfan7/iama_neuroscientist_who_studies_how_cannabis/
Chronic cannabis can actually increase the sensitivity to opioids: you need less opioid than a non-cannabis user to achieve the same level of pain relief. This sensitivity is bi-directional (chronic opioid use enhances cannabinoid sensitivity). We have no idea how long-lasting the changes are.
https://www.sciencedirect.com/science/article/pii/S0028390824004349
Acute kappa opioid receptor blocking disrupts the pro-cognitive effect of cannabidiol in neuropathic rats
This study also confirms the crosstalk between the endocannabinoid and opioid systems; however, several CBD effects are avoided by KOR activity.
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