Repeated Morphine Reduced Brain 2-AG but Left Anandamide Unchanged in Rats
A rat study found that repeated morphine reduced the endogenous cannabinoid 2-AG across several brain regions without changing anandamide. Receptor binding and signaling also changed, but the largest changes did not occur uniformly across the same regions.
Two endogenous lipids were measured directly
Researchers used isotope-dilution gas chromatography/mass spectrometry to measure anandamide and 2-arachidonoylglycerol, or 2-AG, in brain tissue after repeated morphine treatment. Neither compound is administered THC. Their concentrations reflect components of endogenous signaling, rather than establishing that an animal consumed cannabis.
Receptor assays added another layer
Morphine-tolerant rats showed a small but significant reduction in cannabinoid receptor binding in the cerebellum and hippocampus. Agonist-stimulated G protein coupling decreased strongly in the limbic area. Meanwhile, 2-AG content fell in several regions, including the striatum, cortex, hippocampus, limbic area and hypothalamus, without corresponding anandamide changes.
Association with tolerance does not identify one cause
The authors suggested involvement of the cannabinoid system in morphine tolerance. The experiment does not show that reduced 2-AG alone caused the behavioral adaptation or that restoring it would produce a safe treatment. Other mediators could contribute, as the abstract acknowledges.
The findings show why endocannabinoids should be named individually in an evidence summary. Saying that morphine reduced all endocannabinoids would erase a central null finding. Translating these tissue results into a claim about human cannabis effects or opioid treatment would require evidence beyond this experiment.
Related: interpreting cannabis tolerance claims.
Research cited
Viganò D; Grazia Cascio M; Rubino T; Fezza F; Vaccani A; Di Marzo V; Parolaro D. Chronic morphine modulates the contents of the endocannabinoid, 2-arachidonoyl glycerol, in rat brain. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2003). doi:10.1038/sj.npp.1300117. Findings discussed from the study abstract.
