Repeated Morphine Changed Spinal Cannabinoid Receptor Expression in an Experimental Study

An experimental study found increased spinal CB1 and CB2 receptor expression after repeated morphine exposure. Blocking glucocorticoid receptors attenuated both that receptor increase and the development of morphine tolerance, implicating another signaling system in the adaptation.

The exposure route was part of the design

Morphine was administered intrathecally, directly into the spinal fluid compartment, twice daily for six days. The researchers examined cannabinoid receptor expression in the spinal dorsal horn. This tightly controlled exposure differs from oral medication use, inhaled cannabis or a topical consumer product.

A glucocorticoid antagonist modified the changes

Repeated morphine produced a time-dependent increase in both CB1 and CB2 receptors. Co-administration of the glucocorticoid receptor antagonist RU38486 attenuated those increases in a dose-dependent manner. The same treatment regimen also attenuated the development of morphine tolerance. The abstract supports a regulatory relationship between glucocorticoid signaling and spinal cannabinoid receptor expression.

Expression is not the same as clinical benefit

An increase in receptor expression does not by itself establish stronger cannabinoid analgesia, improved functioning or a useful treatment combination. Likewise, two changes occurring under the same intervention do not prove that receptor expression alone fully explains the behavioral tolerance result.

The finding concerns how opioid exposure can alter components of the cannabinoid system. It does not establish a human dosing strategy or show that cannabis prevents opioid tolerance. Any application should retain the spinal administration route and distinguish receptor measurements from treatment outcomes.

Related: interpreting cannabis tolerance claims.

Research cited

Lim G; Wang S; Mao J. Central glucocorticoid receptors modulate the expression of spinal cannabinoid receptors induced by chronic morphine exposure. Brain research (2005). doi:10.1016/j.brainres.2005.08.002. Findings discussed from the study abstract.