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Since at least 1986, the trend has been for THC in general, and especially the Marinol preparation, to be downgraded to less and less stringently-controlled schedules of controlled substances, in the U. This permitted medical use of Marinol, albeit with the severe restrictions associated with Schedule II status.For instance, refills of Marinol prescriptions were not permitted.Due to its partial agonistic activity, THC appears to result in greater downregulation of cannabinoid receptors than endocannabinoids, further limiting its efficacy over other cannabinoids.While tolerance may limit the maximal effects of certain drugs, evidence suggests that tolerance develops irregularly for different effects with greater resistance for primary over side-effects, and may actually serve to enhance the drug's therapeutic window.The psychoactive effects of THC are primarily mediated by the activation of cannabinoid receptors, which result in a decrease in the concentration of the second messenger molecule c AMP through inhibition of adenylate cyclase.

More than 55% of THC is excreted in the feces and ~20% in the urine.

An article published in the April–June 1998 issue of the Journal of Psychoactive Drugs found that "Healthcare professionals have detected no indication of scrip-chasing or doctor-shopping among the patients for whom they have prescribed dronabinol".

The authors state that Marinol has a low potential for abuse.

However, this form of tolerance appears to be irregular throughout mouse brain areas.

THC, as well as other cannabinoids that contain a phenol group, possesses mild antioxidant activity sufficient to protect neurons against oxidative stress, such as that produced by glutamate-induced excitotoxicity.

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