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THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling, as the drug has a relatively low cannabinoid receptor efficacy and affinity.In populations of low cannabinoid receptor density, THC may act to antagonize endogenous agonists that possess greater receptor efficacy.It was listed under Schedule I in 1971, but reclassified to Schedule II in 1991 following a recommendation from the WHO.Based on subsequent studies, the WHO has recommended the reclassification to the less-stringent Schedule III. It is used to treat anorexia in people with HIV/AIDS as well as for refractory nausea and vomiting in people undergoing chemotherapy. THC is also an active ingredient in nabiximols, a specific extract of Cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray for people with multiple sclerosis to alleviate neuropathic pain, spasticity, overactive bladder, and other symptoms.THC is metabolized mainly to 11-OH-THC by the body.This metabolite is still psychoactive and is further oxidized to 11-nor-9-carboxy-THC (THC-COOH).As a result of the rescheduling of Marinol from Schedule II to Schedule III, refills are now permitted for this substance. For that reason, alternative THC-containing medications based on botanical extracts of the cannabis plant such as nabiximols are being developed.

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.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.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.

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