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Scientists discover how to eliminate marijuana ‘high’

A naturally occurring neurosteroid has been found that eliminates the high produced by the psychoactive compound in marijuana by an international team of researchers led by Monique Vallée and Pier Vincenzo Piazza from the Université de Bordeaux in France that was published in the Jan. 2, 2014, issue of the journal Science.

This figure represents the binding of pregnenolone to the type-1 cannabinoid  receptors.  The molecular effects of incoming THC are reduced, and cannabis intoxication is blunted.
Image courtesy of P. Reggio, modified by P.V. Piazza

The neurosteroid precursor pregnenolone is synthesized in the inner brain of humans and mice. Pregnenolone reduces the activity of the type-1 cannabinoid receptors in the brain and effectively removes the capacity for marijuana or the psychoactive compound in marijuana (tetrahydrocannabinol) from producing the intoxicating effects associated with marijuana.

The researchers tested mice and rats with a THC content that was 1,500 percent higher than that required to get the mice and rats high. Mice and rats being stoned was determined by their increased feeding behavior and memory impairment. The high dose of THC also produced an increase in pregnenolone content in the animal’s brains by 3,000 percent.

The researchers conclude that one function of pregnenolone is to prevent excessive stimulation of the cannabinoid receptors in the brain by naturally occurring endocannabinoids and by THC.

The addition of a cannabinoid receptor antagonist prevented the test animals from getting high because the chemical produced a large increase in pregnenolone that effectively prevented access to cannabinoid receptors by THC in marijuana.

The research indicates that the medicinal use of marijuana can be modified to eliminate the high associated with THC and that a chemical pathway to treat addiction to marijuana has finally been established.

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