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Marijuana and the Human Brain

Tolerance, dependence and denial

Herkenham's earlier research mapping the locations of the cannabinoid brain-receptor system helped establish scientific evidence that marijuana is nonaddictive. This new tolerance study builds on that foundation by explaining how cannabinoid tolerance supports rather than contradicts that finding.

"It is ironic that the magnitude of both tolerance (complete disappearance of the inhibitory motor effects) and receptor down-regulation (78% loss with high-dose CP-55,940) is so large, whereas cannabinoid dependence and withdrawal phenomena are minimal. This supports the claim that tolerance and dependence are independently mediated in the brain."

In other words, tolerance to marijuana is not an indication that the drug is addictive.

Norman Zinberg, in 'Drug, Set and Setting' (Yale, New Haven, CT, 1984), explained that the key to understanding the use of any drug is to realize that three variables affect the situation: drug, set and setting. It is now a scientific finding that the pharmacological effects of marijuana do not produce dependency. The use and abuse of marijuana is a function of behavior - interrelated psychological and environmental factors.

Addictive drugs affect behavior through their effects on the brain "reward system" - the production of dopamine, linked to the pleasure sensation. This brain "reward system" has a powerful influence over behavior. Dependence-producing drugs - drugs that, unlike marijuana, affect dopamine production - eventually exert more influence on the user's behavior than any other factor. The effect of addiction on behavior is so profound as to create a condition called denial, in which someone will say or do anything to continue access to the drug.

Denial is a characteristic of drug abuse, and it is largely cultivated by the effects of various drugs on the brain reward system. Herkenham's research provides a clinical basis for claims that denial is not a characteristic of marijuana use.