Because cocaine switches on the stress systems both when it is active and during withdrawal, these systems rapidly become hypersensitive, Dr. Kreek theorizes. This theory about stress and drug addiction is derived in part from studies conducted by Dr. Kreek's group in which addicts were given a test agent called metyrapone. This chemical blocks the production of cortisol in the adrenal glands, which lowers the level of cortisol in the blood. As a result, cortisol is no longer inhibiting the release of CRF from the brain and ACTH from the pituitary. The brain and pituitary then start producing more of these chemicals.
Physicians use metyrapone to test whether a person's stress system is operating normally.
When metyrapone is given to nonaddicted people, the ACTH level in the blood increases. However, when Dr. Kreek and her colleagues administered metyrapone to active heroin addicts, the ACTH level hardly rose at all. When the scientists gave metyrapone to heroin addicts who were abstaining from heroin use and who were not taking methadone, the synthetic opioid medication that suppresses cravings for opiate drugs, the ACTH level in the majority of the addicts increased about twice as high as in nonaddicts. Finally, when the scientists gave metyrapone to heroin addicts maintained for at least 3 months on methadone, the ACTH level rose the same as in nonaddicts. Addicts on heroin underreact because all the excess opioid molecules in the brain greatly inhibit the brain's stress system, Dr. Kreek explains.