Corticotropin-Releasing Factor (CRF)
Stress plays a significant role in addiction. A stress hormone called corticotropin-releasing factor (CRF) is secreted when a subject is placed under stress, and researchers say an “atypical response” to CRF may contribute to relapse by sober addicts.1
CRF activity has also been implicated in withdrawal.2 Originally, withdrawal was explained as dopamine and serotonin depletion after over-stimulation of those systems.3 However, data show stress plays a role in withdrawal separate from the dopamine and serotonin systems.4 Rats bred to be alcohol-dependent were found to have overactive CRF systems,5 and CRF was elevated in other rats in withdrawal from THC, the psychoactive ingredient in marijuana. Increased CRF has also been associated with cocaine and opiate use.6
Like withdrawal, it was originally thought cravings were the result of dopamine depletion. Now, however, stress-induced release of CRFs is recognized as a craving/relapse mechanism operating separately and in addition to the dopamine system. That there may be two separate systems involved in cravings may explain their strength and persistence.
In addition to stress and drugs, CRF can be boosted by a powerful “emotional memories,”7 such as recalling a drug-induced high (for more, click on Learned and Emotional Memories). Experiments demonstrated that alcoholic rats had high expression of a gene (CRH-R1) which engineers the CRF receptor. A drug, antalarmin, which blocked the activation of this gene lessened drinking and “blocked stress-induced reinstatement of drinking,” while having no effect on normal rats. Antalarmin’s efficacy in humans is being investigated.8
Another stress-related protein may also be involved. Brain-derived neurotrophic factor (BDNF) plays a vital role in the growth and maintenance of neurons. Mice who were genetically engineered not to produce BDNF showed increased anxiety and drinking. But when their BDNF was restored to normal through drug therapy their anxiety and drinking returned to normal.9
A study published in the May 2007 issue of Alcoholism: Clinical & Experimental Research, suggests that alcoholics may be particularly vulnerable to stress-related relapse during the first two months of abstinence. Researchers found that the hypothalamic-pituitary-adrenal (HPA) axis, a system which defends against the deleterious effects of stress and is known to be deficient in active alcoholics, does not regain normal function in the newly sober for about two months. Surprisingly, this was the case for both psychological and physical stress. The authors caution alcoholics in recovery to avoid both kinds of stress for the first two months, advice which runs counter to the guidelines at many recovery programs, which attribute an important role for exercise in early recovery.10
1. Drug Abuse: Hedonic Homeostatic Dysregulation Science Magazine, Oct. 3, 1997.
2. Studies Of Brain Shows That Marijuana Can Have The Same Affect As Other Drugs, New York Times, June 27, 1997.
3. Drug Abuse: Hedonic Homeostatic Dysregulation Science Magazine, Oct. 3, 1997.
4. Activation of Corticotropin-Releasing Factor in the Limbic System DuringCannabinoid Withdrawal, Science Magazine, June 27, 1997.
5. Potential Human Use For New Compound To Prevent Alcoholic Behavior, Relapse In Animals By Blocking Stress Response, medicalnewstoday.com, March 12, 2007.
6. Drug Abuse: Hedonic Homeostatic Dysregulation Science Magazine, Oct. 3, 1997.
7. Hardest Habit To Break: Memories of the High, New York Times, October 27, 1998.
8. Receptor and Stress-Induced Alcohol Relapse Linked By Study, medicalnewstoday.com, October 5, 2006.
9. Brain Chemical Plays Critical Role In Drinking And Anxiety, medicalnewstoday.com, August 11, 2006.
10. How Women Think, New York Times Book Review, September 10, 2006.
