Allopregnanolone levels are increased in response to stress (Girdler, 2001); and this response is thought to be adaptive (beneficial) since individuals who do not show it appear to be at increased risk for anxiety disorders (Girdler, 2001). 

Results from both animals and humans have indicated allopregnanolone may blunt the unpleasant effects (e.g., anxiety, irritability, dysphoria) of meth withdrawal and that this action may be due to this hormone’s ability to decrease the effects of dependence and withdrawal on the composition of GABAa receptors in the brain (Finn, 2004). 

Withdrawal from meth appears to be associated with changes in the composition of GABAa receptors (Steketee, 2005; Grubb, 2002); and allopregnanolone has also been shown to inhibit some of the effects of meth in the brain (Kaminski, 2003). Here again, this may be due to its ability to prevent drug-associated changes in the composition of
GABAa receptors. 

Results from experiments described in this section and other similar studies have suggest that there may be a link between meth abuse, hormones in the brain, and changes in the GABAergic system that
may underlie some or all of the symptoms that patients experience
during withdrawal.

Tying It All Together
Scientists believe that allopregnanolone preserves the normal composition of GABAa receptors that might otherwise be lost during stressful situations.  This permits the calming action of GABAergic neurotransmission to operate normally and help us cope with stress and continue to function (Esel, 2006).  However, when individuals have abused methamphetamine and have become dependent on them, there is a chronic increase in allopregnanolone levels in the brain that is followed by a rapid drop went patients try to stop taking meth (Romeo, 1996). When allopregnanolone levels fall, GABAa receptors are no longer protected and changes in their composition that lead to withdrawal symptoms may occur.

WHAT DOES THIS MEAN FOR TREATMENT?
Reducing the severity of withdrawal symptoms has the potential to increase the chance that people tying to stop abusing meth will succeed (Poling, 2007; Trevisan, 1998).  Allopregnanolone, the GABAergic system, and particularly changes in the composition and function of GABAa receptors are now well known to be involved in these symptoms.  Given the key role of GABAa receptor changes in withdrawal symptoms, it is reasonable to suggest that treatments directly or indirectly aimed at preventing or reversing them would be very helpful in the treatment of meth dependence.  In fact, hormonal treatments and other therapies with the potential to preserve or reinstate normal GABAergic function have been shown to be effective in small uncontrolled studies of patients trying to stop methamphetamine use (Wilcox, 2006; Esel, 2006; Wong, 2004).  As our understanding of withdrawal symptoms in patients with meth addiction continues to grow, it is likely that additional therapies aimed at neurohormonal pathways with the potential to preserve normal GABAergic function will be developed.