NEUROCHEMICAL BASIS OF ADDICTION ASSOCIATED WITH DEPLETED DOPAMINE, GLUTAMATE, AND GABA
Modern addiction medicine now recognizes that substance dependency of any kind is a disease process of the brain that features lowered dopamine and glutamate neurotransmitter levels, and the presence of long-term THIQ deposits discovered some years ago in the brains of heroin addicts, sedative abusers, and more recently, alcoholics (the THIQ hypothesis posits that Tetrahydroisoquinalone- THIQ is a byproduct of incomplete aldehyde dehydrogenase metabolism, and is now reported to be a present and a contaminant in cigarette smoke, and was first discovered in the brains of alcohol addicts by Dr. Virginia Davis in Houston). The finding of THIQ in alcoholics and not only heroin addicts is attributed to the work of this Texas cancer researcher who examined the neurochemical levels in brains of known long term winos, and amazingly, found the formerly only heroin-addiction-associated substance, THIQ, present n their brains.
Importantly, as more legitimate research is done in this field of addiction medicine whose experimental basis is beginning only now to gain ground, models of neurochemical bases of addiction in the future may also feature lowered levels of GABA as the disease progresses (which is why during detox from chronic use of alcohol for instance, victims have shakes, can seize, and often experience profound depression, or why when use of addictive substances is chronic, or even periodic, the user feels an immediate contentment, slurred speech, balance deficits, and peace). I am currently exploring this possibility in addition to recent reports claiming, in addition, that cigarette smoke also may contribute increased levels of THIQ in the thalamus, which has been reported to remain in the brains of addicted macaques for up to 7 years post-last use.
The basis of my reasoning regarding GABA level depletion after long-term or chronic addiction of alcohol or benzodiazapines is based on the fact that if GABA is depleted due to continued stimulation from the incredibly potent agonists like alcohol or benzodiazepines during chronic addiction, and if the two substances that wildly boost GABA levels are alcohol and benzodiazapines (and dopamine levels), it is now believed consistent with this neurochemical model of reversible addiction upon long-term abstinence, that such long-term depletion of GABA is why speech, balance disturbances, and “an immediate glow” is experienced with intoxication in both the non-addicted user and in the chronically addicted, as GABA (also dopamine and norepinephrin) is/are “boosted”artificially by the alcohol or controlled substance and becomes chronically depleted, and also why seizures can occur ONLY with withdrawal from alcohol and benzodiazapines.
GABA and DOPA level fluctuations and eventual long-term lowering of the natural levels in the brain is also a potential reason why the continued use of the substances are required to “feel normal,” after acute withdrawal symptoms are experienced chronically, and why addiction is not a result of the addicted person’s will or choice, especially in the context of dopamine and craving.
There also is evidence now that other addictive substances boost the dopamine levels artificially, and thus disturb the so-called normal “hedonic set point” (see Kevin T. McCauley, M.D.-and his films and books from his Institute of Addiction Study-these videos present the state of the art thinking on the neuroscience of addiction) .
Much scientific work is needed in the field of addiction medicine, and I present a link to this hypothesis of Dr. McCauley and other experts in the field here because it is the best current explanation I am aware of which rationally explains why addiction is a disease of choice due to those centers of the brain that harbor the transmitters that control pleasure (DOPA in the thalamus and especially the nucleus acumbens), glutamate (as a memory-capturing transmitter of the pleasures boosted by dopamine increase)-which in turn become artificially agonized by food, drugs, sex, laughter, and other substances/behaviors that release dopamine), and ultimately, GABA (my surmise not Dr. McCauley’s) which is responsible globally throughout the brain as a dampening transmitter that when depleted to extremely low levels as experienced by those in alcohol or benzodiazapine detoxification, causes seizures, and when boosted artificially to high levels with alcohol or benzodiazapines during both periodic and addictive use, creates “a glow,” slurred speech, coordination deficits, and the warm feeling that ]everything is right with the world.
In light of these new neurochemical models of addiction, it should not be overlooked, that Bill Wilson, the co-counder of AA, claimed that as successful for many as Alcoholics Anonymous was, together with “The Program”in abating the disease of alcoholism for many sufferers, he also claimed as important as A.A. was vitamin B3 (Harper’s, The Drunk’s Club-A.A., the Cult that Cures, By Clancy Martin).
Other potentially addiction abatement compounds include, coconut oil, shown now to reverse “clock tests” by Alzheimer’s sufferers in about 3 months, magnesium glyconate as magnesium is chronically depleted in many of us, niacinamide as a more bioactively available form of niacin, progesterone cream, discovered as a result of female trauma patients’ enhanced recovery following catastrophic brain damage, Pregnenolone, DHEA, and bentotiamine (vitamin B1). The role of exercise in addiction recovery cannot be overestimated, as can support groups and of course A.A. But nutrition adjustments as are “huge emotional displacements” as described in Wilson’s big book cannot be over-appreciated.
Clearly, the science of addiction is at its infancy, and could use far more resources and help in reversing addiction. But some key experiments are now in place, as briefly alluded to here, for continued progress. Please see Dr. McCauley’s brief Youtube video here: