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No man is free who can not control himself.
–Pythagoras
Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity
s the biology of addiction has become better–understood in recent decades, the once–common social stigma of addicts as “weak–willed” or morally lacking has given way to the knowledge that those suffering from substance abuse are often nearly incapable of exerting willpower over their affliction. This greater understanding has led, not only to a more compassionate view of the addict’s plight, but to significant improvements in treatment success. Modern treatment of substance abuse, though still far from perfect, is often life–saving precisely because the biology of addiction is now able to be addressed with a greater degree of chemical precision.
When we think of addiction, however, it’s still common for many of us to think merely of the dependence which accrues with the use of substances such as alcohol, nicotine, or opiates. But the same biology which drives substance abuse may also underlie many compulsive and self–destructive behaviors – even those not yet defined as addictions, per se. Some researchers, for example, noting that interventions geared towards combating the modern epidemic of obesity have met with nearly complete failure, have begun to wonder if the treatment of obesity would benefit if the disorder were approached as form of addiction. The implication of this stance is that many overweight and obese people could be seen as having no greater physical control over their attraction to food than, say, alcoholics have over their attraction to alcohol. In many ways, then, obesity could be seen as an even more challenging addiction to treat than alcoholism – though an alcoholic can learn to abstain from alcohol completely, the overweight person can never completely abstain from food.
Of course, this sort of forward–thinking approach has yet to reach the public consciousness en masse, and, unlike addicts, many overweight people in our society are still assumed (at least implicitly) to owe their plight to laziness or their lack of discipline. The relevant research in addiction, however, gives many reasons to hope that the overweight or obese individual may soon be treated with far greater success in the clinical realm, and with far greater compassion within the culture at large.
We’ve seen in previous articles in this series just how important nutritional substances such as magnesium can be in combating mood–related disorders like depression and anxiety. The benefits of these nutrients, it turns out, may also extend to the realm of addiction. There is much evidence to show, in fact, that addiction often takes hold precisely because drugs, food, and alcohol are initially used as forms of “self–medication” for depression and anxiety. But while alcohol, cigarettes, or “comfort foods” may initially boost a person’s mood or calm the nerves, in the longer–term, these substances only serve to make overall health (including depression and anxiety) worse.
So, can correcting the nutritional imbalances which lead to depression and anxiety in the first place also help to curb addiction? The possibility shouldn’t be ignored. As the research advances, it’s become clear that addressing the interrelated disorders of anxiety, depression, and addiction in a physiologically–sound manner will necessarily include significant nutritional support.
In addiction, as in depression and anxiety, we find that the function of the excitatory amino acid, glutamate, plays a major role. Similar to their effects on depression and anxiety, magnesium and related nutrients needed to calm the neuronal storm of excessive glutamate signaling, may also offer significant nutritional support for those struggling with addiction and the many compulsive disorders which have a similar biological basis.
Glutamate In Addiction
For decades it has been known that genetic and environmental factors play complex and often overlapping roles in addiction. But, more recently, the neurochemical study of addiction has offered an even greater insight into the disorder – and, in so doing, has opened up unique avenues of potential treatment.
Most modern addiction research has involved the study of a neurotransmitter, called dopamine. It’s thought that virtually all addictive drugs increase dopamine release in the reward centers of the brain – and as a brain chemical largely involved in triggering motivation, drive, reward, and pleasure, it’s easy to see how dopamine may play a central role in the biology of addiction.
But researchers now know that dopamine isn’t the only substance driving the addictive process. More recently, researchers have begun to find that many chemicals, including the neurotransmitter, glutamate, play major roles in establishing and perpetuating addiction:
Study Link – Glutamatergic mechanisms in addiction.
Quote from the above study:
Traditionally, addiction research in neuroscience has focused on mechanisms involving dopamine and endogenous opioids. More recently, it has been realized that glutamate also plays a central role in processes underlying the development and maintenance of addiction. These processes include reinforcement, sensitization, habit learning and reinforcement learning, context conditioning, craving and relapse.
With what we’ve learned about glutamate’s essential role in memory and learning, it’s not surprising to find that glutamate has now been linked with addiction. In simplified terms, while dopamine may be responsible for the (initial) pleasurable reward associated with addictive substances, and may be responsible for the motivation and drive behind seeking ones substance (or behavior) of choice, it’s the concomitant flood of glutamate which is needed in order for the brain to learn that a certain pleasurable experience was associated with a certain drug, substance, food, or behavior. It’s now thought that the two chemicals act synergistically, as glutamate chemically hardwires the initial dopamine–driven pleasurable experience upon the emotional brain. In this sense, addiction can be seen, biologically, as the process of learning gone awry:
Study Link – Addiction: Making the Connection Between Behavioral Changes and Neuronal Plasticity in Specific Pathways.
Quote from the above study:
There is an emerging consensus that drug addiction is a form of maladaptive learning. Drugs of abuse usurp the neuronal circuitry involved in motivation and reward, leading to aberrant engagement of learning processes. As a result, drug–associated cues can trigger craving and compulsive drug–seeking behavior, and voluntary control over drug use is lost.
Armed with this insight, researchers have found that some chemicals which block the function of glutamate at various neuronal receptors (i.e., glutamate antagonists), may be effective treatments for addiction:
Study Link – In search of a new pharmacological treatment for drug and alcohol addiction: N–methyl–d–aspartate (NMDA) antagonists.
Quote from the above study:
It is hypothesized that NMDA receptors mediate the common adaptive processes that are involved the development, maintenance, and expression of drug and alcohol addiction. Modulation of glutamatergic neurotransmission with NMDA receptor antagonists offers a novel treatment approach.
Complicating matters however, is the fact that some drugs which block glutamate receptors (or impair glutamate signaling) in the short term may do the exact opposite in the longer term. This may be why some anti–glutamate drugs have addictive potential of their own. Anti–glutamate anesthetics with abuse potential, like ketamine and PCP , fall into this category. Another interesting example of a common drug which may exert anti–glutamate activity in the short–term, but which may ultimately increase glutamate’s activity in the longer term is the well–known addictive drug, alcohol.
Alcohol Addiction and Withdrawal
In the short term, alcohol can inhibit glutamate’s activation of the NMDA receptor, thus inhibiting the excitatory flow of calcium into the brain’s neurons. This inhibitory effect reduces neuronal activity, and, as any social drinker can attest, the accompanying sedating effect often serves to reduce inhibitions and anxiety, while elevating mood. In the longer term, however, precisely because alcohol inhibits NMDA receptors, the brain responds defensively by up–regulating, or increasing the number of NMDA receptors in certain structures of the brain:
Study Link – Glutamate receptors in the frontal cortex of alcoholics.
Quote from the above study:
Alcohol has two opposite effects on glutamate receptor ion channel complexes, depending upon the duration of exposure. Acute exposure to alcohol inhibits ion flow through these receptor–channel complexes, whereas chronic exposure up–regulates the number of these receptors and thereby increases ion flow. Acute withdrawal from alcohol results in hyperexcitability and seizures in the presence of up–regulated channels, thereby making postsynaptic neurons vulnerable to excitotoxic damage.
As NMDA receptors increase in number in response to chronic alcohol consumption, the potential for harm increases also – especially if alcohol consumption is ceased “cold turkey.” Without the NMDA–inhibiting effects of alcohol, there occurs massive stimulation of the now–increased number of NMDA receptors. This stimulation is thought to be responsible for delirium tremens, or the “DTs” of alcohol withdrawal. Symptoms of delirium tremens include: hyperexcitability, panic attacks, anxiety, seizures, hypertension, hallucinations, “adrenergic storm,” and cardiac arrhythmia. So while the addiction to alcohol, itself, can certainly be life threatening, the withdrawal process can be deadly as well due to a flood of glutamate activity.
Alcoholics are well–known to exhibit compromised magnesium status, and knowing the integral role magnesium plays in preventing excessive NMDA stimulation via glutamate, it’s not surprising that the symptoms of delirium tremens are the exact same as those of extreme magnesium deficiency. Stimulation of the NMDA receptor removes magnesium from its proper place in the neuron, and some researchers have provided strong evidence that delirium tremens is, in fact, the manifestation of a cellular magnesium deficiency brought on by excessive NMDA stimulation:
Study Link – Delirium tremens: a clinical example of cation pump failure?
Quote from the above study:
We propose that delirium tremens is an example of cell cation pump failure in which magnesium (Mg) deficiency plays an integral role.
It’s often presumed that alcoholics manifest severe magnesium deficiency due to their particularly poor diets – obviously, it’s common for alcoholics to consume alcohol at the expense of nutrient–rich foods. But studies have found that alcohol, itself, causes magnesium to be excreted at an accelerated rate:
Study Link – Effect of Ethanol Administration on Urinary Excretion of Magnesium And Other Electrolytes In Alcoholic And Normal Subjects.
Quote from the above study:
The most significant and consistent finding was a marked increase in magnesium excretion after the administration of ethanol in all ethanol–loaded subjects.
But, in addition to a poor diet and the consumption of substances which deplete magnesium, it may be that the biology of addiction, itself, which causes magnesium deficiency. As evidence, we find that it’s not just addictive substances which are associated with glutamate–driven withdrawal symptoms. The withdrawal from behavioral addictions, in fact, often mimics the withdrawal symptoms of alcoholism. Compulsive gamblers, for example, have been found to exhibit many of the same physical symptoms during withdrawal as alcoholics and those with other substance–base addictions:
Study Link – Cessation of High Frequency Gambling and 'Withdrawal' Symptoms.
Quote from the above study:
The content and frequency of these reported disturbances were similar to those reported by high frequency alcohol drinkers on cessation of drinking and it was suggested that in the context of a study of alcohol and related problems they would be labeled 'withdrawal' symptoms.
Study Link – Self–Reported Withdrawal Symptoms and Pathological Gambling.
Quote from the above study:
Sixty–five percent of the pathological gamblers (vs. only 2% of controls) experienced at least one of the following: insomnia (50%), headaches (36%), upset stomach or diarrhea (34%), loss of appetite (29%), physical weakness (27%), heart racing or palpitations (26%), shaking (19%), muscle aches or cramps (17%), difficulty breathing (13%), sweating (12%), and chills or fever (6.5%). In addition, 91% experienced “cravings” and 87% felt “restless and irritable” when attempting to cut down or stop gambling.
Fittingly, some research suggests that glutamate–modulating agents may be of some benefit in treating gambling addiction:
Study Link – N–Acetyl Cysteine, a Glutamate–Modulating Agent, in the Treatment of Pathological Gambling: A Pilot Study.
Quote from the above study:
The efficacy of NAC lends support to the hypothesis that pharmacological manipulation of the glutamate system might target core symptoms of reward–seeking addictive behaviors such as gambling. Larger, longer, placebo–controlled double–blind studies are warranted.
So, it seems clear that excessive glutamate signaling underlies not only the formation, and perpetuation of addiction, but also the universal symptoms of addiction withdrawal. As a fundamental nutrient responsible for blunting glutamate signaling, magnesium has been shown to offer great promise as a nutritional adjunct to various types of addiction treatment.
Magnesium in Addiction
Magnesium is likely to exert a beneficial effect upon addiction–related neurochemistry via several interrelated mechanisms. Magnesium has, for example, been shown to ease symptoms of opiate withdrawal:
Study Link – The use of magnesium in opioid detoxification and withdrawal.
Similarly, animal studies have found that magnesium administered along with morphine increases the drug’s pain–killing effectiveness while reducing the development of drug dependence:
Study Link – Magnesium Increases Morphine Analgesic Effect in Different Experimental Models of Pain.
Study Link – Magnesium influence on morphine – induced pharmacodependence in rats.
Other human studies show that magnesium may be able to lower opiate use and the craving for cocaine in addicted subjects:
Study Link – A Preliminary, Controlled Investigation of Magnesium L–Aspartate Hydrochloride for Illicit Cocaine and Opiate Use in Methadone–Maintained Patients.
Magnesium may also be of significant benefit for nicotine addiction. Research has shown, for example, that chronic smokers receiving magnesium smoke significantly fewer cigarettes:
Study Link – Magnesium influence on nicotine pharmacodependence and smoking.
Quote from the above study:
Our data show that patients that received magnesium therapy showed a significant decrease in the number of cigarettes smoked and Fagerstrom test after 4 weeks [Fagerstrom score 7.93 +/– 0.17 before magnesium therapy versus 6.78 +/– 0.18 (P < 0.05) after 28 days of magnesium therapy]. In the group of smokers who did not receive magnesium, the Fagerstrom score did not change significantly [Fagerstrom score 7.48 +/– 0.22 initial versus 7.24 +/– 0.19 after 28 days].
Other Related Nutrients
Many nutrients besides magnesium have been used successfully in various facets of addiction treatment. Orthomolecular physicians (i.e., physicians employing the use of nutrients therapeutically) have published many case reports and studies showing that nutrition, even in conjunction with pharmaceutical therapy, can play a major role in the recovery from addiction.
High doses of Vitamin C, for example have been shown to significantly lessen the severity of symptoms associated with heroin withdrawal:
Study Link – Ascorbic acid (vitamin C) effects on withdrawal syndrome of heroin abusers.
Quote from the above study:
The results indicate that high doses of ascorbic acid administered orally, may ameliorate the withdrawal syndrome of heroin addicts.
And, similarly:
Study Link – The use of ascorbic acid and mineral supplements in the detoxification of narcotic addicts.
Levels of all B Vitamins are known to be compromised by addictive substances. For this reason, nutritional support for substance abuse is sure to include a full complex these nutrients. In alcoholism in particular, high doses of Vitamin B3 in the form of niacin (i.e., nicotinic acid) have shown promise in reducing many symptoms of the disease. The study below, for example, found that niacin was effective in improving sleep patterns, mood, and overall functioning in alcoholics, while significantly reducing acquired tolerance to alcohol:
Study Link – Status Report Concerning the Use Of Megadose Nicotinic Acid in Alcoholics.
Like magnesium, zinc is an important mineral nutrient which helps to prevent excessive glutamate–induced neuronal stimulation. Animal studies have found that alcohol intake depletes zinc from the brain, and that the administration of zinc reduces voluntary alcohol consumption in laboratory rats:
Study Link – Reduction of voluntary alcohol consumption under the effects of prolonged–action zinc.
Though more effective than in years past, addiction treatment remains largely unsatisfactory in helping those with addiction regain a normal life. Even among patients who have completed addiction treatment programs, the chronic threat of relapse remains for life. Long–term follow–up studies on previously–treated heroin addicts, for example, have shown that 33 years after treatment, nearly half of the treated patients had died – most of these deaths due to drug overdose or violence. Of the previously–treated addicts still living, 23.5% were incarcerated, and of the non–incarcerated 40.5% reported heroin use within the previous year. Relapse was associated with poorer health overall, and a greater degree of psychological distress and economic hardship.
At the very least, it seems that interventions as promising and as low–cost as nutritional therapy should be given greater attention by addiction researchers. But, if unfamiliar with the existing research, it’s understandable that practitioners may underestimate the therapeutic power of nutrition in combating substance abuse – many treating physicians may wrongly assume that simple nutrients such as vitamin C or magnesium will be no match for powerfully addictive substances such as morphine or heroin.
But it seems strange that the power of proper nutrition has also yet to be recognized in combating another addiction–related public health threat – namely, the modern epidemic of overweight and obesity currently found in many industrialized nations. The medical community often parrots conventional wisdom in imploring overweight people to “eat less and exercise more,” but the scientific literature clearly shows that this approach is almost completely ineffective over any extended period of time. Just like the addiction treatment of decades ago, modern approaches at weight loss lack the biological precision many people need to achieve long–term success.
We’ve noted that the same biology which underlies substance and behavioral addiction may also underlie the often uncontrollable urge to over–consume certain foods. Similar to the treatment of addiction, any attempt at combating overweight or obesity without addressing the underlying biology involved is likely to meet with very little long–term success. In the next Integrated Supplements newsletter, we’ll examine how the nutritional shortcomings of our modern food supply may be triggering the addiction–biology associated with overeating, weight gain, and obesity.
Articles in this Series:
Part 1 – Magnesium and the Mind/Body Connection in Disease
Part 2 – Magnesium – Nature's Calcium Blocker
Part 3 – The Calcium–To–Magnesium Ratio
Part 4 – Glutamate in Mood Disorders
Part 5 – Addiction
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity
Part 6 – Glutamate and The Biology of Addiction in Overweight and Obesity
About Us: At Integrated Supplements, our goal is to bring you the wellness information and products you need to live your life to the fullest. We are dedicated to producing the highest–quality, all–natural nutritional supplements; and to educating the world on the health promoting power of proper nutrition. You can find out more by visiting: www.IntegratedSupplements.com
These statements have not been evaluated by the FDA. No Integrated Supplements product is intended to diagnose, treat, cure or prevent any disease.
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