Addiction: A New Treatment Paradigm

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

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The Biology of Addictions - Understanding to Treat Effectively

As with all difficult diseases that are hard to define and cure, the medical field promotes the idea that the disease of addiction is probably a matter of genetic predetermination. Despite an enormous amount of funded research into this field of study, though, especially with alcoholism, there has been little progress on finding any verifiable and firm genetic link, just the probable genetic inheritance of addiction, and an array of "genetic predispositions and vulnerabilities".

In 2010, experts from the University of Virginia and University of Michigan, Ming D. Li and Margit Burmeister, published a review of the science of the genetics of addiction and stated: "Both linkage and association mapping have identified susceptibility loci for addiction-related phenotypes (composite of traits), especially for alcohol dependence and nicotine dependence. However, few putative (reputed to be) genome linkages have been replicated in independent studies, probably because of genetic heterogenity (the inherent state of being different in kind or nature)." (see this article link below in additional information).

In other words, much evidence points to the possibility that there are a wide variety of of areas of the genetic code that harbor potential alleles or parts of alleles in the code that could be linked to addiction, but none that have been found in replicated studies so far. Research has uncovered a number of genetic variants and susceptibilities that may someday prove to be firmly associated with the complex array of dysfunctions that define addiction biologically, but not yet. These researchers concluded: "the exact nature of the variants and their functions are still unknown", referring to 6 genetic variants linked in some studies to addiction, but not replicated in other studies. These researchers also concluded: "Genetic-wide association studies (GWASs) with large samples should help to identify additional genes, including genes that implicate novel (new) biological pathways involved in addiction." Since current research has identified a cascade of dysfunctions in multiple areas of the brain that define addiction biologically and neurologically, this will be a broad search, especially if this research uncovers new biological pathways. Considering that current research on genomics finds that much of our genetic propensity has to do with variable genetic expressions defined by switches controlled by multiple genes, as well as the epigenome, a large array of molecules that surrounds our genetic core, finding some proof of genetic predeterminism is highly unlikely. Instead, focus is now directed at a complex combination of factors, environmental and biologically intrinsic, that work together to create increased susceptibility to addiction, and most of these factors are under the control of the individual, and the immediate parent (epigenetic traits in prevention), to affect correction or prevent occurrence in an addictive pathology.

The question of genetic causes of addiction will not produce a simple genetic cure in the near future, and this is certain. The study of genetics in addiction is also clearly not related to a predetermined state, either. What is does, or should, point to is how do we use this field of study in actual clinical application. The researchers at The Scripps Institute and National Institute of Drug Abuse found that the 3 stages of addiction, binge, withdrawal and craving, are associated with defined neurological and biological dysfunctions in specific areas of the brain. For instance, the binge stage shows changes in the ventral tegmental and ventral striatum, the withdrawal stage in the extended amygdala, and the craving stage in the prefrontal cortex, basolateral amygdala, hippocampus, insula and dorsal striatum, with disrupted control of inhibition associated with dysfunctions in the cingulate gyrus, prefrontal and frontal cortex. Most of these changes involved neuroadaptation in the mesolimbic dopamine system, affecting the balance of dopamine receptor types over time, and a cascade of changes in the glutamate receptors and serotonergic metabolism leading to dysregulation. The mesolimbic pathway is a dopaminergic (dopamine generating) pathway in the brain, beginning in the ventral tegmental area of the midbrain and connecting to the limbic system via the nucleus accumbens, amygdala and hippocampus, as well as the prefrontal cortex. This pathway is usually described as the reward pathway in the brain. Such study identifies novel therapeutic protocols that could be applied to aiding correction of these dysfunctions, as well as ameliorating the effects of withdrawal, supplying the brain with bioavailability of neurochemicals that are decreased dramatically when the drugs are withdrawn, prompting a cascade of dysfunctions. The dysfunctiions linked to the addiction cycle indicate that the therapy could be adjusted for these stages and their implications, as well as adjusted over the course of therapy to achieve restoration of normal homeostatic function, including genetic expressions of neurohormonal receptors and various protein regulators.

If the patient utilizes a step-by-step sensible protocol to first improve brain health and function, and then correct dysfunctions with the balance of dopamine, serotonin and glutamate receptors and neurotransmitters in the ventral tegmental and ventral striatum during the binging stage, or excessive drug use stage, a gradual normalization and minimalization of drug use may be accomplished before tackling the withdrawal stage. In this stage, protocols could be adopted to correct dysfunctions in the extended amygdala, an area that research has now shown is modulated successfully with specific electroacupuncture stimulation. This array of protocols could lead to a successful third stage, the improved control over craving and control of inhibition, with modulation of the crosstalk between the amygdala, hippocampus and insula, again areas proven to be significantly affected by specific electroacupuncture, and cognitive and behavioral protocols that modulate the prefrontal and frontal cortex. This last stage of the cycle, craving or relapse, involves a cycle of neurohormones that must act in a quantum field to achieve balance and control, and this homeostatic balance must be achieved. The key neurohormones in this cycle involve glutamates, acetylcholine and oxytocin, and their receptor types that must be expressed correctly to establish controlled mood and sense of desire.

Of course, with a disease as complex as addiction, there often must be a mind-body approach taken, and much research in the last few decades has led to increased use of Cognitive Behavioral Therapy (CBT) and emotional regulation to improve the outcomes. If only physical or biological dysfunction is addressed, but the emotional and psychological aspect is ignored, there will obviously be limited benefits for many patients. The utilization of CBT can involve a wide degree of variance and choice, and perhaps the drawback to this approach so far is that expensive and intensive programs have been designed for those with the financial means to put themselves in these programs. As we go forward with more accessible care we see that with a more informed and proactive approach that we could try to individualize such treatment and patients could achieve their goals without going to exclusive and expensive drug and alcohol treatment programs. In the specialty of Traditional Chinese Medicine emotional constraint and imbalance has long been cited as an important factor in disease, and the cycle of emotional regulation in the 5 Element pattern used to help the patient regain better homeostatic control. In TCM the specific emotions have been linked to the visceral systems in the body as well to help elucidate treatment strategies, and the importance of specific aspects of bodily health are related to emotional, or mind, health. While this mind-body approach can be daunting and complex at first, integration of simple short courses of individualized treatment combined with effective counseling and a proactive approach could help tremendously to restore a balanced cognitive and behavioral health. Patients may try an intensive program, or take a simpler approach and step-by-step gain understanding and regain a healthy underlying emotional, psychological and physical homeostasis.

Integrating a more holistic protocol of restorative medicine before entering standard addiction treatment may be the key to long-term success. To restore this homeostatic balance in the addiction cycle, the brain must be able to create or express a number of neurohormonal chemicals, and functional neuroplasticity must be reestablished. Merely supplying the brain with bioavailability of the affected neurotransmitters and stimulating these areas, the dopaminergic pathway, is not enough to fully correct the biological problem, though. MRI studies of the brain show that in the midbrain of patients suffering from addiction, that a loss of dopamine receptors is dramatic, and may occur in a short period of time with certain drugs, such as cocaine, which has been shown to block the dopamine transporter at the neural synapse, and prevent reuptake. Restoration of the dopamine receptor metabolism and expression is needed to get back to normal, even after the symptoms of addiction appear to be quieted.

The holistic treatment protocol must be persistent in the pathology of addiction. Dopamine receptors express in large numbers on neurons and appear to come in types, with GABA and glutamate highly involved in the regulation of these dopamine receptor types. Dopamine receptors are G protein-coupled receptors that are widely expressed in the body and mediate not only mood, but movement control, neuroendocrine secretions (hypothalamus), cognition and emotion, as well as some important autonomic functions, such as blood pressure and sodium homeostasis in the kidneys. Over time, dopamine receptors may be deprived of dopamine and become more sensitive to dopamine, or may be overstimulated by dopamine or dopamine agonists, resulting in decrease in the number of dopamine receptors and desensitization to dopamine. Desensitization is called tolerance, and partially explains the phenomenon of having to use higher dosages of drugs over time to get the same effect. Persistent normalization of dopamine metabolism and homeostasis is needed to fully correct the dysfunctions of dopamine receptor expressions. Merely blocking or inhibiting these dopamine receptors with pharmaceutical drugs may not only cause an array of adverse and unwanted effects, but leave the patient with just another addictive drug to contend with. By utilizing holistic medicine to help normalize this mesolimbic system of dopamine and GABA receptors, with the modulating effects of acupuncture and electroacupuncture, as well as the bioavailability of chemicals needed in this process, obtained from herbal and nutrient medicine, and combined with sensible cognitive and behavioral changes, this homeostasis programmed into the genetic code of the brain can be restored, or reset to normal.

In addiction, the question of physical addiction versus an emotional or mental addictive state has long been debated. Many drugs show strong signs of physical withdrawal symptoms, such as alcohol and opiate drugs, when the addiction cycle is strong, creating flu-like symptoms, delirium tremors, etc. while others show no physical symptoms at all. The physical signs of drug dependence are usually short-lived, even with strong drug addictions such as heroin and other opiates. The development of emotional and mental affective states that grow in strength with chronic drug use with withdrawal are now what most experts use to define addiction. These states are usually modulated by the central nervous system to reduce the intensity of hedonistic motivation and reward responses. Some hypotheses speculate that drugs could affect the areas and processes in the brain that deal with subconscious motivation for species preservation, allowing a compulsion to overuse the drug to supersede the basic instinct for species and self preservation. Other theories are that behavioral repetition plays a major role in defining the compulsion to use the drug more and more, with increased difficulty in breaking free of the "habit". The reinforcement of the idea that these drugs are themselves responsible for the addiction, rather than the user of the drugs, may reinforce this behavioral model. By understanding that the process of addiction is a mix of all of these aspects, biological, neurological, cognitive and behavioral, the hope is that addiction can be dealt with more easily at an early stage, and the addict may believe that he or she is not faced with an overwhelming external force, but something within their control, by utilizing a holistic protocol to address these various aspects of the addiction syndrome, and achieving a number of goals to aid a breaking of the cycle of binge, withdrawal and compulsion to start using again.

The subject of reward and motivation is an important topic to consider in the treatment of addiction. With many drugs, the feeling of reward and motivation appear to be heightened by the increase in dopamine, a neurotransmitter associated with such emotions. Dopamine appears to be balanced in the brain with serotonin to achieve normal emotional states, and modulated by the neurotransmitter GABA (gamma-aminobutyric acid), the chief inhibitory and modulating neurotransmitter in the human central nervous system.

Although technically classified as an amino acid, GABA is never incorporated into a protein, and thus is not like other alpha amino acids. While GABA is like an amino acid and can be supplemented in the diet, it does not cross the brain-blood barrier into the brain intact, and so attempts to use GABA to control brain dysfunction are not effective. Supplementation with GABA may only produce a placebo effect, and not actually effect the real GABA mechanisms in the brain. This does not mean that we cannot affect the GABA system with supplements and stimulation. GABA is synthesized in the brain as needed from glutamate, and this synthesis needs the enzyme L-glutamic acid carboxylase, as well as pyridoxal phosphate (P5P, an active form of Vitamin B6). To provide for improved bioavailability of GABA, one needs to supplement with L-glutamine, P5P, and inositol hexacotinate (an active form of Vitamin B3, or niacin). Such support of GABA bioavailability, along with dopaminergic and serotonergic herbs, and neural modulating herbs and acupuncture stimulation, provide the patient with addiction the tools to correct the neurobiochemical dysfunctions faster as they go through the withdrawal and craving compulsion, and try to adjust their cognitive and behavioral habits. So with an intelligently designed course of supplements, and adjusting of these in dose and time of taking intelligently, the needs of the addict when trying to lessen the cycle of negative emotional affect in withdrawal and the onset of compulsion to resume the drug abuse may be met. In more chronic states of drug abuse, the drug may heighten both dopamine reward and serotonin control, and alter the expression of dopamine, serotonin and glutamate receptors on the neurons. In this case, continued supportive therapy may be needed to achieve a normalization of receptor expression on these neural cells. The process of withdrawal supported by supplements and herbs that provide better bioavailability of the neurotransmitters affected may need to be repeated, with each resumption of the drug use achieving less addictive strength, and each withdrawal syndrome less dramatic in its emotional affect.

Research has revealed that specific acupuncture stimulation affects the addiction dysfunction via modulation of the GABA pathway that is integral to the dopaminergic regulation, as well as the modulation of coordination, or cross-talk, between key areas of the mesolimbic system. For instance, in 2015, experts at the Daegu Haany University College of Korean Medicine, in Daegu, South Korea, and the Mudanjiang Medical University, in Mudanjiang, China, showed that acupuncture stimulation at the point SI5 reduced the craving for morphine in laboratory animals via decrease in c-FOS expression in the ventral tegmental area of the brain and the nucleus acumbens, and this was mediated by the GABA pathway (PMID: 26276453). Prior study by these same experts in 2013 showed that acupuncture stimulation at the point HT7 attenuated the desire for morphine in laboratory animals, and that GABA receptor antagonists blocked this effect, proving that the acupuncture stimulation decreased addiction craving via the GABA system (PMID: 24905174). Control points used in these studies did not have this effect. Such research helps us define the most effective protocol in treating addiction, which needs to vary with the stages of addiction, the binge, withdrawal and craving. By intelligently combining this proven protocol with the appropriate herbal and nutrient medicines studied, the integration of TCM treatment protocols could greatly improve outcomes in addiction therapy.

Research has also found that much of the craving and withdrawal effects in addiction are modulated by the dynorphin/kappa-opioid receptor system, or KOPr. There are many receptors for opioid neurotransmitters in the brain, reacting to endorphin and dynorphin, and other endogenous opioids, such as enkaphlin. The two main types of opioid or opiate receptors are mu and kappa, and the kappa-opioid receptors for dynorphins were found to function as negative reinforcers of addiction, modulating the activity of dopamine, with the mu and kappa opioid dynorphin receptors providing a balancing regulation of dopamine activity. Studies have demonstrated that treatment to decrease the kappa dynorphin receptors and increase the mu dynorphin receptors are effective in the treatment of addiction, as wall as in the treatment of depression. Fortunately, it has long been known that specific types of acupuncture and electroacupuncture stimulation acts on these dynorphin receptors, and does this in a modulating way that helps restore this homeostatic balance. Many studies, over the last 4-5 decades, demonstrate that 2 Hz electroacupuncture significantly stimulates mu and delta opioid neurotransmitter receptors, while 100 Hz stimulates the kappa type. In fact, for decades, standard medicine used these studies to imply that acupuncture stimulation only acted by stimulating these opioid neurotransmitter effects, or endorphins, and thus had only a palliative effect. Little did they know that this effect, one of many measurable effects of acupuncture, would be so useful in treatment of not only pain, but depression, anxiety, addiction, neurodegeneration, and many other diseases. Short courses of frequent electroacupuncture stimulation could benefit greatly in the holistic treatment protocol of addiction.

These studies of the effects of acupuncture on opioid neurotransmitter receptors have now identified specific acupuncture points that relate to specific areas of the brain, and the U.S. National Institutes of Health, as well as other countries health institutes, are now mapping the effects on the brain from all of the main acupuncture points. Obviously, this type of understanding of the mechanisms of addiction and wealth of data concerning specific acupuncture and electroacupuncture effects and mapping of specific point effects can help guide acupuncture therapy in the treatment of addiction and withdrawal from addiction. Not only is this therapeutic protocol safe and effective, but it can be adjusted to help the patient during different phases of the withdrawal and craving. Obviously, a combination of specific herbal and nutrient medicines that are prescribed intelligently to address physiological needs and changes during the addiction and withdrawal cycle, with specific acupuncture and electroacupuncture stimulations designed to address changing needs during the cycle, provide a potential for a remarkable protocol that is sensitive to the changes in the brain during withdrawal and craving. Such research and understanding of the pathophysiology of addiction may provide the patient and the Complementary and Integrative Medicine physician the potential for a very effective and dynamic treatment protocol. Scientific studies cited and linked in Additional Information for this article provide specific information to help guide this acupuncture, herbal and nutrient protocol.

The Glutamate Homeostasis Hypothesis of Addiction is another GABA-related theory that is gaining acceptance, and is also tied to the food industry, which has developed a large array of glutamates for decades to promote desire and addiction to processed and fast foods. Addiction is associated with neuroplasticity in brain in the dopaminergic pathway mentioned above, with the prefrontal cortex assumed to have heirarchy in the regulation of behavior and cognition. The failure of the prefrontal cortex to control drug addiction has been linked to a growing imbalance between synaptic and non-synaptic glutamate and glutamate receptors, which impair communication, or cross-talk, between the prefrontal cortex and the nucleus accumbens. While new pharmaceuticals are being developed to treat addiction with drugs to block or alter glutamate and glutamate receptor functions, a safer approach would be to restore the glutamate homeostasis with a more holistic protocol. This is particularly effective in the negative reward pathway of addiction (in the habenula), which creates a feeling that the craving and anxiety goes away when the addictive substance is consumed. The neurotransmitters acetycholine and glutamate are integral to this system. Research by Ines Ibanez-Tallon at The Rockefeller University in 2015 showed that acetylcholine modulates the glutamate system in the habenula, and that blocking the release of acetylcholine in study animals decreased the negative reward in addiction. Since most neurons release acetylcholine and glutamate simultaneously, though, this finding presents questions. The experiment that stopped acetycholine expression decreased glutamate and glutamate reuptake, but blocking acetylcholine in the human brain would cause many adverse effects, and may be impractical. Restoring the acetylcholine and glutamate homeostasis would make sense, and decrease adverse effects of excitotoxicity and poor mood control. It is obvious that the glutamate metabolism is strongly linked to the acetylcholine metabolism, and that the GABA and dopamine receptor metabolism is strongly linked to the glutamate receptor metabolism. Instead of always seeking a simplified allopathic approach to these biological problems in addiction, why not work towards a more holistic, or quantum, goal. Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) could play an important part in this restorative treatment protocol.

Research in 2014, at the Medical University of South Carolina, also found that the level of oxytocin, a neurohormone produced mainly in the hypothalamus and secreted mainly from the pituitary, is also integral to the glutamate and glutamate receptor metabolism in relation to addiction. Prior studies have shown that changes in the activation of metabotropic glutamate receptor (mGluR) stimulated oxytocin release, and that oxytocin modulates both GABA and glutamate metabolism in various areas of the brain. There is obviously a complex cycle of homeostatic feedback controls that needs to be normalized in addiction. The 2014 study at the University of South Carolina found that "oxytocin mediates cocaine seeking through interaction with the glutamate receptor systems via second messenger cascades in mesocorticolimbic regions." A 2012 study at Shenyang Pharmaceutical University, in China, found that oxytocin affected extracellular glutamate levels by attenuating excess glutamate in the prefrontal cortex and attenuating deficient glutamate in the dorsal hippocampus induced in laboratory animals by methamphetamine. The oxytocin also increased basal GABA in the prefronatal cortex and dorsal hippocampus in these experiments, and inhibited a methamphetamine-induced decrease of GABA in the dorsal hippocampus, benefiting control of mood in withdrawal treatment. All of these studies can be seen in Additional Information and Links to Scientific Studies in this article. Oxytocin has also been found to inhibit the tolerance to opiates, cocaine, and alcohol, decreasing the need for higher dosage, as well as reducing withdrawal symptoms.

Many studies have confirmed the effects of acupuncture stimulation on endogenous generation of oxytocin, linking this to the positive effects of acupuncture in pain relief, facilitation of birth delivery, and even the placebo effect itself. In recent years we have also seen that deep tissue massage, or soft tissue physiotherapy significantly increased oxytocin levels, and that the bioidentical hormone pregnenelone beneficially modulates the glutamate receptor metabolism to enhance oxytocin effects. Of course, synthetic exogenous oxytocin therapy has been created, and of course comes with considerable adverse effects. Treatment with acupuncture and Tui na (deep tissue physiotherapy) in addiction could accomplish a variety of goals in a single treatment, all in a modulatory manner, safe and effective with no adverse effects.

Oxytocin, until recently just associated with childbirth changes in the cervix and uterus, has now been found to be a very important brain hormone with many beneficial effects. Oxytocin is released from the hypothalamus and distributed by the posterior pituitary in the adrenal axis, and is integral to emotional patterns of bonding, social interaction, trust, maternal behavior, and appears in studies to have greater effects in women. Other studies have shown that oxytocin has anti-depressant effects that are linked to its interaction with other neurohormones in a quantum field of biochemical effects, as studies using an oxytocin receptor antagonist did not decrease this anti-depressant effect. Oxytocin receptor expression and interaction with glutamate receptors, both G-protein-coupled receptors that rely on sufficient levels of magnesium and cholesterol to function, are important in establishing improved mood, social behavior and resistance to addiction. A more holistic array of modulating effects in treatment, persistent for some time and integrated with cognitive and behavioral therapy, may be very important in integrative approaches to treating addiction.

What we can deduce from this study of oxytocin effects is that optimal function of the hypothalamus and bioavailability of precursors to glutamate, GABA and acetylcholine may aid in the process of treating addiction immensely. Acupuncture and herbal / nutrient medicine could be an important array of tools in this protocol. Oxytocin is a neurohormone once studied primarily for its role in uterine contractions and labor, and stimulation of nursing reflexes, but was later found to have a variety of important roles in the body, with many studies showing that levels are increased with physical and social bonding, and are often higher during periods of waking during the night. Many studies now confirm the role of oxytocin in psychology, and memory of social bonding, but in a nuanced and modulatory manner. Oxytocin nose spray is now being used medicinally, but with mixed results, as the holistic cycle of neurohormonal balance appears to be more important than just the level of oxytocin. Restoration of this neurohormonal balance is the key to success, and the study of neurohormonal immunopsychology is discovering the importance of such restorative medicine. Many studies have demonstrated that specific acupuncture stimulations modulate oxytocin release, and even stimulation of 13 specific acupuncture points by application of essential oils has shown that oxytocin levels could be increased by such stimulation. The most effective benefits in treatment of addiction would be to utilize a more thorough and holistic approach to restorative balance, though.