Physical Brain Changes That Sustain Addiction

James A. Dadzie

Abstract

Nora Volkow is a renowned research psychiatrist who is credited with identifying addiction as a disease rather than a moral failure. Before her groundbreaking work, most people believed that addictions could be overcome by will power and discipline. Her groundbreaking research was carried out using brain-imaging techniques such as positron emission tomography to investigate the impact of drugs like cocaine and methamphetamine on the human brain.

Introduction

Dopamine itself is a chemical in the brain which is often called the pleasure hormone. It is released when the people experience a pleasurable activity like sex or a drug for instance. Also, when a person receives a reward this chemical is released in the brain. The dopaminergic pathways as the name implies are channels within the brain that transport the neurotransmitter around. 

It had been known for a long time that the dopaminergic pathways in the brain get stimulated through the administration of addictive substances like methamphetamine, cocaine and basically any pleasure-inducing activity, even one as simple as eating (Volkow 2014). There was a missing link, however, between the initial stages of drug use where dopamine is released, and pleasure is experienced. With each administration of the drug, there comes a point where it is no longer as pleasurable as it used to be due to reduced levels of the dopamine neurotransmitter. Despite this fact, drug abusers tend to continually indulge in the use of addictive substances. This was the issue that intrigued Nora Volkow and she decided to investigate. More specifically, Dr. Volkow could not comprehend why even the definite eventual consequences such as institutionalization, poverty and even ostracism were not enough to dissuade drug users from usage. Her curiosity intensified with time and when she began clinical work at the New York University School of Medicine she had the opportunity to do so. She believed then as she does now that if scientists are able to come up with a drug which can interfere with the dopaminergic pathway connected to the frontal lobe it would be possible to keep addiction of different forms in check (Volkow, 2000). In order to make this possible, however, further studies on the issue would be necessary and this she set out to do.

In a review of existing literature on the issue of compulsive and impulsive behavior, Dr. Volkow makes mention of studies that have looked at the activity of the orbitofrontal cortex in persons exhibiting the behaviors (Volkow 2000). In particular she talks about Baxter et al and Model et al to mention but a few. The findings in all their studies gave evidence in support of the idea that patients who suffer from conditions that caused them to be compulsive, impulsive and obsessive all had increased orbitofrontal lobe striatal activation. An even more compelling case study lends greater credence to the idea that patients exhibiting compulsive behavior also have a malfunction within the orbitofrontal cortex. This case study was based on a patient who had had a lesion on his orbitofrontal cortex and this according to the evidence from studies, caused him to indulge in pleasure-inducing activities (Cohen et al 1999). In the review, she identifies the main brain circuit – dopaminergic pathway – whose excitement is sustained for prolonged periods for resulting in drug self-administration. She proceeds to give a brief overview of how this occurs and the symptoms a patient might present as a result. Dr. Volkow finally concludes with some therapies that might be helpful in gaining back control.

Approach

In order to properly investigate the issue thoroughly a proper experimental set up was necessary. This she set out to do and found individuals willing to participate in her study. In all, a total of fifty-eight (58) participants took part in Nora Volkow’s study. Twenty (20) of them were cocaine abusers and thirty-eight (38) were not. For the cocaine dependent subjects, the Diagnostic and Statistical Manual of Mental Disorder (DSM III R) was used to determine whether the participants could be classified as drug abusers or not. The DSM is a series of publications currently in its fourth edition that contains the names of all known psychological and mental disorders with their accompanying symptoms. So, in the case of Dr. Volkow’s experiment, the participants considered cocaine abusers would have met certain criteria and fit definitions of a drug addict in order to be classified as a cocaine abuser. Those assigned to the control condition on the other hand would have displayed none such features.

The advent of Positron Emission Tomography (PET) scans early in the nineties marked a new era in Dr. Volkow’s medical career. It opened up a whole new world of possibilities for a curious science student like her. It was an invaluable tool that she used on her subjects. Her control subjects had no history of head trauma or any medical condition of the brain in particular and the head in general that would skew the data. Brain imaging was done primarily with the help of the PET scans. When carried out on the brain, it produces a three-dimensional image of regions of interest and this helps researchers to have a good idea of the functions of the different brain regions in question.

Some self-report measures were included as well and in particular The Beck Depression Inventory Survey Scale. The BDI scale was used to ascertain the extent to which the cocaine abusers craved the drug during the study. The BDI scale is a set of twenty-one (21) items/questions given to participants as a measure of self-report. This is relevant to the study because the amount of craving experienced is directly related to glucose breakdown in the orbitofrontal lobe. The researchers used fludeoxyglucose (FDG) and N-methylspiroperidol (NMS) to determine the level of metabolic activity and dopamine D2 receptors respectively. FDG contains a form of glucose (sugar) which is the main component that is broken down during metabolism. It also contains very minute amounts of relatively harmless radioactive substance that helps the scanner track where in the brain metabolism is taking place. NMS on the other hand helped to track D2 receptor availability.

Results

The study provided evidence that supports the notion that cocaine abusers have a significantly lower number of D2 receptors in the frontal lobe as compared to normal controls. This is supported by the comparatively lower absorption of NMS in cocaine abusers. The availability of dopamine receptors and the Beck Depression Inventory showed a negative correlation. This means that as the levels of dopamine receptors continued to fall, the experience of increased craving by the cocaine abusers went higher up. Even with the introduction of dopamine agonists subjects still showed no signs of excitation which indicated the level of depletion of the neurotransmitter. Dopamine agonists were useful in this study because of their function. Dopamine agonists mimic the activity of dopamine when they come into contact with dopamine receptors but since the constant use of cocaine in addicts causes a reduction in the receptor, there is no visible activity where there otherwise would have been a lot of them.

Also according to the findings of Nora and her team of researchers, dopamine D2 receptors play a major function in the frontal lobe’s ability to control behavior. Therefore, the implication of their finding is that since these vital receptors fall below normal levels, it is highly likely that this explains their inability to resist the impulsive urge to self-administer. This is because the continuous use of the drug gradually deprives the brain of D2 receptors thereby impairing the individual’s ability to resist the urge to self-administer. The study further discussed the individual’s ability to resist the urge to self-administer and the circumstances that usually leads to relapse. The period immediately following detox in an addict is the most sensitive one for the individual. This is because they are very vulnerable to cues or anything that triggers memories of cocaine usage. The paper suggests that at that point frontal lobe metabolism returns to normal and so do dopamine levels; this causes them to begin craving the drug even more which probably explains why the relapse happens in the first place.

Moving forward, it will be beneficial if pharmaceutical companies are able to make a drug that can interfere with dopamine release and dopamine-dopamine receptor activity in a recovering addict especially in the presence of cues and triggers. In fact in her review of existing literature she mentions gamma vinyl GABA which is an anticonvulsant drug. The mechanism is as follows: to use the inhibitory properties of GABA to reduce level of excitement of neurons. This will cause the excitation phase to be stifled in its infancy as it were to prevent a desire to fulfill the need and urge to indulge the drug of abuse.

Conclusion

Dr. Nora Volkow is a very important person within the scientific community for obvious reasons; but that is not all she is known for. She has gained a lot of respect and admiration from her colleagues and superiors due to her administrative abilities. Without her presence at the National Institute on Drug Abuse (NIDA), mental health in general would not be getting the attention it is receiving now. She has helped to bridge the gap between research and clinical application of empirical findings. In addition to that, her own research continues to shed light on the nature of addiction and how best to deal with it. Nora Volkow is also a strong proponent of a multi-disciplinary approach to mental health issues. This means involving psychologists, medical doctors, administrators, pharmaceutical companies et cetera in designing long-lasting treatments for affected individuals. This idea and approach have begun to gain momentum very fast within the scientific community and has shown some very promising results.

Both the scientific community and the general public have Dr. Volkow to thank, for her relentless efforts and willingness to lead. Her efforts have certainly been useful in enhancing our understanding of addiction as a disease rather than a moral failure.

Discussion

The conclusion of the study was due to the existence of prior evidence in the empirical literature. Prior studies and hence existing knowledge suggested that D2 receptors played a role in executive function. The contribution of this study was to link the seeming inability to control the urges in an addict to a lack of the receptor.

The invention of PET scan at the time of Dr. Volkow’s residency proved vital in her quest to establish a causal link between addiction and D2 receptor density in the forebrain. The reason is attributable to the fact that without the technology it would have been impossible to compare the brain scans of addicts to those of a non-addict. It showed brain regions of high activity and hence the uptake of neurotransmitters relevant to this study in particular. The findings reported by Nora and her team were replicated successfully in obese rats by Johnson & Kenny 2010. The reward circuits in the brain that Nora pointed out to be affected are the same ones faulted by Johnson and Kenny (2010).

Through the efforts of Dr. Nora Volkow, both administratively and in the empirical literature, we have come to know the neural basis of addiction. We can now clearly pinpoint a brain circuit that has always been responsible for addiction but remained relatively unknown. For this, we have Dr. Nora Volkow to thank.