Understanding the neurobiology of addiction – An Interview with Dr. Cardwell Nuckols

Addiction is associated with changes in nerve cell function during which the brain attempts to adapt to a drug’s presence. But how is neurobiology related to addiction and can we predict (or prevent) addiction with the help of science? This and more in our exclusive interview with Dr. Cardwell Nuckols here.

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Current theories of addiction

Recent theories of addiction to chemicals (e.g. cocaine) and processes (e.g. gambling) have postulated that these behaviors are the product of an imbalance between three separate, but interacting, neural systems:

1.  An impulsive, largely amygdala-striatum dependent: a neural system that promotes automatic, habitual and salient behaviors

2.  A reflective, mainly prefrontal cortex dependent: a neural system for decision-making, forecasting the future consequences of a behavior, and inhibitory control

3.  And the insula that integrates interoceptive states into conscious feelings and into decision-making processes that are involved in uncertain risk and reward.

These systems account for poor decision-making (i.e. prioritizing short-term consequences of a decisional option), which can lead to more higher risk of use and relapse. And this is just a start. So, how can we really understand addiction as the condition is related to the brain?

We’ve asked the expert

Dr. Cardwell Nuckols is a leading expert in the field of brain function and addiction recovery. Here, he shares with us his knowledge and helps us understand of the relationship between neurobiology and addiction. We ask him questions like:

  • What is the known relationship between neurology and addiction?
  • Can research/science help us in predicting addiction?
  • What do we folks in addiction recovery really need to know about how our brains work?

Dr. Cardwell C. Nuckols is described as “one of the most influential clinical and spiritual teachers in North America”. His passion and mission is to assist in the integration of emerging scientific research with traditional spiritual and self-help knowledge. Dr. Nuckols’ formal educational background is diverse. He has undertaken formal studies in the areas of chemistry, pharmacology, neurobiology, education and psychology, as well as, a personal interest in the area of nonlinear physics.

If you have any questions on understanding the neurobiology of addiction, please leave them in the comments section below. We will do our best to provide you with a personal and prompt response.

ADDICTION BLOG: To what extent has neurobiology been studied in the field of substance abuse disorders?

DR. CARDWELL NUCKOLS: Since addiction is a brain disease, the foundation of such a statement must be established by neurobiological examination. In your introduction, you stated a number of neurobiological theories of addiction. Over the past 15 years, the increased utilization and precision of neuroimaging has given us a much better picture of what this brain disease looks like.

Neuroimaging gives the researcher clues as to how the drug works in the brain, as well as, the short and long term changes caused by the use of a substance. For example, functional Magnetic Resonance Imaging (fMRI) allows for the visualization of oxygenation and blood flow associated with certain brain activities. From such imaging, the brain’s response to cocaine cues can be observed. A structural MRI can show how chronic drug use can change shrink or enlarge different areas of the brain. Positive Emission tomography (PET) scans can show changes in metabolism in the brain before and after use.

It is the totality of the changes that occur in the brain over time that allows an understanding of not only what each drug does to the brain, but what happens when an individual continues to use the substance even after adverse consequences create the behavioral foundation of drug addiction.

ADDICTION BLOG: What are some of the cornerstone studies that have changed the way we understand addiction?

DR. CARDWELL NUCKOLS: There are two findings in the last 10-15 years that seem to be very important because of their clinical application.

1. The first of these is the discovery of the A-1 allele of the dopamine D2 receptor gene. The A-1 allele is a different configuration of the gene that would normally be involved in developing dopamine D-2 receptors. This particular gene is found in about one-third of the population, especially those with alcoholism in their blood lines. One of the major consequences of such a gene involves a low density of dopamine D2 receptors in the reward center (specifically the nucleus accumbens in the striatum).

Individuals with this allele often talk about how they didn’t feel happy growing up when comparing themselves to others, didn’t feel like they fit in and may describe problems with attention and motivation. For these individuals alcohol and drugs raised their dopamine levels when they started to use.

The major difficulty here is when a person quits using the alcohol or other drug, they still have the genetic problem. Interestingly enough there is some evidence using animal models that active participation in groups such as treatment and self-help groups can change genetic expression and improve dopamine functioning in the reward areas of the brain.

2. The discovery that there is much more to addiction than dopamine has also helped to better understand addiction. Even if dopamine reward is negated, animals will still continue to drug seek. Glutamate is involved in this seeking and is associated with the prefrontal cortex going off line and an elevated response to triggers or cues as the user reaches more severe stages of their addiction. Glutamate is also involved with the cognitive inflexibility found during early recovery.

Taken in total, the association of glutamate with the continued use despite adverse consequences stage of addiction gives us a neurobiological understanding of the words “powerless” and “unmanageability” as described in the First Step of Alcoholics Anonymous.

ADDICTION BLOG: Where are we now in our understanding of the relationship between neurobiology and addiction?

DR. CARDWELL NUCKOLS: Neurobiological changes lead to the hallmark features of addiction: craving, tolerance and physical dependence, including the acute abstinence syndrome.

The brain is a very neuroplastic organ. In other words, it responds to the environment. The term epigenesist means anything that changes genetic expression above the level of the gene (for example, a non-enriched environment versus an enriched environment). When alcohol and drugs are placed in the brain in higher doses and over a period of time, there are predictable changes that can take place. This describes the brain disease.

On the other hand, neuroplastic changes are also the hallmark of recovery. New neurons can form in areas of the brain especially those associated with learning – the prefrontal cortex, amygdala, striatum and the hippocampus. These positive brain changes are called recovery.

As mentioned above, an enriched environment such as a positive support group can alter dopamine functioning. An enriched environment enhances dopaminergic functioning while a non-enriched one does the opposite. This is one of the reasons stress can be so devastating to those in recovery. Both early developmental trauma and functional life stress as observed in a workaholic can lead to reduced dopaminergic activity and eventually craving.

ADDICTION BLOG: Can you explain to us the phenomenon of craving? Are we right to believe that craving is central to the condition of addictive patterns?

DR. CARDWELL NUCKOLS: From the DSM-5 perspective, craving itself is not necessary to diagnose a substance use disorder. However, craving is a condition that is generally present when individuals start to increase their use and reliance upon a chemical solution.

The presence of cravings correlates with increases in a region of the brain called the striatum an area associated with drug craving and reward-seeking behavior. However, there are many other brain areas involved in craving. For example, the hippocampus is involved in memory. The amygdala and the insula are involved in strong emotion and body sensations. The nucleus accumbens will release a little dopamine when the brain registers cues that remind it that drug use is forthcoming. In other words, the alcoholic or addict is “getting off” even before they actually use.

One way to think about cravings is to consider habit formation. Cravings are a programmed response to environmental signals that have been connected to drug use through experience (think Pavlov’s dog). Cravings are strong memories that are linked to the effect of drugs on the brain’s neurochemistry. Neuroimaging studies have shown intense brain activation when pictures that are linked to drug use (like a pipe or a syringe) are shown to addicts.

The immense neurotransmitter release that is often brought on by the use of drugs is responsible both for the experience and the lasting effects on learning. Memories are really the brain re-experiencing an event. It makes sense that reliving a drug, sex, or other past-compulsive experience would cause a serious emotional reaction and a strong memory of the event. When one remembers, cortical areas associated with the sights, sounds, smells, and thoughts related to the event are activated in a manner very similar to the initial experience. These strong learned associative memories can be triggered by anything that reminds the user of the positive aspects of their using experience (i.e. people, places and things).

ADDICTION BLOG: What role does repetitive behavior have in changing the choices we make?

DR. CARDWELL NUCKOLS: Repetitive behaviors lead to strong associative memories. As Donald Hebb, the Canadian psychologist, stated, “Neurons that fire together wire together.” This is true whether we are talking about the cues and triggers that lead to relapse or the changing of behaviors that lead to recovery.

In a habit, the brain reduces emphasis on decision making. Pattern unfolds automatically unless you find a new routine. After craving develops, one cannot extinguish a bad habit, you can only change it. Seemingly diverse choices — drug taking, eating quickly despite weight gain, and compulsive cleaning or checking — have an underlying common thread: rather that a person making a choice based on what they think will happen, their choice is automatic or habitual.

About 40% of people’s daily activities are performed each day in almost the same situations. Habits emerge through associative learning. We find patterns of behavior that allow us to reach goals. We repeat what works, and when actions are repeated in a stable context, we form associations between cues and response.

When a habit begins the whole brain is activated as it actively processes all of the stimuli. After this phase, the higher brain begins to reduce level of activation. Then, even the memory centers reduce activity. The basal ganglia has now taken control of recalling the patterns and acting on them. Cues and reward become intertwined creating a craving (conditioning).

To change a habit, one must address the same cues and rewards as before and feed the craving by inserting a new routine. Almost any habit can change if you keep the same cues and the same reward. Alcoholics Anonymous changes the habit loop and it succeeds because it helps use the same cues and get the same rewards, but shifts the routine.

ADDICTION BLOG: Is there such as thing as a predisposition towards addiction? If so, how is this mapped in the central nervous system (CNS)? If not, how does addiction develop in the CNS?

DR. CARDWELL NUCKOLS: This seems like a straightforward question but the answer is very complex. There is certainly a hereditary pattern found with alcoholism and other drug addictions. Both genetics and environment are important in the development of addiction.

It is estimated that 50% (a range of 40-60%) of the contribution is genetic. However, there a number of genes involved and certain variations in certain genes can make one more vulnerable to a substance use disorder. Think of it as a rheostat. Certain genetic variations turn the rheostat up making one more vulnerable while other variation may turn the rheostat down making one less vulnerable.

For example, let’s look at FAAH which stands for fatty acid amide hydrolase. FAAH is a protein and the instructions about how to make it, how much to make and when are all written in genetic code on a specific gene. FAAH is an enzyme that acts like a chemical screwdriver to deactivate anandamide. Anandamide is an endogenous cannabinoid related to the mood altering chemicals found in marijuana.

Anandamide is specifically responsible for regulating our level of anxiety. It is often called the “bliss” molecule (Ananda is Sanskrit for “bliss”). If you make less of it, you are going to be more prone to anxiety. In fact, many who consume cannabis do so because the cannabinoids in marijuana (specifically tetrahydrocannabinol) help people cope with feelings of anxiety. There is a variant of the FAAH gene that weakens the activity of FAAH. This causes you to have less FAAH and more anandamide. People with this variation are less prone to anxiety and may have an aversion to marijuana.

The A-1 allele of the dopamine D2 receptor gene mentioned above is another example of how genetic variation make us more vulnerable to addiction. Remember that you can have the genetic tendencies but if the environmental agent is not introduced (in this case alcohol and drugs) the tendency does not manifest itself as addiction.

ADDICTION BLOG: What are some of the crucial principles that we in addiction recovery need to understand about how the brain works?

DR. CARDWELL NUCKOLS: The most important concept in addiction recovery is the brain’s capacity for neuroplasticity. In as little as two minutes a new synapse can start to form or a dendrite start to branch out. In as little as seven days a new habit can form in the brain. Of course, this means work; doing the same recovery-oriented behaviors over and over again. As AA would say, “Keep it simple” and, “Take the body and the mind shall follow.” Also, “One day at a time,” and, “Keep coming back.”

Neuroplasticity refers to the brain’s ability to restructure itself after training or practice. In many ways, neuroplasticity is what makes personal growth and development possible at its most basic level. With the understanding that change is indeed possible, one is able to focus on the ways in which you’d like to grow instead of whether or not it’s achievable for you. Remember, the area of your brain you use or stimulate is the area that will grow and strengthen.

Recovery is at the same time both simple and difficult. During the progression of addiction to the point of continuing use despite adverse consequences, the prefrontal cortex goes “offline.” As this occurs, the alcoholic or addict has diminishing control over the impulses and urges of the lower brain. This was the case of Bill Wilson, the co-founder of Alcoholics Anonymous. Although he swore on the family Bible to his wife Lois that he would change his drinking ways, as soon as he got around the people, places and things that triggered alcohol consumption he had no ability to handle his desire for the drink.

Recovery can be understood as a process of bringing the prefrontal cortex back on line or, in the case of those from non-enriched and/or traumatic environments requiring habilitation, developing the prefrontal cortex. There is research that shows the level of prefrontal availability is correlated with the potential for recovery. The more the prefrontal is developed, the greater the chances for recovery.

ADDICTION BLOG: How important is education RE: Neurobiology to addiction recovery?

DR. CARDWELL NUCKOLS: It has been my experience that patients in treatment centers really like to understand both addiction and recovery in terms of how it all works in the brain. For example, by showing the individual how addiction causes the brain to lose its top down regulatory ability, the patient can understand that theirs is not a question of morality or poor will power but the result of a brain disorder.

I also believe the patient deserves to know as much as we can teach them about their disorder. Hopefully, someone who has a life threatening problem such as addiction would want to know as much as possible about their disease. Education also serves as a confrontational tool as they compare themselves with an accurate description of their illness.

Since the alcoholic and addict in early recovery can take in information but cannot use this information to create the knowledge of change, the way education is presented is critically important. To give the individual a 60 minute didactic or video is not good educational technique. There needs to be a feedback loop such that the clinician can evaluate what the patient learned from the session and how this is going to be used to change their behavior.

I generally recommend a 15-20 minute video clip or didactic followed by a sentence completion form that asks:

  • I think…
  • I feel…
  • I learned…
  • My future behavior will change…

The patients typically need help in translating the information into what they learned and how it will change their behavior.

ADDICTION BLOG: Does an understanding of biological processes alone help people to stop using?

DR. CARDWELL NUCKOLS: The understanding of neurobiology is no substitute for working a cognitive-behavioral and spiritual program of recovery. To understand does not necessarily equate with change.

Since addiction is a biopsychosocial illness and a spiritual malady, all areas from the psychological to the behavioral, cognitive and spiritual need to be fully addressed. This is called working a program of recovery and generally involves treatment plus social support such as AA, NA or any of the 12 Step recovery groups.

With this being said,each person has to find their own way and may find other means of support more helpful to them (i.e. church or another form of self-help). Although recovery is a personal issue and only the patient can take the necessary steps, it is expressed best in community where the patient by working their spiritual program with honesty and integrity then becomes able to help others in need.

Lastly, it has been my experience that knowing about your illness and even taking the necessary cognitive-behavioral steps if typically not enough. When the first big life crisis hits the individual will typically go back to what worked for them in the past: alcohol and drugs. It is the spiritual growth of the recovering person that gets them through the tough spots in life.

ADDICTION BLOG: What new developments are on the horizon for neurobiological treatments?

DR. CARDWELL NUCKOLS: In regard to pharmaceutical research, there are both top-down and bottom-up approaches in the search for medications that might help manage the symptoms of substance use disorders.

In the top down approach, medications that have already shown effectiveness for another disease or disorder and have passed the FDA’s safety and efficacy standards can be considered for their possible therapeutic effect for those suffering from addictive disorders. This is generally termed off-label use of the medication unless or until the FDA approves the medication for use with substance use disorders.

For example, buprenorphine has been used for many years in hospitals for its pain relieving ability. It represents a new class of medication called a partial agonist. Buprenorphine has a long half-life and a high affinity for mu opioid receptors and when it is used properly blocks the receptor sites such that use of an agonist opioid such as heroin, oxycodone and hydrocodone has little or no effect due to receptor blockade.

The bottom-up approach is a long and expensive road involving numerous clinical trials to show safety and efficacy. This generally involves a new drug that is being investigated, for example, to treat addiction. Since the price tag for such an approach can be in the 100’s of millions of dollars, this is usually fund by the pharmaceutical industry. It is a long, slow and expensive process that even if proven to be safe and effective takes a long time to get to market.

An example of the bottom-up approach and another interesting area of research involves the development of vaccines for use in addictive disorders. Vaccines for nicotine and for methamphetamine have gone beyond the dreaming stage. The National Institute on Drug Abuse (NIDA) awarded “visionary” grants to two scientists who believe that in the not-too-distant future, vaccines will be available not just for smallpox and whooping cough but also for substance abuse.

Current medications for drug abuse have only had limited success for drugs such as cocaine, nicotine, methamphetamine, and heroin. The use of vaccines is an entirely new approach. The antibodies generated from anti-drug vaccines can bind to the target drug (nicotine, methamphetamine, etc.) and form the antibody-drug compound molecules that are too large to cross the blood-brain barrier. This reduces the quantity of drug entry into the brain and inhibits the psychoactive effects of the drug.

If this antibody capacity is effective enough, it can lead to a reduction in drug use or even reduce the possibility of a relapse. Anti-addiction vaccines are designed for the following goals:

(a)  helping addicts achieve initial abstinence
(b)  preventing relapse after a drug-dependent patient completes withdrawal and is attempting to remain drug-free
(c)  enhancing behavioral therapies when combined with other anti-addiction medications
(d)  potentially preventing addiction in high-risk populations

ADDICTION BLOG: Is there anything else you would like to share with our readers?

DR. CARDWELL NUCKOLS: One last thought: in order for our recovery rates to see a marked improvement, the addictions and mental health fields need to learn how to effectively address the issue of trauma especially early life developmental trauma. In watching the profiles of the chronic recidivists (excluding the chronically mentally ill), the vast majority have issues above and beyond their addiction which is often self-medication gone awry.

Dr. Cardwell C. Nuckols is a clinical consultant to American Addiction Centers and serves as the Chair of their Clinical Advisory Board. He is also President of Cardwell C. Nuckols & Associates and author of over 30 books and workbooks. He is a national and international lecturer and is one of the most sought after spiritual and clinical trainers in North America.
About the author
Lee Weber is a published author, medical writer, and woman in long-term recovery from addiction. Her latest book, The Definitive Guide to Addiction Interventions is set to reach university bookstores in early 2019.
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