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The Science of Addiction

What is addiction?  The answer varies depending on who you ask. Google it and you will get hundreds of answers.  “ A biopsychosocial disorder characterized by compulsive use of the drug, obsession and preoccupation with the drug and continued drug use despite consequences” is a brief but comprehensive definition.  The American Society of Addiction Medicine (ASAM) website has a great but lengthy description of addiction. There are even books written on this subject. Almost all definitions include the common themes of loss of control, craving and/or obsession with the drug and continued drug use despite negative consequences. 

Addiction is accepted in the medical field as a chronic medical disease like diabetes, high blood pressure and AIDS.  In the 1930s (and before) addiction was thought of as a moral failing and lack of willpower. People with addiction were often expected by friends and family to stop using without help.  Treatment was in the form of punishment. However, research supporting addiction as a medical disease traces back to the 1940s. The Supreme Court declared addiction as a disease in 1962, the American Psychiatric Association followed in 1967; and the American Medical Association reaffirmed the definition in 1967.  But despite support from the medical field and the government, the disease concept of addiction remains controversial to some (although that number gets smaller and smaller).  

So what exactly is a disease?  Just like we identify an airplane as an airplane by it’s color shape, location and so on, a disease is a disease because of certain characteristics.  1) It has a clear biological basis, 2) a unique set of signs and symptoms 3) a predictable course and outcome and 4) An inability to control the cause.  In comparing diabetes and addiction they both have a biological basis: with diabetes the issue is with the pancreas, with addiction the issues is with the reward pathway of the brain.  Both have signs and symptoms: diabetes symptoms can include frequent urination, excessive thirst and extreme fatigue, addiction symptoms include obsession with the drug, continued use and inability to control use.  Both have a predictable outcome: if left untreated, each will lead to worsening of symptoms and subsequent death. Finally, the cause of either disease can not be controlled: diabetes involves changes in the cells of the pancreas, addiction involves changes in cells of the brain.  No one would choose to be a diabetic just like no one would choose to be an addict. The good news is both diseases can be treated to change their course and outcome.

 

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As mentioned above, addiction is a defect of the reward system of the brain.  The reward system of the brain consists of the ventral tegumental area (VTA), the nucleus accumbens and the prefrontal cortex.  This is sometimes called the primitive brain or “lizard brain”. Communication between these areas is a result of changes in polarization or charge in the cells of the brain called neurons.  Neurons have a receiving end (dendrite) and communicating end (axon). Between the receiving end and communicating end is a very tiny space called a synapse. Neurotransmitters (small molecules and tiny proteins in the brain) are released into the synapse by the axon.  They bind to receptors on the dendrite which set off a cascade of signals that communicate with neurons in other areas of the brain.

  

 

 

Several neurotransmitters are known to be involved in drug addiction. 

Dopamine: affects brain processes that control movement, motivation, emotional response and the ability to experience pleasure.  

Serotonin: involved in temperature regulation, sensory perception and mood control

Acetylcholine: released when nerves meet muscles, muscle contraction

GABA: strongly inhibits neurons

Glutamate: strongly excites neurons

These neurotransmitters and their effects in the brain are often the target of drugs of abuse.   Serotonin action is the target of many drugs used in treatment of depression. LSD is known to act on serotonin receptors.  Nicotine targets an acetylcholine receptor in the brain. GABA is directly effected by benzodiazepines like Valium and Xanax.  Alcohol acts through an effect on GABA and glutamate. 

The most studied neurotransmitter involved in the pleasurable and addictive effects of drugs is dopamine.  Changes in dopamine release and reuptake are involved in the euphoria of drug use. During drug use dopamine is released and signals to our brain that we are having a pleasurable experience.  It tells our brain to remember this environment (sites, sounds, smells and taste) because it is associated with a positive experience. This is why addicts can be triggered by things other than the drug; the sight of a needle for a heroin addict or touching a wine glass for an alcoholic.  Cocaine and methamphetamine directly target dopamine levels in synapses. With cocaine and methamphetamine use, dopamine levels surge 2-10 times higher than the levels of dopamine present as a result of healthy pleasurable experiences like eating or sex. Continued and repetitive use leads to persistently high levels of dopamine in the synapse.  Over time neurons will decrease the number of dopamine receptors so they are not constantly bombarded with a dopamine signal. Because the number of receptors at the synapse is significantly decreased by drug use, healthy pleasurable activities no longer signal “pleasure” or reward” and the addict starts to need the drug to feel “normal” and excessively high doses of the drug to get “high”.  In the absence of the drug the addict often feels depressed and finds little pleasure in activities. This usually improves over time as dopamine receptors regenerate. In the picture below dopamine receptor activity is shown in red. The picture on the left is a brain image of a non-cocaine user. The pictures on the right show the brain of a cocaine user one and four months after stopping use.  Dopamine activity is depleted in cocaine users but continues to increase over time if the cocaine user abstains.

Why is it that some people who use drugs become addicted while others who use drugs do not?  Is it nature, nurture or both? First it is important to identify the cellular cause of addiction.  In diabetes we know that the pancreatic cells are not producing enough insulin. In the brain we know that communication within the reward pathway has been dysregulated.  Specifically, we know that disruption of the neuron activity is caused by changes in neurotransmitter activity. An addiction is therefore due to neurotransmitter function dysregulation or a “hijacked brain”.  Dysregulation could be disruption of neurotransmitter production and release or receptors for these neurotransmitters might not work correctly.

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This dysregulation may be present before exposure to a drug due to genetics.  Something in our DNA may make us more susceptible to addiction. For example, low levels of dopamine or it’s receptors may be present from birth.  When there is exposure to a drug dopamine levels in the synapse will increase. These individuals are likely to become addicted because a drug will increase their dopamine levels to “normal” and beyond.  In support of this there are several research studies which show that dopamine levels are lower in the brain in depressed subjects. One article demonstrates dopamine levels are even lower after recurrent episodes of depression.

Alternatively, continued exposure to a drug may lead to neurotransmitter dysregulation within the “reward” system of the brain.  The process of changes in the brain is called neuroadaptation. This would explain why some people become addicted after years of use.

Lastly, neurotransmitter dysregulation could be the result of exposure to a stressor, like trauma.  DNA can be modified in a way that effects how a gene is expressed without changing the DNA code. The study of this field is called epigenetics.  Exposure to trauma is known to cause epigenetic changes. The DNA of military service members who are eventually diagnosed with Post-Traumatic Stress Disorder (PTSD) has been shown to be modified post deployment in comparison to their DNA pre deployment.  

This image demonstrates changes in brain metabolism in several mental disorders with PET scan.

In all likelihood the “highjacked brain” or neurotransmitter dysregulation is the result of some combination of the factors discussed; genetics, drug exposure and environment.

Now that addiction has been established as a disease of the brain how is it treated?  As a chronic disease addiction can be treated but not cured. This is the case for other medical diseases like AIDS and diabetes.  Treatment is an ongoing process that lasts a lifetime but symptoms can be very well controlled with the right treatment. Treatment of addiction is colloquially referred to as “being in recovery”.  Recovery quite literally means “a return to a normal state of health, mind, or strength”. Being in recovery to many means “on the right path”. So how do you get there? For most this involves multiple modalities including medical management, psychotherapy, structure and community.  Figuring out how to coordinate this can be difficult. In the beginning many people need help to establish their care. It can be dangerous to just stop your drug of choice and you may need a “time out” to take on this huge life change. WeRecover can help you. You’ll be asked a few questions about your medical history, drug/alcohol, health insurance and budget in a short, online questionnaire.  WeRecover will generate a list of reputable treatment facilities that fit your needs and budget. And it doesn’t cost anything. Finding treatment on your own can be overwhelming and stressful. Let WeRecover help you get to the start of a new life.

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References

  1. Erickson, CK. The Science of Addiction.  New York: W.W Norton and Company Inc., 2018.
  2. Pizzgalli, D et al., “Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder: In Vivo Positron Emission Tomography and Postmortem Evidence”, JAMA Psychiatry 2019; 76(8): 854-861
  3. Roth, TL, “How Traumatic Experiences Leave Their Signature”, Frontiers in Psychiatry 2014, 5: 93.
  4. drugabuse.gov
  5. www.psychologytoday.comwww.
  6. quora.com
  7. www.scistyle.com

 

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