Drug Use in Philadelphia - Neurobiological Mechanisms of Drug Seeking Behaviors

Neuroadaptations and Addiction 

Drug addiction is a complex and daunting issue that impacts millions of individuals in the United States every year. Philadelphia, home to one of the largest open-air drug markets in the United States, reports over 1,400 fentanyl-related overdose deaths per year [1]. Understanding the complex neurobiological mechanisms behind addiction, long-term drug use, and continued drug-seeking behaviors–as well as the long-term neurological changes that result from drug use– is key to effectively treating substance abuse disorders. A key factor to consider when aiming to understand the impact of drug use on the brain is neuroadaptations. 

Central to understanding addiction are neuroadaptations–biological changes to the brain’s structure and function caused by long-term drug use [2]. These changes occur as the brain adapts to increased levels of dopamine and serotonin, neurotransmitters that have increased signaling due to long-term drug use [3]. Both of these neurotransmitters play an essential role in mood, reward, emotional regulation, and motivation, highlighting their role in addiction [2]. Over time, these adaptations increase the likelihood of long-term addiction, complicating recovery efforts for individuals with long-term exposure [4].

The Role of Dopamine in Addiction

It is impossible to discuss neurological processes relating to addiction without discussing the complex and vital role that dopamine plays within our neurobiology. Dopamine catalyzes and controls various behaviors and systems within the brain, such as learning and memory, attention, and complex executive functions like long-term reasoning and decision-making [5]. 

The dopamine pathway specializes in the reward system, which governs feelings of pleasure and motivation. Under the reward prediction model, dopamine neurons adjust their firing rates based on the difference between expected and actual rewards [4]. When a reward exceeds expectations, such as the effects of substance use–dopamine neurons increase their firing rates. Conversely, reduced rewards result in a decrease in dopamine neuron firing rates. This process is known as incentive salience [3]. Substances such as fentanyl disrupt the brain’s dopamine processing system, causing substantial dopamine surges. 

Stages of Addiction 

Addiction studies reveal that long-term drug-seeking behaviors are observed through a three-stage addiction cycle: increased incentive salience, decreased brain reward and increased stress, and compromised executive function [6].

During the first stage, initial substance intake of opiates increases dopamine firing in the basal ganglia [4]. Over time, incentive salience creates connections between the pleasurable experiences caused by drug use and external cues. These external cues, such as people and environments, are associated with pleasurable feelings that motivate urges. 

In the second stage, individuals experience negative physical and psychological withdrawal effects from drug use. This stage also includes diminished baseline pleasure due to activation of the extended amygdala [4]. 

The final stage exhibits preoccupation/anticipation in which the prefrontal cortex–a region responsible for decision-making and impulse control–cannot regulate itself. Long-term drug users begin to display compulsive drug-seeking behaviors due to the dysregulation of this region, causing decreased impulse control and long-term planning ability [6]. Withdrawal symptoms amplify the effects during which drug use naturally increases in an attempt to counteract negative physical and psychological effects [6]. This increased drug intake shifts behaviors from impulsive to compulsive and leads individuals to lose control of executive function. 

The length of the three stages of the addiction cycle varies per individual. However, its intensity heightens as the stress system becomes more active and the reward system is overworked. This is in comparison to healthy individuals, where the stress response system is regulated and less active. Over time, the abnormalities in dopaminergic and serotonergic transmission lead to long-term damage to the reward system [4].

Treatment and Challenges

The neurological complexity of addiction poses significant challenges to finding treatments. This requires that addiction treatment be catered to individuals on a case-by-case basis, highlighting that a one-size-fits-all approach is impractical and poses the risk of unsuccessful treatment methods and future relapse. 

Withdrawal symptoms, both behavioral and molecular effects, present major challenges for individuals in active addiction. On a behavioral level, individuals exhibit heightened agitation, anxiety, insomnia, and nausea. Molecularly, withdrawal causes changes in feedback inhibition in endogenous ligands, which play a key role in regulating the cortisol response to stress, leading to amplified withdrawal symptoms [2]. 

Understanding neurological processes that trigger drug abuse is essential to understanding treatment methods. An analysis of the first stage of the addiction cycle indicates that incentive salience plays a key role in continued drug-seeking behaviors. Incentive salience occurs as individuals begin to relate factors independent of the substance with feelings of euphoria. As a result, drug addiction begins to incorporate people, places, and activities that further encourage the addiction cycle. To reduce the effects of incentive salience, trauma-based therapies like cognitive behavioral therapy (CBT) reduce impulsive behaviors through positive reinforcement [4]. CBT therapy also aids in challenging positive connotations with addiction by working to break down these habit-forming thought patterns. Modern addiction treatment plans also approach addiction from a more neuroscience-based perspective than traditional practices and also aim to treat psychiatric disorders from a neurobiological approach backed by clinical findings [3].

Modern treatment plans also focus on incorporating coping strategies to aid individuals in maintaining sobriety through techniques that redirect negative emotions and stressors. These strategies empower individuals to overcome negative and stressful situations that would have previously motivated drug use [7]. Long-term, successful use of coping strategies helps to further solidify sobriety by building self-confidence and reinforcing positive changes. By fostering a sense of self-confidence, an individual can maintain long-term recovery. 

Breaking the Stigmas of Addiction 

To effectively combat addiction, researchers need to look outwards within the community and break stigmas associated with it. Historically perceived as a moral failing or character flaw, addiction is now understood as a complex neurological disorder supported by scientific research and evidence-based studies.These stigmas create a false and harmful narrative and increase barriers to treatment and recovery. 

Within Philadelphia, extensive drug and policy reform is necessary to address the city’s drug crisis. Due to Philadelphia’s large open-air drug market, the Philadelphia City Council must directly address the root of the city’s drug crisis to ensure individuals achieve successful and long-term recovery. They need to address issues like poverty and accessibility to harmful substances. Additionally, they must implement proactive methods to support those suffering from addiction. Providers should offer treatment options that acknowledge and respect all individuals while maintaining humility and compassion. By addressing the neurobiological complexities of addiction and implementing compassionate, evidence-based treatment strategies, we can break the stigmas surrounding addiction and pave the way for effective, long-term recovery within our communities.

References

1. Drug Enforcement Administration. (n.d.). Operation Engage: Philadelphia. https://www.dea.gov/engage/operation-engage-philadelphia#:~:text=Synthetic%20opioids%2C%20primarily%20illicit%20fentanyl,Black%20and%20Hispanic%20overdose%20deaths

2. Gupta, S., & Kulhara, P. (2007). Cellular and molecular mechanisms of drug dependence: An overview and update. Indian Journal of Psychiatry, 49(2), 85-90. https://doi.org/10.4103/0019-5545.33253 

3. Semaan, A., & Khan, M.K. (2023). Neurobiology of addiction. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK597351/# 

4. Koob, G. F., & Volkow, N. D. (2010). Neurocircuitry of addiction. Neuropsychopharmacol 35, 217-238. https://doi.org/10.1038/npp.2009.110 

5. Bowirrat, A., & Oscar-Berman, M. (2004). Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome. American Journal of Medical Genetics part B: Neuropsychiatric Genetics, 132B(1), 29-37. https://doi.org/10.1002/ajmg.b.30080

6. Uhl, G. R., Koob, G. F., & Cable, J. (2019). The neurobiology of addiction. Annals of the New York Academy of Sciences, 1451(1), 5–28. https://doi.org/10.1111/nyas.13989 

7. Larimer, M. E., Palmar, R. S., & Marlatt, G. A. (1999). Relapse prevention. an overview of Marlatt’s cognitive-behavioral model. Alcohol research & health :The Journal of the National Institute on Alcohol Abuse and Alcoholism, 23(2), 151-160. 

8. Feltenstein, M. W., See, R. E., & Fuchs, R. A. (2021). Neural substrates and circuits of drug addiction. Cold Spring Harbor Perspectives in Medicine. https://doi.org/10.1101/cshperspect.a039628 

9. O'Brien C. P. (2009). Neuroplasticity in addictive disorders. Dialogues in Clinical Neuroscience, 11(3), 350–353. https://doi.org/10.31887/DCNS.2009.11.3/cpobrien 

10. Kozak, K., Lucatch, A. M., Lowe, D. J. E., Balodis, I. M., MacKillop, J., & George, T. P. (2019). The neurobiology of impulsivity and substance use disorders: Implications for treatment. Annals of the New York Academy of Sciences, 1451(1), 71-91. https://doi.org/10.1111/nyas.13977 

11. American Psychological Association. (2017). Cognitive behavioral therapy for PTSD. https://www.apa.org/ptsd-guideline/patients-and-families/cognitive-behavioral#:~:text=CBT%20treatment%20usually%20involves%20efforts,behavior%20and%20motivation%20of%20others