Addiction is defined as having a craving or dependence to a substance, thing, or activity. Addiction can be tied to a natural reward such as sleep, food, etc. whereas it can also be tied to an unnatural reward such as substances. Unnatural addictions such as drugs or alcohol can be life threatening at times and turn into a horrific cycling pattern if trying to withdraw and stop usage.

In the brain there are three areas of the brain an addiction behavior can go through:

1. The first is the basal ganglia, the portion of the brain that controls the reward response to the substance use and helps to form the habits around substance use.
2. The second is the extended amygdala that associates with the feelings of discomfort, anxiety, stress that usually follows substance withdrawal.
3. The third is the prefrontal cortex which controls the ability to have control over the substance usage.

Figure 1: The different areas of the brain affected by addiction. https://www.ncbi.nlm.nih.gov/books/NBK424849/

The overwhelming effects of addiction occurs when this cycle repeats itself and the addiction grows stronger after making those rewarding affects attainable with the substance rather than without.

Studies suggest that individuals with an addiction to substances have a reduction in sensitivity for the brain’s reward system (brain circuits with dopamine receptors). Therefore, once pleasurable or stimulating activities no longer have the same effect as they once did, an individual going through withdrawal symptoms will want to regain the same pleasurable feelings the reward system once provided but only be able to do this through the substance.

At the more neuronal level, during the withdrawal stage there is an activation of the stress neurotransmitters in the extended amygdala. These NTs include corticotrophin-releasing factor (CRF), norepinephrine, and dynorphin. These neurotransmitters have been shown to play a key role in negative feelings associated with withdrawal. Therefore, to get rid of the negative emotions from withdrawal a lot of individuals tend to use the substance again. In other words, the individual is experiencing negative reinforcement every time they use the substance again to rid themselves of the negative emotions and this is how the cycle continues.

Taking a closer look at the brain it is important to understand the difference between an addicted brain versus an unaddicted brain to a substance. In the control brain, VTA dopaminergic neurons project to NAc whereas with the addicted brain neurons there is an increase of dopamine in NAc (Nucleus accumbens) leading to tolerance, sensitization, and adaptation to the substance. In the addicted brain, the VTA neuron appears smaller as the NAc portion is larger in size with more branching, leading to the effects of becoming addicted to a substance and unable to stop.

Figure 2: Image of neurons in the brain from Nestler article (2005).

Overall, addiction starts as a choice and turns into a gray area where the choice of using a substance is no longer there. As there has been some controversy on whether addiction is a disease, in the future when we learn more about addiction and what more is happening in the brain can we decipher if the individual has a choice or if that choice is no longer there once the brain creates tolerance, sensitization, and adaptation to the substance.

References:

Substance Abuse and Mental Health Services Administration (US), Office of the Surgeon General (US), and US Department of Health and Human Services. 2016. Facing Addiction in America: The Surgeon General’s Report on Alcohol, Drugs, and Health. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK424849/

Nestler, Eric. 2005. Is there a common molecular pathway for addiction? Nature Neuroscience: Neurobiology of Addiction.

Leyton, Marco. 2013. Are addictions diseases or choices? Journal of Psychiatry & Neuroscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3692718/

Addiction on the Molecular Level

Addiction is a significant issue in today’s society. Addiction is defined as a compulsive and persistent dependence on a substance or behavior that has negative consequences. Some of the most common types of addiction are substance addiction (addiction to drugs, alcohol, and tobacco), natural addiction (addiction to food, binge eating disorder) and behavioral addiction (addiction to gambling, video games, and social media).

Addiction can have a significant impact on an individual’s life as well as the lives of those close to them. It can result in physical and mental health issues, financial difficulties, social isolation, and legal complications. Addiction can also have a negative impact on the larger community by causing crime, violence, and other social problems.

Addiction is particularly problematic in today’s society due to a number of factors. For starters, addictive substances and behaviors are more widely available, thanks to the proliferation of online gaming and social media platforms. Second, there is less social stigma attached to addiction, which may make it easier for people to engage in addictive behaviors without fear of being judged. Finally, many people lack access to effective addiction treatment and support services, making it difficult for them to overcome their addiction and live a healthy life.

Drug abuse can activate several signaling pathways in the brain, leading to the development of addiction. The following are some of the most common signaling pathways involved in drug abuse:

1. Dopamine pathway: The mesolimbic dopamine pathway, which is a circuit of brain regions involved in reward and motivation, is one of the key pathways identified by Dr. Nestler and his colleagues. This pathway is activated when a person engages in rewarding behavior or takes an addictive drug, and dopamine is released in the nucleus accumbens, a key region of the brain’s reward circuitry. This dopamine release reinforces and motivates the individual to repeat the behavior.
2. Glutamate pathway: The glutamate pathway is responsible for learning and memory. Drugs of abuse can activate this pathway, leading to changes in synaptic plasticity, which can lead to drug cravings and addiction.
3. GABA pathway: The gamma-aminobutyric acid (GABA) pathway is responsible for the brain’s inhibitory system. Drugs of abuse can disrupt the balance of GABA signaling, leading to an increase in excitatory signaling, which can lead to drug cravings and addiction.
4. Endocannabinoid pathway: The endocannabinoid system is responsible for regulating appetite, pain, and mood. Drugs of abuse can activate the endocannabinoid pathway, leading to changes in appetite and mood.

Moreover, repeated drug use or addictive behavior causes the brain to adapt, resulting in long-term changes in gene expression and synaptic plasticity. Dr. Nestler has identified a number of specific molecular pathways involved in these adaptations, such as changes in gene expression of various transcription factors, epigenetic DNA modifications, and changes in synaptic plasticity and neuroplasticity.

While there may not be a single common molecular pathway for addiction, Dr. Nestler’s research has contributed to the identification of some of the key molecular and cellular mechanisms that underpin addictive behavior. This understanding is critical for the development of new treatments and interventions to assist individuals in overcoming addiction and leading healthy, fulfilling lives.

sources:

https://moodle.cord.edu/pluginfile.php/1266921/mod_resource/content/4/Nestler%202005.pdf
https://www.ncbi.nlm.nih.gov/books/NBK424849/figure/ch2.f5/

Addiction to drugs of abuse plagues all corners of America. From needles littering the streets of major urban centres to the hover of prescription opioid abuse in rural areas, it is a growing dilemma. Access to care is stretched and the problem is getting worse.. In fact, a release from the National Centre for Drug Abuse statistics reports that half of reporting individuals (aged 12 and up) have used illicit drugs at least once. There have been 700,000 deaths from opioid overdose alone since 2000. As this crisis has grown, solutions of varying degrees have arisen. Safe-drug use facilities have been proposed to help limit street drug use from an increasingly addicted population while others are working to stop distribution of drugs of abuse in its tracks. However, amongst proposed solutions, some of the fundamental causes of addiction can be forgotten. A review by Eric J. Nestler in Nature Neuroscience back in 2005 dives into what causes addiction at a cellular and molecular level.

The Dopamine System

Otherwise referred to as the brain’s reward circuitry, the dopamine system plays a critical role in why drug addiction can develop. This system can be found in the ventral tegmental area of the midbrain and is also where the dopaminergic neurons within it target areas of the forebrain. A specific pathway is formed in this area called the VTA-NAc pathway. Drugs activate the transmission of the neurotransmitter dopamine within the pathway. When there is continuous activation of the circuit, tolerance to dopamine can occur while at the same time a sensitisation to the neurotransmitter develops. This occurs in combination with withdrawal symptoms that increase drug-seeking behaviour. Sudden withdrawal from use of a drug activates the central corticotropin releasing factor system; this will increase drug withdrawal symptoms. Drug use has also been linked to hypofrontality which is decreased function of the frontal lobe, which is responsible for complex thought processes. Hypofrontality can thus lead to less control over drug-seeking behaviour.  With both dysfunction of normal reward signalling in the dopamine system, and increased drug withdrawal, addiction can ensue and magnify itself quickly. 

Changes Occur Right Away

Another change occurs to the actual shape of neurons within this system. The neuron is much like a tree. The end of it that receives messages are projections called dendrites that are much like the leaves and branches that make a tree canopy. Drug use and addiction has been shown to affect the morphology of this “dendritic arbour.” Chronic cocaine, amphetamine, or nicotine exposure have shown increases in dendritic arborisation. This increase in the dendritic arbour contributes to drug sensitivity which furthers addiction in an individual. This process changes the actual shape of the neuron and helps demonstrate how persistent addiction can become. The figure below depicts the difference in size between the dendrites of addicted versus non-addicted individuals. 

Figure 1. This is from Figure 2 of Nestler (2005) comparing the size difference between addicted and control dendrites.

What Should We Do?

With the addiction crisis we face, all cards need to be put on the table, but this review can help us understand two things that show addiction as a persistent disease rather than that of a mental toughness discussion. Drug addiction affects the brain’s sensitivity to dopamine making drug exposure have higher and quicker highs. It also leads to permanent morphological change to the neurons themselves affecting multiple parts of the brain’s reward pathway. Drug exposure can start the addiction process from the start and needs to be considered when exposing persons to drugs of abuse. The same also comes to the fact that environments contribute to someone’s susceptibility to drug reuse. Environments that systemically cue drug use amongst individuals will make fighting addiction a constant battle. However, armed with this knowledge, we can have empathy for those in their fight against addiction and continue to face this challenge in our future.

“Drug Abuse Statistics,” National Center For Drug Abuse Statistics, accessed 28 February 2023, https://drugabusestatistics.org

Eric J. Nestler, “Is there a common molecular pathway for addiction?” Nature Neuroscience 8, no. 11 (2005), 1445-1449

“Supervised Consumption Services,” Harm Reduction, accessed 28 February 2023, https://harmreduction.org/issues/supervised-consumption-services/