UNDERSTANDING ADDICTION, TREATMENT AND RECOVERY

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Addiction, whether related to legal or illicit substances, involves compulsive and repetitive use of drugs, which is linked to substance use disorder (SUD). This medical condition is characterised by behavioural, cognitive, physical, neurobiological, and emotional alterations. SUD is commonly understood through three stages: intoxication, withdrawal, and craving. Despite the differences among various addictive substances, they share common neurobehavioral traits, including dysregulation of neurobiological systems associated with reward, stress, emotion, and executive functions. SUDs are among the leading causes of disability in both industrialised and developing nations, resulting in millions of years of life lost due to early mortality. Leading causes of disability in both industrialised and developing countries result in millions of years of life lost due to early mortality.

Specifically, alcohol and tobacco rank among the top four risk factors for mortality worldwide. It is estimated that cigarette smoking causes more than 480,000 fatalities annually in the United States, while alcohol-related factors account for over 88,000 deaths. Since 1999, the number of other drug overdose deaths in the U.S. has more than tripled, reaching over 70,000 in 2017. According to a 2018 study conducted by the Substance Abuse and Mental Health Services Administration (SAMHSA), there are over 50 million illicit drug users, including over 10 million opioid abusers, over 16 million heavy drinkers, and 27 million daily smokers in the U.S. alone. The success of SUD therapy is still insufficient despite the existence of alternative treatment options and effective drugs (apart from cocaine addiction). More than 60% of Americans who got addiction treatment relapsed within a year, according to the 2016 United States Surgeon General's Report. This underscores the difficulties in maintaining recovery (i.e., maintaining long-term drug abstinence and well-being). Treatment results and recovery from SUDs remain extremely restricted despite decades of scientific research and the tremendous economic burden (about $740 billion annually in the United States alone).

Numerous drugs for pharmacological treatments, as well as various non-pharmacotherapies, including behavioural, cognitive, and social interventions, have been developed as a result of scientific research on addiction (see the thorough reviews in this collection). Alcohol, nicotine, and opioid use disorders are among the SUDs that have been treated using these intervention techniques. Unfortunately, since cocaine has a complicated effect on the central nervous system (CNS—the brain and spinal cord) and because it is challenging to find therapeutic targets, there are currently no effective and focused treatments for treating cocaine addiction. Many variables connected to the nature of the illness impede the efficiency of proven therapies, especially for those with severe SUDs. For example, SUDs impact the brain and other systems and essential organs, such as the liver, lungs, cardiovascular, and digestive systems, irrespective of their aetiology. Substance abuse can modify how the immune and endocrine systems operate and cause epigenetic modifications that have broad biological repercussions. Furthermore, with polysubstance use, each substance may have a unique and interacting effect on these systems.

Research discoveries over the past twenty years have significantly increased the understanding of the neurobiological causes and complexity of the sickness caused by SUDs. Medication by itself may lessen the severity of the condition or disorders. Current research suggests that a combination of therapeutic intervention strategies, including evidence-based behavioural/cognitive therapies and pharmaceutical treatments, is needed to achieve effective treatments and long-term recovery from SUDs (newer therapies using brain stimulation and other nontraditional approaches are also in development).

Even though we thoroughly understand how addiction affects behaviour and the underlying neurobiology, little is known about how the impacted biological systems interact with the environment and at the molecular, cellular, and system levels as SUDs develop and recover. Finding effective long-term therapy for SUDs is difficult due to several variables. Among the recognised characteristics shared by all SUDs is individual variability in how well a person responds to treatment. Genetic determinants (e.g., sex and other forms of gene heterogeneity), variations in metabolic responses to medications, comorbidity with SUDs (e.g., alcohol and nicotine addiction or cocaine and other drugs) and with other illnesses (e.g., depression, HIV infection, and trauma), and the severity and behavioural manifestations of SUDs are some of how these differences are reflected. Additional factors include

• the social context and support,

• the availability and affordability of treatment costs, and

• the desire and level of commitment to therapy or therapies.

The following relationships are currently poorly understood, which makes it challenging to create effective treatment plans:

1. The molecular mechanisms, synaptic plasticity, and mechanisms underlying the interactions among the affected neural circuits and their relationship to behavioural changes and the functioning of the rest of the central nervous system

2. The causal relationships between neurobiological changes in the brain and their effects on the peripheral systems and vice versa (e.g., the interaction between the peripheral and central inflammatory systems in depression and addiction and the gastrointestinal hormone ghrelin release and its effect on the central nervous system in alcohol craving)

3. The degree to which social relationships and environmental factors modify neurobiological mechanisms in brain circuitries in patients with SUDs.

These issues represent essential knowledge gaps that need ongoing support for pertinent multidisciplinary research that might encourage creative thinking and breakthroughs from the involved scientific groups.

In addition to relying on the unwavering self-determination of those who have SUDs to alter their behaviour patterns (i.e., seeking treatment and stopping substance use), successful SUD treatment and recovery also necessitate a coordinated effort and support from specialised medical professionals, social communities, industries, and governmental actions, as well as scientific discoveries. Encouraging more medical professionals with specialised training in treating SUD is essential, as it provides them with the most up-to-date clinical skills and scientific knowledge to apply evidence-based therapy tools and customise treatments based on individual variations. Removing stigmas associated with SUD treatment for patients also requires ongoing efforts to increase social support and raise understanding that SUDs are medical conditions.

Current developments in fundamental and translational research are starting to change our understanding of science and may provide novel therapeutic targets for the treatment of SUD. Werner et al. (2019) discovered a hitherto unidentified molecular mechanism that underlies the expression of a chromatin remodeler called INO80 in the brain's nucleus accumbens (NAc), its interaction with the E3 ubiquitin ligase Trim3 protein, and its role in mediating cocaine craving in rats following extended periods of drug abstinence. The development of much-needed pharmaceutical targets for the treatment of cocaine use disorder is probably going to be advanced by this discovery. According to the study by Adeluyi et al. (2019), there is strong evidence that nicotine and nicotine withdrawal alter the morphology of microglia, a non-neuronal cell, and activate their functions in the NAc. These modifications cause neuronal oxidative stress and anxiety-like behaviour in male mice by dramatically changing proinflammatory signalling and upregulating the epigenetic expression of NADPH oxidase 2 (Nox2) mRNA. Flannery et al. (2019) found that acute nicotine abstinence significantly increased the activity of the habenula, a subcortical interface between the limbic system and the brain's basal ganglia. This was linked to altered hedonic processing and increased tobacco craving in a separate study with chronic adult smokers who were not seeking treatment. They demonstrated the neurobiological effectiveness of nicotine replacement therapy in reducing nicotine cravings by using functional magnetic resonance imaging to show that administering nicotine or varenicline, a partial agonist of the nicotine receptor, significantly decreased habenula activity. Understanding the neurological causes of nicotine addiction and desire is still a significant research goal, as smoking is the greatest avoidable cause of death, and only approximately 5% of those who try to stop are successful. As is well known, nonpharmacological treatments are essential to the effective management of SUDs. Neurophysiological evidence supporting the effectiveness of Mindfulness-Oriented Recovery Enhancement (MORE) therapy, an integrated behavioural and cognitive treatment for opioid dependence, was shown in the Garland et al. (2019) research. They demonstrated that chronic opioid users may improve their responsiveness to natural rewards, decrease their cravings for opioids, and correct brain activity linked to hedonic dysregulation and opioid-cue reactivity through an 8-week MORE training programme. Another fascinating study by Chang et al. (2019) showed that rats' brain circuits linked to ethanol withdrawal are activated when they receive relatively noninvasive peripheral stimulation with acupuncture at a particular location (Shenmen HT7). By activating the endorphinergic input to the NAc, upregulating the β-endorphin levels in the NAc, and decreasing neuronal activity in the arcuate nucleus of the hypothalamus, acupuncture at HT7, which is homologous to the human acupoint, significantly reduced alcohol self-administration and ethanol withdrawal tremor. These scientific advancements and ongoing initiatives will undoubtedly create new research avenues and more potent evidence-based treatment plans for SUD recovery.

It is well established that governmental policies and laws play a crucial role in drug use prevention, treatment, and recovery (see the thorough reviews in this collection for more information). Given fresh scientific findings and understanding, it will unavoidably be required to update or create new rules and regulations around drug use, substance dispensing goods, and treatment accessibility. In the United States, the Centres for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH) have extensive scientific resources, the most recent data on SUDs, and information about treatment. To speed up and progress preclinical trials and animal models to human studies, the NIH is also making a significant effort to promote and fund translational research.

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To conclude, people with an addiction are unable to regulate their behaviour. They will stop at nothing to satisfy their cravings for drugs, alcohol, or other substances, even if it means losing their jobs, their friendships, or their families. What about addiction causes people to act in such harmful ways? And why is quitting so tricky? It's a frequent misconception that addiction is a moral issue or a choice and that all you need to do is stop. However, this couldn't be further from the reality, according to Dr. George Koob, head of the National Institute on Alcohol Abuse and Alcoholism at the National Institutes of Health. ''Addiction indeed alters the brain, and restoring it to its natural form requires much effort. The greater your use of drugs or alcohol, the more disruptive it is to the brain''.

Researchers have discovered that a large portion of addiction's strength comes from its capacity to take over and even kill important brain areas designed to aid in our survival.

Healthy habits like eating, exercising, and spending time with loved ones are rewarded with a healthy brain. It accomplishes this by activating brain regions that produce positive emotions, encouraging you to repeat those actions. On the other hand, a healthy brain encourages your body to react swiftly with alarm or terror when you're in danger so you can escape. The frontal lobes of your brain can assist you in determining if the repercussions of engaging in a problematic behaviour—such as eating ice cream before supper or purchasing items you cannot afford—are worth the risk.

However, the natural hardwiring of beneficial brain functions may start to act against you when you begin to develop an addiction to a drug. Alcohol and drugs have the power to take over your brain's reward and pleasure pathways, making you crave more and more. Your emotional danger-sensing circuits may also go into overdrive due to addiction, causing you to experience worry and anxiety even when you're not using drugs or alcohol. At this point, rather than using drugs or alcohol for their enjoyable benefits, people frequently do so to avoid feeling awful. Furthermore, frequent drug use might harm the brain's critical frontal lobe, which is responsible for forming decisions. The prefrontal cortex is the exact place that ought to assist you in identifying the adverse effects of abusing addictive substances.

The reason why some people develop addictions and others do not is still a mystery to scientists. Different types of addiction have been related to certain gene types, and addiction tends to run in families. However, not every member of an impacted family is inevitably at risk for addiction. "There isn't a single gene that makes you susceptible, like diabetes or heart disease," Koob adds.

 Other variables might also increase addiction risk. "All of these social factors—being exposed to extreme stress, growing up with an alcoholic, or experiencing abuse as a child—can contribute to the risk for alcohol addiction or drug abuse," Koob adds. "And the earlier you start using drugs or drinking underage, the higher your chance of developing an alcohol use disorder or addiction later in life."

Additionally, scientists supported by the NIH are testing new treatments that might improve the efficacy of current ones. The potential of magnetic brain stimulation and mindfulness meditation to repair brain circuitry damaged by addiction is being investigated. Researchers are also looking at the possibility of vaccines that might stop drugs like cocaine, nicotine, and others from getting into the brain.

To find publicly funded addiction treatment centres in your state, call 1-800-622-HELP or visit https://findtreatment.samhsa.gov/.

To your health,

Nwabekee.

REFERENCE

Biology of addiction (2024) National Institutes of Health. Available at: https://newsinhealth.nih.gov/2015/10/biology-addiction.

Xu, B. and LaBar, K.S. (2019) 'Advances in understanding addiction treatment and recovery', Science Advances, 5(10). doi:10.1126/sciadv.aaz6596.