Addiction: what is it, symptoms, causes, treatment, prognosis

What is addiction?

The usual definition addictions (eng. addiction - addiction, addiction, addiction) is "a state of dependence on a certain substance, thing or activity." Medically speaking, addiction is “a chronic relapsing disorder characterized by compulsive seeking substances (drugs), continued use, despite the harmful effects, and long-term changes in to the brain. "

The two main concepts of addiction include substance dependence (drug addiction), which is neuropsychiatric disorder characterized by a repeated desire to constantly take substances, despite its harmful effects. Non-substance addiction (behavioral addiction) is not drug / drug related, but includes behavior similar to that found in substance use, for example, pathological gambling, food addiction, Internet addiction, gambling, sexual addiction, as well as mobile phone addiction, social networks.

Causes

There is a complex interplay of neuroscience, genetics and the environment - nature and nurture - which affect the development of addiction, alcohol use disorder or other addictive states. Rewarding activity is known evidence that supports the neurobiological underpinnings of addiction. However, observations regarding the dopamine reward system cannot exclude or diminish the potential contribution learning and memory in the hippocampus and emotional regulation in the amygdala as possible etiologies in development and maintenance addiction.

The influence of genetics on addictive behavior has been hypothesized using the transcription factor delta-fosB. Delta-fosB may be one of the mechanisms by which substance abuse can induce changes in the brain and contribute to the addiction phenotype. Delta-fosB, a member of the Fos family of transcription factors, accumulates in a subset of neurons in the nucleus accumbens and dorsal striatum after repeated administration of prohibited substances. Research has also shown that a similar accumulation of delta-FosB in the brain is observed after compulsive running, which suggests that delta-FosB can accumulate in many types compulsive behavior.

Moreover, the way people deal with stress psychologically, physically and biochemically plays an important role. when viewed in the context of parental control, psychological or cognitive deficits and level stress.

Preclinical studies have shown that exposure to stress - especially at an early age with child abuse and regular troubles - enhances self-medication and is a provoking factor in many relapses in former or current persons with addiction. In particular, there are marked changes in the corticotropin-releasing factor and the hypothalamic-pituitary-adrenal axis (CRF / HPA axis) and autonomic arousal. Basically, stress refers to the processes that involve “perceiving, evaluating, and responding to harmful, threatening, or provoking events or stimuli.” Stress can be beneficial, and persistent exposure to such stress leads to feelings of control and confidence. However, any "stress" that becomes prolonged or chronic can become unpredictable and uncontrollable, resulting in a loss of control or confidence and the development of homeostatic dysregulation. This homeostatic dysregulation creates vulnerabilities for substance-related behaviors and tendencies.

Research in laboratories in Latin America highlights the link between single nucleotide polymorphisms (SNPs) in stress-related genes and addiction. SNPs can interact with stress hormones, transcription factors, and cytokines. This interaction could be a potential way to identify reliable biomarkers of vulnerability to drug abuse and relapse. Other studies also suggest that CRF receptors in the lateral septum and ventral tegmental areas, especially the CRF2-alpha-R isoform, are potential therapeutic targets for treatment drug addiction. Secreted by glycolipoproteins of the Wnt family, the Wnt pathway / beta-catenin may be a critical neural substrate for the interaction between stress and addictive behavior. Researchers have also studied the cannabinoid system as a promising target for stress relapses in addicts.

Thus, addiction is constantly rooted in stressful situations, especially when it lasts throughout early childhood. Environmental risk factors such as impulsivity, inadequate parental supervision and delinquency are also common among chemical and behavioral manifestations of addiction. Research shows that people who exhibit one problematic behavior may face other problems. Socio-demographic risk factors associated with poverty, geography, family and groups peers can also affect the occurrence and course of both narcotic and non-narcotic addiction.

Epidemiology

Due to cultural differences, the proportion of individuals who develop drug or behavioral addiction over a period of time (i.e. e. prevalence) varies over time, by country, and by demographic characteristics of the country's population (e.g., by age group, socioeconomic status, etc.).

- Asia.

The prevalence of alcohol dependence is not as high as in other regions. In Asia, alcohol consumption is influenced not only by socio-economic factors, but also by biological ones.

The overall prevalence of smartphone ownership is 62%, ranging from 41% in China to 84% in South Korea. Moreover, participation in online games ranges from 11% in China to 39% in Japan. Hong Kong has the highest number of teens reporting daily or higher internet use (68%). Internet Addiction Disorder is highest in the Philippines, according to the IAT (Internet Addiction Test) at 5% and CIAS-R (Chen's Revised Internet Addiction Scale) at 21%.

- Europe.

In 2015, the estimated prevalence of heavy episodic alcohol use among the adult population was 18.4% (over the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% in 2017 use of cannabis, amphetamine, opioids and cocaine. The death rate from alcohol and illicit drugs was the highest in Eastern Europe.

- United States.

Based on a representative sample of US youth in 2011, the prevalence of dependence on alcohol and illicit drugs throughout life is estimated at about 8% and 2-3% respectively. Based on representative samples of the US adult population in 2011, the 12-month prevalence of alcohol and illegal drug addiction was estimated at approximately 12% and 2-3%, respectively. The lifetime prevalence of prescription drug use is about 4.7%.

As of 2016, about 22 million people in the United States needed treatment for addiction to alcohol, nicotine, or other drugs.

According to a 2017 poll by the Pew Research Center, nearly half of adults of the US population knows a family member or close friend who at some point in his life struggled with drug abuse addiction.

In 2019, opioid addiction was declared a national crisis in the United States. In an article in Washington Post it said that "America's largest pharmaceutical companies flooded the country with painkillers from 2006 to 2012, even as it became apparent that they were fueling addiction and overdoses."

- Russia.

According to Rosstat, the total number of patients diagnosed with alcohol dependence (alcoholism) in 2017. amounted to 37% - 1.3 million people.

According to law enforcement and health authorities, at the beginning of 2001, the total number of Russian citizens who use drugs on a regular basis exceeded 2.2 million. More than 60% of drug addicts were people aged 16-30 and almost 20% were schoolchildren.

In 2003, the number of drug users was estimated at about 4 million.

As of the beginning of 2011, there were over 2.5 million drug addicts in Russia.

In 2016, the chief freelance narcologist of the Ministry of Health of the Russian Federation, Evgeny Brun, said that about 8,000 drug addicts die from an overdose in Russia every year.

Diagnostics

History and physical signs vary greatly depending on the substance taken, the time since ingestion, and the route of administration. For example, most forms of alcoholic intoxication are accompanied by slurred speech, ataxia and a violation of judgment. This process, depending on the dose and timing of administration, can quickly lead to depression CNS, coma and multiple organ failure. This progress applies to ethanol, methanol, isopropanol and ethylene glycol.

With regard to cocaine and other stimulants, patients often have acute displays of anxiety, potential psychosis, and related vital signs (tachycardia, tachypnea, high blood pressure, etc.). Treatment begins with reducing anxiety, stabilizing vital functions, and preparing rapid response teams for patients with worsening conditions.

There are also significant differences depending on the stage of addiction and the substance inducing dependence. There are five stages of addiction:

1. First use
   1. They are naive patients in the sense that they have not yet felt the effects of their substance. This could be a prescription for a new pain reliever, or the first peer pressure experiment.
2. Continued use
   1. People begin to return to drugs that they no longer "need" but which they need most, as they notice that the feeling of being high quickly wears off.
3. Tolerance
   1. Patients at this stage realize that they need large doses of the drug in order to experience the previous high.
4. Physical affection
   1. Patients begin to show physical signs of withdrawal from use. Worse, patients no longer feel "normal" without using the substance.
5. Addiction
   1. These patients may be on one of the two sides of the coin. They may be upset by prolonged use, but they may need it despite serious life problems that have arisen, or they may deny their addiction and continue to dig in addiction.

The above descriptions of the stages disclose the expected presentation of the patient's addiction. The history and physical examination depend on the stage of the disease. The patient who seeks help for the first time is likely not to experience an acute disorder (with the exception of active trauma / chronic pain) or have physical signs of withdrawal when going to the clinic or emergency department help. A tolerant patient usually tells a story that requires an increase in the dose of their medication or a resumption of the dose. The addicted patient may experience acute withdrawal symptoms with symptoms that differ depending on the substance. Alcohol withdrawal is manifested by signs of autonomic dysregulation that cause the greatest concern - alcoholic delirium and convulsions.

- Analysis and visualization.

Laboratory values ​​(blood and urine), images, and specific tests vary depending on the root of the addiction. If it is a psychoactive substance, there may be obvious abnormalities in the complex metabolic panel (CMF) and complete blood count (CBC) values, as well as in psychoanalysis and behavioral screening. The following is an abbreviated list and summary of the most common addictive substances and the expected assessment results for healthcare professionals:

1. Alcohol.
   1. Ethanol:
      • Complete blood count - chronic use can cause an increased (average corpuscular volume) of red blood cells with megaloblastic anemia due to folic acid deficiency.
      • CMP - blood urea nitrogen / creatinine may be higher than baseline, glucose may be chronically low, and electrolytes may be disrupted due to dehydration.
        1. The anion gap will increase in acute intoxication with a reduced CO2 content and a reduced bicarbonate content, which is reflected in an active acidotic state.
      • The same will happen with methanol, plus ophthalmic problems will appear. Requires regular eye exams in the emergency room.
      • Ethylene glycol leads to renal failurerequiring serial levels of blood urea nitrogen / creatinine and GFR to monitor renal function; Stones in the kidneyscontaining oxalic acid are common, resulting in a bloody urine test.
2. Cocaine.
   1. Obvious sympathetic attraction, expressed through an increase in vital functions. Patients usually have tachycardia and tachypnea. Patients may have acute psychosis.
      • In case of intoxication, a troponin series, a cardiac stress test, and even cardiac catheterization may be required. Due to the narrowing of the coronary vessels, troponins are regularly increased.
3. Opioids. Unlike stimulants such as cocaine, opioids have parasympathetic symptoms such as bradycardia, hypotension, miosis, hypothermia and sedation. A disturbing factor is sedation, leading to respiratory depression.

Visualization research methods.

Although not common in clinical practice, imaging can be included in the addiction assessment panel. The researchers found that a decrease in the number of dopamine 2 receptors (DA D2) correlated with decreased activity of the anterior cingulate cortex (AUC) and orbitofrontal cortex (OFC) in persons who abuse cocaine.

Liquid chromatography / mass spectrometry and SIP.

Some of the substances used (kratom) and abuse (bath salts) are not detected on routine urine drug tests or blood tests. For example, liquid chromatography / mass spectrometry and ion mobility spectrometry (IMS) are used to detect kratom.

Treatment

- Behavioral therapy.

A meta-analytic review of the effectiveness of various behavioral therapies for the treatment of drug dependence and behavioral addiction has shown that cognitive behavioral therapy (e.g. relapse prevention and contingency management), motivational interviewing, and support groups have been effective interventions at a moderate scale effect.

Clinical and preclinical data indicate that sustained aerobic exercise, especially endurance exercise (such as marathon running), actually prevent the development of certain addictions and are an effective adjunctive treatment for drug addiction, in particular from psychostimulants.

Regular aerobic exercise based on magnitude (i.e. duration and intensity) reduces risk addiction, which appears to be due to the reversal of drug-induced neuroplasticity addiction. One review noted that exercise can prevent drug addiction by altering delta-FosB or c-Fos. immunoreactivity in the striatum or other parts of the reward system.

Aerobic exercise reduces self-medication, decreases the likelihood of relapse, and produces opposite effects on dopamine signaling. D2 receptor (DRD2) in the striatum (increased DRD2 density) compared to effects caused by dependence on multiple drug classes (decreased density DRD2). Consequently, continuous aerobic exercise may lead to better treatment outcomes when used as an adjunct drug dependence treatment.

- Medicines.

Alcohol addiction.

Alcohol, like opioids, can cause severe physical dependence and withdrawal symptoms such as delirium tremens. Therefore, treatment for alcohol addiction usually involves a combined approach to address the problem of addiction and addiction at the same time. Benzodiazepines have the largest and best evidence base in the treatment of alcohol withdrawal and are considered the gold standard for alcohol detoxification.

Pharmacological treatments for alcohol dependence include drugs such as naltrexone (opioid antagonist), disulfiram, acamprosat and topiramate. These drugs are not intended to replace alcohol, but to affect the urge to drink, either by directly reducing cravings, such as in the case of acamprosate and topiramate, or by creating unpleasant effects with alcohol, as is the case disulfiram. These drugs can be effective if treatment is continued, but adherence can be a problem. since alcoholic patients often forget to take medication or stop taking due to excessive side effects effects. According to Cochrane (Cochrane Collaboration), the opioid antagonist naltrexone has been shown to be effective in the treatment of alcoholism, the effect of which lasts 3 to 12 months after the end of treatment.

Behavioral addictions.

Behavioral addiction is a treatable disease. Treatment options include psychotherapy and psychopharmacotherapy (i.e. e. drug treatment) or a combination of both. Cognitive Behavioral Therapy (CBT) is the most common form of psychotherapy used to treat behavioral addictions; it focuses on identifying patterns that trigger compulsive behavior and making lifestyle changes to promote healthier behavior. Since CBT is considered a short-term therapy, the number of treatment sessions usually ranges from 5 to 12. During the session, therapists will guide patients through the topics of identifying the problem, recognizing their thoughts, related to the problem, identifying any negative or false thoughts and changing the negative and false thinking.

While CBT does not cure behavioral addiction, it does help manage the condition in a healthy way. There are currently no drugs approved for the treatment of behavioral addictions in general, but some medications used to treat drug addiction can also be helpful for certain behavioral dependencies. Any unrelated psychiatric disorder should be controlled and differentiated from factors contributing to the development of addiction.

Cannabinoid addiction.

As of 2010 there are no effective pharmacological treatments for cannabinoid addiction. A 2013 review of cannabinoid addiction noted that the development of CB1 receptor agonists that have reduced interaction with β-arrestin 2 signaling, may be therapeutically useful.

Nicotine addiction.

Another area in which drug treatment is widely used is the treatment of nicotine addiction, which is usually includes the use of nicotine replacement therapy, nicotinic receptor antagonists, or nicotinic partial agonists receptors. Examples of drugs that act on nicotinic receptors and have been used to treat nicotine addiction include antagonists such as bupropion and the partial agonist varenicline.

Opioid addiction.

Opioids are physically addictive, and treatment is usually directed towards eliminating it.

Physical addiction is treated with substitution drugs such as Suboxone or Subutex (both of which contain the active ingredients of buprenorphine) and methadone. While these drugs can help maintain physical dependence, the goal of opiate maintenance therapy is to control pain and addiction. The use of substitute drugs increases the addicted person's ability to function normally and eliminates the negative consequences of illicit receipt of controlled substances. After stabilization of the prescribed dosage, treatment enters the maintenance phase or the phase of gradual dose reduction.

Methadone substitution therapy is carried out in all countries of America, Western Europe, many countries of Eastern Europe and the Baltic states, and in most of the CIS countries, except for Russia and Turkmenistan. As of 2009, in 106 countries of the world where substitution therapy programs are carried out, more than a million patients have participated in them.

In Russia, any use of methadone is prohibited by law for any purpose.

Addiction to psychostimulants.

As of May 2014 there is no effective pharmacotherapy for any form of addiction to psychostimulants. Reviews from 2015, 2016 and 2018 showed that the use of selective TAAR1 agonists has significant therapeutic potential as a treatment for psychostimulant addictions; however, as of 2018, the only compounds known to act as selective TAAR1 agonists are experimental drugs.

Forecast

The evidence is pretty clear about the long-term effects of drug addiction: those diagnosed died 22.5 years earlier than those who did not. This lifespan is associated with the toxic effects of substances on several systems, including but not limited to the cardiac, respiratory, and neurological systems. In addition, a five-year study on alcohol and drug dependence treatment found that older people have favorable long-term outcomes compared to younger people; in particular, the elderly (especially older women) have been found to have a 30-day abstinence rate of 52% compared to 40% in younger adults. Factors such as the influence of social networks and gender play a role in these numbers along with age.

At this point, there is a clear relationship between changes in mortality risk over time when addicted patients begin treatment and the amount of therapy received. Their final prognosis depends on these factors.

Complications

From the point of view of chronic alcohol use, the expected complications are Wernicke's encephalopathy and Korsakoff syndrome. Wernicke's encephalopathy is accompanied by the triad of confusion, ophthalmoplegia and ataxia (although usually only one is present in 20% of cases). On CT and MRI, classic signs include atrophy of the bilateral mammillary bodies and areas of the hippocampus.

Liver steatosis is a common complication of chronic alcohol use resulting from cholesterol esters, phospholipids and triglycerides, ultimately formed as a result of alcohol-induced ROS production, which alter lipid metabolism.

Chronic high alcohol consumption is the most important risk factor when considering chronic pancreatitis. The process begins with acute excessive alcohol consumption, which, due to the toxic effects of alcohol metabolism, over time causes inflammatory and fibrotic changes in pancreas. In particular, the stellate cells of the pancreas are activated, resulting in the expected fibrotic changes.

Cardiomyopathy - another documented complication expected from chronic use alcohol as a result of oxidative stress, impaired calcium handling and dysfunction mitochondria.

Cocaine addiction and intoxication lead to coronary heart disease, psychosis and fatal arrhythmias that require urgent care to mitigate the consequences.

In terms of behavior, addiction leads to multiple withdrawal and relapse episodes (average 7).