The layman's definition of addiction is a "fact or condition of being addicted to a particular substance, thing, or activity." Medically it is a "chronic, relapsing disorder characterized by compulsive drug seeking, continued use despite harmful consequence, and long-lasting changes in the brain." This current Oxford English dictionary definition can be traced back to Roman law in which addiction was a "formal giving over by sentence of the court." The concept finds meaning in the relinquishment of control by the "addicted" person identical to how drug-dependent patients succumb to the cravings for their drug of choice. Two main concepts of addiction involve substance addiction (drug addiction), which is a neuropsychiatric disorder characterized by a repeating desire to take a drug continuously despite the drug's harmful consequences. Non-substance addiction (behavioral addiction) does not involve a drug but includes similar behaviors as when one uses a drug such as pathological gambling, food addiction, internet addiction, gaming, sex addiction, and mobile phone addiction.
There is a complex interplay of neurobiology, genetics, and environment --nature and nurture-- that play into the development of addiction, alcohol, and other drugs use disorder(AODUD). Reward activity is a piece of known evidence that supports the neurobiological underpinnings of addiction. However, observations implicating the dopamine reward system may not exclude or downplay the potential contribution of learning and memory in the hippocampus and emotional regulation in the amygdala as possible etiologies in the development and maintenance of an addiction.
The implication of genetics across addictive behaviors was suggested via the transcription factor Delta-FosB. Delta-FosB may be among the mechanisms by which the abuse of drugs can produce changes in the brain and contribute to the addiction phenotype. Delta-FosB, a member of the Fos family of transcription factors, accumulates within a subset of neurons of the nucleus accumbens and dorsal striatum after multiple administrations of illicit drugs. Studies also found that similar accumulation of Delta-FosB in the brain after compulsive running, a finding that suggests that Delta-FosB may accrue in many types of compulsive behaviors.
Furthermore, how individuals handle stress psychologically, physically, and biochemically play significant roles when seen in the context of parental use, psychological or cognitive deficits, and level of stress.
Preclinical research has shown that stress exposures – especially in early life with child maltreatment and regular adversity – enhance drug self-administration and are the precipitating factors to many relapses in former or current individuals with addiction. Specifically, there are notable changes in the corticotropin-releasing factor and the hypothalamic-pituitary-adrenal axis (CRF/HPA) and autonomic arousal. In essence, stress refers to processes that involve “perception, appraisal, and response to harmful, threatening or challenging events or stimuli.” Stress can be useful and persevering through such stress results in feelings of mastery and accomplishment. However, any “stress” that becomes prolonged or chronic has the potential to become unpredictable and uncontrollable, resulting in loss of sensations of mastery or adaptability and development of homeostatic dysregulation. This homeostatic dysregulation creates vulnerability for drug-seeking behaviors and tendencies and, unfortunately, possibly addiction.
Studies in Latin American laboratories highlight the association between single nucleotide polymorphisms (SNPs) in stress-related genes and addiction. SNPs may interact with stress hormones, transcription factors, and cytokines. This interaction may be a potential pathway to identify reliable biomarkers of vulnerability to drug abuse and relapse. Other studies also suggest that CRF receptors in the lateral septum (LS) and the ventral tegmental area (VTA), specifically the CRF2-alpha-R isoform, as a potential therapeutic target for drug addiction. The Wnt family of secreted glycolipoproteins -Wnt/beta-catenin pathway may be a critical neural substrate for the interaction between stress and addictive behavior. Researchers also studied the cannabinoid system as a promising target for stress-induced relapse on drugs.
In summary, addiction consistently finds its roots in stressful contexts, particularly when prolonged throughout early childhood. Environmental risk factors such as impulsivity, inadequate parental supervision, and delinquency also are common across chemical and behavioral expressions of addiction. Studies suggest that individuals who engage in one problem behavior are likely to engage in another problem. Sociodemographic risk factors related to poverty, geography, family, and peer groups can also influence the onset and course of both substance addiction and non-substance addiction.
A study done in 2005, reflecting on the 2001 National Household Survey of Drug Abuse, found that out of 55561 subjects, 33576 reported alcohol use within the past year. Ultimately the study found a slightly higher prevalence of abuse-to-dependence in males to females with (2.1 to 1) and (1.6 to 1), respectively. Per a research study in 2014, 7% of the American population meets the criteria for the diagnosis of alcohol misuse or alcoholism. In 2010, the World Health Organization( WHO) estimated there were about 208 million people around the world who suffer from alcohol use disorder. In 2016, globally, alcohol dependence was the most prevalent of the substance use disorders, but the most common drug use disorders in 2016 were cannabis and opioid. Amphetamine and cocaine use was less frequent.
Designer drugs are illicitly produced drugs that are chemical analogs to preexisting psychoactive or analgesic molecules. These drugs can be more potent than known controlled or uncontrolled substances. There is a growing international concern that designer drugs are manufactured and distributed to circumvent drug laws and evade interdiction. Designer drugs keep changing depending on the location. Among them are synthetic stimulants like bath salts, a synthetic cathinone; a synthetic version of tetrahydrocannabinol (THC) called k2 or spice; a norepinephrine-dopamine reuptake inhibitor and a member of the cathinone and pyrovalerone classes called flakka; synthetic designer hallucinogens called N-bomb, solaris; a highly potent synthetic opioid-non-fentanyl derived novel synthetic opioids: U-47700, called "U4," "pink," or "pinky, U-49900, AH-7921, or MT-45. Methylenedioxy-derivatives of amphetamine and methamphetamine is a very group of designer drugs. The most used chemical use is 3,4-methylenedioxymethamphetamine (MDMA-ecstasy). The use of designer drug use is mostly encountered among young males who are in the 15 to 25 years of age, and who frequent clubs, raves, and house parties. In 1993, the National Institute on Drug Abuse survey reported an estimate of 2% of all American college students who admitted to using MDMA in the previous 12 months. The use of designer drug use is mostly encountered among young males who are in their 15 to 25 years of age, who frequent clubs, raves, and house parties. Several studies estimated that between 6 and 17% of American college students had used synthetic cannabinoids drugs at least once. Around 1% of young Europeans between the ages of 14 and 18 used synthetic cannabinoids drugs at least once in their lifetime. Deaths by overdose were found to be increased by adulterants in products sold as heroin, or as counterfeit pain killers in North America and Canada. In a city like Miami (United States of America), there was an increase of 600% in fentanyl-related deaths reported from 2014 to 2015. Fatalities from these novel synthetic opioids were also reported from North America, Latin America, Canada, Asia, Europe, and Africa.
Abuse of prescription medicines involves central nervous depressants (benzodiazepines, non-benzodiazepines, and barbiturates), prescription opioids (hydrocodone, oxycodone, fentanyl, and codeine), and prescription stimulants (dextroamphetamine, dextroamphetamine/amphetamine combination product, and methylphenidate). Deaths from prescription opioid overdose were five times higher in 2016 than in 1999. In 2012, the National Center for Health Statistics reported that pain relievers (opioids) were involved in more "drug poisoning deaths" than heroin and cocaine, for example.
Around 9.7% of students in grades 7 to 12 reported using dextromethorphan recreationally in 2013, compared with 6.9% in 2011 based on the Ontario Student Drug Use and Health Survey. Most of the calls to poison control were related to dextromethorphan-related, and these calls involved adolescent males. Other types of over-the-counter medicines (OTC) are used to treat dysphoric mood states and sleep problems. Acetylsalicylic acid (ASA) or acetaminophen use of more than 4 g per day for an extended time is considered misuse.
Extracts of many leaves were found to possess a powerfully addictive substance, and among them are extracted from a tree of the Mitragyna speciosa (kratom). Kratom is the subject of attention worldwide. Many reported exposure calls to poison centers related to kratom use, by year, increased from 2010 to 2015. Kratom (M. speciosa) misuse, among multiple compounds of the leaf, appears to be increasing in the Western world at an alarming rate with reported deaths.
The pathophysiology of addiction revolves around the concepts of synaptic plasticity, specifically LTP (long term potentiation) and LTD (long term depression). Long term potentiation is the phenomena of strengthened neural connections over time and with increased stimuli. Long-term depression is the decrease in the responsiveness of a neural signal with stimulation. These are the same processes involved in learning and habit formation. The biochemical proof of these processes' involvement in drug addiction is founded in the same molecules undergoing upregulation in both cases - extracellular signal-regulated protein kinase (ERK), cyclic AMP response element-binding (CREB), ELK-1, and Fos. Rats treated to suppress ERK stopped preferring the caged area with cocaine over the cage area with normal saline. Eventually, CREB, ELK-1, and Fos all decreased, each known to be involved with LTP and drug misuse.
Biochemical studies have shown the involvement of a dynorphin A (DYN) and K-opioid receptor (KOPr) system. This system is found throughout the brain and spinal cord. Specifically, KOPr is found within brain circuits that regulate mood and motivation through dopaminergic and glutamatergic neurotransmitters. Ultimately, studies have shown that dysregulation in this system has led to not only the anhedonia and depressive symptomatology of withdrawal but drug-craving and drug-seeking behaviors as well.
These are but two processes and systems known to be integral to addiction development. Further research will continue to illuminate pivotal features that can be ultimately manipulated to treat the addiction.
Furthermore, research has implicated dopamine as a pivotal player in terms of neurological changes in the brain of an addict. Large and fast increases have been associated with the onset and maintenance of addiction. As the addiction becomes chronic, dopamine actually decreases and eventually results in changes in the prefrontal region of the brain; specifically the orbitofrontal cortex and cingulate gyrus.
Being the most common and costly intoxication, this activity will review the toxicokinetics of alcohol intoxication. Upon intake, alcohol begins metabolism with extensive first-pass metabolism catalyzed by the enzyme alcohol dehydrogenase (ADH). While all our cells in our body are capable of metabolizing alcohol, most occur in the liver with ADH and CYP2E1 (though CYP450 enzymes do not become active until reaching chronic abuse or ingesting substantial amounts). Ethanol is metabolized initially to acetaldehyde, which gets further metabolized in mitochondria to acetate via acetaldehyde dehydrogenase. While acetate will enter the peripheral circulation for utilization in reactions as the key intermediate acetyl CoA, acetaldehyde forms in addicts, causing injury through activation of immune processes. This reaction finds particular relevance in alcoholic liver disease as ADH and ALDH1 reduce all stores of NAD+ to NADH, affecting NAD+-requiring enzymes like lactate and pyruvate dehydrogenase. The eventual damage is the result of reactive oxygen species (ROS). Typically, glutathione (GSH) stores neutralize ROS, but alcohol depletes GSH stores leaving ROS unchecked. For example, ROS interacts with lipids to undergo lipid peroxidation resulting in malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE), which can go on to form protein adducts. Thus, it becomes clear that alcohol metabolism specifically through the generation of ROS and depletion of reducing agents such as GSH, causes damage to multiple organs in the body such as liver, lung, muscle, and brain.
For reference: The average rate of alcohol metabolism is 7g/hr or roughly one drink/hr.
History and physicals vary vastly depending on the substance ingested, time since ingestion, and route of ingestion. For example, most forms of alcohol intoxication present with slurred speech, ataxia, and impaired judgment. This process, depending on the dose and time-frame of ingestion, can quickly spiral towards CNS depression, coma, and multiorgan failure. This progression applies to ethanol, methanol, isopropanol, and ethylene glycol.
In terms of cocaine and other stimulants, expect an acute patient with anxiety, potential psychosis, and sympathetically-driven vital signs (tachycardia, tachypnea, high blood pressure, etc.). Management begins with decreasing anxiety, stabilizing vitals, and preparing rapid response teams for deteriorating patients.
Also, significant variations are seen based on the stage of addiction and addicted substance. The five stages of addiction are as follows:
The above descriptions of stages reveal the expected presentation of the addicted patient. History and physical examination will vary based on which the stage of the condition. A first use patient will likely not be in acute distress (barring active trauma/chronic pain) or have physical signs of withdrawal when they present to your clinic or emergency room. The tolerant patient will typically present with a story that necessitates increasing the dose of their medication or unexpected refill. The addicted patient can present in acute withdrawal with symptoms that vary based on the substance. Alcohol withdrawal will present with signs of autonomic dysregulation to the most worrisome, delirium tremens and seizures.
Lab values (blood and urine), imaging, and specific tests vary depending on the root of the addiction. If it is a psychoactive substance, there may be obvious derangements in the comprehensive metabolic panel (CMP) and complete blood count (CBC) values as well as in the psychoanalysis and behavioral screening. The following is an abbreviated list and summary of common addicted substances and potential evaluation expectations for healthcare professionals:
Please refer to the clinical pearls section for screening criteria in detail, such as CAGE, AUDIT, and the CIWA criteria.
An evaluation commonly used for addiction screening is the Addiction Severity Index (ASI). The screening evaluates seven domains that include:
While the screening lacks in special populations such as the homeless, it has been extensively cross-reviewed to show significant reliability and validity in being the foundation of treatment plans for addicted patients.
Although, not routine in clinical practice, imaging may be integrated into the panel of evaluation of addiction. Researchers found that reduction in dopamine2 (DA D2) receptors correlated with decreased activity in anterior cingulate gyrus CG and orbitofrontal cortex OFC In detoxified cocaine abusers.
Liquid Chromatography/Mass Spectrometry and IMS
Some of the substances of use (kratom) and misuse (bath salts) are not identifiable on a regular urine drug screen or blood work. Liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) methods are used to detect kratom, for example.
Intoxications regularly go hand-in-hand with addictions as they can either be the subject of the addiction or the propelling factor towards behavioral disruptions and suicidal tendencies. For that reason, refer to the following list of intoxications/overdoses and their respective antidotes.
Further management involves monitoring and maintaining patient vital signs. Once again, this is dependent on the stage of presentation of the patient and the subject of the addiction.
While multiple pharmacological treatments are available to the two most common substance addictions – smoking tobacco and alcohol – group meetings and psychological and social support are by far the most effective.
Pharmacologically, alcohol dependence is treatable with disulfiram, naltrexone, and acamprosate. Each has its place in alcohol dependence and addiction. Disulfiram is effective for the patient who recently quit and needs help maintaining abstinence as any consumed alcohol will cause relatively quick hangover-type symptoms meant to deter further drinking. Naltrexone removes the sensation of reward/pleasure with drinking to begin and maintain abstinence, and acamprosate minimizes the initial withdrawal symptoms as you work on becoming abstinent. Acute management of alcohol intoxication during episodes of relapse is treatable with long-acting benzodiazepines such as chlordiazepoxide or diazepam.
For tobacco dependence pharmacologically, there is currently bupropion and varenicline. Off-label uses exist for drugs like clonidine which is an alpha-2 agonist for managing high blood pressure; also, there is nortriptyline, a member of the TCA class of antidepressants. Both of the latter drugs are effective if started before quitting. As for bupropion, the pill is used to cut down your craving for, and thus addiction to, tobacco. Varenicline helps curb the craving for nicotine as well as decreasing withdrawal symptoms. Along with these options, there are various nicotine patches, gums, sprays, and lozenges.
Ultimately, however, these pharmacological interventions must be combined with non-pharmacological methods for optimal efficacy and to limit and prevent the progression of substance use from developing to misuse to dependence. For example, in terms of nicotine dependence, it has been shown that pharmacological treatments employed with physician advice and empathy results in approximately double the rate of long-term abstinence.
Of interest, more addicts have overcome their addiction in their way vs the amount enrolled in a program (12-step, CBT, etc). For these reasons, consideration is necessary for whether to treat an addict or not. If you do plan to initiate treatment, a joint plan that involves the input of the patient will yield better results than without it.
In terms of addictions, the differential should include ruling out the root causes of the addiction. Potential root causes are as follows:
Bipolar disorder – more than half of patients with substance abuse disorder have bipolar disorder, and significant mood fluctuations can present in the patient.
Post-traumatic stress disorder (PTSD) – common concurrence amongst alcohol abusers, PTSD should be screened for in all addicts. While the two are separate conditions with separate signs and symptoms, treating the root of the PTSD can mitigate or eliminate the overlying addiction.
Since most cases of intoxication involve episodes of altered mental status, a helpful mnemonic for the emergency room physician is the following:
Stages of addiction: refer above to the history and physical discussion to review the stages of addiction.
Stages of recovery/change from addiction include:
The evidence is quite clear on the long-term effects of drug dependence with those diagnosed dying 22.5 years earlier than those without the diagnosis. This lifespan is related to the toxic effects of substances on multiple systems, including – but not limited to – the cardiac, respiratory, and neurological systems. Also, a five-year study on alcohol and drug rehabilitation treatment found that older adults have favorable long-term outcomes versus young adults; specifically, older adults (especially older women) were found to have 52% 30-day abstinence rates versus a 40% younger adult rate. Factors such as social networks and gender play a role alongside age in these numbers.
Based on the current research on addiction, practitioners need to shift the management of patients from an acute paradigm to a chronic disease paradigm. Furthermore, we need to bolster the screening, intervention, and overall management of the condition. Urgency is necessary for this shift as 6.9 million or 2.8% of the US population is currently under threat of the mortality risk associated with illicit drug use. However, before any change gains traction, current research must bolster the evidence of decreased mortality with decreases in prevalence and incidence of addiction.
As of now, there is a clear relationship between the changes in mortality risk with the time at which patients afflicted with addiction enter treatment and the amount of therapy they receive. Their ultimate prognosis depends on these factors.
In terms of chronic alcohol use, Wernicke encephalopathy and Korsakoff syndrome become expected complications. With Wernicke encephalopathy comes the triad of confusion, ophthalmoplegia, and ataxia (though usually, only one is present 20% of the time). On CT and MRI imaging, classic findings include atrophy of the bilateral mammillary bodies and hippocampal areas.
Hepatic steatosis is a common complication of chronic alcohol use that results from cholesterol esters, phospholipids, and triglycerides formed ultimately from alcohol-induced ROS formation altering lipid metabolism.
Chronic heavy alcohol consumption is the most important risk factor when considering chronic pancreatitis. The process begins with acute heavy consumption, which through toxic effects of alcohol metabolism, induce inflammatory and fibrotic changes in the pancreas over time. Specifically, the pancreatic stellate cells become activated, resulting in the expected fibrotic changes.
Cardiomyopathy is another documented complication that is expected as a result of chronic alcohol use resulting from oxidative stress, disruptions in proper calcium handling, and mitochondrial dysfunction.
Cocaine addiction and intoxication lead to myocardial ischemia, psychosis, and fatal arrhythmias that require acute management for mitigation of effects.
From a behavioral perspective, addiction leads to multiple episodes of withdrawal and relapses (the average being 7).
Rehabilitation treatment becomes the cornerstone of managing an addicted patient from sobering up to maintaining their remission. Since the 1960s, various modalities have found public and private aid such as methadone clinics, free outpatient treatment programs, and residential community treatment sites.
Among the most common and effective programs include the 12-step programs; this is category includes AA (Alcoholics Anonymous), Narcotics Anonymous, and Cocaine Anonymous. This is a form of peer support groups that are commonplace in addiction management with the dual benefit of aiding drug addiction reform and co-occurring mental health problems. Some of the positive outcomes of these programs include increased self-confidence, self-efficacy and healthy coping strategies for addicts to maintain their abstinence. Overall, rehabilitation care for addiction management includes failsafes that prevent relapse from happening through pharmacological deterrents and peer-support groups.
Many times psychiatry consults are necessary as the addiction stems from underlying behavioral/psychological issues. However due to the many medical or surgical complications associated with addiction, medical, surgical or trauma consults are also necessary to address impending death due to myocardial infarction, acute kidney failure, rhabdomyolysis encountered with stimulants like cocaine and amphetamine, respiratory arrest and coma by overdose on prescribed or non-prescribed opioids, and motor vehicle accident leading to head injury and traumatic brain injury.
Deterrence is dependent on proper screening criteria for early signs of potential addiction as well as early childhood education. School programs such as DARE represent a positive effort to curb drug use and experimentation before it becomes a problem. However, patient education, while it is most effective prior to the development of health problems, has a place at any stage of addiction. As stated above, patients are more likely to reach and maintain abstinence and institute positive lifestyle changes if physicians and other health care professionals engage in consistent and positive encouragement of the patient.
Moderate alcohol consumption is defined as 1 drink/day for women and up to 2 drink/day for men. Studies have revealed that this low to moderate alcohol use has been demonstrated to lower the risk of coronary heart disease.
The average rate of alcohol metabolism is approximately 7g/hour which is equal to 1 drink/hour.
Cage criteria for alcoholism screening:
Each yes gets a +1, and each no gets a 0 for a total of 4 and a low of 0. However, CAGE falls short in lower severity situations. For these (if provided with ample time for interviewing) refer to AUDIT:
Each question has four potential categories for responses allowing each category a max of 4 and a low of 0. Scores less than 3 are consistent with normal alcohol consumption.
Patients less than or equal to a score of 8 do not require medical treatment whereas those above do.
While patients addicted to opioids may develop a tolerance for all other side effects, constipation and miosis remain constant despite the dosage — screen patients with these side effects before signs and symptoms of respiratory depression and other vital sign depressions.
Although variable amongst the states, typical BAC levels that define alcohol intoxication 80 to 100 mg/dL (.08 to 0.1% BAC). For the chronic user, these levels may take increasing times to reach.
Sober time calculator – (BAC (mg/dL) – legal limit) / 20mg/dL/hr = time to sobriety
Avoid bupropion in patients with a current or past history of eating disorders as this lowers the threshold for seizure side-effects.
As discussed above, addiction is a very complex condition with multiple episodes of reaching abstinence and falling into relapse; this is why an interprofessional healthcare team is vital in treatment.
Treatment begins with risk factor identification and diagnosis by the physician but quickly grows to involve interprofessional teams to help the patient maintain their abstinence. With comprehensive questioning, primary care physicians can screen patients using criteria such as the Addiction Severity Index and more to identify at-risk patients. These patients should be followed up closely over the years. At the same time, social and familial support can be called upon to prevent the progression to addiction.
Once diagnosed, the swift involvement of a psychiatrist and dietician are essential. The psychiatrist can help uncover root causes for the addiction while the dietician can help maintain the patient's overall health. The positive attitude and self-control required to reach and maintain abstinence find pitfalls in poor nutrition and energy reserves.
During relapses, nurses play pivotal roles. They can help track patient vitals, and proper medication and fluids are provided promptly to manage acute intoxications and aid the patient back towards abstinence.
Pharmacists are also essential members of the interprofessional team dealing with addiction. They may be the first to notice addictive behaviors if the addiction involves prescription drugs. They are also good resources for detoxification, assisting clinicians in treatment and rehab centers, and verifying dosing and checking for drug interactions.
Also discussed above, 12 step programs that involve peer support are integral to the development and maintenance of abstinence. The mentioned players - primary care physician, ER physician, nurses, 12 step programs, dietician, psychiatrists - all have well-researched roles in the success of diagnosing and managing addiction patients. [Level I]
The interprofessional team of clinicians, nursing, specialists, psychological professional, pharmacists, dieticians, and social workers must all coordinate their actions and information to achieve the best possible patient outcomes for addiction disorders. [Level V]
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