Pathology of Drug Abuse

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Tobacco and Smoking

Smoking tobacco leads to the greatest number of problems of any drug in use in the world today. Smoking contributes to more than 7 million deaths each year worldwide. These deaths are mainly the result of increased numbers of lung cancers as well as increased numbers of cases of atherosclerotic heart disease and emphysema of the lung. Smoking increases the risk for cancers of the bladder, pancreas, kidney, and cervix. There is an increased risk for gastritis and gastric ulceration in persons who smoke. Cataracts of the crystalline lens of the eye occur with increased frequency in smokers. (GBD, 2017)

Women who are pregnant and who smoke put their fetuses at increased risk for spontaneous abortion, ectopic pregnancy, placental abruption, placenta praevia, premature labor, and preterm birth, stillbirth,low birth weight, and small for gestational age (SGA) compared to women who do not smoke during pregnancy. Prenatal maternal smoking is also associated with risk of sudden unexplained death in infancy. (Gould et al, 2020)

Vaping

Electronic cigarettes (e-cigarettes) produce an inhaled vapor. The major chemical component of the vapor is nicotine, but additional toxic constituents include metals, volatile organic compounds (VOCs such as benzene and toluene), nitrosamines, and Vitamin E acetate (VEA). Thus, the substitution of vaping for traditional cigarette smoking does not eliminate health hazards, but only trade one set of problems for another set. Nicotine by itself is highly addictive and promotes continued usage, leading to more exposure to the additional toxic compounds inhaled with the nicotine. Adolescent brains are more susceptible to this addiction. Persons using e-cigarettes are more likely to also use traditional tobacco products, compounding health risks. (Walley et al, 2019)

E-cigarette use is linked to poisoning, immediate inhalation toxicity, and lung injury. Environmental effects include waste, fires, and generation of indoor airborne particulate matter. The nicotine e-cigarettes can cause dependence in non-smokers, and young non-smokers who use e-cigarettes are more likely than non-users to initiate smoking and to become regular smokers. (Banks et al, 2023)

Short-term health risks of e-cigarettes include increased airway resistance and increased exhaled carbon monoxide (CO). CO binds to hemoglobin tightly to displace oxygen. Airway resistance reduces optimal lung function. (Stockley et al, 2018)

Radiologic imaging studies document a variety of lung injury patterns associated with vaping. Patterns include hypersensitivity pneumonitis, diffuse alveolar hemorrhage, diffuse alveolar damage, acute eosinophilic pneumonia, giant cell interstitial pneumonia, and lipid pneumonia. These injuries can acutely lead to diminished lung function. A more long-term pattern of injury is organizing pneumonia with fibroblast proliferation and collagen deposition - features of scar tissue formation that reduces lung capacity. (Henry et al, 2019)

Pathologic findings with vaping confirm the imaging patterns. Acute lung injury patterns include diffuse alveolar damage and organizing pneumonia. Microscopic pathologic findings include bronchiolitis, mucosal edema, sloughing of the bronchiolar epithelium, eosinophils, and peribronchiolar organization following accumulation of macrophages. There can be fibrinous exudates and type 2 pneumocyte hyperplasia. More severe injury can lead to diffuse alveolar damage with formation of hyaline membranes. There can be progression to chronic inflammation and fibroblast plugs in bronchioles. Clinical features associated with these pathologic alterations include fever, night sweats, weight loss, dyspnea, cough, nausea, and vomiting. (Butt et al, 2019) (Mukhopadhyay et al, 2020)

EVALI (e-cigarette or vaping product use associated lung injury) describes the acute respiratory illness related to toxic effects of substances inhaled in vaping. Findings include shortness of breath, cough, chest pain, and fever, along with hypoxia and tachycardia. The inhaled compounds can produce toxic effects upon cells in the respiratory tract and induce neutrophilic inflammation. Thus, EVALI can mimic infectious diseases of the lungs, and should be considered in persons with recent e-cigarette use. (Krishnasamy et al, 2020) (Park et al, 2022)

Alcohol Abuse

The abuse of alcohol (ethanol) contributes to many deaths per year worldwide. It can also be a cause for drug overdose leading to death from ingestion of a large amount of alcohol, and second only to opioid overdose in number of drug-related deaths. Almost 1 in 5 visits to an emergency department involve prior use of alcohol. (https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-related-emergencies-and-deaths-united-states)

Chronic alcohol use leads to liver disease that can be manifested initially as fatty change (steatosis). Excessive alcohol ingestion over many years can lead to micronodular cirrhosis. A cirrhotic liver leads to portal hypertension and the complication of bleeding esophageal varices with massive, life-threatening gastrointestinal hemorrhage. There is also an increased risk for hepatocellular carcinoma arising in a cirrhotic liver. Acute excessive alcohol consumption can lead to alcoholic hepatitis. Laboratory testing of a blood specimen for evidence of ethanol ingestion includes phosphatidylethanol for recent (within 2 weeks) and carbohydrate-deficient transferrin for chronic use. (Patel and Flamm, 2023)

In the brain, alcohol use disorder predisposing to poor dietary intake lacking nutrients can lead to thiamine deficiency with neurotoxicity and development of Wernicke–Korsakoff syndrome (WKS), with components of Wernicke encephalopathy and Korsakoff’s psychosis, with higher mental function affected by confusion and confabulation. Acute Wernicke encephalopathy is a potentially reversible condition characterized by confusion, oculomotor disturbances, and ataxia. Continued alcohol use leads to permanent brain damage. (Nutt et al, 2021)

Abrupt cessation of alcohol ingestion in persons who are chronic alcohol users predisposes to alcohol withdrawal Symptoms, and signs within 8 to 24 hours include transient visual, auditory or tactile hallucinations. There can be progression to withdrawal-related seizures which, if not treated may progress to life-threatening delirium tremens. (Day and Daly, 2022)

Alcohol use during pregnancy can lead to fetal alcohol spectrum disorders, also termed the fetal alcohol syndrome (FAS). The risk increases with the time and amount of exposure, but there is no completely safe level of maternal alcohol consumption. This syndrome is estimated to occur in 1 in 100 live births, but the actual incidence is probably higher. Whenever a pregnant woman stops drinking, she reduces the risk of having a baby with FAS. Damage to the fetus from FAS cannot be reversed. Later in development, affected children have increased behavioral problems and learning disabilities. There are no specific, distinctive morphologic findings, so it is challenging to diagnose. The most common deformity with FAS is moderate to severe growth retardation. The three most distinctive features are a thin upper lip, smooth philtrum, and short palpebral fissures. (Popova et al, 2023)

Additional FAS anomalies include microcephaly, long and narrow forehead, hypotelorism, maxillary and mandibular hypoplasia, narrow palpebal fissures, thin elongated philtrum and vermillion border of the upper lip, temporomandibular joint disorders, and dental malocclusion. Ocular problems include microphthalmia, coloboma, nystagmus, strabismus, and ptosis. The physical anomalies tend to become less apparent as the child ages. (Mukherjee et al, 2006)

Opiates

Opiates by themselves have minimal pathologic tissue effects. Higher doses of more powerful opiates can lead to respiratory depression and death. Persons who really need the pain relief that opiate medications can offer do not become addicted, but unfortunately tolerance may develop over time, requiring higher doses to maintain analgesia. The major problems with opiate abuse are the psychosocial consequences, the infections from route of administration (injection), and possible overdose with death. (Torres-Lockhart et al, 2022)

An opioid epidemic in the 21st century has been driven by increasing demand and increasing supply, particularly of synthetic opioid compounds. The prescription opiate most often abused is fentanyl, which has great affinity for the mu opioid receptor, and is 80 to 100 times more potent than morphine, producing an intense, temporary euphoria. (Liu et al, 2018) An overdose is treated with naloxone, and the synthetic opioids require higher doses of naloxone. (Walker, 2023) In the U.S. in 2022, of over 100,000 deaths from drug overdose, about 80% were due to opiates, mainly synthetic opioids. (https://blogs.cdc.gov/nchs/2023/05/18/7365/)

Psychosocial problems related to behavioral issues from drug dependence. Drug-seeking behaviors result in lack of concern for oneself or others. If the route of administration is intravenous, without attention to sterile technique, there is increased risk for infection. Withdrawl from chronic opiate usage typically results in marked physiologic and psychologic disturbances such as pupillary dilation, tachycardia, yawning, lacrimation, rhinorrhea, piloerection, abdominal cramping, nausea, vomiting, diarrhea, muscle or bone pain, irritability, restlessness, anxiety, and insomnia. (Torres-Lockhart et al, 2022)

Oxycodone, best known by the trade name OxyContin®, is a controlled release form of opioid analgesic prescribed to treat moderate to severe pain of constant and prolonged duration. Persons abusing this medication risk addiction and death, particularly if oxycodone is used in association with other drugs. Abusers may progress to usage by intravenous injection and to usage of other opiates or drugs of abuse. (Hays, 2004)

Intravenous Drug Abuse

Many drugs can be injected intravenously. The drugs themselves may have the major effect of impairment of mental function, but the route of administration can have serious complications. Injection of drugs with needles that are not sterile leads to the potential for a wide variety of infections. Such infections include: human immunodeficiency virus (the causative agent for AIDS), viral hepatitis (particularly hepatitis B and C), and bacterial infections. (Marks et al, 2022)

Persons with a history of intravenous drug abuse also are more likely to have tuberculosis of the lungs. The drug heroin can produce a nephropathy in the kidney that resembles focal segmental glomerulosclerosis. In addition, a "talc granulomatosis" can occur because many injected drugs have been adulterated with an inert substance (such as talcum powder) to "cut" or dilute the amount of drug. (Milroy and Parai, 2011)

Cocaine

Cocaine can exert a variety of effects. The major acute effects producing pathologic conditions result from the increased circulating catecholamine levels with cocaine use. These increased catecholamines can produce vasoconstriction. The lesions can include acute hemorrhages and infarction in the brain. Cerebral infarction can occur within 3 hours of cocaine use even in young persons. Subarachnoid haemorrhage is often associated with rupture of a berry aneurysm. Intraparenchymal haemorrhage can occur in the basal ganglia and thalamus. (Milroy and Parai, 2011)

Ischemic changes in the heart from small artery narrowing and sclerosis lead to contraction band necrosis of the myocardium and possible sudden death. With chronic usage, the myocardium develops interstitial fibrosis, and the heart becomes enlarged. Atheroma formation in artereis as well as arterial dissection can occur. (Milroy and Parai, 2011) Combining cocaine use with ethanol use can compound the myocardial damage. (Awtry and Philippides, 2010)

Pregnant mothers who use cocaine can affect their fetuses from abnormalities of placental function leading to low birth weight babies or an increased risk for placental abruption. Maternal cocaine use increases the risk for spontaneous abortion. (Kuczkowski, 2007)

Persons with cocaine intoxication (not necessarily related to the drug level) may develop a state of iatrogenic psychosis (cocaine psychosis) with "excited delerium" in which they are markedly agitated and combative and develop hyperthermia, often of a severe degree (to 106 F). Organ damage can accompany this state of excited delerium and may include rhabdomyolysis of muscle, hepatotoxicity, and renal failure. Disseminated intravascular coagulation (DIC), hypotension, and sudden death are additional complications. (Devlin and Henry, 2008)

Methamphetamine

Methampetamine is a stimulant drug with inotropic effects upon the cardiovascular system. Methamphetamine is metabolized to amphetamine, which is also a stimulant. Methamphetamine and amphetamine have similar effects to cocaine on the cardiovascular system. The heart may have such stress placed upon it that there are ischemic changes to the myocardial fibers. Chronic use leads to hypertrophy, interstitial fibrosis and microvascular disease. The myocardial effects are made worse by concomitant ethanol use. (Milroy and Parai, 2011)

Heart with ischemic changes, microscopic.

Amphetamines also damage both the serotonergic and dopaminergic systems of the central nervous system. Alterations of the dopaminergic system may persist even after years of abstinence from use of methamphetamine and may be associated with deficits in motor and cognitive performance. (Gouzoulis-Mayfrank and Daumann, 2009)

CNS toxicity of methamphetamine may be the result of both hyperthermia as well as direct effects upon individual cells. A dose-related increase in body temperature occurs with acute ingestion of methamphetamine. This can potentiate acute effects of methamphetamine upon the blood-brain barrier and upon neurons, leading to edema. (Kiyatkin and Sharma, 2009)

Methamphetamine and cocaine use can cause tooth decay that mainly affects the facial (outward) smooth and interproximal regions of teeth. The xerostomia patients experience may promote consumption of soft drinks with sugar. (Milroy and Parai, 2011)

GHB

Gamma-hydroxybutyrate (GHB) is a metabolite of the neurotransmitter gamma aminobutyric acid (GABA) and also functions as a neurotransmitter by affecting the dopaminergic system. GHB may also potentiate the effects of endogenous or exogenous opiates. GHB was introduced into the U.S. in 1990 as a purported stimulant to muscle growth during sleep, but it was soon banned because of problems with overdose and adverse reactions. Moreover, GHB is no longer used as an anesthetic agent because of the risks. However, Gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are readily available as industrial solvents and when consumed are metabolized to GHB. The effects of GHB are primarily on the brain. GHB gained reputation as a euphoric and sexual performance enhancing agent. Its effects can be potentiated by alcohol and by benzodiazepines. The ingestion of GHB results in drowsiness and dizziness with the feeling of a "high" within 10 to 20 minutes and lasting up to 4 hours. There are a multitude of dose dependent adverse effects that can occur within 15 minutes to an hour, including: headache, nausea, vomiting, hallucinations, loss of peripheral vision, and nystagmus. These findings generally subside in 2 hours to 4 days. More severe acute toxicity includes respiratory depression, bradycardia, seizures, and reduced level of consciousness to deep coma. It is difficult to predict how much GHB will produce an overdose. Withdrawl from GHB can have an onset in 12 hours and last up to 12 days. In rare instances, deaths have occurred from these adverse effects. (Timby et al, 2000) (Tay et al, 2022)

Ecstasy

The methylene-dioxy derivatives of amphetamine and methamphetamine are "designer drugs" that generically are termed "ecstasy" and include 3,4-methylenedioxy-methamphetamine, also known as "Adam," 3,4-methylenedioxy-ethylamphetamine (MDEA), also known as "Eve," and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), also known as "Methyl-J" or "Eden." A "designer drug" is a compound that is chemically altered from the form of a controlled substance in order to produce special effects and to bypass legal regulations. MDMA and similar compounds are "entactogens" that act upon serotonergic pathways in the brain to give users a feeling of euphoria, energy, and a desire to socialize. These immediate effects last approximately 3 to 6 hours. (Fineschi et al, 1999) (Christophersen, 2000)

The adverse effects of ecstasy use may include hyperthermia, liver toxicity, and neuropsychiatric effects. Severe dehydration leading to excessive fluid intake and water intoxication. Cardiovascular effects are similar to methamphetamine. There can be memory deficits, confusion, depression, and sleep problems even weeks after taking this drug. (Milroy and Parai, 2011)

MDMA experimentally causes selective and persistent lesions of central serotonergic nerve terminals. MDMA users can have residual alterations of serotonergic transmission, and though at least partial recovery may occur after long-term abstinence, functional sequelae may persist even after longer periods of abstinence. Long term use may be accompanied by long-lasting brain damage and memory impairment. (Carter et al, 2000) (McQuire, 2000) (Gouzoulis-Mayfrank and Daumann, 2009)

A syndrome including hyperthermia, disseminated intravascular coagulation, rhabdomyolysis, hepatic failure, and renal failure has been reported with MDMA use, findings similar to the excited delirium of cocaine use. In addition persons using MDMA may develop acute fulminant hepatitis with liver failure, and possible death, that can occur days to weeks following drug use. (Scully et al, 2001)

Cannabinoids (marijuana)

Some of the most widely used psychoactive agents include derivatives from the hemp plant Cannabis, typically containing the active compound delta-9-tetrahydrocannabinol (THC). The most common form is marijuana. Hashish is stronger, with more active drug. Throughout much of human history for the past 4000 years, preparations of Cannabis contained small amounts of THC, less than 1%. In the latter part of the 20th century, Cannabis plants with higher THC concentrations and processing of the plants to yield more potent products with greater amounts of THC became widely employed. (Hall and Degenhardt, 2009)

The plant products are typically smoked and the drug absorbed into the blood via respiratory tract. The drug acts through cannabinoid receptors in brain and elsewhere in the body. These receptors normally interact with short acting and less potent endogenous compounds (endocannabinoids) that affect brain function. THC induces mild euphoria, relaxation, and perceptual alterations for up to 2 hours following usage. The lifetime risk for THC dependence is about 9% and nearly double that for persons beginning regular use in adolescence. Only tobacco (32%) and alcohol (15%) dependence are more common. (Hall and Degenhardt, 2009)

During adolescence, the brain undergoes modification of neurons with proliferation, migration, differentiation, and pruning of synapses that promote brain development for adulthood. Cannabinoids alter those processes and increase the risk for subsequent development of psychoses, including schizophrenia. (Malone et al, 2010) Adolescent users of Cannabis are less likely to complete schooling and more likely to become unemployed than nonusers. (Hall and Degenhardt, 2009)

Acute adverse reactions to THC include anxiety, panic, and psychosis, more often in persons with no prior use of the drug. Impairments in attention, perception, and motor coordination affect ability to perform critical tasks such as operating a motor vehicle, increasing the risk for accidents. Since Cannabis is smoked, there are irritant effects upon the respiratory tract. There is risk for airway inflammation and for emphysema. (Murtha et al, 2022) There is risk for chronic bronchitis and lung cancer. Effects upon the cardiovascular system increase the risk for myocardial infarction in adults. (Hall and Degenhardt, 2009) A high-fat diet and ethanol use upregulate hepatic cannabinoid receptors so that THC may promote development of fatty liver. (Purohit et al, 2010)

Some regular Cannabis users develop severe nausea with vomiting (cannabinoid hyperemesis) and the urge to bathe frequently in warm water for relief of these symptoms. Either the effects of the THC upon cannabinoid receptors near the thermoregulatory center of the hypothalamus, or upon cannabinoid receptors in splanchnic vasculature may play a role. The warm water exposure redirects blood flow to peripheral vasculature. (Patterson et al, 2010)

Synthetic Cannabinoids (spice drugs)

The so-called 'spice drugs' are synthetic cannabinoid compounds that can bind to brain cannibinoid receptors CB1 and CB2. Their structural chemistry is not like the tetrahydrocannabinol (THC) found in the cannabis of marijuana. Binding to the CB1 receptor produces strong but short-lived psychoactive effects and potential complications due to unknown pharmacologic effects and toxicity. They are 2 to 100 times more potent than THC because both parent drug and metabolites are potent THC receptor agonists, while marijuana is a partial agonist. (Liu et al, 2018) (Roque-Bravo et al, 2023)

Adverse cardiovascular and pulmonary reactions reported include tachycardia, hypertension, chest pain, arrhythmias, tachypnea, cough, and dyspnea. Mental status changes include altered consciousness, hallucinations, racing thoughts, and seizures. Psychosis, withdrawal, and death have been reported with usage of these compounds. Users of these drugs are at risk due to their variability as well as their potency. As is the case with drugs of abuse in general, there is no safety factor of quality control in production or packaging, so the amount one is getting is unpredictable. (Roque-Bravo et al, 2023)

Initially, synthetic cannabinoids were mainly JWH compounds (after the initials of the scientist who synthesized them) with predominantly sympathomimetic effects. Subsequently, compounds of the XLR-11 and CID families have appeared that produce CNS depressant effects and bradycardia. They are also full cannabinoid receptor agonists. The synthetic cannabinoids may not be detected by routine urine drug screening methods. (Sud et al, 2018)

Synthetic Cathinones, or PABS ("bath salts")

The synthetic cathinones are one form of "designer drug" with modified chemical structures from a natural form and designed to mimic or amplify the effect of a natural source psychostimulant. These compounds are typically sold as "bath salts" (PABS) but have nothing to do with bathing. Instead are psychoactive "uppers" that are synthetic forms of cathinones. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant, indigenous to eastern Africa and the Arabian Peninsula, which is chewed as "khat" for a mild stimulant effect. (Daziani et al, 2023)

Derivative synthetic cathinones being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. They mainly contain methylenedioxypyrovalerone (MDPV), which is structurally related to pyrovalerone and pyrrolidinophenone compounds that inhibit norepinephrine-dopamine reuptake. Therefore, they cause central nervous system stimulation and sympathetic stimulation. They are marketed as aphrodisiacs and stimulants. (Prosser and Nelson, 2012)

They are absorbed quickly through mucosal surfaces (nasal, oral, gastric, rectal). Only a few milligrams produce a high, but the quantities marketed may be 100 times that amount, increasing the risk for overdose. Their effects peak at 90 minutes following ingestion and last for 3 or 4 hours before the user "crashes". Long-term users of PABS may develop tolerance, and abstinence can lead to withdrawal and intense craving. (Ross et al, 2011)

The toxicity from PABS may include extreme sympathetic stimulation with tachycardia, hypertension, shortness of breath, blurred vision, dry mouth, and hyperthermia. There can be markedly altered mental status with severe panic attacks, agitation, paranoia, hallucinations, and violent behavior such as self-mutilation, suicide attempts, and homicidal activity. Seizures may occur. Rhabdomyolysis can develop. Deaths have been reported, most often from alpha-pyrrolidinopentiophenone ("flakka"). The toxicity profile includes the worst effects of other drugs of abuse including lysergic acid diethylamide (LSD), phencyclidine (PCP), methylenedioxymethamphetamine ("ecstasy"), cocaine, and methamphetamine. Routine drug screens do not detect PABS. (Ross et al, 2011; Liu et al, 2018)

Mitragynine ("kratom")

The kratom plant grows in Southeast Asia and from it can be extracted the psychoactive alkyloid mitragynine, and in small quantities 7-hydromitragynine, which is more potent. At low doses it produces a stimulant effect. At high doses it has a sedative effect as an agonist at the mu opioid receptor. (Liu et al, 2018)

Anabolic-Androgenic Steroids

The use of anabolic-androgenic steroids (AAS) has increased substantially over the past 4 decades. These drugs are used mainly for their effect of increasing muscle mass for the desired goal of increasing athletic performance and enhancing physical appearance. However, such drugs do not increase the level of skill in performance and cardiovascular function--the major enhancers to most sports-related activities. (Sjöqvist et al, 2008) (Thirumalai and Anawalt, 2023)

Both oral and injectable compounds are used, more often the latter. Users may cycle on and off usage to avoid complications, but prolonged usage brings many adverse effects. In men these include: testicular atrophy, decreased testosterone production, gynecomastia, decreased sex drive, infertility, baldness, hypertension, heart disease, and tendon injuries. In women, the adverse effects reported include: decreased breast size, fluid retention, hypertension, and sleep disorders. Physical changes such as testicular atrophy and gynecomastia in men, or breast atrophy in women, are often not reversible even after stopping the drugs. Adolescents taking AAS may have diminished bone growth and shorter stature. AAS may produce cholestatic jaundice; they reduce the level of HDL cholesterol to promote atherogenesis and heart disease. (Sjöqvist et al, 2008) (Thirumalai and Anawalt, 2023)

The major psychiatric effects of AAS use include changes in mood, worse with greater usage. While using the drugs increased aggression and mania can occur. Off the drugs depression occurs. The combination resembles bipolar disorder, a disabling mental health disorder. Such adverse effects could significantly impact athletic performance negatively and decrease sexual function. In short, AAS can prevent the very things that they are supposed to enhance. (Thirumalai and Anawalt, 2023)

The most serious complication of AAS use is an increased risk for heart disease and sudden death. Anabolic steroids decrease HDL cholesterol and increase cardiac size. Myocardial fibrosis can occur, similar to cardiomyopathy. Hypertension induced by AAS further increases heart size. These effects may persist even after use of AAS has been stopped, increasing the risk for morbidity and mortality. Anabolic steroids have been shown to enhance the coronary artery response to catecholamines released during periods of stress, and this may play a role in the sudden cardiac deaths reported with their use. Contraction band necrosis, indicative of ischemia, has been observed in such deaths. (Fineschi et al, 2001)

The use of growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin at high, non-physiologic amounts, as anabolic hormonal substances has no significant effect upon increasing muscle mass. Instead, such compounds over time lead to disease states: acromegaly with disfiguring soft tissue changes, diabetes mellitus, hypertension, heart disease, and nerve damage. (García-Arnés and García-Casares, 2023)

Improper methods of injection with lack of sterile technique increase the risk for transmissible infections, including viral hepatitis B, viral hepatitis C, and human immunodeficiency virus (HIV). (Thirumalai and Anawalt, 2023)

Blood Doping

Increasing the amount of circulating red blood cells with their oxygen-carrying hemoglobin is a physiologic adaptation to living at a higher altitude with less atmospheric oxygen. Increasing hemoglobin by 10% will increase oxygen utilization (VO₂ max) by 5 to 10% for sports where endurance is essential. The quick method is blood transfusion. Such practices are banned in competitive sports, and there are continuing attempts by athletes to mask such practices while methods for detection continue to evolve. (García-Arnés and García-Casares, 2023)

Why do sudden deaths occur in athletes who use human recombinant eryrthropoietin ("epo") but very infrequently in patients with anemia who really need it? The drug has predictable results in anemic patients, and raises red cell mass, but not typically above normal. In healthy persons, particularly athletes who do not need more erythropoietin, there are unpredictable results, including an increase in the number of red blood cells (RBCs) into a polycythemic range with increase in blood viscosity to the point of thrombosis (clotting). That could lead to stroke, myocardial infarction, retinal artery occlusion (blindness), and pulmonary thromboembolism. There is also another rare but frightening complication: the development of antibodies, not only to the human recombinant form but also naturally occurring erythropoietin, leading to a condition called "pure red cell aplasia" with transfusion dependence for life. How is the recombinant form detected? The recombinant products include glycan isoforms that differ from natural erythropoietin, and those can be detected in a urine sample. (John et al, 2012) (García-Arnés and García-Casares, 2023)

Laboratory Testing

Testing for the presence of drugs can be performed on body fluids, principally urine and blood. Urine is easier to obtain, and it is likely to contain both drugs and their metabolites, but detection is qualitativem, since quantification is modified by fluid intake. Blood is obtained when quantification is needed, as for blood ethanol.

Screening can include immunoassays that require less equipment and skill in interpretation, but may have cross-reactivity with related drugs that may not be classified as drugs of abuse (e.g., codeine in cough medicines can cross react with opiate drugs of abuse).

Confirmation of screening test results, or primary detection of compounds not easily detected by other means, is done by mass spectroscopy (MS). The first step is chromatography for separation of the drug compounds in a gas phase (gas chromatography (GC) or liquid phase (liquid chromatography, or LC). the next step is mass spectroscopic analysis of the separated compounds. Thus, the method can be GC-MS or LC-MS. (Liu et al, 2018)

References

Awtry EH, Philippides GJ. Alcoholic and cocaine-associated cardiomyopathies. Prog Cardiovasc Dis. 2010;52:289-299.

Banks E, Yazidjoglou A, Brown S, et al. Electronic cigarettes and health outcomes: umbrella and systematic review of the global evidence. Med J Aust. 2023 Apr 3;218(6):267-275. doi: 10.5694/mja2.51890.

Bedene A, Dahan A, Rosendaal FR, van Dorp ELA. Opioid epidemic: lessons learned and updated recommendations for misuse involving prescription versus non-prescription opioids. Expert Rev Clin Pharmacol. 2022 Sep;15(9):1081-1094. doi: 10.1080/17512433.2022.2114898.

Butt YM, Smith ML, Tazelaar HD, et al.Pathology of Vaping-Associated Lung Injury. N Engl J Med. 2019 Oct 2. doi:10.1056/NEJMc1913069.

Carter N, Rutty GN, Milroy CM, Forrest AR. Deaths associated with MBDB misuse. Int J Legal Med. 2000;113:168-170.

Christophersen AS. Amphetamine designer drugs - an overview and epidemiology. Toxicol Lett. 2000;112-113:127-131.

Day E, Daly C. Clinical management of the alcohol withdrawal syndrome. Addiction. 2022 Mar;117(3):804-814. doi: 10.1111/add.15647.

Daziani G, Lo Faro AF, Montana V, et al. Synthetic Cathinones and Neurotoxicity Risks: A Systematic Review. Int J Mol Sci. 2023 Mar 25;24(7):6230. doi: 10.3390/ijms24076230.

Devlin RJ, Henry JA. Clinical review: Major consequences of illicit drug consumption. Crit Care. 2008;12:202.

Fineschi V, Baroldi G, Monciotti F, Reattelli LP, Turillazzi E. Anabolic steroid abuse and cardiac sudden death. Arch Pathol Lab Med. 2001;125:253-255.

Fineschi V, Centini F, Mazzeo E, Turillazzi E. Adam (MDMA) and Eve (MDEA) misuse: an immunohistochemical study on three fatal cases. Forensic Sci Int. 1999;104:65-74.

García-Arnés JA, García-Casares N. Doping and sports endocrinology: growth hormone, IGF-1, insulin, and erythropoietin. Rev Clin Esp (Barc). 2023 Mar;223(3):181-187. doi: 10.1016/j.rceng.2023.01.005.

GBD 2017 Risk Factor Collaborators. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1923-1994. doi: 10.1016/S0140-6736(18)32225-6.

Nutt D, Hayes A, Fonville L, Zafar R, Palmer EOC, Paterson L, Lingford-Hughes A. Alcohol and the Brain. Nutrients. 2021 Nov 4;13(11):3938. doi: 10.3390/nu13113938.

Gould GS, Havard A, Lim LL, The Psanz Smoking In Pregnancy Expert Group, Kumar R. Exposure to Tobacco, Environmental Tobacco Smoke and Nicotine in Pregnancy: A Pragmatic Overview of Reviews of Maternal and Child Outcomes, Effectiveness of Interventions and Barriers and Facilitators to Quitting. Int J Environ Res Public Health. 2020 Mar 19;17(6):2034. doi: 10.3390/ijerph17062034.

Gouzoulis-Mayfrank E, Daumann J. Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines. Dialogues Clin Neurosci. 2009;11:305-317.

Hall W, Degenhardt L. Adverse health effects of non-medical cannabis use. Lancet. 2009;374:1383-1391.

Hays LR. A profile of OxyContin addiction. J Addict Dis. 2004;23:1-9.

John MJ, Jaison V, Jain K, Kakkar N, Jacob JJ. Erythropoietin use and abuse. Indian J Endocrinol Metab. 2012;16:220-227.

Henry TS, Kligerman SJ, Raptis CA, Mann H, Sechrist JW, Kanne JP. Imaging Findings of Vaping-Associated Lung Injury. AJR Am J Roentgenol. 2019 Oct 8:1-8. doi: 10.2214/AJR.19.22251.

Kiyatkin EA, Sharma HS. Acute methamphetamine intoxication brain hyperthermia, blood-brain barrier, brain edema, and morphological cell abnormalities. Int Rev Neurobiol. 2009;88:65-100.

Krishnasamy VP, Hallowell BD, Ko JY, et al. Update: Characteristics of a Nationwide Outbreak of E-cigarette, or Vaping, Product Use–Associated Lung Injury — United States, August 2019–January 2020. MMWR Morb Mortal Wkly Rep 2020;69:90–94. DOI: http://dx.doi.org/10.15585/mmwr.mm6903e2.

Kuczkowski KM. The effects of drug abuse on pregnancy. Curr Opin Obstet Gynecol. 2007;19:578-585.

Liu L, Wheeler SE, Venkataramanan R, Rymer JA, Pizon AF, Lynch MJ, Tamama K. Newly emerging drugs of abuse and their detection methods: an ACLPS critical review. Am J Clin Pathol. 2018;149(2):105-116.

Malone DT, Hill MN, Rubino T. Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models. Br J Pharmacol. 2010;160:511-522.

Marks LR, Nolan NS, Liang SY, Durkin MJ, Weimer MB. Infectious Complications of Injection Drug Use. Med Clin North Am. 2022 Jan;106(1):187-200. doi: 10.1016/j.mcna.2021.08.006.

McGuire P. Long term psychiatric and cognitive effects of MDMA use. Toxicol Lett. 2000;112-113:153-156.

Milroy CM, Parai JL. The histopathology of drugs of abuse. Histopathology. 2011 Oct;59(4):579-93. doi: 10.1111/j.1365-2559.2010.03728.x.

Mukherjee RA, Hollins S, Turk J. Fetal alcohol spectrum disorder: an overview. J R Soc Med. 2006;99:298-302.

Mukhopadhyay S, Mehrad M, Dammert P, et al. Lung Biopsy Findings in Severe Pulmonary Illness Associated With E-Cigarette Use (Vaping). Am J Clin Pathol. 2020;153(1):30-39.

Murtha L, Sathiadoss P, Salameh JP, Mcinnes MDF, Revah G. Chest CT Findings in Marijuana Smokers. Radiology. 2022 Nov 15:212611. doi: 10.1148/radiol.212611.

Park JA, Crotty Alexander LE, Christiani DC. Vaping and Lung Inflammation and Injury. Annu Rev Physiol. 2022 Feb 10;84:611-629. doi: 10.1146/annurev-physiol-061121-040014.

Patel PV, Flamm SL. Alcohol-Related Liver Disease Including New Developments. Clin Liver Dis. 2023 Feb;27(1):157-172. doi: 10.1016/j.cld.2022.08.005.

Patterson DA, Smith E, Monahan M, Medvecz A, Hagerty B, Krijger L, Chauhan A, Walsh M. Cannabinoid hyperemesis and compulsive bathing: a case series and paradoxical pathophysiological explanation. J Am Board Fam Med. 2010;23:790-793.

Popova S, Charness ME, Burd L, Crawford A, Hoyme HE, Mukherjee RAS, Riley EP, Elliott EJ. Fetal alcohol spectrum disorders. Nat Rev Dis Primers. 2023 Feb 23;9(1):11. doi: 10.1038/s41572-023-00420-x.

Prosser JM, Nelson LS. The toxicology of bath salts: a review of synthetic cathinones. J Med Toxicol. 2012 Mar;8(1):33-42.

Purohit V, Rapaka R, Shurtleff D. Role of cannabinoids in the development of fatty liver (steatosis). AAPS J. 2010;12:233-237.

Roque-Bravo R, Silva RS, Malheiro RF, Carmo H, Carvalho F, da Silva DD, Silva JP. Synthetic Cannabinoids: A Pharmacological and Toxicological Overview. Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:187-209. doi: 10.1146/annurev-pharmtox-031122-113758.

Ross EA, Watson M. Goldberger B. "Bath salts" intoxication. N Engl J Med 2011; 365:967-968.

Salihu HM, Wilson RE. Epidemiology of prenatal smoking and perinatal outcomes. Early Hum Dev. 2007;83:713-720.

Scully RE, Mark EJ, McNeely WF, et al. Case 6-2001: Case records of the Massachusetts General Hospital. New Engl J Med. 2001;344:591-599.

Sjöqvist F, Garle M, Rane A. Use of doping agents, particularly anabolic steroids, in sports and society. Lancet. 2008;371:1872-1882.

Stockley J, Sapey E, Gompertz S, Edgar R, Cooper B. Pilot data of the short-term effects of e-cigarrette vaping on lung function. European Respiratory Journal. 2018, 52 (suppl 62) PA2420; DOI: 10.1183/13993003.congress-2018.PA2420.

Sud P, Gordon M, Tortora L, Stripp M, Borg D, Berman A. Retrospective Chart Review of Synthetic Cannabinoid Intoxication with Toxicologic Analysis. West J Emerg Med. 2018 May;19(3):567-572.

Tay E, Lo WKW, Murnion B. Current Insights on the Impact of Gamma-Hydroxybutyrate (GHB) Abuse. Subst Abuse Rehabil. 2022 Feb 9;13:13-23. doi: 10.2147/SAR.S315720.

Timby N, Eriksson A, Bostrom K. Gamma-hydroxybutyrate associated deaths. Am J Med. 2000;108:518-519.

Torres-Lockhart KE, Lu TY, Weimer MB, Stein MR, Cunningham CO. Clinical Management of Opioid Withdrawal. Addiction. 2022 Sep;117(9):2540-2550. doi: 10.1111/add.15818.

Walter K. Fentanyl Overdose. JAMA. 2023 Jan 10;329(2):184. doi: 10.1001/jama.2022.22462.

Walley SC, Wilson KM, Winickoff JP, Groner J. A public health crisis: electronic cigarettes, vape, and JUUL. Pediatrics. 2019;143(6). pii: e20182741. doi: 10.1542/peds.2018-2741.