Injection Drug Use

With recent UN reports estimating that as many as 14.2 million individuals inject substances worldwide, injectable drug use continues to be a growing global concern given the increased risk for various health-related consequences faced by these individuals.[1]

Although most persons who inject drugs (PWID) do so by injecting their drugs intravenously, subcutaneous injection (ie, "skin-popping") is also common, as is intramuscular injection, which may occur intentionally or when an individual misses the vein or the subcutaneous space. Injecting drug use is associated with many local and systemic complications as well as with the transmission of infectious diseases via needle sharing and/or sexual activity. The most commonly injected drug is heroin, but amphetamines, buprenorphine, benzodiazepines, barbiturates, cocaine, and methamphetamine also are injected. Treatment of PWID may be complicated by social and political barriers to treatment and by a lack of resources for public health approaches to treatment.

Both illegal drug production and injecting drug use have been globalized in recent years. Although three countries – the United States, Russia, and China – continue to account for nearly half of all individuals who inject drugs, populations of PWID have increased worldwide; notably, the introduction of and rapid increase in injecting drug use is associated with dramatic increases in HIV infection in some areas. In China, Central Asia, and in several Eastern European countries, injection drug use is the primary risk factor for HIV infection. Further, there is concern that stressors related to the global COVID-19 pandemic may further exacerbate this public health issue.

When injecting a drug intravenously, the individual introduces a bolus of this substance into the vein, producing a rapid and powerful drug high. The onset of drug effects is about 15–30 seconds for the intravenous route and 3–5 minutes for the intramuscular or subcutaneous route. Drug effects from inhaling (ie, smoking) a substance can begin in 7–10 seconds and drug effects from intranasal use (ie, transmucosal absorption) can begin in 3–5 minutes.

Injected substance use causes many medical problems by introducing pathogens and other contaminants into the body via shared needles, a lack of sterile preparation, and poor injection techniques. Medical problems also arise from damage caused by the substances themselves (eg, morbidity and mortality associated with drug overdose). The injected drugs also may not be pure; they may be cut with irritants, such as talc, lactate, or quinine.

The injected substance is also associated with life-threatening or lethal outcomes. Death from the direct toxic effects of a heroin overdose itself is usually associated with respiratory depression, coma, and pulmonary edema. Death from the direct effects of cocaine is often associated with cardiac dysrhythmias and conduction disturbances, leading to myocardial infarction, stroke, and possible sudden death.

Frequency

According to the 2021 World Drug Report of the United Nations Office on Drugs and Crime (UNODC), 269 million people used an illicit drug in 2018. By the year 2030, this number is expected to increase to 299 million people – an 11% increase. 

The joint UNODC/WHO/UNAIDS/World Bank estimate for the number of people who injected drugs (PWID) worldwide in 2019 is 11.2 million (range: 8.9 million to 14.2 million), corresponding to 0.22% (range: 0.18 to 0.28%) of the population aged 15–64 years. Injecting drug use remains highly prevalent in Eastern Europe, Central Asia and Transcaucasia and North America, with rates that are 5.7, 2.8, and 2.5 times the global average, respectively. In terms of the number of PWID worldwide, most of them reside in East and South-East Asia (27%), North America (16%), and Eastern Europe (15%).[1]

Among people ages 12 years and older in 2019, 57.2 million people used illicit drugs in the past year, according to the National Survey on Drug Use and Health (NSDUH). Among people ages 12 years and older, the percentage who used illicit drugs in the past year increased from 17.8% (or 47.7 million people) in 2015 to 20.8% (or 57.2 million people) in 2019.[2]

In the United States, the Center for Disease Control (CDC) noted an increase in substance use and drug overdose deaths during the COVID-19 pandemic. Between June 2020 and June 2021, the number of drug overdose deaths in the United States increased by nearly 19%. There is also concern that the number of PWID has presumably also grown during the pandemic and may continue to grow due to the mental health impacts of the pandemic.[3]

Mortality/Morbidity

Morbidity and mortality may result from a wide range of factors including but not limited to: infection secondary to injecting drug use, sequelae of injection with adulterants added to the drug mixture, sequelae of the drug use itself, drug overdose, or violence associated with drug use.

• According to the CDC, about 1 in 10 new HIV diagnoses in the United States are attributed to injection drug use or male-to-male sexual contact after injection drug use. Adult and adolescent PWID accounted for 10% (3,864) of the 37,968 new HIV diagnoses in the United States  and dependent areas in 2018 (2,492 cases were attributed to injection drug use and 1,372 to male-to-male sexual contactd and injection drug use).[4]  Of the 3,864 PWID newly diagnosed with HIV, most were men.

• Another significant source of HIV infection for women is sex with partners who use injection drugs. An estimated 61% of AIDS cases in women can be attributed to injecting drug use or to sex with partners who use injection drugs. Females may use more shared injecting drug use equipment than males.[5]

• Besides direct transmission of HIV, injecting drug use also contributes to the spread of HIV infection by perinatal transmission and by sexual contact with individuals who do not inject drugs.[6] Injecting drug use is also associated with increased levels of high-risk sexual behavior.

• Worldwide, 40–60% of individuals who use injection drugs are estimated to be positive for hepatitis B, and 60–70% are positive for hepatitis C virus (HCV). HCV rates are high even in countries with low HIV seroprevalence. Injecting drug use is responsible for approximately 60% of HCV infections in the United States. New HCV infections in the United States have declined since 1989,[7]  but the incidence and prevalence of HCV remains high. The spread of HCV is rapid among those who are new to injecting drugs; in the United States, following initiation of injecting drug use, 50–80% become infected with HCV within 6–12 months. Reductions in risky injection-related practices among young users may improve both the burden of chronic HCV infection-related liver disease and elevated viral load-related poor treatment response.[8] Another option for reducing HCV transmission is encouraging users to use intranasal drugs as an alternative to injection drugs.[9] For related information, see Medscape's Hepatitis B and Hepatitis C Resource Centers.

• The mortality from all causes in individuals who use injection drugs is estimated to be 3–4% per year.

Demographics

Worldwide, 70–90% of those who use injection drugs are believed to be male.

The purity of heroin has been increasing, and its cost has been decreasing. Because of these factors and because of their initial desire to avoid injecting drug use, many adolescents and young adults in the United States and Europe using heroin for the first time try snorting, sniffing, or smoking heroin. New noninjecting heroin users have been known to make a transition to injecting drug use when their need for heroin use intensifies.

Among adolescents who inject drugs, early school truancy and expulsion may be a predictor of increased injecting drug use. A younger age of initiation into injecting drug use is associated with more frequent reports of risky drug use and sexual practices, as well as higher rates of HIV infection.[10]

Chemical dependency treatment provides education and skills training regarding abstinence from drug use. For those individuals who are not yet able to abstain from injecting drug use, harm reduction approaches are used to educate about methods of safer injection, including the use of clean needles, sterile injection techniques, and safe disposal of needles.[11]  Such outreach approaches are effective in promoting behavior change and slowing the spread of HIV and other infections.[12, 13]

Informal needle exchange programs in the United States began as early as the 1970s. In 1988, the New York City Health Department began the first government-sponsored needle exchange program in the United States. Usually, needle exchange programs operate by exchanging the used needles for an equal number of clean needles and syringes. Needle exchange programs may make referrals for chemical dependency treatment and medical treatment and may participate in other public health initiatives, such as distributing condoms and arranging HIV testing.

In some areas, needles and syringes are available for purchase from a pharmacy without a prescription. Those who purchase needles and syringes from pharmacies are less likely to participate in high-risk activities, such as using the services of crack houses or shooting galleries.

Several countries have developed harm reduction programs with different methods, including the introduction of syringe vending machines[14]  and safe injecting areas or rooms.

Programs that distribute injectable naloxone to individuals for use in suspected overdose situations have been implemented in many larger US cities.

To reduce risks associated with injecting drug use, clinicians and public health workers must raise awareness of the health consequences and risks of injection, make contact with the target population by improving access and outreach, provide the means to change risky behavior, and gain political and community support for the measures introduced.

Obtain a complete history of the individual's past alcohol and drug use, including the following:

• Age of onset for each drug used

• Frequency of use

• Quantities used

• Progression of use with time

• Medical and psychiatric symptoms associated with use

• Routes of administration for each drug

• Means of obtaining drugs or money for drugs

• Longest periods of abstinence from drug use

• History of prior chemical dependency treatments

Ask those who report injecting drug use which injecting sites they use, whether they use new or used needles, and whether they share other items used in the preparation of drugs for injection (eg, cookers, cotton). Ask those who share needles and syringes whether they attempt to clean the needles (eg, by using a bleach kit distributed by outreach workers).

Other risks associated with injecting drug use include contaminated drug solutions, buying ready-filled syringes, and sharing rinse water. "Backloading" is a practice in which a dealer transfers the drug solution from a larger syringe to a syringe provided by the user. "Flashblood" is a practice initially reported among sex workers in Dar es Salaam, in which an individual draws blood back into the syringe after having injected heroin, and then passes the syringe to another individual to inject the blood in the belief that this will prevent withdrawal symptoms.

Individuals may inject substances that are not supposed to be injected, such as pulverized (and unsterile) pills mixed with liquid. The liquid used to prepare drugs for injection is usually water, although use of lemonade and vinegar for this purpose has also been reported.

Ask about a history of prior systemic or local infections secondary to injecting drug use.

Begin with a standard physical assessment, paying special attention to signs of current injecting drug use, such as needle tracks. Other physical signs related to alcohol and drug use may also be present.

Common injection sites, such as the antecubital areas, should be inspected for evidence of recent injection. Some individuals may also use more unusual sites for injection, such as veins in the feet, hands, groin, and even the neck. As individuals who use injection drugs age and commonly used veins sclerose, these individuals may select progressively more dangerous sites. Hospitalized patients and patients who receive intravenous medication may inject drugs into their indwelling intravenous lines.

Check vital signs because changes are commonly associated with alcohol and drug intoxication and withdrawal, as well as with systemic infections secondary to injecting drug use. Stimulants, such as cocaine, may cause hyperthermia, an easily treatable yet easily overlooked condition. Persons who are intoxicated may also present with hypothermia, especially if they have been confused and wandering outside in cold weather.

Perform a mental status examination including the following considerations:

• Pay special attention to level of alertness because many drug and alcohol intoxication and withdrawal states can produce changes in alertness and orientation.
• Assess affect and mood and note whether suicidal ideation or intent is present. Drugs of abuse may cause or exacerbate depression and suicidal ideation.
• Assess thought content and the presence or absence of hallucinations, delusions, or paranoid ideation and ask the patient whether these phenomena seem to be exacerbated or caused by drug use. Many patients with drug-induced delusions or hallucinations are in fact aware of the relationship between their drug use and the delusions or hallucinations.
• Determine the presence or absence of homicidal or violent intent and ask whether the patient has guns at home.

The neurobiological mechanisms that underpin substance use disorders are thought to be complex and multifactorial including genetic predisposition and environmental stressors. At a neurocircuitry level, craving for addictive drugs is associated with increased activation of brain reward areas, including the nucleus accumbens and other brain areas. Drug use directly or indirectly elevates dopamine levels in the mesolimbic pathway of the brain, producing a pleasurable and positively reinforcing high.

Neuronal changes in specific brain regions (ie, neuroadaptation) occur in response to repeated drug use. Thus differences exist in the brains of addicted and nonaddicted individuals, and these differences can be demonstrated by brain imaging techniques.

Those who use drugs experience a compulsion to use the addictive drug regardless of negative consequences.

Those who use drugs may make the transition from noninjecting drug use to injecting drug use as their dependence on the drug becomes more severe. Injecting drug use is a popular route of drug administration because the injected substance has almost 100% bioavailability, and the onset of the drug high is fairly rapid, generally 15–30 seconds.

Those who use drugs use nonsterile injecting equipment largely because of the scarcity of sterile needles and syringes. Many people will use sterile needles and syringes if provided access to them. Making sterile injecting equipment available, either for purchase or via a needle exchange program, decreases rates of HIV and hepatitis B infections.

Local problems associated with injecting drug use include abscess, cellulitis, septic thrombophlebitis, local induration, necrotizing fascitis, gas gangrene, pyomyositis, mycotic aneurysm, compartmental syndromes, and foreign bodies (eg, broken needle parts) in local areas. The most common causative organisms reported are Staphylococcus aureus or Staphylococcus epidermidis, streptococci, and gram-negative bacilli.

Systemic problems associated with injecting drug use are HIV infection, hepatitis B or C, pneumonia or lung abscess from septic emboli to the lung, acute and subacute bacterial endocarditis, group A beta-hemolytic streptococcal septicemia, osteomyelitis, septic arthritis, candidal and other fungal infections, tetanus, clostridial myonecrosis, malaria, and amyloidosis. The endocarditis that occurs in individuals who inject drugs involves the right-sided heart valves; a recent review found no explanation for this predilection.[15]  A rare case of needle embolization to the lung has been reported.

The following lab tests may be useful when performing workup in persons who inject drugs (PWID):

• Comprehensive metabolic panel

• CBC count with differential

• Hepatitis B surface antigen and surface antibody

• Hepatitis C antibody

• Rapid plasma reagent (RPR) test

• HIV serum antibody test (performed in 2 steps, with a screening test such as the enzyme-linked immunosorbent assay [ELISA] and a confirmatory test such as the Western blot)

• Purified protein derivative (PPD) test

• Urine screen for common drugs of abuse

Other tests

An electrocardiogram (ECG) is a rapidly available clinical tool that can help clinicians manage patients who overdose.

Medical care of individuals who use injection drugs should focus on initial management of local or systemic complications of injecting drug use and then on referral to appropriate chemical dependency treatment programs.[16, 17]

• Some patients may have multiple medical problems and contributory socioeconomic status. They may lack medical insurance and/or a stable place to live; this may be further complicated by psychiatric illness including a substance use disorder. Therefore, each patient requires a comprehensive physical examination including a mental status exam as well as a thorough history. The patient possibly may not know what he or she has injected because many of the street drugs are altered or laced with other substances.

• These individuals may have undergone many poorly coordinated episodes of prior medical, mental health, and chemical dependency treatments by several different providers. Facilitating coordination of medical, mental health, and chemical dependency care can avoid duplication of services and, hopefully, assist the patient in adhering to the treatment regimen.

Individuals treated in hospital emergency departments for acute illness may be difficult to evaluate because of medical problems, poor nutrition, debilitation, and drug and alcohol intoxication or withdrawal. Also, at times, they may be unwilling to accept further treatment. Many localities have legal provisions for holding such individuals in the emergency department while they are intoxicated, until they can be stabilized enough for a safe discharge. Once the withdrawal symptoms and other medical symptoms are under control, referrals for chemical dependency treatment may be made.

Treatment of alcohol and drug dependence is generally voluntary, unless psychiatric reasons are present that justify involuntary admission. Some countries mandate forms of inpatient and outpatient chemical dependency treatment, such as the drug court system in many parts of the United States.

Using the strengths of families and natural support systems can help engage individuals in treatment.[18] Employee assistance programs may also be helpful in treatment engagement.

In April 2014, the FDA approved naloxone (Evzio) as an autoinjector dosage form for home use by family members or caregivers. The product delivers 0.4 mg that may be administered either IM or SC in the anterolateral aspect of the thigh. The device includes visual and voice instruction, including directions to seek emergency medical care immediately after use.[19]

Because addiction is a complex biopsychosocial problem, effective drug treatment must be comprehensive and must attend to the multiple needs of the individual. Comprehensive treatment might include behavioral therapy; pharmacotherapy; substance use monitoring; self-help groups; family therapy; parenting groups; case management; mental health services; medical services; screening for infectious diseases; and assistance with housing, legal problems, educational needs, and child care. Drug treatment teaches individuals to cope with drug cravings, to avoid relapse to drug use, and to deal with relapse if it occurs.

Addiction is a treatable disease. Treatment for drug addiction reduces the risk of HIV infection. Drug treatment reduces criminal activity and also improves the individual's chances for employment.

In 2005, the Centers for Disease Control and Prevention recommended use of a 28-day course of antiretroviral therapy to prevent HIV infection in those who have had substantial risk for HIV exposure via injecting drug use. The antiretroviral therapy must be initiated within 72 hours of exposure.[20]

Consultation with an expert in chemical dependency, if available, may help with collecting a complete chemical use history, determining the level of chemical dependency treatment needed, and negotiating the logistics of referral to addiction treatment facilities and self-help groups.

Consultation with an infectious disease specialist may be needed to determine the diagnosis and treatment of infectious diseases associated with injecting drug use.

A consultation with a psychiatrist, if psychiatric symptoms are present, helps determine whether these symptoms are preexisting or whether they are drug induced. A psychiatrist will recommend appropriate treatment for these problems.

• Many psychiatric symptoms and mental status changes may occur in alcohol and drug intoxication and withdrawal states. Intoxication with opioids, sedative hypnotics, and alcohol produces central nervous system depression, resulting in slurred speech, ataxia, and decreased alertness. Alcohol and sedative hypnotic withdrawal may produce delirium. Stimulants such as cocaine and amphetamines may cause or exacerbate mood symptoms, producing euphoria or irritability in the intoxicated state and irritability or depression in the withdrawal state.

• Psychiatric symptoms related to alcohol and drug use generally decrease and gradually resolve in the first few days and weeks of abstinence from alcohol and drugs. However, these symptoms may be quite severe initially and may require psychotropic medication or hospitalization. Differentiating acute drug-related symptoms from symptoms related to a preexisting psychiatric disorder may be difficult. Obtaining information about past periods of alcohol and drug abstinence from the patient and family may be helpful. If during a prolonged period of abstinence, psychiatric symptoms gradually improved without medication, these symptoms might be secondary to alcohol or drug use. If the psychiatric symptoms remained consistent or worsened during the period of abstinence, an independent psychiatric illness might be present.

• History of drug-related violence, suicidal ideation or attempts, and the presence of weapons in the home also are important areas to assess because they are related to admission, referral, and treatment decisions.

• Alcohol and drug use may worsen the psychiatric symptoms and clinical course for patients with preexisting serious psychiatric illnesses, such as affective disorder and schizophrenia. Alcohol and drug use in patients with severe psychiatric disorders has been associated with increased unemployment, housing problems, violence, and psychiatric rehospitalization.

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Class Summary

Individuals who have injected heroin or other opioids for long periods may need referral for opioid replacement therapy with methadone, buprenorphine, or buprenorphine/naloxone where such programs are available. In the United States, physicians who wish to prescribe buprenorphine must take a certification course. Levo-alpha-acetylmethadol (LAAM) has also been used for opioid replacement therapy, but use of LAAM has been less common because of concerns about severe QT prolongation secondary to LAAM.

Opioid replacement therapy reduces injecting drug use and thus reduces the mortality and morbidity associated with injecting drug use, including the transmission of HIV and HCV.

When individuals who are opioid dependent (including those who are on opioid replacement therapy) need analgesia, the clinician should be aware that these individuals may be tolerant to the analgesic effects of opioids; thus, they may require higher doses for pain control. Individuals taking naltrexone (an opioid antagonist) for opioid or alcohol dependence, also require higher doses of opioid analgesics to overcome the opioid blockade and provide pain relief.

Methadone (Dolophine)

Inhibits ascending pain pathways, diminishing the perception of and response to pain. In most countries, methadone is administered initially in the setting of a drug treatment program, both to prevent diversion (selling) of supply and to assure that counseling and other services also are provided.

Rate of dose increase and maximum dose often depend on program regulations and on federal and state regulations in the United States.

Patients who cannot take anything by mouth may be administered methadone IM, usually in a divided dose.

Buprenorphine (Subutex)

Mixed agonist-antagonist narcotic with central analgesic effects for moderate to severe pain. Used sublingually for the initial detoxification treatment of opioid addiction. Produces agonist/antagonist effects at the opioid mu receptor. The agonist effect is limited by a ceiling effect (ie, higher doses [>16 mg] do not produce more analgesia). The sublingual product is called Subutex.

Buprenorphine and naloxone (Suboxone)

Used sublingually for the maintenance detoxification treatment (unsupervised phase) of opioid dependence following induction with sublingual buprenorphine (Subutex). Contains both buprenorphine (an opiate agonist/antagonist) and the opiate antagonist naloxone. Naloxone has been added to guard against IV abuse of buprenorphine by individuals physically dependent on opiates.

Levomethadyl (ORLAAM)

Indicated for management of opioid dependence. No other recommended uses exist. In most countries, levomethadyl is administered initially in the setting of a drug treatment program, both to prevent diversion (selling) of supply and to assure that counseling and other services also are provided.

Class Summary

Inhibit opioid effects by inhibiting opioid agonists at receptor sites. FDA approval of extended-release IM naltrexone for the prevention of relapse to opioid dependence was based on data from a 6-month, multicenter, randomized, phase 3 study, which met its primary efficacy endpoint and all secondary efficacy endpoints. Once monthly treatment with extended-release IM naltrexone showed statistically significant higher rates of opioid-free urine screens compared with placebo (p< 0.0002).

Naltrexone (Revia, Vivitrol)

Used in combination with clonidine for rapid (4-5 d) detoxification.

Very effective long-acting opioid antagonist that was thought to be an ideal maintenance agent because it blocks receptor sites and, hence, opioid reinforcing properties. However, clinical results are not very promising when compared with methadone maintenance. Craving may continue during naltrexone maintenance. For groups of patients such as health care professionals or business executives for whom external incentives to stay away from drugs are important, naltrexone therapy has been very effective.

Long-acting parenteral suspension indicated for prevention of relapse to opioid dependence following opioid detoxification. Also indicated for treatment of alcohol dependence in patients who have been able to abstain from alcohol in an outpatient setting prior to treatment initiation.

Naloxone (Evzio, Narcan)

Naloxone is a short-acting, pure opioid antagonist that is used to reverse opioid intoxication. If patients do not respond to multiple doses of naloxone, consider alternative causes of unconsciousness. Need of ongoing substance abuse treatment should be established while caring for overdose. The injectable solution is available in vials and syringes (0.4 mg/mL, 1 mg/mL) for IV/IM/SC administration by healthcare providers. It is also available as an autoinjector (delivers 0.4 mg IM/SC) for home use by family or caregivers.