The editors and current author would like to thank and acknowledge the significant contribution of the previous author of this chapter from the 2004 first edition Dr. Anthony P.S. Guerrero. This current third edition chapter is a revision and update of the original author's work.

A 16 year old female is brought to the emergency room by her father, who thinks his daughter is using drugs and wants her to get treatment. The father reports she has often seems high, with sleeplessness for several days in a row, unusual euphoria, pressured speech, hyperactivity (e.g., cleaning the bathroom), paranoia, and some aggressive behaviors. The pediatric resident begins to advise him that this behavior is typical of cocaine intoxication; however, with encouragement from the supervising emergency physician, the resident gathers further history. When the resident speaks with the patient alone, she says she uses "ice" or "batu" (crystal methamphetamine), roughly two or three times per week, smoking it by pipe. She obtains it from her friends. She also admits to occasional marijuana use and weekend drinking of alcohol but denies blackouts, hallucinations, or incapacitating withdrawal symptoms. Although previously an above average student, she has been truant from school and has failed most of her classes for the past year. She has also run away from home on several occasions. She gives vague answers when asked about sexual history.

Her past medical history is otherwise negative. Family history is significant for a history of heavy alcohol use and a possible psychiatric condition. Her parents are divorced. There is no history of abuse or domestic violence.

Exam: VS T37.5, HR 110, RR 18, BP 130/80. She is somewhat restless and guarded, with poor eye contact and brief answers. HEENT is significant for slightly dilated pupils. Heart shows regular rhythm and elevated rate. Pelvic examination is refused. The remainder of physical examination is normal.

Labs: Urine toxicology is positive for methamphetamine, negative for others. Her blood alcohol level is negative. Electrocardiogram is significant for sinus tachycardia, otherwise normal.

Clinical course: Child psychiatry is called; outpatient followup is recommended. Her primary care physician is called to help to arrange for enrollment into an adolescent substance abuse treatment program.

Substance use is common among adolescents. In the United States, at least 50% of adolescents have misused a drug at least once and 12.5% of adolescents have used an illicit substance in the past year (1). However, according to the Monitoring the Future Survey, substance use among adolescents in the U.S. has declined during 2020-2021, possibly due to the COVID-19 pandemic (2). In Hawai'i, the lifetime substance use rate among teens is lower than the national average, but teens who have used substances report higher usage of marijuana, methamphetamine, and heroin (1).

In general, the most common substance misused by teens in the U.S. is alcohol (1). Cigarette use has declined among adolescents, but there has been a rise in marijuana and nicotine (cigarette smoking, vaping e-cigarettes) use (3). There are also substances that are more commonly used in certain age groups. Younger adolescents are more likely to use inhalants, while older adolescents are more likely to use synthetic cannabinoids ("K2", "spice") or prescription medications such as opioids or stimulants (e.g., Adderall) (4). Table 1 provides a complete list of substances commonly used by adolescents and their physiologic effects.

Table 1: Substances commonly used by adolescents and their physiologic effects (5, 6)

Substance	Mechanism of Action	Effects
Depressents ("downers") - Alcohol - Benzodiazepines (e.g., Rohypnol ("roofies"))	Stimulates GABA-A receptors, promoting behavioral inhibition	Drowsiness, decreased anxiety, impaired reaction time and coordination, amnesia. Risk for respiratory depression and seizures during withdrawal.
Stimulants ("uppers")	- - - - -	- - - - -
- Methamphetamine and amphetamines (Adderall, Ritalin)	Competitively inhibits dopamine transport + binds to VMAT (vesicular monoamine transporter), depleting synaptic vesicles which causes quick release of dopamine.	Methamphetamine: Paranoia, anxiety, bruxism, "meth mites" (skin excoriations), dental caries, appetite suppression, arrhythmia. Amphetamines: increased alertness, appetite suppression, possible cardiac dysfunction.
- Cocaine	Inhibits dopamine transporter, decreasing clearance of dopamine from synaptic cleft.	Vasoconstriction, paranoia, anxiety, mydriasis, increased risk for sudden cardiac death or stroke.
- Nicotine	Nicotinic receptor agonist which causes increased dopamine release from NAcc (nucleus accumbens)and prefrontal cortex.	Pleasure, relaxation, increased risk for heart and lung disease.
Cannabinoids	- - - - -	- - - - -
- Marijuana	Binds to cannabinoid receptors in brain. THC (tetrahydrocannabinol) is the psychoactive component. Euphoria, drowsiness/relaxation, slowed reaction time, increased appetite, dry mouth; anxiety.
- Synthetic cannabinoids (K2, Spice)	Synthetic cannabinoids are often more potent than marijuana.	Tachycardia, agitation, hallucinations and paranoia, anxiety, vomiting.
Opioids (heroin, oxycodone, fentanyl)	Binds to mu receptors on inhibitory neurons.	Pain relief, euphoria, miosis, constipation, drowsiness, nausea. Risk for respiratory depression. IV drug use associated with increased risk for endocarditis, hepatitis C, HIV.
Hallucinogens	- - - - -	- - - - -
- Ecstacy/MDMA	Binds to serotonin transporter (SERT), increasing serotonin in brain.	Lowered inhibition and enhanced sensory perception, increased need for sensation (e.g., physical intimacy), hyperthermia, dehydration which can cause water intoxication (hyponatremia, seizures).
- LSD ("acid")	Activates serotonin (5-HT2A) receptors.	Dissociation, emotional lability, paranoia, hallucinations.
- Psilocybin ("shrooms")		Psychosis, muscle weakness, panic, drowsiness, nausea.
- PCP (phencyclidine)	NMDA (N-methyl-D-aspartate) receptor antangonist, blocking update of dopamine and norepinephrine.	Paranoia, anxiety, impaired coordination, rhabdomyolysis, increased risk for violence
Inhalants - Aerosols (e.g., paint cans, spray deodorants, hairsprays) - Glue - Gasoline - Nitrous oxide ("whippets")	Dependent on substance used.	Initial euphoria, drowsiness, headaches, lightheadedness, sudden sniffing death (encephalopathy, arrhythmias). Nitrites cause enhanced sexual pleasure, tachycardia, vasodilation. Effects are rapid and short-lasting.
Over the counter medications	- - - - -	- - - - -
- Dextromethorphan	Weak cough suppresant.	In higher than recommended doses: euphoria, slurred speech, increased HR and BP, nausea.
- Loperamide (Immodium)	Anti-diarrheal.	In higher than recommended doses: euphoria.
Anabolic steroids (nandrolone, dromostanolone)	Binds to androgen receptors to increase muscle size and strength.	Acne, hypogonadism or gynecomastia (males) or hyperandrogenism (females), "roid rage" (extreme emotional lability).

Interestingly, substances vary in popularity according to their perceived risks and benefits. A phenomenon known as "generational forgetting" refers to the prevalence of use of older substances rising as the perception of their dangers decrease. It applies to substances such as inhalants, LSD (lysergic acid diethylamide), and ecstasy (MDMA or 3,4-methylenedioxy-methamphetamine). With the legalization of marijuana in several states, this may also cause adolescents to perceive it as safe and may be a key contributor to the recent increases in marijuana use among this age group (7).

It is important to recognize the difference between the two terms "substance use" and "substance use disorder" (SUD). Substance use refers to occasional or recreational use of a substance while SUD describes the inability to control one's substance use which negatively affects their daily functioning and/or causes distress. Most adolescents who engage in substance use do not develop a subsequent SUD (3,8); however, for those who have SUD, only about 10% to 15% receive adequate treatment (8). This is why pediatricians play an integral role in evaluating and managing SUDs, medical problems related to substance use, and other related conditions which may go under-recognized or under-managed in this high-risk population.

Risk Factors

Adolescents engage in substance use for various reasons: to fit in with their peers, self-medicating to feel better from physical and mental conditions, to do better in sports or academics, or out of sheer curiosity (4). Peer influences and cultural pressures have an especially significant impact on adolescent substance use. Risk factors for substance use resulting in adverse adulthood outcomes include positive perceptions of substance use in peer groups, minimal family support, difficulties in academics, and history of childhood sexual abuse (9). There is also a strong correlation between emotional trauma and substance use. Adolescents who experienced trauma are more likely to use illicit substances or develop SUD, especially if they have PTSD (post-traumatic stress disorder) (10,11).

SUD has a complex etiology with both genetic and environmental etiologies (6). Risk factors for SUD include family history of substance use, psychiatric conditions such as depression and anxiety, and low self-esteem (12). Temperament also plays a role in susceptibility to developing SUD. Adolescents with behavioral issues, both externalizing and internalizing, are at higher risk for SUD (8). Adolescents who partake in risky behaviors, are impulsive, or who have reduced attention spans are also more likely to develop SUD (8). Of note, stimulant treatment for ADHD (attention deficit hyperactivity disorder) does not increase one's risk for having SUD (4).

Complications

Substance use is a major safety hazard for adolescents and contributes to the top three causes of death in this age group (accidents, suicide, and homicide). It can also worsen depression, anxiety, and impulse control. Substance use has detrimental effects on daily functioning, not limited to impaired academic performance, unsafe sexual practices, and criminal behaviors. IV drug use increases the risk for endocarditis, hepatitis C, and HIV. Unsafe sexual practices as a result of substance use or to obtain substances increases the risk of unintentional pregnancies and STIs (sexually transmitted infections). Chronic use or polysubstance use may also cause CNS (central nervous system) dysfunction. (8)

Diagnostic Criteria

According to the DSM-V (13), SUD is defined as a problematic pattern of use of an intoxicating substance in which at least two criteria based around behaviors, tolerance, and withdrawal need to be met (see Table 2). However, for adolescents, this criteria may not account for some developmentally normative behaviors. For example, adolescents have a tendency to seek excitement from risky behaviors due to underdevelopment of the prefrontal cortex (8). Because substance use is typically done in social settings, they are not as likely to neglect social interactions in favor of substance use (8). Adolescents are also less likely to have symptoms of withdrawal and may not have difficulty controlling use due to environmental restrictions typically put on teens (8).

Table 2. DSM-V Criteria for Substance Use Disorder (13)

A problematic pattern of use of an intoxicating substance characterized by at least 2 of the following criteria within the past 12 months: 1. Substance is often taken in larger amounts than intended or over a longer period of time than intended. 2. Persistent desire to use substance or unsuccessful efforts to cut down use. 3. Lot of time spent obtaining substance, using substance, or recovering from its effects. 4. Craving to use substance. 5. Recurrent substance use results in failure to uphold roles in work, school, or home. 6. Continued use of substance despite social or interpersonal problems from use. 7. Social, occupational, or recreational activities given up or reduced due to substance use. 8. Recurrent substance use in dangerous situations. 9. Use of substance despite knowledge that recurring physical or psychological issue is caused by substance use. 10. Tolerance-need for increased amounts of substance to get same effects of intoxication, OR decreased effect with using the same amount of substance. 11. Withdrawal-symptoms following stopping substance use or substance is taken to relieve/avoid those symptoms.

Screening

The primary care setting is the optimal place to screen for adolescent substance use. There are several questionnaires that can be used as screening tools. The most well-known and recommended screening tool is the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble) questionnaire (see Table 3). Others include the Problem Oriented Screening Instrument for Teenagers (POSIT), Alcohol Use Disorders Identification Test (AUDIT) (14). Making substance use screening a regular part of the well-child visit can help to reduce stigma around substance use (4). When conducting these screenings, confidentiality is of great importance as many teens fear their substance use may be revealed to their parents or law enforcement. The recommended method for screening is for parents or guardians to be present for part of the clinical visit, but having them leave the room for a confidential discussion between the adolescent and physician (14).

Table 3. CRAFFT Screening Questionnaire

Part A. During the past 12 months, did you: 1. Drink any alcohol (more than a few sips)? 2. Smoke any marijuana or hashish? 3. Use anything else to get high (including illegal drugs, OTC and prescription drugs, things sniffed or "huffed")?

If Yes to any of above, then ask all 6 CRAFFT questions. No to all, then ask only first question.

Part B. 1.Have you ever ridden in a car driven by someone (including yourself) who was high or had been using alcohol or drugs? 2. Do you ever use alcohol or drugs to relax, feel better about yourself, or fit in? 3. Do you ever use alcohol or drugs while you are alone? 4. Do you ever forget things you did while using alcohol or drugs? 5. Do your family or friends ever tell you that you should cut down on your drinking or drug use? 6. Have you ever gotten in trouble while you were using alcohol or drugs?

A score of 2 items or more on Part B indicates further assessment is needed.

In addition to using screening tools, physicians should perform a careful history and physical examination and address other concerns. Symptoms of substance use are more often behaviors, such as changes in peer groups, declining academic performance, and worsening relationships with people in their lives (4). It may also manifest as mood changes (withdrawn, irritated, depressed), general fatigue, decreased self-care, and changes in eating or sleeping habits (4). In gathering history, if a teen admits to substance use, the physician needs to gather information about the extent and circumstances of use, and if SUD is suspected, determine why the substance use progressed to substance misuse (8). Physical findings indicating substance use may be helpful in opening discussions about the use and its significance (8). Laboratory testing is not usually indicated unless there are findings indicating the benefits of testing outweigh the practical and ethical drawbacks (7).

Treatment and Prevention

The pediatrician must always consider substance use as a possibility, and must be prepared to manage any life threatening effects of either intoxication or withdrawal. All substances can potentially cause acute allergic or other serious idiosyncratic reactions which may lead to death. These should be managed accordingly, with priority attention always given to airway, breathing, and circulation. Withdrawal should also be managed accordingly, as improper treatment can also result in death. Table 4 lists methods of acute management for commonly used substances.

Table 4. Managing intoxication and withdrawal of commonly used substances

Substance	Management for intoxication	Management of withdrawal
Alcohol	Supportive care- monitoring vitals, prevent breathing problems, nutritional supplementation.	Benzodiazepines (long-acting preferred) + thiamine and electrolyte replacement.
Opioids	Naloxone	Buprenorphine or methadone + medications for symptom relief if needed.
Methamphetamine, cocaine	Quiet, supportive environment with frequent reorientation to person, place, and time. Benzodiazepines for agitation.	N/A
Hallucinogens	Quiet, supportive environment with frequent reorientation to person, place, and time. Benzodiazepines or antipsychotics (haloperidol) for agitation.	N/A

In addressing substance use in teens, education is key. Brief interventions can be staged for adolescents who admit to substance use. In these interventions, it is important to highlight how substance use can be harmful in multiple aspects (physical and mental health, relationships with family and friends, school performance) (4). In addressing both substance use and SUD, motivational interviewing (MI) is an effective method aimed to promote the exploration of ambivalent feelings around stopping substance use to elicit positive behavioral changes (14).

There are no formal protocols for treating SUD in adolescents; however, the first-line modality of treatment is psychotherapy. There are various types of psychotherapy. Cognitive-behavioral therapy (CBT) is a well-known method of psychotherapy that can be used to treat both SUD and co-existing mental health conditions. CBT can be done in an individual or group setting (4). In group therapy, some may incorporate the 12-Step philosophy of Alcoholics Anonymous and Narcotics Anonymous (8). Table 5 lists more information about CBT and other forms of behavioral interventions used. In addition, technology-based interventions show promise in this age group (8). There are few medications that are FDA-approved to treat SUD in adolescents. Three medications, buprenorphine, methadone, and naltrexone, may be used in older adolescents with opioid use disorder (15).

Table 5. Behavioral interventions for treating SUD in adolescents (4)

Behavioral Intervention	Description
Cognitive-behavioral therapy (CBT)	Focuses on recognition of distorted thinking patterns and triggers and developing positive coping mechanisms (emotional regulation, problem solving).
Contingency management	Uses low-cost incentives to reinforce positive behaviors; substitution of reinforcement from substance use to reinforcement from healthier activities.
Motivational enhancement therapy (MET)	Based on same theory as motivational interviewing; used more as adjunct to motivate patients to do other types of treatment.
Based on same theory as motivational interviewing; used more as adjunct to motivate patients to do other types of treatment	Based on 12-Step philosophy to accept one’s life is not in control from substance use, that willpower alone will not resolve substance use, and abstinence from use is needed.

The majority of adolescents with SUD are treated in the outpatient setting (8). However, if resources to treat SUD are not adequate in the primary care setting, pediatricians should not hesitate to consult with specialists or refer patients to specialized treatment (4). Treatment needs to address the whole person including the driving forces, such as mental health or emotional trauma, behind continued substance use, not just physical manifestations (14). No matter what setting treatment is conducted in, it needs to account for possible gender differences, ethnic disparities, and community values (e.g., stigma) and norms around substance use (4). In addition, follow-up is extremely important. This is especially the case for adolescents who do not complete treatment (8). Virtual or phone visits are shown to be as effective as in-person visits (8).

Substance use prevention is a critical part of the adolescent pediatric visit. Often, the primary care physician can be a credible source of information about the long-term side effects of substance use, such as liver damage from alcohol, serious brain damage from inhalants, and lung pathologies (e.g., emphysema, lung cancer) from tobacco or marijuana. Also, the primary care physician may have significant familiarity with the patient and their family and can be helpful in personalizing this information. However, in order to foster truly effective preventative measures, physicians need to work with the community they practice in. Prevention programs should customize their goals and interventions to the community, taking into account the specific demographics, cultures, and social determinants of health (7,14). Promising public health interventions focus on enhancing social skills in order to resist substance use fueled by peer pressure and negative social influences (7).

Above all, physicians should be compassionate and professionally responsible towards adolescents who use substances and adolescents with SUD. They should recognize substance use as complex with both medical and emotional manifestations and should respect the seriousness of its complications and co-morbidities.

Questions
1. The prevalence of lifetime use of a substance among adolescents in the United States is closest to: a.10%, b.20%, c.30%, d.50%, e.70%

2. True/False: Stimulant treatment of ADHD (attention deficit hyperactivity disorder) increases risk for future substance use.

3. True/False: Death may occur during intoxication with alcohol or an illicit substance.

4. True/False: Death may occur during withdrawal from alcohol or an illicit substance.

5. Match the following substances with their associated syndromes:

a. Alcohol	i Sudden sniffing death
b. Ecstasy	ii. Lung cancer
c. Inhalants	iii. Rhabdomyolysis during intoxication
d. Cigarettes	iv. Wanting to touch/be touched during intoxication
e. Methamphetamine	v. Seizures during withdrawal
f. PCP	vi. Bruxism, paranoia, skin excoriations

References
1. National Center for Drug Abuse Statistics. Drug Use Among Youth: Facts & Statistics. https://drugabusestatistics.org/teen-drug-use/. Accessed March 24, 2022.
2. National Institute on Drug Abuse. Monitoring the Future Survey. https://www.drugabuse.gov/drug-topics/trends-statistics/monitoring-future/monitoring-future-study-trends-in-prevalence-various-drugs. Accessed March 23, 2022.
3. Gray KM, Squeglia LM. Research Review: What have we learned about adolescent substance use? Journal of child psychology and psychiatry. 2018;59(6):618-627.
4. National Institute on Drug Abuse. Principles of Adolescent Substance Use Disorder Treatment: A Research-Based Guide. https://nida.nih.gov/publications/principles-adolescent-substance-use-disorder-treatment-research-based-guide/frequently-asked-questions. Accessed March 23, 2022.
5. National Institute on Drug Abuse. Commonly Used Drug Charts. https://nida.nih.gov/drug-topics/commonly-used-drugs-charts. Accessed March 26, 2022.
6. Lüscher C. Drugs of Abuse. In: Katzung BG, Vanderah TW. eds. Basic & Clinical Pharmacology, 15e. McGraw Hill; 2021. Accessed March 27, 2022.
7. Kaul P. Adolescent Substance Abuse. In: Hay Jr. WW, Levin MJ, Abzug MJ, Bunik M. eds. Current Diagnosis & Treatment: Pediatrics, 25e. McGraw Hill; 2020. Accessed March 22, 2022.
8. Kaminer Y, Simkin DR, Bagot KS. Substance-Related Disorders in Adolescents. In: Ebert MH, Leckman JF, Petrakis IL. eds. Current Diagnosis & Treatment: Psychiatry, 3e. McGraw Hill; 2019. Accessed March 22, 2022.
9. Centers for Disease Control and Prevention. High_risk Substance Use Among Youth. https://www.cdc.gov/healthyyouth/substance-use/index.htm. Accessed March 26, 2022.
10. Carliner H, Keyes KM, McLaughlin KA, et al. Childhood Trauma and Illicit Drug Use in Adolescence: A Population-Based National Comorbidity Survey Replication–Adolescent Supplement Study. J Am Acad Child Adolesc Psych. 2016;55(8):701-708. https://sdlab.fas.harvard.edu/files/sdlab/files/carliner_jaacap_8-2016.pdf. Accessed March 26, 2022.
11. Basedow LA, Kuitunen-Paul S, Roessner V, Golub Y. Traumatic Events and Substance Use Disorders in Adolescents. Front Psychiatry. 2020;11:559. Published 2020 Jun 18. doi:10.3389/fpsyt.2020.0055
12. Friedman LS. Adolescents. In: Feldman MD, Christensen JF, Satterfield JM, Laponis R (eds). Behavioral Medicine: A Guide for Clinical Practice, 5th edition. McGraw Hill; 2019. Accessed March 22, 2022.
13. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed., American Psychiatric Association, 2013.
14. Kulak JA, Griswold KS. Adolescent Substance Use and Misuse: Recognition and Management. Am Fam Physician. 2019;99(1):689-696.
15. The Society for Adolescent Health and Medicine. Medication for Adolescents and Young Adults with Opioid Use Disorder. J Adolesc Health. 2021;68(3):632-636.

Answers to questions
1.d, 2.False, 3.True, 4.True
5.a=v . alcohol=seizures during withdrawal
5.b=iv . ecstacy=wanting to be touched during intoxication
5.c=i . inhalants=sudden sniffing death
5.d=ii . cigarettes=lung cancer
5.e=vi . methamphetamine=bruxism, paranoia, skin excoriations
5.f=iii . PCP=rhabdomyolysis during intoxication