Methamphetamine Use Disorder

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Methamphetamine Use Disorder

Methamphetamine is a powerful, highly addictive central nervous system stimulant that can be injected, smoked, snorted, or ingested orally (1). It takes the form of a white odorless, bitter-tasting crystalline powder that easily dissolves in water or alcohol (5). Crystal methamphetamine is a form of the drug that looks like glass fragments or shiny, bluish-white rocks.It is a derivative of amphetamine, which was widely prescribed in the 1950s and 1960s as a medication for depression and obesity (1).In the 1950s, amphetamines were sold in tablets over-the-counter (OTC). Amphetamines were also found as an ingredient in inhalers in 1959.By 1967, 31 million prescriptions had been written in the United States. Amphetamine is used to treat attention-deficit/hyperactivity disorder (ADHD) and narcolepsy, a sleep disorder (1). Common prescription drug names that you may recognize are Adderall®, Vyvanse™, and Dexedrine®.Methamphetamine was developed early in the 20th century from its parent drug, amphetamine, and was used originally in nasal decongestants and bronchial inhalers (2).Like amphetamine, methamphetamine causes (2):

  • Increased activity.
  • Increased talkativeness.
  • Decreased appetite.
  • Pleasurable sense of well-being or euphoria.

Methamphetamine differs from amphetamine, at comparable doses (2):

  • Much greater amounts of the drug get into the brain, making it a more potent stimulant.
  • It has a longer-lasting and more harmful effect on the central nervous system.
  • These characteristics make it a drug with high potential for widespread misuse.

Control Status

Amphetamine and methamphetamine have been classified as Schedule ll stimulants, which means they have the potential for abuse and a currently acceptable medical use (in FDA-approved products). Pharmaceutical products are available only through a prescription that cannot be refilled.

Methamphetamine Use in the United States

Among people aged 12 or older in 2021, 0.9% (or about 2.5 million people) reported using methamphetamine in the past 12 months (2).In 2022, an estimated 0.2% of 8th graders, 0.3% of 10th graders, and 0.5% of 12th graders reported using methamphetamine in the past 12 months (2).Among people aged 12 or older in 2021, an estimated 0.6% (or about 1.6 million people) had a methamphetamine use disorder in the past 12 months (2).In 2021, approximately 32, 537 people died from an overdose involving psychostimulants with abuse potential other than cocaine (primarily methamphetamine) (2).Misuse of MethamphetamineIllicit methamphetamine is also referred to as:

  • Speed.
  • Meth.
  • Ice.
  • Crystal.
  • Crank.

Smoking or injecting methamphetamine puts the drug very quickly into the bloodstream and brain, causing an immediate, intense “rush” and amplifying the drug’s addiction potential and adverse health consequences (2).Snorting or oral ingestion produces euphoria – a high, but not an intense rush.

  • Snorting produces effects within 3 to 5 minutes (2).
  • Oral ingestion produces effects within 15 to 20 minutes (2).

Methamphetamine is most often misused in a “binge and crash” pattern. The pleasurable effects disappear even before the drug concentration in the blood falls significantly, users try to maintain the high by taking more of the drug. Some people indulge in a form of binging known as a “run,” foregoing food and sleep while continuing to take the drug for up to several days (2,5,6,7).

Manufacturing Methamphetamine

Currently, most methamphetamine in the United States is produced by transnational criminal organizations (TCOs) in Mexico (2,8). This methamphetamine is highly pure, potent, and low in price. The drug can easily be made in clandestine laboratories, with relatively inexpensive over-the-counter ingredients such as pseudoephedrine, a common ingredient in cold medications.To curb production of methamphetamine, Congress passed the Combat Methamphetamine Epidemic Act in 2005 which requires that pharmacies and other retail stores keep logs of purchases of products containing pseudoephedrine and limits the amount of those products an individual can purchase per day (2).Mexico has tightened its restrictions on pseudoephedrine and other methamphetamine precursor chemicals. But manufacturers adapt to these restrictions via small or large-scale “smurfing” operations (2):

  • Obtaining pseudoephedrine from multiple sources, below legal thresholds.
  • Using multiple false identifications.

Manufacturers in Mexico are also increasingly using a different production process (called P2P which stands for pseudoephedrine’s precursor chemical, phenyl-2-propranone) to make methamphetamine that does not require pseudoephedrine (2).When methamphetamine is smuggled into the United States in powder or liquid form by way of alcoholic beverages, fuels, water or even vehicle fluids, the domestic conversion laboratories transform it into crystal methamphetamine. These laboratories do not require a significant amount of equipment, so they can be small in size and thus easily concealed, which presents challenges to law enforcement agencies (2).It involves many easily obtainable chemicals that are hazardous (2):

  • Acetone.
  • Anhydrous ammonia (fertilizer).
  • Ether.
  • Red phosphorous.
  • Lithium.

Additional products used in the production of methamphetamine.Methamphetamine production is also an environmental concern.Toxicity from these chemicals can remain in the environment around a methamphetamine production lab long after the lab has been shut down, causing a wide range of damaging effects to health. Because of these dangers, the U.S. Environmental Protection Agency has provided guidance on cleanup and remediation of methamphetamine labs (2).Health effects short-term

  • Increase in wakefulness, physical activity, and decreased appetite.
  • Euphoria and rush.
  • Can cause a variety of cardiovascular problems, including rapid heart rate, irregular heartbeat, and increased blood pressure.
  • Increased respiration rate.
  • Hyperthermia (elevated body temperature).
  • Convulsion may occur with methamphetamine overdose and if not treated immediately, can result in death (2,5,6).

Along with euphoria (the pleasurable high) which is still poorly understood, methamphetamine use releases very high levels of the neurotransmitter dopamine in the reward circuit, which “teaches” the brain to repeat the pleasurable activity of taking the drug.Dopamine is involved in motivation and motor function and its release in the reward circuit is a defining feature of addictive drugs. This elevation is also thought to contribute to the drug’s deleterious effects on nerve terminals in the brain.

Health effects long-term

  • Addiction.
  • Psychosis; paranoia, hallucinations, and repetitive motor activity.
  • Changes in brain structure and function.
  • Deficits in thinking and motor skills.
  • Increased distractibility.
  • Memory loss.
  • Aggressive or violent behavior.
  • Mood disturbances.
  • Severe dental problems.
  • Weight loss.

Abusers need to take higher and higher doses of the drug, take it more frequently, or change how they take it in an effort to get the desired effect.Chronic methamphetamine abusers may develop difficulty feeling any pleasure other than that provided by the drug, fueling further abuse.Withdrawal from methamphetamine occurs when a chronic abuser stops taking the drug. Symptoms of withdrawal include (7):

  • Depression.
  • Anxiety.
  • Fatigue.
  • Intense craving for the drug.

Psychotic symptoms can sometimes last for months or years after a person has quit using methamphetamine, and stress has shown to precipitate spontaneous recurrence of methamphetamine psychosis in people who use methamphetamine and have previously experienced psychosis (9).Studies in chronic methamphetamine users have also revealed severe structural and functional changes in areas of the brain associated with emotion and memory, which may account for many of the emotional and cognitive problems observed in these individuals (10,11,12).Oral Health – “meth mouth”Illicit use of methamphetamine leads to devastating effects on dentition. These individuals have poor oral hygiene. The chief complaint of methamphetamine users is xerostomia (3).Without the protective effects of saliva, caries development in these individuals is rampant (4). Caries are also caused by high-sugar intake in the absence of protective saliva. The acidic substances used to manufacture methamphetamine has also been implicated as a cause of tooth decay and wear in users. Bruxism occurs as a result of drug-induced hyperactivity (3).

Misuse During Pregnancy

  • Increased rates of premature delivery and stillbirths.
  • Placental abruption (separation of the placental lining from the uterus).

Babies, prenatally, exposed to methamphetamine (13,14):

  • Small size at birth.
  • Lethargy.
  • Heart and brain abnormalities.

A large NIDA-funded prospective, longitudinal study examined developmental outcomes in infants and children born to mothers who misused methamphetamine (15 – 23):In infancy, they were more likely to show:

  • Decreased arousal.

  • Increased stress.

  • Poor quality of movement.

By ages 1 and 2, toddlers showed delayed motor development.Preschool and school-aged children had subtle but significant attention impairments and were more likely to have cognitive and behavioral issues in school related to difficulties with self-control and executive function.Treatments for Methamphetamine Use DisorderThe most effective treatments for methamphetamine addiction are behavioral therapies.Cognitive-BehavioralThe Matrix Model is a 16-week comprehensive behavioral treatment approach that combines behavioral therapy, family education, individual counseling, 12-step support, drug testing, and encouragement for non-drug related activities (2).Contingency ManagementThese provide tangible incentives in exchange for engaging in treatment and maintaining abstinence.Motivational incentives for Enhancing Drug Abuse Recovery (MIEDAR), is an incentive-based method for promoting cocaine and methamphetamine abstinence. This has demonstrated efficacy among methamphetamine misusers through NIDA’s National Drug Abuse Clinical Trials Network (24).Pharmacological TreatmentsThere are currently no medications that counteract the specific effects of methamphetamine or that prolong abstinence from and reduce the use of methamphetamine by an individual addicted to the drug.However, there is a two-drug combo that appears to be promising for Methamphetamine Use Disorder.A study published online January 14, 2021, in the New England Journal of Medicine, indicated the combination of naltrexone and bupropion results in a response rate almost six times greater than with a placebo in patients with moderate or severe methamphetamine use disorder (25).Bupropion, a stimulant-like antidepressant, acts through the norepinephrine and dopamine systems and might ameliorate the dysphoria associated with methamphetamine withdrawal that drives continued use.Naltrexone, an opioid-receptor antagonist, has been shown to be an effective treatment for opioid use disorder.The results of this small, open-label trial supported the development of the current randomized, double-blind, multisite trial known as ADAPT-2 (Accelerated Development of Addictive Pharmacotherapy Treatment for Methamphetamine Use Disorder). It was effective at reducing methamphetamine use at 6 weeks.A new study published online June 10, 2024, in Addiction, found extended-release injectable naltrexone combined with extended-release oral bupropion (NTX + BUPN) for moderate or severe methamphetamine use disorders was associated with a significant decreased in the use of methamphetamine.This new study is the second phase of the multicenter ADAPT-2 trial conducted between 2017 and 2019 in 403 participants with methamphetamine use disorder. In the first stage, 109 people received NTX + BUPN and 294 received placebo.This current analysis measured change in methamphetamine use during weeks 7-12 of the trial and in posttreatment weeks 13-16. Statistically significant reductions in methamphetamine use from weeks 13-16 corresponds to the conclusion of treatment in week 12 (26).Nonpharmacological TreatmentsThese types of treatments do not involve the use of medications.TMS – Transcranial Magnetic StimulationThis is a noninvasive method of stimulating the brain using magnetic pulses for therapeutic purposes. This work is in the very early stages as researchers pursue studying this approach for substance use disorders (27).NeurofeedbackAlso called neurotherapy or neurobiofeedback is a type of biofeedback that uses real-time displays of brain activity, most commonly electroencephalography, to teach people how to regulate their own brain function. In one study, neurofeedback used in treatment for methamphetamine use disorder reduced addiction severity and improved mental health and overall quality of life (28).Vaccines and AntibodiesMethamphetamine vaccines, which recruit the body’s immune system to keep drugs from entering the brain, are currently being tested in animals, (29) and a human clinical trial is currently underway to test an immunologic agent called a monoclonal antibody, which binds methamphetamine and neutralizes it before it can exert its effects.ConclusionMethamphetamine misuse continues to be a widespread epidemic.Methamphetamine misuse raises the risk of contracting or transmitting HIV and hepatitis B and C, not only for individuals who inject the drug, but also for noninjecting users (2).It is associated with a culture of risky sexual behavior, both among men who have sex with men and in heterosexual populations and may be attributed to the fact that methamphetamine and related stimulants can increase libido. Data does indicate an association between methamphetamine misuse and the spread for HIV among men who have unprotected sex with men (2).Regardless of how methamphetamine is taken, its strong effects can alter judgment and inhibition and lead people to engage in risky behavior like unprotected sex.The consequences of methamphetamine misuse takes a terrible toll on the individual abuser psychologically, medically, and socially.

  • Memory loss.
  • Aggression.
  • Psychotic behavior.
  • Damage to the cardiovascular system.
  • Malnutrition.
  • Severe dental problems.
  • Contributes to increased transmission of infectious diseases, such as hepatitis B and C and HIV/AIDS.

Beyond the devastating effects on an individual’s health, methamphetamine misuse affects whole communities:

  • Crime increases.
  • Unemployment rises.
  • Child neglect or abuse is prevalent.

References

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  2. NIDA. Overview. National Institute on Drug Abuse website. https://nida.nih.gov/publications/research-reports/methamphetamine/overview. February 24, 2023. Accessed July 21, 2024.

  3. Donaldson M, Goodchild JH. Oral health of the methamphetamine abuser [published correction appears in Am J Health Syst Pharm. 2006 Nov 15;63(22):2180]. Am J Health Syst Pharm. 2006;63(21):2078-2082. doi:10.2146/ajhp060198

  4. Hamamoto DT, Rhodus NL. Methamphetamine abuse and dentistry. Oral Dis. 2009;15(1):27-37. doi:10.1111/j.1601-0825.2008.01459.x

  5. Chomchai C, Chomchai S. Global patterns of methamphetamine use. Curr Opin Psychiatry 2015;28:269-74.

  6. Panenka WJ, Procyshyn RM, Lecomte T, et al. Methamphetamine use: A comprehensive review of molecular, preclinical and clinical findings. Drug Alcohol Depend 2013;129:167-79.

  7. Courtney KE, Ray LA. Methamphetamine: an update on epidemiology, pharmacology, clinical phenomenology, and treatment literature. Drug Alcohol Depend 2014;143:11-21.

  8. Administration USDoJDE. 2018 National Drug Threat Assessment 2018.

  9. Glasner-Edwards S, Mooney LJ. Methamphetamine psychosis: epidemiology and management. CNS Drugs 2014;28:1115-26.

  10. Thompson, P.M.; Hayashi, K.M.; Simon, S.L.; Geaga, J.A.; Hong, M.S.; Sui, Y.; Lee, J.Y.; Toga, A.W.; Ling, W.; and London, E.D. Structural abnormalities in the brains of human subjects who use methamphetamine. J Neurosci 24:6028–6036, 2004.

  11. Chang, L.; Alicata, D.; Ernst, T.; and Volkow, N. Structural and metabolic brain changes in the striatum associated with methamphetamine abuse. Addiction 102(Suppl 1):16–32, 2007.

  12. London, E.D.; Simon, S.L.; Berman, S.M.; Mandelkern, M.A.; Lichtman, A.M.; Bramen, J.; Shinn, A.K.; Miotto, K.; Learn, J.; Dong, Y.; Matochik, J.A.; Kurian, V.; Newton, T.; Woods, R.; Rawson, R.; and Ling, W. Mood disturbances and regional cerebral metabolic abnormalities in recently abstinent methamphetamine abusers. Arch Gen Psychiatry 61:73–84, 2004.

  13. Wouldes, T.; LaGasse, L.; Sheridan, J.; and Lester, B. Maternal methamphetamine use during pregnancy and child outcome: What do we know? N Z Med J 117:U1180, 2004.

  14. Smith, L.M.; LaGasse, L.L.; Derauf, C.; Grant, P.; Shah, R.; Arria, A., Huestis, M.; Haning, W.; Strauss, A.; Della Grotta, S.; Liu, J.; and Lester, B.M. The Infant Development, Environment, and Lifestyle Study: Effects of prenatal methamphetamine exposure, polydrug exposure, and poverty on intrauterine growth. Pediatrics 118(3):1149–1156, 2006.

  15. Smith LM, Lagasse LL, Derauf C, et al. Prenatal methamphetamine use and neonatal neurobehavioral outcome. Neurotoxicol Teratol. 2008;30(1):20-28. doi:10.1016/j.ntt.2007.09.005

  16. Kiblawi ZN, Smith LM, Diaz SD, et al. Prenatal Methamphetamine Exposure and Neonatal and Infant Neurobehavioral Outcome: Results from the IDEAL Study. Substance abuse: Official publication of the Association for Medical Education and Research in Substance Abuse. 2014;35(1):68-73. doi:10.1080/08897077.2013.814614.

  17. Wouldes TA, LaGasse LL, Huestis MA, DellaGrotta S, Dansereau LM, Lester BM. Prenatal methamphetamine exposure and neurodevelopmental outcomes in children from 1 to 3 years. Neurotoxicology and teratology. 2014;42:77-84. doi:10.1016/j.ntt.2014.02.004.

  18. Kiblawi, Z.N.; Smith, L.M.; LaGasse, L.L.; Derauf, C.; Newman, E.; Shah, R.; Arria, A.; Huestis, M.; DellaGrotta, S.; Dansereau, L.M.; Neal, C.; and Lester, B. The effect of prenatal methamphetamine exposure on attention as assessed by continuous performance tests: Results from the Infant Development,

  19. Environment, and Lifestyle study. J Dev Behav Pediatr 34(1):31–37, 2013.

  20. Himes SK, LaGasse LL, Derauf C, et al. Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results. Therapeutic drug monitoring. 2014;36(4):535-543.

  21. Smith LM, Diaz S, LaGasse LL, et al. Developmental and behavioral consequences of prenatal methamphetamine exposure: a review of the Infant Development, Environment, and Lifestyle (IDEAL) Study. Neurotoxicology and teratology. 2015;51:35-44. doi:10.1016/j.ntt.2015.07.006.

  22. Eze N, Smith LM, LaGasse LL, et al. School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5 Year Follow-Up From The Infant Development, Environment, and Lifestyle (IDEAL) Study. The Journal of pediatrics. 2016;170:34-38.e1. doi:10.1016/j.jpeds.2015.11.070.

  23. Diaz S, Smith LM, LaGasse, LL, et al. Effects of Prenatal Methamphetamine Exposure on Behavioral and Cognitive Findings at 7.5 Years of Age. The Journal of Pediatrics. 2014;164:1333-38. doi: 10.1016/j.jpeds.2014.01.053.

  24. Petry, N.M.; Peirce, J.M.; Stitzer, M.L.; Blaine, J.; Roll, J.M.; Cohen, A.; Obert, J.; Killeen, T.; Saladin, M.E.; Cowell, M.; Kirby, K.C.; Sterling, R.; Royer- Malvestuto, C.; Hamilton, J.; Booth, R.E.; Macdonald, M.; Liebert, M.; Rader, L.; Burns, R.; DiMaria, J.; Copersino, M.; Stabile, P.Q.; Kolodner, K.; and Li, R. Effect of prize-based incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs: A National Drug Abuse Treatment Clinical Trials Network study. Arch Gen Psychiatry 62(10):1148–1156, 2005.

  25. Trivedi MH, et al. Bupropion and naltrexone in methamphetamine use disorder, N Eng J Med 2021;384:140-53. DOI: 10.1056/NEJMoa2020214

  26. Li MJ, Chau B, Belin T, et al. Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial. Addiction. Published online June 10, 2024. doi:10.1111/add.16529

  27. Makani R, Pradhan B, Shah U, Parikh T. Role of Repetitive Transcranial Magnetic Stimulation (rTMS) in Treatment of Addiction and Related Disorders: A Systematic Review. Curr Drug Abuse Rev 2017;10:31-43.

  28. Rostami R, Dehghani-Arani F. Neurofeedback Training as a New Method in Treatment of Crystal Methamphetamine Dependent Patients: A Preliminary Study. Appl Psychophysiol Biofeedback 2015;40:151-61.

  29. Collins KC, Schlosburg JE, Bremer PT, Janda KD. Methamphetamine Vaccines: Improvement through Hapten Design. J Med Chem 2016;59:3878-85.


Cynthia Blair RN MA–July 2024

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