Throughout the last decade there has been a sharp increase in methamphetamine and cocaine use as well as cocaine and methamphetamine associated deaths. Methamphetamine deaths increased fivefold to 10.1 deaths per 100,000 men and 4.5 deaths per 100,000 women from 2012 to 2018. Like other substances of abuse, methamphetamine use is linked to a variety of very serious health consequences including dependence and overdose deaths. Unlike opioid overdoses, which can be reversed by naloxone, there is no treatment for methamphetamine overdose. The highest overdose rates were among American Indians and Alaskan Natives, who had overdose rates of 26.4 and 15.6 per 100,000 men and women, respectively [1]. In 2019, 2 million people reported using methamphetamines in the last year, compared to 1.6 million on average from 2015 to 2018 [2]. The most recent CDC data show that deaths have continued to increase and that the COVID-19 pandemic has played a role as well in overdose death increases. Methamphetamine deaths are at least partially attributable to synthetic fentanyl-like opioids being adulterants in street supplies. Overdose deaths involving cocaine (21%) and other psychostimulants like methamphetamine (46%) rose dramatically in the latest CDC report. In 2015, synthetic opioids were involved in only 18 percent of all overdose deaths; in 2020, it appears to be more than 60 percent [3].
History has shown that stimulant epidemics follow opioid epidemics [4]. In recent years, methamphetamine deaths have surpassed deaths from heroin and prescription opioids (but not deaths from synthetic fentanyl, which have steeply increased) [5]. Methamphetamine use may be increasing because it is cheaper, manufactured rather than grown and thereby easier to produce than other stimulants like cocaine. This makes methamphetamines less expensive for buyers and gives higher profit margins for those that produce and sell it.
Methamphetamine is most commonly used in conjunction with other drugs (polysubstance use). Many opioid drug users state that they have shifted to using methamphetamines because it is cheaper or because they fear the increased presence of fentanyl in heroin and other products sold as opioids (although methamphetamines can also be contaminated with fentanyl). Additionally, like how cocaine and opioids can be combined into a speedball, today opioids and methamphetamines are often combined to produce both highs and to reduce the depressive effects of opioids with the stimulative effects of methamphetamine [6].
Methamphetamine poses its own set of risks: addiction, damage to the body and brain, overdose, and increasing contamination with fentanyl and other toxic adulterants. Like cocaine, methamphetamine is highly reinforcing. Administration fuels binge use and often leads to major health problems in addition to craving and substance use disorder. The treatment for methamphetamine overdose has not advanced very much in the last 50 years and life-saving options remain limited. Because of these factors, prevention is the more important intervention while more effective treatments are developed for those with methamphetamine use disorder.
How does methamphetamine affect the body?
Methamphetamine use has both short- and long-term effects on the brain and body. Methamphetamine is toxic to the brain — studies have found that methamphetamine can cause similar damage to brain tissue as traumatic brain injuries [7]. Acute use can cause short-term psychiatric symptoms, such as anxiety, hyper ability, disturbed speech patterns, and aggression. For some people these symptoms are not temporary. Long-term use can cause methamphetamine-induced psychosis, which includes hallucinations, delusions, and paranoia that can persist after long periods of abstinence. This methamphetamine-induced psychosis has similar symptoms to naturally occurring psychosis but does not respond as well to standard treatments [8].
In terms of its effects on the body, methamphetamine is rapidly absorbed by many organs and chronic use can harm the heart, lungs, and kidneys, among other organs [8]. Intravenously injecting methamphetamine increases one’s risk of contracting infections such as Hepatitis C and HIV which are spread through shared injection supplies like needles.
People who use methamphetamine can also experience an overdose. A methamphetamine overdose usually occurs because the body becomes severely overheated while on the drug, leading to organ failure. It can also occur due to strain on the cardiovascular system that causes heart failure or a stroke. Common symptoms of a methamphetamine overdose include chest pain, high or low blood pressure, difficulty breathing, irregular heartbeat, seizures, hallucinations/psychosis, and hyperthermia (overheating). If someone is using methamphetamine and experiences these symptoms, they should seek medical attention immediately. Most methamphetamine overdoses take place when new users take too high of a dose [9], however, all methamphetamine users are susceptible to overdoses from contaminants such as fentanyl.
What are adulterants?
Illicit drugs, by definition, are not made by pharmaceutical companies that are under FDA quality and supervisory standards. Instead, “Breaking Bad” type labs and various sundry dealers make methamphetamine and sell it regardless of its purity. The physical and mental health risks associated with methamphetamine are significant and increase when drug dealers mix methamphetamines with unknown substances, called adulterants. Adulterants are products added to a pure drug to increase the volume of the product and/or enhance its effects. In the past, drug suppliers would cut drugs with largely harmless compounds like lactose and sucrose in order to increase their bulk. Recently, however, there has been an influx of more pernicious pharmaceutical throwaways added to the drug supply, as well as dangerous synthetic opioids like fentanyl.
A study published in 2021 tested street drugs for various adulterants, many of which could not be detected without special forensic tests. It found toxic pharmaceuticals and impurities throughout the drug supply, identifying up to seventeen different toxic adulterants in a single unit of cocaine or heroin. These included pharmaceuticals that damage the heart, lungs, liver, immune system, and brain, especially when unknowingly taken in high amounts and mixed with one another. These adulterants were not only found to increase the risk of overdose in some cases, but also incite health problems which on their own can lead to hospitalization and death. For example, Levamisole, a veterinary pharmaceutical often found in cocaine, causes a precipitous drop in white blood cells, leading to potentially life-threatening infections. This recent increase of toxic adulterants in the drug supply contributes to harm and overdose in those who consume methamphetamine [10].
While some heroin users have switched to using methamphetamine, citing that they no longer feel supplies are safe due to the increasing presence of synthetic opioids like fentanyl. However, fentanyl has been increasingly found in methamphetamines as well, likely due to cross-contamination during production. According to Nora Volkow, director of the National Institute for Drug Abuse, fentanyl is especially dangerous for methamphetamine users who do not have a tolerance for opioids, which puts them at increased risk for overdose [11]. In 2018, more than half of the overdose deaths related to psychostimulants like methamphetamines involved opioids [2]. One key intervention to prevent these overdoses is to encourage methamphetamine users and those in their network to carry naloxone, even if they do not use opioids. Naloxone can save the lives of methamphetamine users who overdose on opioids unknowingly due to using methamphetamine adulterated with fentanyl [12].
What treatment exists for methamphetamine use disorder?
Currently, the only available treatment for stimulant use disorders are behavior-based therapies. Unlike opioids, which have several medications (MOUDs) to treat overdose and reduce withdrawal and cravings, no medical treatments have been FDA approved for methamphetamine use yet.
A study published in 2021 examined a combination of medicines used and approved for the treatment of obesity, that may help some patients with methamphetamine use disorder. The study combined two drugs: naltrexone, a drug used to treat opioid and alcohol use disorders, and bupropion, an antidepressant also known as Wellbutrin which has also been used in the past to treat cigarette use disorders. The study sought to measure the effectiveness of this drug combination in helping to attain short-term abstinence in individuals with methamphetamine use disorder who took the medications as directed.
Researchers used a double-blind, randomized clinical trial to see whether patients responded to the naltrexone and bupropion compared to a placebo. They gathered participants with methamphetamine use disorder and split them into two groups. For six weeks one group was given extended-release injections of naloxone and extended-release daily oral bupropion and the other was given placebos. Many patients dropped out of this research study mid-way and were not included. The researchers defined a response as at least three out of four urine samples negative for methamphetamine in weeks five and six. In the first six weeks, less than 1 out of 5 of patients who stayed in the study or 16.5% of patients given naltrexone and bupropion showed a response, compared to only 3.4% of those who received the placebo.
The researchers then took those in the placebo group who did not respond and randomly split them again into two groups. Again, for six more weeks they gave one group naltrexone and bupropion and the other received the placebo. In this second stage, 11.4% of those given naltrexone and bupropion showed a response compared to 1.8% of placebo. Overall, 13.6% of those given naltrexone and bupropion responded compared to 2.5% of the placebo group [13]. While the treatment was a strong enough signal that such a combination might be helpful compared to the placebo, only about 1 in 9 people responded to it. Methamphetamine use disorder is a chronic and relapsing condition characterized by binges and periods of exhaustion and abstinence. It is too early to say whether naltrexone plus bupropion might become an approved FDA treatment, but it is a good beginning.
Why it matters.
The steep rise in methamphetamine overdoses in recent years represents a new, second epidemic coinciding with what many see as the end of the opioid epidemic. Methamphetamine use has numerous severe consequences for users, some of which may persist after use is stopped. Consequences of use are exacerbated by the increasing presence of adulterants such as throwaway pharmaceuticals and fentanyl in the drug supply. This crisis highlights the need for more diverse treatments for methamphetamine overdose and use disorder, especially medication assisted treatments. While preliminary treatments are under study, further research and more widespread awareness and prevention efforts, such as naloxone distribution, are needed to help reduce overdose deaths moving forward.
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food.
References
Han, B., Cotto, J., Etz, K., Einstein, E.B., Compton, W.M., Volkow, N.D. (2021). Methamphetamine overdose deaths in the US by sex and race and ethnicity. JAMA Psychiatry, 78(5), 564–567. doi:10.1001/jamapsychiatry.2020.4321.
Centers for Disease Control and Prevention (2021). Drug overdose deaths: Other drugs. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention. https://www.cdc.gov/healthywater/drinking/public/water_diseases.html.
Baumgartner, J.C., Radley, D.C., (2021 August 16). The drug overdose toll in 2020 and near-term actions for addressing it. The Commonwealth Fund. https://www.commonwealthfund.org/blog/2021/drug-overdose-toll-2020-and-near-term-actions-addressing-it.
Musto, D. (1999). The American Disease: Origins of narcotic control. Oxford University Press.
National Institute for Health Care Management Foundation (2021). Stimulant deaths on the rise, compounded by rise in synthetic opioids. Washington, DC: National Institute for Health Care Management. https://nihcm.org/publications/stimulant-deaths-on-the-rise-compounded-by-rise-in-synthetic-opioids.
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Gold, M.S., Kobeissy, F.H., Wang, K.K., Merlo, L.J., Bruijnzeel, A.W., Krasnova, I.N., & Cadet, J.L. (2009). Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biological Psychiatry, 66(2), 118–127. https://doi.org/10.1016/j.biopsych.2009.02.021.
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The University of Arizona. (n.d.). Methamphetamine overdose. https://methoide.fcm.arizona.edu/infocenter/index.cfm?stid=216
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Goodnough, A. (2021, April 14). Overdose deaths have surged during the pandemic, C.D.C. data shows. The New York Times. https://www.nytimes.com/2021/04/14/health/overdose-deaths-fentanyl-opiods-coronaviurs-pandemic.html
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