Methamphetamine and Amphetamine-Type Stimulants

"Deaths involving cocaine and psychostimulants have increased in the United States in recent years; among 70,237 drug overdose deaths in 2017, nearly a third (23,139 [32.9%]) involved cocaine, psychostimulants, or both. From 2016 to 2017, death rates involving cocaine and psychostimulants each increased by approximately one third, and increases occurred across all demographic groups, Census regions, and in several states. In 2017, nearly three fourths of cocaine-involved and roughly one half of psychostimulant-involved overdose deaths, respectively, involved at least one opioid. After initially peaking in 2006, trends in overall cocaine-involved death rates declined through 2012, when they began to rise again. The 2006–2012 decrease paralleled a decline in cocaine supply coupled with an increase in cost. Similar patterns in death rates involving both cocaine and opioids were observed, with increases for cocaine- and synthetic opioid-involved deaths occurring from 2012 to 2017. From 2010 to 2017, increasing rates of deaths involving psychostimulants occurred and persisted even in the absence of opioids."

"● The age-adjusted rate of drug overdose deaths involving cocaine increased slightly from 1.6 deaths per 100,000 standard population in 2002 to 2.5 in 2006, decreased to 1.3 in 2010, then increased to 8.2 in 2022; the rate in 2022 was 12.3% higher than the rate in 2021 (7.3) (Figure 5).

"● The age-adjusted rate of drug overdose deaths involving psychostimulants with abuse potential (subsequently, psychostimulants), which includes methamphetamine, amphetamine, and methylphenidate, was 4.0% higher in 2022 than the rate in 2021 (10.4 compared with 10.0).

"● The age-adjusted rate of drug overdose deaths involving psychostimulants increased more than 34 times from 2002 (0.3) to 2022 (10.4), with different rates of change over time."
 

"What is methamphetamine?
"Methamphetamine is a powerful, highly addictive stimulant that affects the central nervous system. Crystal methamphetamine is a form of the drug that looks like glass fragments or shiny, bluish-white rocks. It is chemically similar to amphetamine, a drug used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy, a sleep disorder.

"How do people use methamphetamine?
"People can take methamphetamine by:

"• smoking
"• swallowing (pill)
"• snorting
"• injecting the powder that has been dissolved in water/alcohol"

"Findings

"The percent of US overdose deaths involving both fentanyl and stimulants increased from 0.6% (n = 235) in 2010 to 32.3% (34 429) in 2021, with the sharpest rise starting in 2015. In 2010, fentanyl was most commonly found alongside prescription opioids, benzodiazepines, and alcohol. In the Northeast this shifted to heroin-fentanyl co-involvement in the mid-2010s, and nearly universally to cocaine-fentanyl co-involvement by 2021. Universally in the West, and in the majority of states in the South and Midwest, methamphetamine-fentanyl co-involvement predominated by 2021. The proportion of stimulant involvement in fentanyl-involved overdose deaths rose in virtually every state 2015–2021. Intersectional group analysis reveals particularly high rates for older Black and African American individuals living in the West.

"Conclusions

"By 2021 stimulants were the most common drug class found in fentanyl-involved overdoses in every state in the US. The rise of deaths involving cocaine and methamphetamine must be understood in the context of a drug market dominated by illicit fentanyls, which have made polysubstance use more sought-after and commonplace. The widespread concurrent use of fentanyl and stimulants, as well as other polysubstance formulations, presents novel health risks and public health challenges."

"Few stimulant-specific harm reduction responses are implemented globally. Though NSPs and drug consumption rooms (DCRs) can be accessed by people who use stimulants, existing harm reduction services might not always be adequate for their needs.^[34] For example, stimulant use is associated with more frequent injection than opioids, but limits in NSPs on the number of syringes that can be acquired at any one time represent a particular barrier for those injecting stimulants. Stimulants are also more likely to be smoked or inhaled than opioids, but not all DCRs permit inhalation on premises, and smoking equipment is rarely distributed. However, safer smoking kits for crack cocaine, cocaine paste and ATS are distributed in several territories, including Portugal^[5][35] and harm reduction programmes for people who use non-injectable cocaine derivatives are in place in several countries in Latin America. There have been promising pilot programmes in Asia focusing on people who use methamphetamine, including outreach programmes distributing safer smoking kits, plastic straws, harm reduction education, and access to testing and treatment for HIV, hepatitis C, TB and other sexually transmitted diseases (see page 75 in Asia Chapter 2.1).

"Drug checking (services that enable people to voluntarily get the contents of their drugs analysed) is an important harm reduction intervention for people who use stimulants. These services are implemented in at least nine countries in Western Europe³, are available in the United States, Australia and New Zealand, and are increasingly available in Latin America⁴. Eight countries in Eurasia⁵ have some form of drug checking services through distribution of reagent test kits at music festivals and nightlife settings. Other methods of drug checking include the use of mobile testing equipment to determine the contents of what is sold using tiny samples of the product, allowing for identification of both drugs and contaminants. Though availability of drug checking is growing globally from a low baseline, implementation faces serious legal barriers in many countries as it involves handling controlled substances, and drug checking services often require formal exemption from drug laws in order to operate legally.

"No approved substitution therapy for ATS exists, although pharmacologically-assisted treatment with methylphenidate for ATS users was authorised by the government in Czechia during the COVID-19 pandemic, and in Canada, the British Columbia Centre on Substance Use released interim clinical guidance recommending the prescription of dexamphetamine and methylphenidate to people who use stimulants.^[36]"

"Among people aged 12 or older in 2019, 0.7 percent (or 2.0 million people) used methamphetamine in the past year (Figure 15 and 2019 DT 7.2). These estimates of past year methamphetamine use in 2019 were higher than those in 2016 and 2017, but they were similar to those in 2015 and 2018.

"Aged 12 to 17
"Among adolescents aged 12 to 17 in 2019, 0.2 percent (or 41,000 people) used methamphetamine in the past year (Figure 15 and 2019 DT 7.5). The percentage of adolescents who used methamphetamine in the past year remained stable between 2015 and 2019.

"Aged 18 to 25
"Among young adults aged 18 to 25 in 2019, 0.8 percent (or 275,000 people) used methamphetamine in the past year (Figure 15 and 2019 DT 7.11). The percentage of young adults who were past year methamphetamine users was stable between 2015 and 2019.

"Aged 26 or Older
"Among adults aged 26 or older, the percentage who were past year methamphetamine users increased from 0.5 percent (or 1.1 million people) in 2016 to 0.8 percent (or 1.7 million people) in 2019 (Figure 15 and 2019 DT 7.14). The percentage of adults in this population in 2019 who used methamphetamine in the past year was higher than the percentages in 2016 and 2017, but it was similar to the percentages in 2015 and 2018."

"Of the 1,220,143 deaths with involved drugs listed on the death certificate, 130 560 (10.7% of all decedents) were found to have stimulants listed. Among stimulant-involved deaths, 93,689 decedents (71.8%) were men, the median (interquartile range) age was 45 (34-54) years, and 98,635 (75.5%) were White (Table). Of these, 120,803 certificates (92.5%) listed only illicit stimulants, 5544 (4.2%) listed only medical stimulants, and 3524 listed both types (2.7%). Among illicit stimulants, there were 77,013 deaths (61.9%) involving cocaine, 49,602 deaths (39.9%) involving methamphetamine, and 817 deaths (0.7%) involving 3,4-methylenedioxymethamphetamine. Among medical stimulants, there were 8240 deaths (90.9%) involving amphetamine, 295 deaths (0.3%) involving methylphenidate, and 615 deaths (0.7%) involving pseudoephedrine. Among all 3 stimulant groups, the proportion of deaths that also involved opioids was substantial; concomittant use of benzodiazepines and antidepressants was also not uncommon.

"Stimulant mortality has risen rapidly since 2010 (Figure). The mortality rate involving all stimulants rose from 2.913 deaths per 100,000 population in 2010 to 9.690 in 2017. Mortality rates increased among all medical stimulants (ARR, 1.226; 95% CI, 1.202-1.250), amphetamine (ARR, 1.118; 95% CI, 1.082-1.155), cocaine (ARR, 1.234;95% CI, 1.222-1.245), and methamphetamine (ARR, 1.278; 95% CI, 1.261-1.295)."

"The estimates presented in this article find important evidence of the potential consequences of the rapid expansion of the MA supply in Ohio, which can help inform the public health consequences of a similar expansion across the US. We find that relatively more MA detected by crime labs is either unrelated to or associated with a small, but measurable decrease in the overall risk of unintentional overdose death. This is not to say that MA is safe or cannot cause overdose deaths. Our findings are not that the combination of MA and fentanyl is in fact safer than fentanyl on its own. As our estimates are only showing averages, it could certainly be the case that an increase in MA availability makes illicit drug consumption more deadly for some people or at particular dose levels. Rather, given the context of extremely dangerous synthetic opioids, our estimates should be interpreted as showing that a relative increase in the availability of less deadly drugs, especially if they are replacing synthetic opioids, may reduce the overall number of overdose deaths, at least in the short-run. Furthermore, we do not investigate the substantial, non-fatal health consequences of MA use such as psychosis and cardiovascular disease, which may be increasing even if deaths decline.

"The exact mechanism linking MA to overdose deaths is not clear. Is it that MA use directly reduces the risk of overdose when used concurrently with opioids? If the animal data are applicable to humans, is MA co–use with fentanyl reducing opioid overdose risk at some doses and increasing it at others? Is it that MA use allows people to lengthen the duration between opioid use or substitute away from opioids entirely? This is supported by recent research showing that some people find MA helpful for managing opioid withdrawal (Ondocsin et al., 2023). Or is MA supply simply correlated with a reduction in overdose death, and we are missing a key unobservable omitted variable, such as greater migration to substance use treatment, that is positively correlated with MA supply?"

"Recent trials with extended-release formulations and higher dosages of PPs [Prescription Psychosimulants], particularly prescription amphetamines, have shown promising results promoting abstinence from cocaine and reducing drug use. PPs’ potential as an “agonist-type” treatment seems to be better explored with higher dosage regimens and at clinical settings that have direct observed dosing available. The results from patients with comorbid opioid use disorders are particularly encouraging, and this may be due to the fact that high dosages of potent PPs were used, and this population is already enrolled to a healthcare facility that offers daily attendance, supervised medication intake, evidencebased psychosocial interventions, and a wide-range of ancillary services. A widely used and successful model of treating opioid use disorder or incorporating mobile technology solutions to monitor and enhance medication adherence may now be assessed for treatment of individuals with psychostimulant use disorder and incorporate prescription amphetamines as an agonist intervention. Considering the major public health impact of untreated PSUD, and the absence of the widely accepted pharmacological intervention, there is an urgent need to conduct implementation studies of this treatment approach."

"In a harm reduction setting, a FTS might be used to test the drug residue in a cooker or baggie for fentanyl before use of the drug. Our results show that the concentrations of diphenhydramine, methamphetamine, and MDMA commonly found in street drugs are at levels that could generate false positives on the FTS. Many cookers and small baggies hold about 0.75–1 mL of water. If we assume there is 5 mg of methamphetamine in the container that is diluted with 1 mL of water, the concentration of methamphetamine will be 5 mg/mL and would trigger a false positive on the FTS. If the residue were dissolved with 10 mL of water, the methamphetamine concentration would be 0.5 mg/mL and would render a true negative on the FTS. If the drug residue instead consisted of 95% methamphetamine and 5% fentanyl, the 10 mL dilution would ensure that the methamphetamine concentration would not interfere with the FTS while the true positive result would come from the fentanyl present in the sample. As practical guidance for harm reduction groups, a dilution with at least 50 mL of water will provide a good margin of error for accurate detection of fentanyl in cooker or powder residues while avoiding false positives from other drugs. Over dilution is not a likely problem; the FTS is sensitive enough that if there was just 0.5 mg of fentanyl residue in a cooker and it is dissolved in a 10-L bucket of water (50 µg/L or 50 ng/mL), the FTS will still detect the fentanyl present."

"Polysubstance use may increase the risk of opioid overdose [36, 37] but although studies have found associations between overdose and combined use of heroin with other sedatives [38], the literature on overdose risk from heroin-stimulant combinations is limited [19, 39]. Goofball use has been associated with larger networks of PWID [19], which while potentially protective against overdose, may increase the likelihood of sharing injection equipment and contribute to transmission of bloodborne infections. Additionally, participants reported using methamphetamine to alter their sleep schedules or that methamphetamine use kept them awake for days, and the impact of sleep disturbances on susceptibility to opioid overdose needs additional study.

"Consistent with other studies [20], several respondents strongly believed in the ability of methamphetamine to prevent and reverse opioid overdose. Set against this are statistical data that show greater frequency of overdose among individuals co-using methamphetamine and heroin compared to people solely using heroin [19, 40] and rising numbers of deaths involving combinations of fentanyl and methamphetamine [41]. Increased mortality from co-use of these substances could represent greater co-use of methamphetamine overall or escalating fentanyl saturation of the opioid market but does not explain the lay belief in the possible protective effects of methamphetamine against opioid overdose.

"A potential explanation arises from recent mouse-model data which shows a bi-directional effect of amphetamine on fentanyl-depressed respiration depending on amphetamine dosage. Lower amphetamine doses depressed respiration after fentanyl, increasing the likelihood of overdose but higher amphetamine doses elevated respiration [42]. If applicable to humans, this finding may help to explain the apparent contradiction of methamphetamine both increasing and reducing the risks of fatal overdose and could lead to the development of important harm reduction strategies. However, more specific research on this drug interaction in humans is needed to understand this causal pathway.

"The importance of dosage and drug sequence when using methamphetamine to mitigate adverse respiratory effects of opioids, fentanyl in particular, requires further study. Order of use may not be evident in post-mortem toxicology and the interaction of these drug mechanisms over time needs further exploration. Amidst rising amphetamine-related hospitalizations [43, 44], research should also consider other specific morbidity risks posed by co-use of opioids and methamphetamine, including how non-injection modes of use (i.e. smoking, snorting [45]) may impact morbidity and mortality (e.g. by reducing HIV/HCV or overdose risks)."

"Methamphetamine use is increasing in the wake of the opioid crisis in the United States (U.S.). Increases in the use of this highly addictive stimulant have been documented in the health literature^1,2 as well as in the national media.³ In Denver, Colorado, and Seattle, Washington, the increase in methamphetamine use has predominantly involved a growing proportion of people who inject drugs (PWID) using both methamphetamine and heroin, either separately or in a single injection commonly known as a goofball.^1,2 (Goofball can also be smoked.) Data from San Diego, California, and Tijuana, Baja California, Mexico have also demonstrated high levels of co-injection of methamphetamine and heroin.⁴

"Although existing literature provides some insight into the characteristics and circumstances of people who inject goofball, the available data remain very limited. We previously published an analysis of data from syringe services program (SSP) clients in the Seattle area between 2009 and 2017, and found that people who used goofball were significantly more likely than other PWID to be young, homeless, inject daily, and self-report an opioid overdose.² Additional data on specific injection behaviors, other health outcomes, and interest in treatment among people who inject goofball are needed to understand how to most effectively implement harm reduction and substance use treatment efforts. In addition, it is important to focus on people whose primary drug is goofball to determine how the needs of this potentially high acuity group may differ from people predominantly using other drugs."

"Findings from these recent surveys of SSP clients in Seattle showed that goofball use is common, with over half of respondents reporting using heroin and methamphetamine together. Moreover, PWID whose main drug was goofball reported considerable health risks and morbidity, including more frequent injection, femoral and jugular vein injection, public injection, abscesses and skin infections, infected blood clots and blood infections, and endocarditis. They also reported more overdose-related risk including injecting alone and witnessing both opioid and stimulant overdoses. At the same time, the majority of PWID who reported that goofball was their main drug also reported interest in reducing or stopping their drug use. In light of the opioid crisis in the U.S., it is critical for stakeholders to recognize the substantial and growing overlap between opioid and methamphetamine use, acknowledge the contextual factors that may be driving the combined use of these drugs, and develop health interventions accordingly.

"Polysubstance use is a global phenomenon, especially the use of opioids in combination with stimulants, and has been associated with high levels of HIV and other negative health outcomes.^9–11 Prior opioid-stimulant co-use research has mostly focused on speedball. At present, there is limited epidemiologic data on the unique health effects of combined heroin and methamphetamine use. Due to the shorter half-life of heroin relative to methamphetamine,¹² people using goofball may re-dose when the effects of heroin wane but before the effects of methamphetamine have worn off, potentially leading to the unsafe injection behaviors or overdose.

"A very high proportion (82.5%) of people whose main drug was goofball were homeless or unstably housed. This aligns with dramatic increases in homelessness in the Seattle area.¹³ Many other observed associations with goofball use are correlated with homelessness. People living outdoors may use stimulants to counter the depressant effects of opioids to remain more aware of their possessions and surroundings.¹⁴ However, further research is needed to better understand the motivations and causes of the increase in methamphetamine use, particularly among this largely homeless population with high levels of risk and vulnerability."

"In the Seattle area, the increase in methamphetamine use has paralleled an increase in methamphetamine-involved deaths, many of which also involved opioids.³⁵ Although we did not find that people who primarily use goofball were more likely than others to experience an opioid overdose or stimulant overdose/overamp, several behaviors associated with overdose were higher in this group including more frequent injection and injecting alone. Moreover, people who primarily use goofball were the most likely to witness opioid and stimulant overdoses, highlighting the critical importance of engaging this group in overdose prevention services. Fortunately, naloxone possession was also highest in this group, suggesting that these efforts have been successful."

"The role of co-use of heroin and methamphetamine in overdose requires greater exploration. Intentional co-use of heroin and methamphetamine is increasing in the US, whether in simultaneous injection as a ‘goofball’, sequential injection or other combined modes, including smoking and snorting. Supply changes have played a part in widespread distribution of ‘ice’ or ‘cream’, a more potent and lower price Mexican-sourced methamphetamine supplanting the domestic product [10, 16].

"‘Goofball’ was originally a term for barbiturate-type drugs with the earliest mention in the literature as heroin-methamphetamine injection in 2005 [17]. Heroin and methamphetamine co-use (referred to in some locations as a goofball and in others as a speedball, which historically has been a combination of heroin and cocaine) is spreading in locations as varied as Seattle, Washington; San Diego, California; Denver, Colorado; and Dayton, Ohio [18,19,20,21]. Qualitative research has found many people who use drugs (PWUD) believe methamphetamine can prevent or reverse opioid-related overdoses [20] and reduce withdrawal severity [22]. A study in Vancouver, Canada, found that practitioners used goofballs bi-directionally, both to enhance the individual effects of opioids and methamphetamine and to control for each drug’s negative effects [23]. However, knowledge about forms of co-use of methamphetamine and heroin, particularly from recent years, is needed to understand rising mortality among people using methamphetamine."

"Motives for using methamphetamine with heroin/fentanyl can be conceptualized as forming three thematic categories: ‘intrinsic use’, representing the inherent pleasure of the combination or self-medication of particular conditions; ‘opioid assisting use’ in which methamphetamine helped manage existing heroin/fentanyl use and ‘reluctant or indifferent use’. All 30 individuals had some experience using methamphetamine, whether separately or combined with heroin.

"We heard about and witnessed several ways that people used the two drugs, including simultaneous or alternating injections along a temporal spectrum. Daily order of dosing was another important and varied aspect of goofball use, with participants’ strategies dependent upon time of day, activity level, social situations and other factors. Most participants prioritized heroin over methamphetamine due to managing both opioid withdrawal and limited financial resources. Participants generally used the term ‘heroin’ to describe heroin, heroin adulterated with fentanyls and fentanyls without heroin; this language is reproduced in this paper to incorporate both drugs. Participants used the term ‘speedball’ to indicate co-injection of heroin and methamphetamine simultaneously, and generally did not use this term to refer to use separated in either time or mode of use (snorting, smoking). Ratios of heroin to methamphetamine within a speedball varied significantly among participants based on opioid tolerance, social situations and personal preference.

"The co-use of heroin and methamphetamine, known locally as a ‘speedball’, a term used elsewhere to describe a cocktail of heroin and cocaine, gained popularity among our sample within the last several years, and was virtually unknown before approximately 2015. This was despite the earlier presence of domestically produced ‘shake and bake’Footnote1 methamphetamine in the local drug culture, albeit recently less widely available than the newer ice. Heroin was also a latecomer to the area, with evidence suggesting that the local market developed from 2012 onwards [35]. Among participants where the order of drug progression was clear, all had initiated their opioid use with prescription opioid pills, but had transitioned to heroin after the pills became prohibitively expensive and more difficult to obtain."

"Increases in methamphetamine indicators reported in 2012 continued into 2013. These increases reversed a mostly declining trend since 2007. All CEWG area representatives reported increasing, stable, or mixed indicators in 2013, compared with 2012. Twelve of 19 CEWG area representatives reported increasing methamphetamine indicators in the 2013 reporting period; these were Atlanta, Cincinnati, Denver/Colorado, Detroit, Los Angeles, Minneapolis/St. Paul, St. Louis, San Diego, San Francisco, Seattle, South Florida/Miami-Dade and Broward Counties, and Texas. Mixed methamphetamine indicators (with some increasing, some decreasing, and some stable) were reported for 2013 by CEWG representatives from Maine and Phoenix. Indicators were low and stable in this reporting period in Boston, Chicago, New York City, and Philadelphia. Methamphetamine levels continued to be very low relative to other drugs in the Baltimore/Maryland/Washington, DC, area."

"Methamphetamine is a highly addictive psychostimulant with evidence of neurotoxic properties (1–3) and is consistently ranked as one of the most harmful illicit substances—both to the person using and to society (4, 5). Methamphetamine use disorder is a chronic relapsing condition increasingly associated with harms that include mental and physical illness, intimate partner violence, family disruption, health care system pressures, homelessness, crime, and mortality (6–10). At present, there are no approved medications to treat methamphetamine use disorder, despite a large body of research investigating potential pharmacological interventions (10–12). The most effective non-pharmacological evidence-based intervention for the management of methamphetamine use disorder is contingency management, a non-psychotherapy behavioral approach that most often involves monetary-based reinforcement for drug-negative urine specimens (13, 14). In practice, psychotherapy is often the standard of care given resource limitations in real world settings, including cognitive behavioral therapy and motivational interviewing. Multiple barriers to treatment exist, such as stigmatizing experiences within the health care system and existing treatment options not meeting patient needs (15). Moreover, people who use methamphetamine consistently demonstrate more challenges in treatment and recovery compared to those using other substances (16, 17). A recent systematic review estimated methamphetamine treatment drop-out rates to be 53.5% (95% CI: 16.5, 87.0), the highest compared to other substances, including the psychostimulant cocaine, with the average drop-out across all substances being 30.4% (95% CI: 27.2-33.8) (18)."

"Nightwork—meaning all jobs that are executed during nighttime—increased as cities became connected to electricity in the early twentieth century, and as economies became more connected globally through the internet. In the current 'gig economy' — dominated by those jobs in which people are paid by the task, rather than receiving a fixed salary — work never stops. Part of this 'performance' has to do with adapting to the different temporal demands of the labor market—in other words, the management of sleep and wakefulness. As Crary (2013, p. 17) notes, our modern economies '[undermine] distinction between day and night, between light and dark, and between action and repose … the planet becomes re-imagined as a non-stop work site or an always open shopping mall of infinite choices, tasks, selections, and digression.'

"But working at night is not necessarily good for us. Melatonin, the hormone involved in the regulation of our biological clock, is released when we are exposed to daylight. Our bodies follow circadian rhythms of approximately 24-hour cycles, and as Kamps warned me, these rhythms have an impact on our mental and metabolic health (Roenneberg et al. 2003).

"Humans have a long history using chemicals to tinker with our circadian rhythms, with caffeine being the most ubiquitous substance used to stay awake, one that is accepted globally as beneficial despite its addictive properties. Historians trace the use of coffee back to the fifth century, in the Sufi monasteries of Mocha, now known as Yemen (Weinberg and Bealer 2001). Caffeine stimulates the central nervous system by blocking the action of adenosine (which causes drowsiness) on its receptors. The popular food writer Pollan (2020), in a recent analysis of caffeine, suggests that without this substance the industrial revolution wouldn’t have happened. Studies in sports medicine attest to caffeine’s positive effects in adults, including increased endurance and strength, improved reaction time, and delayed fatigue (Graham 2001; Sökmen et al. 2008). Adverse effects of caffeine, if taken in high amounts, include disturbed sleep, increased blood pressure, and physical addiction. Caffeine is considered safe to ingest up to about 150 mg per day (or two cups of coffee).

"In addition to caffeine, those working at night often resort to cocaine and amphetamines for stamina and to stay awake. The use of cocaine for endurance goes back to the Incas in Peru who for thousands of years have chewed coca leaves for this purpose. The alkaloid cocaine, derived from the plant, was only isolated in the mid-nineteenth century. Amphetamines were discovered shortly thereafter by chemists. In On Speed Rasmussen (2008) traces the history of this category of drugs, showing how early twentieth-century pharmacies in the United States sold invigorating tonics containing cocaine and nasal decongestants containing amphetamines. Its first major use was during World War II, when soldiers used it to boost their performance and alertness, and to suppress appetite (see also Braswell 2005; Rawson et al. 2006). In Japan, it was given to soldiers before they performed their 'kamikaze' suicide bombing missions; in England, 73 million amphetamine tablets were made available to pilots so they would not fall asleep (Braswell 2005). Three years after the war, in 1948, the Japanese Ministry of Health prohibited the production of both tablet and powder form of methamphetamine. Similar moves were made in the United States but, interestingly, the medical establishment continued to defend its legal status and deny its addictive potential. It was only when its use grew further, and more evidence about its addictive potential came to light, that the United States finally passed the 1974 Drug Control Act (Rawson et al. 2006)."

"In Brooklyn, Mandler (2016, 2018) found that the most common chemicals used to stay awake during the night shift were energy drinks, cocaine, and the ADHD drug Adderall. Cocaine helped his interlocutors stay alert during shifts, while also engaging in the party, which was a challenge."

"Methamphetamine questions were introduced in 1999 because of rising concern about use of this drug; but a decline in use has been observed among all five populations in the years since then, although young adults did not show declines until 2005. In 2007 this decline continued in all five populations, and was significant in grades 8 and 12, with little further change thereafter, except for a jump up among 12th graders in 2011 and among young adults in 2012. In 2012 use in all five populations was at very low rates of annual prevalence — particularly among college students (0.2%). These substantial declines occurred during a period in which there were many stories in the media suggesting that methamphetamine use was a growing problem — an example of the importance of having accurate epidemiological data available against which to test conventional wisdom."

"Measures on the use of crystal methamphetamine (ice) (a crystallized form of methamphetamine that can be smoked, much like crack) have been included in MTF [Monitoring The Future] since 1990. The use of crystal methamphetamine increased between the early and late 1990s among the three populations asked about their use: 12th graders, college students, and young adults. However, use never reached very high levels. The estimates are less stable than usual due to the relatively small samples asked about this drug, but it appears that among 12th graders crystal methamphetamine use held fairly steady from 1999 through 2005 (when it was 2.3%); since then it has declined to 0.8% in 2012. Use rose somewhat among college students and other young adults until 2005, before dropping substantially since then. After their peak levels were reached in 2005, college students and young adults showed substantial drops in annual prevalence to 0.6% by 2012."

"Primarily on the basis of self-reported responses to general population surveys, a total of 34 million people aged 15–64, or 0.7 per cent of the global population, are estimated to have used amphetamines in the past year, and almost 20 million (0.4 per cent) are estimated to have used “ecstasy”-type substances. Some of those users had used both types of substances. The two most commonly used amphetamines are amphetamine and methamphetamine.

"The global estimate of amphetamines use was similar in 2010, with 33 million past year users or 0.7% of the population aged 15-64. However, these estimates have to be interpreted with caution owing to the lack of data from major consumer countries in Asia where other market indicators, such as seizures and prices, suggest an expansion over the last decade.

"Qualitative information based on perceptions of trends reported by national experts to UNODC shows a continued increase both in terms of the use of amphetamines and the number of people in treatment for amphetamines over the past decade.²⁵ However, data for 2020 show that this increasing trend has paused and that the number of people in treatment for amphetamines may have decreased, consistent with an overall decrease in treatment as a result of the COVID-19 pandemic.^e Trends derived from such qualitative information are consistent with the available supply indicators, such as prices and seizures, which indicate continued global expansion of the market for amphetamines. Qualitative information of this type suffers from methodological limitations, but it has an advantage in that it takes into consideration small-scale studies and expert observations regarding countries where drug use surveys are not regularly implemented.

"Qualitative information on trends in the use of “ecstasy” was not reported by countries before the implementation by UNODC of its new data collection tool (the updated annual report questionnaire, which came into use in 2020), thus qualitative reports of trends in “ecstasy” use are limited to the period 2019– 2020. These reports suggest a moderate increase globally. At the same time, studies from countries where “ecstasy” is used in recreational settings suggest that the use of “ecstasy” declined more than any other drug during the pandemic in those countries.^f"

"In 2018, 205,000 people aged 12 or older initiated methamphetamine use in the past year (Figures 26 and 30), which averages to about 560 people per day who initiated methamphetamine use (Table A.3A). The number of past year initiates in 2018 for methamphetamine use was similar to the numbers in 2015 to 2017. In 2018, an estimated 31,000 adolescents aged 12 to 17 used methamphetamine for the first time in the past year (Figure 30). The number of adolescents in 2018 who were methamphetamine initiates was similar to the numbers in 2015 to 2017.

"Also in 2018, an estimated 68,000 young adults aged 18 to 25 and 106,000 adults aged 26 or older initiated methamphetamine use in the past year (Figure 30). The number of young adults who initiated methamphetamine use averages to about 190 young adult initiates per day (Table A.3A). Among young adults and adults aged 26 or older, the numbers of methamphetamine initiates in 2018 were similar to the corresponding numbers in 2015 to 2017."

Amphetamine-Type Stimulants

"In 2014, the estimated 1.6 million people aged 12 or older who were current nonmedical users of stimulants included 569,000 people who were current methamphetamine users (Figure 8). Thus, almost two thirds of current nonmedical users of stimulants in 2014 who were aged 12 or older reported current nonmedical use of prescription stimulants but not methamphetamine.
"These numbers of nonmedical users of stimulants and methamphetamine users represent 0.6 percent of the population aged 12 or older who were current nonmedical users of stimulants (Figure 9) and 0.2 percent who were current users of methamphetamine in 2014 (Figure 10). The percentage of the population aged 12 or older in 2014 who were current nonmedical users of stimulants was higher than the percentages for most years between 2005 and 2012. Meanwhile, the percentage of the population aged 12 or older in 2014 who were current users of methamphetamine was similar to the percentages for most years between 2002 and 2013."

"A more recent study using a demand-side approach estimates that the annual retail value of the U.S. methamphetamine market is between $3 and $8 billion, with a best guess of $5 billion.¹² The margin of error is large because the footprint of methamphetamine use does not match the footprint of the data collection system. Methamphetamine use in the United States is concentrated in certain regions, and it is not primarily an urban drug, whereas data collection systems are centered in urban areas. Moreover, because there have been dramatic shifts in methamphetamine consumption and production during the past decade, estimates are highly dependent on the year analyzed. While there are considerable uncertainties, the amphetamine market is clearly smaller than the cocaine and cannabis markets in North America, smaller than the cocaine market in South America, and potentially smaller than markets for other drugs elsewhere in the hemisphere as well. However, data are not available to provide a detailed analysis for all regions."

"In fact, according to National Drug Threat Survey (NDTS) 2006 data, 38.8 percent of state and local law enforcement officials nationwide report methamphetamine as the greatest drug threat to their areas, a higher percentage than that for any other drug."

"Law enforcement pressure and strong precursor chemical sales restrictions have achieved marked success in decreasing domestic methamphetamine production. Mexican DTOs, however, have exploited the vacuum created by rapidly expanding their control over methamphetamine distribution -- even to eastern states -- as users and distributors who previously produced the drug have sought new, consistent sources. These Mexican methamphetamine distribution groups (supported by increased methamphetamine production in Mexico) are often more difficult for local law enforcement agencies to identify, investigate, and dismantle because they typically are much more organized and experienced than local independent producers and distributors. Moreover, these Mexican criminal groups typically produce and distribute ice methamphetamine that usually is smoked, potentially resulting in a more rapid onset of addiction to the drug."

"During Vietnam both the Air Force and Navy made amphetamines available to aviators. Intermittently since Vietnam up through Desert Storm the Air Force has used both amphetamines and sedatives in selected aircraft for specific missions."

"A paranoid psychosis may result from long-term use; rarely, the psychosis is precipitated by a single high dose or by repeated moderate doses. Typical features include delusions of persecution, ideas of reference (notions that everyday occurrences have special meaning or significance personally meant for or directed to the patient), and feelings of omnipotence. Some users experience a prolonged depression, during which suicide is possible. Recovery from even prolonged amphetamine psychosis is usual but is slow. The more florid symptoms fade within a few days or weeks, but some confusion, memory loss, and delusional ideas commonly persist for months."

"Preliminary 2008 availability and seizure data indicate a strengthening in domestic methamphetamine availability and domestic methamphetamine production, and an increase in the flow of methamphetamine into the United States from Mexico—most likely attributable to the efforts of methamphetamine producers in both countries to reestablish the methamphetamine supply chain in the face of disruptions and shortages that began occurring in early 2007. Throughout 2007 methamphetamine availability decreased in U.S. drug markets, causing instability in the methamphetamine supply chain. Prior to 2007, U.S. drug markets relied on the strong flow of methamphetamine produced in Mexico, a supply system established in 2005 and strengthened in 2006. However, ephedrine and pseudoephedrine restrictions in Mexico resulted in a decrease in methamphetamine production in Mexico and reduced the flow of the drug from Mexico to the United States in 2007 and from January through June 2008."

"Transmission of HIV and hepatitis B and C can be consequences of methamphetamine abuse. The intoxicating effects of methamphetamine, regardless of how it is taken, can also alter judgment and inhibition and lead people to engage in unsafe behaviors, including risky sexual behavior. Among abusers who inject the drug, HIV and other infectious diseases can be spread through contaminated needles, syringes, and other injection equipment that is used by more than one person."

"Some amphetamines, including dextroamphetamine, methamphetamine, and the related methylphenidate, are widely used medically to treat attention-deficit hyperactivity disorder, obesity, and narcolepsy, thus creating a supply subject to diversion for illicit use. Methamphetamine is easily manufactured illicitly."

"Following Desert Storm an anonymous survey of deployed fighter pilots was completed. 464 surveys were returned (43%). For Desert Storm: 57% used stimulants at some time (17% routinely, 58% occasionally, 25% only once). Within individual units, usage varied from 3% to 96%, with higher usage in units tasked for sustained combat patrol (CAP) missions. Sixty one percent of those who used stimulants reported them essential to mission accomplishment."

Effects

"Amphetamines enhance release of catecholamines, increasing intrasynaptic levels of norepinephrine, dopamine, and serotonin. The resulting marked ?- and ?-receptor stimulation and general CNS excitation account for the “desired” effects of increased alertness, euphoria, and anorexia, as well as the adverse effects of delirium, hypertension, hyperthermia, and seizures. Effects of amphetamines are similar, varying in intensity and duration of psychoactive effects; MDMA and its relatives have more mood-enhancing properties, perhaps related to a greater effect on serotonin. Amphetamines can be taken orally as pills or capsules, nasally by inhaling or smoking, or by injection.
"Chronic effects: Repeated use of amphetamines induces dependence. Tolerance develops slowly, but amounts several 100-fold greater than the amount originally used may eventually be ingested or injected. Tolerance to various effects develops unequally. Tachycardia and increased alertness diminish, but hallucinations and delusions may occur.
"Amphetamines typically cause erectile dysfunction in men but enhance sexual desire. Use is associated with unsafe sex practices, and users are at increased risk of sexually transmitted infections, including HIV infection. Amphetamine abusers are prone to injury because the drug produces excitation and grandiosity followed by excess fatigue and sleepiness."

"Many psychologic effects of amphetamines are similar to those of cocaine; they include increased alertness and concentration, euphoria, and feelings of well-being and grandiosity. Palpitations, tremor, diaphoresis, and mydriasis may also occur during intoxication.
"Binges (perhaps over several days) lead to an exhaustion syndrome, involving intense fatigue and need for sleep after the stimulation phase.

"Amphetamines are CNS stimulants and are used both medicinally and as drugs of abuse. Amphetamines are generally taken recreationally and to enhance performance (e.g., truck drivers staying awake). Ecstasy falls within this category, and as a methylated amphetamine derivative it also has hallucinogenic properties. Amphetamines have been associated with crash occurrence and could logically be associated with driving impairment both in the stimulation and withdrawal stages; in the latter case especially as the drug interacts with fatigue."

" A paranoid psychosis may result from long-term use; rarely, the psychosis is precipitated by a single high dose or by repeated moderate doses. Typical features include delusions of persecution, ideas of reference (notions that everyday occurrences have special meaning or significance personally meant for or directed to the patient), and feelings of omnipotence. Some users experience a prolonged depression, during which suicide is possible. Recovery from even prolonged amphetamine psychosis is usual but is slow. The more florid symptoms fade within a few days or weeks, but some confusion, memory loss, and delusional ideas commonly persist for months.
"Users have a high rate of severe tooth decay affecting multiple teeth; causes include decreased salivation, acidic combustion products, and poor oral hygiene."

"Although no stereotypical withdrawal syndrome occurs when amphetamines are stopped, EEG changes occur, considered by some experts to fulfill the physical criteria for dependence. Abruptly stopping use may uncover or exacerbate underlying depression or precipitate a serious depressive reaction. Withdrawal is often followed by 2 or 3 days of intense fatigue or sleepiness and depression."

"Methamphetamine increases the release and blocks the reuptake of the brain chemical (or neurotransmitter) dopamine, leading to high levels of the chemical in the brain, a common mechanism of action for most drugs of abuse. Dopamine is involved in reward, motivation, the experience of pleasure, and motor function. Methamphetamine’s ability to rapidly release dopamine in reward regions of the brain produces the intense euphoria, or 'rush,' that many users feel after snorting, smoking, or injecting the drug."

"Further contributing to the threat posed by the trafficking and abuse of methamphetamine, some chemicals used to produce methamphetamine are flammable, and improper storage, use, or disposal of such chemicals often leads to clandestine laboratory fires and explosions. National Clandestine Laboratory Seizure System (NCLSS) 2003 data show that there were 529 reported methamphetamine laboratory fires or explosions nationwide, a slight decrease from 654 reported fires or explosions in 2002."

"Toxic chemicals used to produce methamphetamine often are discarded in rivers, fields, and forests, causing environmental damage that results in high cleanup costs. For example, DEA's annual cost for cleanup of clandestine laboratories (almost entirely methamphetamine laboratories) in the United States has increased steadily from FY1995 ($2 million), to FY1999 ($12.2 million), to FY 2002 ($23.8 million). Moreover, the Los Angeles County Regional Criminal Information Clearinghouse, a component of the Los Angeles HIDTA, reports that in 2002 methamphetamine laboratory cleanup costs in the combined Central Valley and Los Angeles HIDTA areas alone reached $3,909,809. Statewide, California spent $4,974,517 to remediate methamphetamine laboratories and dumpsites in 2002."

"Illicit production of methamphetamine may involve hazardous materials that are toxic, corrosive, flammable, or explosive. Such materials include anhydrous ammonia, sulfuric acid, hydrochloric acid, red phosphorous, lithium metal, sodium metal, iodine, and toluene. Upon discovery, the hazardous materials contained at clandestine drug laboratory locations are classified and managed as hazardous wastes."

"The incidence of clandestine drug laboratories has grown dramatically in the past 10 years. For example, in Fiscal Year 1992, the DEA's National Clandestine Laboratory Cleanup Program funded approximately 400 removal actions and by fiscal year 2001, the DEA Program funded more than 6,400 removal actions."