Significant public health problems associated with methamphetamine (MA) production and use in the United States have emerged over the past 25 years. Although the popular press (Newsweek, Aug 8, 2008), has called MA “America’s Most Dangerous Drug” there has been considerable controversy about the size of the problem. Epidemiological indicators have given a mixed picture. National surveys of the adult U.S. population and school-based populations have consistently been used to support the position that MA use is a relatively minor concern (NSDUH, 2006; Johnston & O’Malley, 2007). However, many other data sources, including law-enforcement groups, welfare agencies, substance abuse treatment program admission data, data on criminal justice populations, and state/county executives indicate that MA is a very significant public health problem for many communities throughout much of the country (NDIC, 2007b; NACO, 2005, 2006; NIDA CEWG, 2007). In this article, we describe (1) the historical underpinnings of the MA problem, (2) trends in the epidemiological nature of the MA problem, (3) key subgroups at risk for MA problems, (4) the health and social factors associated with MA use, (5) interventions available for addressing the MA problem, and (5) lessons learned related to the MA problem.

Psychotic symptoms and syndromes are frequently experienced among individuals who use methamphetamine, with recent estimates of up to approximately 40% of users affected. Though transient in a large proportion of users, acute symptoms can include agitation, violence, and delusions, and may require management in an inpatient psychiatric or other crisis intervention setting. In a subset of individuals, psychosis can recur and persist and may be difficult to distinguish from a primary psychotic disorder such as schizophrenia. Differential diagnosis of primary versus substance-induced psychotic disorders among methamphetamine users is challenging; nevertheless, with careful assessment of the temporal relationship of symptoms to methamphetamine use, aided by state-of-the art psychodiagnostic assessment instruments and use of objective indicators of recent substance use (i.e., urine toxicology assays), coupled with collateral clinical data gathered from the family or others close to the individual, diagnostic accuracy can be optimized and the individual can be appropriately matched to a plan of treatment. The pharmacological treatment of acute methamphetamine-induced psychosis may include the use of antipsychotic medications as well as benzodiazepines, although symptoms may resolve without pharmacological treatment if the user is able to achieve a period of abstinence from methamphetamine. Importantly, psychosocial treatment for methamphetamine dependence has a strong evidence base and is the optimal first-line treatment approach to reducing rates of psychosis among individuals who use methamphetamines. Prevention of methamphetamine relapse is the most direct means of preventing recurrence of psychotic symptoms and syndromes. Long-term management of individuals who present with recurrent and persistent psychosis, even in the absence of methamphetamine use, may include both behavioral treatment to prevent resumption of methamphetamine use and pharmacological treatment targeting psychotic symptoms. In addition, treatment of co-occurring psychiatric disorders including depression and anxiety is important as a means of preventing relapse to methamphetamine use, which is often triggered by associated symptoms.

Background Methamphetamine (MA) use has been linked anecdotally to rampant dental disease. The authors sought to determine the relative prevalence of dental comorbidities in MA users, verify whether MA users have more quantifiable dental disease and report having more dental problems than nonusers and establish the influence of mode of MA administration on oral health outcomes. Methods Participating physicians provided comprehensive medical and oral assessments for adults dependent on MA (n = 301). Trained interviewers collected patients' self-reports regarding oral health and substance-use behaviors. The authors used propensity score matching to create a matched comparison group of nonusers from participants in the the Third National Health and Nutrition Examination Survey (NHANES III). Results Dental or oral disease was one of the most prevalent (41.3 percent) medical cormorbidities in MA users who otherwise were generally healthy. On average, MA users had significantly more missing teeth than did matched NHANES III control participants (4.58 versus 1.96, P < .001) and were more likely to report having oral health problems (P < .001). Significant subsets of MA users expressed concerns with their dental appearance (28.6 percent), problems with broken or loose teeth (23.3 percent) and tooth grinding (bruxism) or erosion (22.3 percent). The intravenous use of MA was significantly more likely to be associated with missing teeth than was smoking MA (odds ratio = 2.47; 95 percent confidence interval = 1.3-4.8). Conclusions Overt dental disease is one of the key distinguishing comorbidities in MA users. MA users have demonstrably higher rates of dental disease and report long-term unmet oral health needs. Contrary to common perception, users who smoke or inhale MA have lower rates of dental disease than do those who inject the drug. Many MA users are concerned with the cosmetic aspects of their dental disease, and these concerns could be used as behavioral triggers for targeted interventions. Clinical Implications Dental disease may provide a temporally stable MA-specific medical marker with discriminant utility in identifying MA users. Dentists can play a crucial role in the early detection of MA use and participate in the collaborative care of MA users.

Issues Prescription opioid misuse in the USA has increased over threefold since 1990 to epidemic proportions, with substantial increases in prescription opioid use also reported in other countries, such as Australia and New Zealand. The broad availability of prescription pain medications, coupled with public misconceptions about their safety and addictive potential, have contributed to the recent surge in non-medical use of prescription opioids and corresponding increases in treatment admissions for problems related to opioid misuse. Given competing pressures faced by physicians to both diagnose and treat pain syndromes and identify individuals at risk for addictive disorders, the use of opioids in the treatment of pain poses a significant clinical challenge. Approach This paper reviews the interaction between pain and opioid addiction with a focus on clinical management issues, including risk factors for opioid dependence in patients with chronic pain and the use of assessment tools to identify and monitor at-risk individuals. Treatment options for opioid dependence and pain are reviewed, including the use of the partial μ agonist buprenorphine in the management of concurrent pain and opioid addiction. Implications Physicians should strive to find a reasonable balance between minimising potential adverse effects of opioid medications without diminishing legitimate access to opioids for analgesia. Conclusions The article discusses the need to identify methods for minimising risks and negative consequences associated with opioid analgesics and poses research directions, including the development of abuse-deterrent opioid formulations, genetic risk factors for opioid dependence and opioid-induced hyperalgesia as a potential target for medication therapy.

Background Cannabis use disorder (CUD) is a prevalent and impairing condition, and established psychosocial treatments convey limited efficacy. In light of recent findings supporting the efficacy of N-acetylcysteine (NAC) for CUD in adolescents, the objective of this trial was to evaluate its efficacy in adults. Methods In a 12-week double-blind randomized placebo-controlled trial, treatment-seeking adults ages 18–50 with CUD (N=302), enrolled across six National Drug Abuse Treatment Clinical Trials Network-affiliated clinical sites, were randomized in a 1:1 ratio to a 12-week course of NAC 1200 mg (n=153) or placebo (n=149) twice daily. All participants received contingency management (CM) and medical management. The primary efficacy measure was the odds of negative urine cannabinoid tests during treatment, compared between NAC and placebo participants. Results There was not statistically significant evidence that the NAC and placebo groups differed in cannabis abstinence (odds ratio = 1.00, 95% confidence interval 0.63 – 1.59; p=0.984). Overall, 22.3% of urine cannabinoid tests in the NAC group were negative, compared with 22.4% in the placebo group. Many participants were medication non-adherent; exploratory analysis within medication-adherent subgroups revealed no significant differential abstinence outcomes by treatment group. Conclusions In contrast with prior findings in adolescents, there is no evidence that NAC 1200 mg twice daily plus CM is differentially efficacious for CUD in adults when compared to placebo plus CM. This discrepant finding between adolescents and adults with CUD may have been influenced by differences in development, cannabis use profiles, responses to embedded behavioral treatment, medication adherence, and other factors.

Objectives Physical exercise has been shown to benefit diverse medical and behavioral conditions. This study assesses the feasibility and efficacy of an 8-week endurance and resistance training program on fitness measures in individuals undergoing residential treatment for methamphetamine (MA) dependence. Methods A total of 39 MA-dependent individuals were randomized to 3 days/week of exercise training (ET, n=15) or health education without training (EA, n=14) over 8 weeks. Aerobic performance (VO2max) was measured by indirect calorimetry, body composition by skinfolds, muscle strength by 1-repetition maximum (1-RM) and endurance at 85% of 1-RM for both leg press (LP) and chest press (CP). Results A total of 29 individuals completed the study for a 74% adherence rate. Baseline characteristics (mean±SD) were balanced between groups: age 31±7 years; height=1.74±0.07 m; weight 82.0±15.0 kg. The ET group significantly improved VO2max by 0.63±0.22 L/min (+21%), LP strength by 24.4±5.6 kg (+40%) and CP strength by 20.6±5.7 kg (+49%). The ET group increased LP and CP endurance by 120% and 96%, respectively and showed significant reductions in body weight of 1.7±2.4 kg (−2%), % body fat of 2.8±1.3% (−15%) and fat weight 2.8±1.8 kg (−18%). All changes were significant (P<0.001) for ET, and no changes were seen for the EA group. Conclusions Individuals recovering from methamphetamine dependence showed substantial improvements in aerobic exercise performance, muscle strength and endurance, and body composition with exercise training. These findings demonstrate the feasibility of an exercise training intervention in these participants and also show excellent responsiveness to the exercise stimulus resulting in physiological changes that might enhance recovery from drug dependency.

Objectives Elevated mortality has been observed among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system. Methods Mortality data were linked with electronic health records of 2,576 OUD patients cared for in a large university health system from 2006–2014. Results There were 465 deaths confirmed (18.1% of the study participants), corresponding to a crude mortality rate of 48.6 per 1000 person-years and standardized mortality ratio of 10.3 (95% CI, 9.4–11.3). Drug overdose and disorder (19.8%), cardiovascular diseases (17.4%), cancer (16.8%), and infectious diseases (13.5%, including 12% hepatitis C virus [HCV]) were the leading causes of death. HCV (HR: 1.99; 95% CI, 1.62– 2.46) and alcohol use disorder (HR: 1.27; 95% CI, 1.05–1.55) were two clinically important indicators of overall mortality risk. Tobacco use disorder (AHR: 2.58; 95% CI, 1.60–4.17) was associated with increased risk of cardiovascular death, HCV infection (AHR: 2.55; 95% CI, 1.52–4.26) with cancer mortality risk, and HCV (AHR: 1.92; 95%CI, 1.03–3.60) and alcohol use disorder (AHR: 5.44; 95% CI, 2.95–10.05) with liver-related mortality risk. Conclusions Patients with OUD in a general healthcare system demonstrated alarmingly high morbidity and mortality, which challenges health care systems to find innovative ways to identify and treat patients with substance use disorder.

Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BP ND )) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n = 10) or one that received equal-time health education training (n = 9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [ 18 F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BP ND . At baseline, striatal D2/D3 BP ND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BP ND , whereas those in the education group did not. There were no changes in D2/D3 BP ND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.