Psychedelic Therapy: A Primer for Primary Care Clinicians-3,4-Methylenedioxy-methamphetamine (MDMA).

BACKGROUND: After becoming notorious for its use as a party drug in the 1980s, 3,4-methylenedioxy-methampetamine (MDMA), also known by its street names "molly" and "ecstasy," has emerged as a powerful treatment for post-traumatic stress disorder (PTSD). AREAS OF UNCERTAINTY: There are extensive data about the risk profile of MDMA. However, the literature is significantly biased. Animal models demonstrating neurotoxic or adverse effects used doses well beyond the range that would be expected in humans (up to 40 mg/kg in rats compared with roughly 1-2 mg/kg in humans). Furthermore, human samples often comprise recreational users who took other substances in addition to MDMA, in uncontrolled settings. THERAPEUTIC ADVANCES: Phase III clinical trials led by the Multidisciplinary Association for Psychedelic Studies (MAPS) have shown that MDMA-assisted psychotherapy has an effect size of d = 0.7-0.91, up to 2-3 times higher than the effect sizes of existing antidepressant treatments. 67%-71% of patients who undergo MDMA-assisted psychotherapy no longer meet the diagnostic criteria for PTSD within 18 weeks. We also describe other promising applications of MDMA-assisted psychotherapy for treating alcohol use disorder, social anxiety, and other psychiatric conditions. LIMITATIONS: Thus far, almost all clinical trials on MDMA have been sponsored by a single organization, MAPS. More work is needed to determine whether MDMA-assisted therapy is more effective than existing nonpharmacological treatments such as cognitive behavioral therapy. CONCLUSIONS: Phase III trials suggest that MDMA is superior to antidepressant medications for treating PTSD. Now that MAPS has officially requested the Food and Drug Administration to approve MDMA as a treatment for PTSD, legal MDMA-assisted therapy may become available as soon as 2024.

Rural communities face more than an opioid crisis: Reimagining funding assistance to address polysubstance use, associated health problems, and limited rural service capacity.

PURPOSE: Rural communities in the United States face unique challenges related to the opioid epidemic. This paper explores the substances and substance-related health problems that pose the greatest concern to rural communities that received funding to address the opioid epidemic and examines their reported capacity to address these challenges. METHODS: This paper analyzed data collected as part of quarterly progress reporting from multisector consortiums across 2 cohorts of grantees funded to reduce the morbidity and mortality of opioids. Consortium project directors ranked the top 3 issues in their community in each of the following categories: (1) drugs of concern; (2) drugs with the least capacity to address; (3) related problem areas of concern (eg, neonatal abstinence syndrome [NAS]); and (4) related problem areas with the least capacity to address. FINDINGS: Methamphetamines, fentanyl, and alcohol were the substances rated as most problematic in rural communities funded to address the opioid epidemic across all reporting periods. Over 40% of respondents ranked methamphetamine as a top concern and the substance they had the least capacity to address. This was nearly double the percentage of the next highest-ranked substance (fentanyl). Overdoses, NAS, and viral hepatitis constituted the top-ranking related concerns, with limited capacity to address them. CONCLUSIONS: Multiple drug and concomitant problems coalesced on rural communities during the opioid epidemic. Funding communities to address substance use disorders and related problems of concern, rather than targeting funding toward a specific type of drug, may result in better health outcomes throughout the entire community.

Associations between Circumstances Surrounding Overdose and Underlying Classes of Polysubstance Overdose Deaths.

BACKGROUND: The overdose crisis is worsening, with polysubstance overdose deaths involving psychostimulants increasing in the U.S. Substance-specific prevention and intervention activities may not be as effective for polysubstance use, so we sought to classify substances used among overdose decedents to identify unique factors related to these classes. METHODS: We used data from the Nevada State Unintentional Drug Overdose Reporting System, Jan 2019-Jun 2021, which comes from death certificates, coroner/medical examiner reports, and postmortem toxicology. Latent class analysis, multinomial logistic regression, and Chi-squared tests determined underlying drug use classes, differences in characteristics and circumstances surrounding overdose, and assessed relationships between circumstances and drug use classes. RESULTS: We identified four latent classes: (1) prescription drugs (19.1%), (2) predominately methamphetamine (31.4%), (3) multi-drug (28.9%), and (4) opioid and stimulant (20.6%). Compared to other classes, the prescription drug class had a higher percentage of female decedents, from rural counties, with mental health diagnoses, who died at home. The predominately methamphetamine class had a higher percentage of decedents experiencing homelessness. The multi-drug use class had higher percentage of younger and Hispanic decedents. Those in the opioid and stimulant class had higher odds of being recently released from an institutional setting, compared to the multi drug class. CONCLUSIONS: These underlying classes were associated with several characteristics and circumstances that can prove useful for prevention, treatment, and harm reduction agencies when designing programs and interventions to target specific groups of people at-risk for drug overdose.

Virological suppression among gay, bisexual, and other men who have sex with men living with HIV in Vancouver, Canada: A longitudinal cohort study from 2012-2017.

INTRODUCTION: In 2010, British Columbia (BC) implemented HIV Treatment as Prevention (TasP) as policy. We examined trends in virologic suppression and determinants of significant viremia among a prospective biobehavioural cohort of men who have sex with men (gbMSM) in Vancouver from 2012-2017. METHODS: Respondent-driven sampling was used to recruit sexually active gbMSM (≥16 years) who completed biannual study visits with a computer-assisted self-interview and clinical CD4 and viral load (VL) testing. We linked participant data with the BC HIV Drug Treatment Program to obtain antiretroviral dispensing and VL data. We conducted a trend analysis of VL suppression using univariable generalized estimating equation (GEE) multi-level modelling and multivariable GEE to identify factors associated with episodes of VL ≥200 copies/mL. RESULTS: Of 774 participants, 223 were living with HIV at baseline and 16 were diagnosed during follow-up (n = 239). We observed a significant trend towards reduced levels of unsuppressed VL (>200 copies/mL) from 22% (07/2012-12/2012) to 12% (07/2016-12/2016) (OR:0.87; 95%CI:0.83-0.91 for each 6-month period). Among those with at least one follow-up visit, (n = 178, median follow-up = 3.2 years, median age = 46.9 years), younger age (aOR:0.97; 95%CI:0.94-0.99, per year), ecstasy use (aOR:1.69; 95%CI:1.13-2.53), crystal methamphetamine use (aOR:1.71; 95%CI:1.18-2.48), seeking sex via websites (aOR:1.46; 95%CI:1.01-2.12), and lower HIV treatment optimism (aOR:0.94; 95%CI:0.90-0.97) were associated with episodes of elevated viremia. CONCLUSIONS: During a period when TasP policy was actively promoted, we observed a significant trend towards reduced levels of unsuppressed VL. Continued efforts should promote HIV treatment optimism and engagement, especially among younger gbMSM and those who use ecstasy and crystal methamphetamine.

Treatment of Malignant Hyperthermia During Interfacility Transport of a Patient With Methamphetamine Toxicity.

Malignant hyperthermia (MH) is a rare disorder that leads to a hypermetabolic response; if unrecognized, it can quickly lead to serious morbidity and mortality. It is imperative that critical care transport providers are able to recognize and initiate treatment for MH. A 33-year-old man presented to the emergency department with seizures and altered mental status after ingesting methamphetamine. The patient was intubated in the emergency department with succinylcholine and propofol. After intubation, the patient became tetanic, hyperthermic, and hypercarbic. Given the concern for MH, the patient was treated with dantrolene and transported by helicopter air ambulance to the affiliated quaternary care center where he progressed to multiorgan failure and died. MH is a genetic disorder that manifests after exposure to certain stimuli, most notably inhaled anesthetics and succinylcholine. The hypermetabolic response is triggered by unregulated release of intracellular calcium secondary to a dysfunctional calcium channel. MH is often diagnosed clinically. Early clinical manifestations of MH include an increase in end-tidal carbon dioxide, tachycardia, muscle rigidity, and hyperthermia. For prehospital clinicians, the most likely offending agent is succinylcholine. The pharmacologic treatment of MH is dantrolene. Prompt recognition and treatment of MH can decrease morbidity and mortality.

Logical fallacies and misinterpretations that hinder progress in translational addiction neuroscience.

Substance use disorders (SUDs) are heterogeneous and complex, making the development of translationally predictive rodent and nonhuman primate models to uncover their neurobehavioral underpinnings difficult. Neuroscience-focused outcomes have become highly prevalent, and with this, the notion that SUDs are disorders of the brain embraced as a dominant theoretical orientation to understand SUD etiology and treatment. These efforts, however, have led to few efficacious pharmacotherapies, and in some cases (as with cocaine or methamphetamine), no pharmacotherapies have translated from preclinical models for clinical use. In this theoretical commentary, we first describe the development of animal models of substance use behaviors from a historical perspective. We then define and discuss three logical fallacies including 1) circular explanation, 2) affirming the consequent, and 3) reification that can apply to developed models. We then provide three case examples in which conceptual or logical issues exist in common methods (i.e., behavioral economic demand, escalation, and reinstatement). Alternative strategies to refocus behavioral models are suggested for the field to better bridge the translational divide between animal models, the clinical condition of SUDs, and current and future regulatory pathways for intervention development.

Exploring the Interactions between Non-Medical Methamphetamine Use and Prescribed Buprenorphine or Naltrexone in Opioid Use Disorder Treatment Retention.

OBJECTIVES: Our objectives were to examine the impact of methamphetamine use on opioid use disorder (OUD) treatment retention in patients prescribed either buprenorphine/buprenorphine-naloxone (BUP-NX) or naltrexone/extended-release naltrexone (XR-NTX), while also exploring the role of other risk factors that may modify the impact of methamphetamine use. METHODS: We conducted an exploratory retrospective study examining OUD treatment retention in 127 patients in Ohio (USA). Patients were prescribed either BUP-NX or naltrexone/XR-NTX. Cox proportional hazard regression was used to compare time to dropout of treatment between patients positive and negative on screening for methamphetamines at intake, estimate the association between other risk factors and time to dropout, and test interactions between risk factors and methamphetamine status. RESULTS: Among patients prescribed naltrexone/XR-NTX, those positive for methamphetamines had almost three times the risk of treatment dropout (AHR = 2.89, 95% CI =1.11, 7.07), significantly greater (interaction p = .039) than the methamphetamine effect among those prescribed BUP-NX (AHR = 0.94, 95% CI = 0.51, 1.65). Early in treatment, being prescribed BUP-NX was strongly associated with a greater risk of treatment dropout (at baseline: AHR = 2.90, 95% CI = 1.33, 7.15), regardless of baseline methamphetamine use status. However, this effect decreased with time and shifted to greater risk of dropout among those prescribed naltrexone/XR-NTX (non-proportional hazard; interaction with time AHR = 0.66, 95% CI = 0.49, 0.86), with the shift occurring sooner among those positive for methamphetamine at baseline. CONCLUSIONS: Additional support should be provided to patients who use methamphetamines prior to starting OUD treatment.

"It's Crazy What Meth Can Help You Do": Lay Beliefs, Practices, and Experiences of Using Methamphetamine to Self-Treat Symptoms of Opioid Withdrawal.

BACKGROUND: Across the U.S., methamphetamine use is expanding among people who use illicit opioids (PWUIO). Motives for methamphetamine use must be contextualized within the experiences of PWUIO, who may use methamphetamine not only to achieve euphoria, but also as a tactic of self-management. The overall aim of this study is to contextualize lay beliefs, practices, and experiences of methamphetamine use as a form of self-treatment of symptoms related to chronic opioid use among PWUIO in the Dayton Metro Area of Southwest Ohio, an epicenter of the ongoing opioid crisis. METHODS: This paper draws on two phases of interviews conducted with 38 individuals who use both heroin/fentanyl and methamphetamine. This paper primarily analyzes qualitative data but includes supplementary information from the structured interview component. Qualitative interview sections were transcribed in their entirety and thematically analyzed. RESULTS: Participants described learning about methamphetamine as a tactic to treat opioid withdrawal symptoms through social networks and through personal experimentation. Many participants suggested that methamphetamine was helpful in relieving exhaustion, alleviating some acute physical symptoms of opioid withdrawal, and providing a psychological distraction, although some admitted that methamphetamine use could incur additional health risks. To effectively use methamphetamine as a tactic of self-treatment, participants emphasized the importance of timing and dosing. DISCUSSION: Among PWUIO in the Dayton area, methamphetamine use as a tactic to self-manage opioid withdrawal must be studied in relation to historical and evolving patterns of illicit opioid use and associated risks. More research is needed to understand the long-term health impacts of this emergent practice of polydrug use.

Meta-Analysis of Methamphetamine Modulation on Amyloid Precursor Protein through HMGB1 in Alzheimer's Disease.

The deposition of amyloid-beta (Aß) through the cleavage of amyloid-beta precursor protein (APP) is a biomarker of Alzheimer's disease (AD). This study used QIAGEN Ingenuity Pathway Analysis (IPA) to conduct meta-analysis on the molecular mechanisms by which methamphetamine (METH) impacts AD through modulating the expression of APP. All the molecules affected by METH and APP were collected from the QIAGEN Knowledge Base (QKB); 78 overlapping molecules were identified. Upon simulation of METH exposure using the "Molecule Activity Predictor" feature, eight molecules were found to be affected by METH and exhibited activation relationships on APP expression at a confidence of p = 0.000453 (Z-score = 3.51, two-tailed). Core Analysis of these eight molecules identified High Mobility Group Box protein 1 (HMGB1) signaling pathway among the top 5 canonical pathways with most overlap with the 8-molecule dataset. Simulated METH exposure increased APP expression through HMGB1 at a confidence of p < 0.00001 (Z-score = 7.64, two-tailed). HMGB1 is a pathogenic hallmark in AD progression. It not only increases the production of inflammatory mediators, but also mediates the disruption of the blood-brain barrier. Our analyses suggest the involvement of HMGB1 signaling pathway in METH-induced modulation of APP as a potential casual factor of AD.

The rising tide of methamphetamine use in elderly trauma patients.

BACKGROUND: Methamphetamine (METH) is associated with an elevated risk of injury and the outcomes in the elderly remain unclear. We analyzed METH's impact in elderly trauma patients. METHODS: Retrospective analysis (2009-2018) of trauma patients at a Level I trauma center. Elderly patients were defined as age ≥55. Substance use was identified by blood alcohol test and urine drug screen. Cox proportional hazard model was used to assess patient and injury characteristics with mortality. RESULTS: Of 15,770 patient encounters with substance use testing, 5278 (34%) were elderly. Elderly METH use quadrupled over time (2%-8%; p < 0.01). Elderly METH + patients were more likely to require surgical intervention (35% vs. 17%), mechanical ventilation (15% vs. 7%), and a longer hospitalization (6.5 vs. 3.6 days) compared with elderly substance negative. Multivariate analysis showed increasing age, ventilator use, and injury severity were associated with mortality (ps < 0.01); METH was not related to mortality. CONCLUSION: Substance use in elderly trauma patients increased significantly. METH use in elderly trauma patients is a risk factor for significantly greater resource utilization.

Associations between methamphetamine use and lack of viral suppression among a cohort of HIV-positive persons who inject drugs in Hai Phong, Vietnam.

OBJECTIVE: We assessed the association between methamphetamine use and lack of viral suppression among a cohort of HIV-seropositive persons who inject drugs (PWID) in Hai Phong, Vietnam. DESIGN: Cohort study with random effects logit modeling and mediation analysis for antiretroviral therapy (ART) adherence. METHODS: PWID were recruited from October 2016 to October 2017; HIV-seropositive PWID were enrolled in a cohort to assess HIV viral loads, changes in drug use, risk behaviors, and ART adherence during 24-month follow-up. Methamphetamine use in last 30 days was divided into three categories: 0 days (no use), 1-19 days (intermediate), and 20 or more days (heavy). Bivariate and a multivariable random effects logit models were used to assess the relationship between methamphetamine use and not being virally suppressed. We also assessed self-reported ART adherence as a mediating factor. RESULTS: A total of 645 HIV-seropositive PWID were included at baseline; 95% male, average age 40 (SD = 6.4). At baseline, methamphetamine use in last 30 days was 64% no use, 32% intermediate use, 4% heavy use. Approximately 74% of PWID reported high/complete adherence; 76% were at viral suppression. In random effects analysis, recent methamphetamine use was associated with not being virally suppressed during follow-up (adjusted odds ratio: 1.84, 95% confidence interval: 1.06, 3.17); the effect was not explained by a mediating effect of self-reported adherence to ART. CONCLUSION: Recent methamphetamine use is associated with not being virally suppressed among PWID. The results of this study indicate the need for targeted interventions for methamphetamine use with special focus on those with HIV infection.

Use of Amphetamine-Type Stimulants Among Emergency Department Patients With Untreated Opioid Use Disorder.

STUDY OBJECTIVE: Concurrent use of amphetamine-type stimulants among individuals with opioid use disorder can exacerbate social and medical harms, including overdose risk. The study evaluated rates of amphetamine-type stimulant use among patients with untreated opioid use disorder presenting at emergency departments in Baltimore, MD; New York, NY; Cincinnati, OH; and Seattle, WA. METHODS: Emergency department (ED) patients with untreated opioid use disorder (N=396) and enrolled between February 2017 and January 2019 in a multisite hybrid type III implementation science study were evaluated for concurrent amphetamine-type stimulant use. Individuals with urine tests positive for methamphetamine, amphetamine, or both were compared with amphetamine-type stimulant-negative patients. RESULTS: Overall, 38% of patients (150/396) were amphetamine-type stimulant positive; none reported receiving prescribed amphetamine or methamphetamine medications. Amphetamine-type stimulant-positive versus -negative patients were younger: mean age was 36 years (SD 10 years) versus 40 years (SD 12 years), 69% (104/150) versus 46% (114/246) were white, 65% (98/150) versus 54% (132/246) were unemployed, 67% (101/150) versus 49 (121/246) had unstable housing, 47% (71/150) versus 25% (61/245) reported an incarceration during 1 year before study admission, 60% (77/128) versus 45% (87/195) were hepatitis C positive, 79% (118/150) versus 47% (115/245) reported drug injection during 1 month before the study admission, and 42% (62/149) versus 29% (70/244) presented to the ED for an injury. Lower proportions of amphetamine-type stimulant-positive patients had cocaine-positive urine test results (33% [50/150] versus 52% [129/246]) and reported seeking treatment for substance use problems as a reason for their ED visit (10% [14/148] versus 19% [46/246]). All comparisons were statistically significant at P<.05 with the false discovery rate correction. CONCLUSION: Amphetamine-type stimulant use among ED patients with untreated opioid use disorder was associated with distinct sociodemographic, social, and health factors. Improved ED-based screening, intervention, and referral protocols for patients with opioid use disorder and amphetamine-type stimulant use are needed.

State of the art treatment options for Pakistan's opioid, alcohol and methamphetamine crisis.

The literature review was planned to discuss the extent of opioid, alcohol and methamphetamine use disorder in Pakistan, the neurobiology of opioids, alcohol and methamphetamine, the importance of medication-assisted treatment and recommendations for Pakistan. A PubMed literature search was conducted and newspaper articles were also reviewed. In per capita terms, Pakistan is reported to be the most heroin-addicted country in the world. Pakistan has a significant alcohol abuse issue as well. The newest epidemic is that of crystal methamphetamine or "ice" which is consuming the youth and urban elite. There are long-term structural and functional changes in the opioid-addicted brain and factors that influence the vulnerability to addiction. The genesis of Pakistan's opioid epidemic is critical to understand as the country became victim to the proximity to, and politics of, Iran and Afghanistan. There is poor resource allocation for the treatment of substance use disorder, especially in comparison to what is spent on counter-terrorism. Addiction has had a devastating effect on children and the youth of Pakistan. It is vital to recognise addiction as a chronic disease comparable to diabetes, hypertension and asthma; and not a personal weakness. Medication-assisted treatment includes using buprenorphine-naloxone and naltrexone for opioid use disorder, injectable naltrexone for alcohol use disorder, and mirtazapine and bupropion for amphetamine use disorder. Coordination between the healthcare system, the Anti-Narcotics Force, the pharmaceutical industry and parliament is important. A university-affiliated addiction centre should be developed so it can provide guidance with research and treatment. Buprenorphine-naloxone and injectable naltrexone are urgently needed at an institutional level for the treatment of opioid and alcohol use disorder.

Methamphetamine Use and Its Correlates among Individuals with Opioid Use Disorder in a Midwestern U.S. City.

Background: U.S. is experiencing a surging trend of methamphetamine use among individuals who use opioids. More research is needed to characterize this emerging "twin epidemic." Objectives: The study aims to identify social and behavioral characteristics associated with methamphetamine use among individuals with opioid use disorder (OUD) in the Dayton, Ohio, area, an epicenter of the opioid crisis and an emerging frontier of methamphetamine epidemic. Methods: 357 adult individuals with current OUD were recruited using targeted and respondent-driven sampling. Structured interviews collected information on social and drug use characteristics. Multivariable Logistic Regression was used to identify characteristics associated with the past 6-month use of methamphetamine. Results: 49.7% were female, and 88.8% were non-Hispanic whites. 55.6% used methamphetamine in the past 6-months, and 84.9% reported first use of methamphetamine after initiation of illicit opioids. Methamphetamine use was associated with homelessness (aOR = 2.46, p = .0001), lifetime history of diverted pharmaceutical stimulant use (aOR = 2.97, p < .001), injection route of heroin/fentanyl use (aOR = 1.89, p = .03), preference for fentanyl over heroin (aOR = 1.82, p = .048), lifetime history of extended-release injectable naltrexone (Vivitrol)-based treatment (aOR = 2.89, p = .003), and more frequent marijuana use (aOR = 1.26, p = .04). Discussion: The findings point to the complexity of motivational and behavioral pathways associated with methamphetamine and opioid co-use, ranging from self-treatment and substitution behaviors, attempts to endure homelessness, and greater risk taking to experience euphoria. More research is needed to understand the causal relationships and the association between methamphetamine and Vivitrol use. Public health responses to the opioid crisis need to be urgently expanded to address the growing epidemic of methamphetamine use.

Complicaciones cardiovasculares de las metanfetaminas: estudio de 6 casos / Cardiovascular complications of methamphetamines: Study of 6 cases

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Perceived Risk of Heroin in Relation to Other Drug Use in a Representative US Sample.

Low perception of risk is a risk factor for heroin use. Research is needed to determine whether this risk factor for heroin use is affected by the use of other drugs. Data were analyzed from participants in the 2015/2016 National Surveys on Drug Use and Health who denied lifetime heroin use (N= 110,102). We examined how recency of use of various drugs and number of drugs used relate to perceptions that using heroin is not a great risk. Results from multivariable models suggest that no lifetime drug use, and recent prescription opioid misuse and methamphetamine use, in particular, were associated with higher odds of perceiving that heroin use is not of great risk. Recent marijuana use was associated with lower odds of reporting that heroin use is not of great risk. Use of more drugs in one's lifetime, past year, and/or past month tended to be associated with lower odds of reporting heroin use as not a great risk. Prevention experts should consider that recent prescription opioid misuse in particular is a risk factor for the lower perception of risk, while individuals reporting no lifetime drug use may also require better education regarding harms associated with heroin use.

Deep Brain Stimulation of Nucleus Accumbens for Methamphetamine Addiction: Two Case Reports.

BACKGROUND: Methamphetamine (MA) addiction is one of the most prevalent socioeconomic and health problems worldwide. In recent years, deep brain stimulation (DBS) has increasingly been used for the treatment of addiction. CASE DESCRIPTION: This study reports on 2 MA-dependent patients who received DBS of the nucleus accumbens (NAc). During the approximately 2-year follow-up period, one patient (A) remained abstinent and presented with positive emotional experiences, whereas the other (B) had no significant psychobehavioral changes during stimulation at low-to-moderate voltages and subsequently relapsed. Through coregistration of preoperative magnetic resonance imaging with postoperative computed tomography/magnetic resonance imaging, the DBS electrode of patient A was confirmed to be accurately implanted in the NAc, whereas one side of the electrode of patient B deviated from the target. CONCLUSIONS: These case reports demonstrate that NAc-DBS maybe a possible treatment option for MA addiction.

Correlates of Validity of Self-Reported Methamphetamine Use among a Sample of Dependent Adults.

BACKGROUND: Self-reported data are widely used in substance-use research, yet few studies have assessed the validity of self-reported methamphetamine use compared to biological assays. OBJECTIVES: We sought to assess the validity and correlates of validity of self-reported methamphetamine use compared to urine toxicology (UTOX). METHODS: Using a sample of methamphetamine-dependent individuals enrolled in a randomized controlled pharmacotherapy trial in the United States (n = 327 visits among 90 participants), we calculated sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the kappa coefficient of self-reported methamphetamine use in the past 3 days compared to UTOX, as well as the NPV of self-reported methamphetamine use over an extended recall period of 1 month. We used multivariable logistic regression models to assess correlates of concordance between self-reported methamphetamine use and UTOX. RESULTS: The sensitivity of self-reported methamphetamine use in the past 3 days was 86.7% (95% confidence intervals (95%CI): 81.4%-91.4%), the specificity was 85.3% (77.7-91.3), the PPV was 91.5% (86.9-94.8), and the NPV was 78.0% (69.4-86.1), compared to UTOX (kappa = 0.71). The NPV over the extended recall period was 70.6% (48.0-85.7). In multivariable analyses, validity of self-reported methamphetamine use was higher for older participants but lower during follow-up compared to baseline and when polysubstance use or depressive symptoms were reported. Conclusions/Importance: Our sample of methamphetamine-dependent adults reported recent methamphetamine use with high validity compared to UTOX. Validity increased with age but decreased when participants reported depressive symptoms or polysubstance use as well as later in the study timeline and during longer recall periods.

Chiral Analysis of Methamphetamine in Oral Fluid Samples: A Method to Distinguish Licit from Illicit Drug Use.

Methamphetamine (MAMP) is a popular illicit drug abused for its central nervous system stimulating effects. MAMP is also used therapeutically in the treatment of overeating disorders, narcolepsy, attention deficit disorder, in over-the-counter (OTC) products to ease nasal congestion. MAMP exists in two enantiomeric forms, dextrorotary (d-MAMP) or levorotary (l-MAMP). The compounds are similar in chemical structure, simply differing in the orientation of functional groups around the asymmetric carbon. In part because of the availability of l-MAMP in OTC nasal inhalers, forensic guidelines require a sample to contain greater than 20% d-MAMP to consider illicit drug use when interpreting results. Standard analytical methods readily detect MAMP in biological specimens but cannot resolve the enantiomeric composition of the sample. Specialized analytical techniques based on chiral separation of the enantiomers are required to differentiate d-MAMP from l-MAMP. Our laboratory sought to develop and validate a method for the analysis of oral fluid specimens for d/l-MAMP using a chiral derivatizing agent and traditional reverse phase liquid chromatography tandem mass spectrometry (LC-MS-MS). MAMP was extracted from dilute oral fluid samples using Strata-XC solid phase extraction (SPE) cartridges and derivatized with Marfey's reagent. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 columns. Linearity, accuracy and precision, recovery, matrix effects and specificity of the method were all within acceptable criteria. Intraday accuracy ranged from 93.3 to 103.4% and precision 0.1 to 1.6%. Interday accuracy ranged from 90.0 to 103.4% and precision 3.8 to 11.6%. Finally, having previously tested positive for MAMP using non-chiral analysis, 256 de-identified authentic oral fluid samples were analyzed using this validated method. 98% of all samples tested positive for d-MAMP at greater than 20%.