Treatment retention and reductions in blood alcohol concentration (BAC) during the first 90 days of a telehealth program for alcohol use disorder.

Background: Alcohol use disorder (AUD) treatments, including medications, are increasingly offered via telehealth.Objective: This study characterizes 90-day treatment retention and changes in objectively measured blood alcohol concentration (BAC) in a large cohort receiving AUD telehealth.Methods: Patients received AUD treatment through Ria, a virtual (telehealth) program offering AUD treatment that is tailored to patient goals (e.g. abstinence or controlled drinking). Patients were encouraged to complete breathalyzer readings twice daily for measurement-based care. We characterized rates of 90-day treatment retention (i.e. completing a BAC reading or medical/coaching encounter on the 90th day or later) and used growth curve analyses to model changes in daily estimated peak BAC over 90 days.Results: Of 4121 patients (51.5% women), 50.1% had 90-day treatment retention (n = 2066, 52.2% women). Most patients received prescriptions for AUD medications (84.6%) and completed encounters with medical providers (86.7%) and coaches (86.1%). Patients with 90-day retention provided 184,817 BAC readings in the first 90 days. Growth curve analyses revealed significant reductions in daily estimated peak BAC (p < .001) from a mean of 0.092 (day 1) to 0.038 (day 90). Similar magnitudes of BAC reduction were observed for men and women and for patients with abstinence and controlled drinking goals.Conclusion: Telehealth appears to be a viable approach to delivering AUD treatments in a manner that promotes drinking reductions. Telehealth approaches can yield reductions in objectively measured BAC, including for some patient subgroups that have historically faced greater stigma in AUD treatment settings, such as women and people with non-abstinence drinking goals.

Gabapentin Enacarbil Extended-Release for Alcohol Use Disorder: A Randomized, Double-Blind, Placebo-Controlled, Multisite Trial Assessing Efficacy and Safety.

BACKGROUND: Several single-site alcohol treatment clinical trials have demonstrated efficacy for immediate-release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended-release (GE-XR) (HORIZANT® ), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD). METHODS: Men and women (n = 346) who met DSM-5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double-blind GE-XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period. RESULTS: The GE-XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol-related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side-effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications. CONCLUSIONS: Overall, GE-XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE-XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.

Intensive Motivational Interviewing for Heavy Drinking among Women.

OBJECTIVES: Women suffer more severe consequences related to heavy drinking than men. Relative to men, women who are heavy drinkers experience higher severity of medical, psychiatric, and social problems, even when they have fewer years drinking. Currently there are few gender-specific, evidence-based interventions for heavy drinking among women. METHODS: A randomized clinical trial was conducted with 215 women with alcohol problems. Half were randomly assigned to receive a 9-session, "Intensive Motivational Interviewing" (IMI) intervention (N=107) and half were randomly assigned to a standard single session of MI (SMI) along with 8 sessions of nutritional education (N=108) to achieve time equivalence. Both conditions received weekly outpatient group counseling. Follow-up interviews were conducted at 2 months. Primary outcomes included percent drinking days (PDD), percent heavy drinking days (PHDD, 4+ drinks), and the Addiction Severity Index (ASI) Alcohol scale. Longitudinal changes were assessed using generalized estimating equations (GEE). RESULTS: The sample was predominantly white (83.3%), college educated (61.4%), and married (53.5%). The mean age was 50.9 (sd = 11.3). Relative to baseline, both study conditions showed significant reductions in PDD, PHDD, and ASI alcohol severity (p<.001). Among heavy drinkers, defined as women drinking 14+ days to the point of intoxication over the past 30 days at baseline (N=153), those assigned to IMI (n=67) showed larger reductions in PDD (p<.01) and PHDD (p<.05) at 2-months compared to women receiving SMI. CONCLUSIONS: Findings support the efficacy of IMI for heavy drinking among women. Additional studies are needed that assess drinking over longer time periods.

Changes in psychiatric symptoms among persons with methamphetamine dependence predicts changes in severity of drug problems but not frequency of use.

BACKGROUND: Few studies have examined how changes in psychiatric symptoms over time are associated with changes in drug use and severity of drug problems. No studies have examined these relationships among methamphetamine (MA)-dependent persons receiving motivational interviewing within the context of standard outpatient treatment. METHODS: Two hundred seventeen individuals with MA dependence were randomly assigned to a standard single session of motivational interviewing (MI) or an intensive 9-session model of MI. Both groups received standard outpatient group treatment. The Addiction Severity Index (ASI) and timeline follow-back (TLFB) for MA use were administered at treatment entry and 2-, 4-, and 6-month follow-ups. RESULTS: Changes in ASI psychiatric severity between baseline and 2 months predicted changes in ASI drug severity during the same time period, but not changes on measures of MA use. Item analysis of the ASI drug scale showed that psychiatric severity predicted how troubled or bothered participants were by their drug us, how important they felt it was for them to get treatment, and the number of days they experienced drug problems. However, it did not predict the number days they used drugs in the past 30 days. These associations did not differ between study conditions, and they persisted when psychiatric severity and outcomes were compared across 4- and 6-month time periods. CONCLUSIONS: Results are among the first to track how changes in psychiatric severity over time are associated with changes in MA use and severity of drug problems. Treatment efforts targeting reduction of psychiatric symptoms among MA-dependent persons might be helpful in reducing the level of distress and problems associated with MA use but not how often it is used. There is a need for additional research describing the circumstances under which the experiences and perceptions of drug-related problems diverge from frequency of consumption.

Text messaging for addiction: a review.

Individuals seeking treatment for addiction often experience barriers due to cost, lack of local treatment resources, or either school or work schedule conflicts. Text-messaging-based addiction treatment is inexpensive and has the potential to be widely accessible in real time. We conducted a comprehensive literature review identifying 11 published, randomized controlled trials (RCTs) evaluating text-messaging-based interventions for tobacco smoking, four studies for reducing alcohol consumption, one pilot study in former methamphetamine (MA) users, and one study based on qualitative interviews with cannabis users. Abstinence outcome results in RCTs of smokers willing to make a quit attempt have been positive overall in the short term and as far out as at six and 12 months. Studies aimed at reducing alcohol consumption have been promising. More data are needed to evaluate the feasibility, acceptability, and efficacy of this approach for other substance use problems.

A cognitive behavioral therapy-based text messaging intervention for methamphetamine dependence.

Psychosocial treatments for methamphetamine dependence are of limited effectiveness. Thus, a significant need exists for add-on therapy for this substance user disorder. The aim of this study was to develop and test a novel text messaging intervention for use as an adjunct to cognitive behavioral group therapy for methamphetamine users. Text messaging has the potential to support patients in real-time, around the clock. We convened two meetings of an expert panel, held three focus groups in current and former users, and conducted 15 semi-structured interviews with in-treatment users in order to develop a fully automated, cognitive behavioral therapy-based text messaging intervention. We then conducted a randomized, crossover pre-test in five users seeking treatment. Participants' ratings of ease of use and functionality of the system were high. During the pre-test, we performed real-time assessments via text messaging on daily methamphetamine use, craving levels, and the perceived usefulness of messages; 79% of scheduled assessments were collected. The odds of messages being rated as "very" or "extremely" useful were 6.6 times (95% CI: 2.2, 19.4) higher in the active vs. placebo periods. The intervention is now ready for testing in randomized clinical trials.

Gender Differences in Psychiatric Symptoms among Methamphetamine Dependent Residents in Sober Living Houses.

OBJECTIVES: Although psychiatric symptoms among methamphetamine (MA) dependent individuals have been studied in treatment programs, they have not been examined in services designed to support sustained recovery in the community (e.g. sober living houses). In addition, some disorders more common among women, such as somatoform and bulimia, have been understudied among MA dependent individuals. This study aimed to examine psychiatric symptom differences between MA dependent men and women who we entering sober living houses (SLHs). METHODS: Two hundred forty five individuals were interviewed within one week of entering SLHs. Instruments included a DSM IV based measure for MA dependence, a psychiatric screen (the Psychiatric Diagnostic Screening Questionnaire), demographics, recent substance use and recent use of services. RESULTS: Of the 245 participants, 103 men and 25 women met criteria for MA dependence. Womenwith MA dependence reported more psychiatric symptoms than men. They also trended toward reporting more psychiatric symptoms than non-MA dependent women. For men, psychiatric symptoms did not vary between those with and without MA dependence. Some understudied disorders (e.g., somatoform) had large proportions of women meeting the screening criteria. CONCLUSIONS: Additional research is needed on understudied psychiatric disorders that are common among MA dependent women. SLH's should consider ways to address psychiatric symptoms among MA dependent individuals, especially women. Strategies could include increasing linkages with professional mental health services as well as developing peer oriented strategies for managing symptoms.

A method to quantify illicit intake of drugs from urine: methamphetamine.

Qualitative urinalysis can verify abstinence of drug misuse but cannot detect changes in drug intake. For drugs with slow elimination, such as methamphetamine (MA), a single episode of abuse can result in up to 5 days of positive urine drug screens. Thus, interventions that produce substantial decreases in drug use but do not achieve almost complete abstinence are classified as ineffective. Using nonpharmacologic doses of deuterium-labeled l-methamphetamine (l-MA-d(3)) we have developed a simple, robust method that reliably estimates changes in MA intake. Twelve subjects were dosed with 5 mg of l-MA-d(3) daily and challenged with 15, 30, and 45 mg of nonlabeled d-MA (d-MA-d(0)) after reaching plasma steady status of l-MA-d(3). Urinary concentration ratios of d-MA-d(0) to l-MA-d(3) provided clear separation of the administered doses with as little as 15-mg dose increments. Administered doses could not be resolved using d-MA-d(0) concentrations alone. In conclusion, the urinary [d-MA-d(0)]:[l-MA-d(3)] provides a quantitative, continuous measure of illicit MA exposure. The method reliably detects small, clinically relevant changes in illicit MA intake from random urine specimens, is amenable to deployment in clinical trials, and can be used to quantify patterns of MA abuse.

Psychiatric comorbidity in methamphetamine dependence.

The primary aim of the present study was to assess the prevalence of psychiatric comorbidity in a large sample of methamphetamine (MA)-dependent subjects using a validated structured clinical interview, without limitation to sexual orientation or participation in a treatment program. The secondary aim was to assess whether the prevalence of psychiatric comorbidities varied by gender. Structured clinical interviews (SCIDs) were administered to 189 MA-dependent subjects and lifetime prevalence of DSM-IV diagnoses was assessed. Across the sample, 28.6% had primary psychotic disorders, 23.8% of which were substance-induced; 13.2% had MA-induced delusional disorders and 11.1% had MA-induced hallucinations. A substantial number of lifetime mood disorders were identified that were not substance-induced (32.3%), whereas 14.8% had mood disorders induced by substances, and 10.6% had mood disorders induced by amphetamines. Of all participants, 26.5% had anxiety disorders and 3.7% had a substance-induced anxiety disorder, all of which were induced by MA. Male subjects reported a higher percentage of MA-induced delusions compared to female abusers. Given the impact of MA psychosis and other drug-induced symptoms on hospitals and mental health services, the description and characterization of comorbid psychiatric symptoms associated with MA use is of paramount importance.

Substance use and motivation: a longitudinal perspective.

BACKGROUND: Motivation to change substance use behavior is an important component of the recovery process that has usually been studied at entry into treatment. Less studied, but equally important, is the measurement of motivation over time and the role motivation plays in subsequent substance use. OBJECTIVES: The present study sought to examine longitudinal motivation toward sobriety among residents of sober living houses. METHODS: Sober living residents (n = 167) were followed at 6-month intervals over an 18-month period and assessed for motivation and substance use outcomes at each study interview. Motivation was measured using the costs and benefits subscales of the Alcohol and Drug Consequences Questionnaire (ADCQ) and substance use outcomes included the Addiction Severity Index (ASI) alcohol scale, ASI drug scale, and peak density of substance use (number of days of most use in a month). RESULTS: Participants reported higher benefits than costs of sobriety or cutting down substance use at every study time point. Using lagged generalized estimating equation models, the ADCQ costs predicted increased severity for alcohol, drugs, and peak density, whereas the benefits subscale predicted decreased drug and peak density. CONCLUSION: Longitudinal measurement of motivation can be a useful clinical tool to understand later substance use problems. SCIENTIFIC SIGNIFICANCE: Given the mixed findings from prior studies on the effects of baseline motivation, a shift toward examining longitudinal measures of motivation at proximal and temporal intervals is indicated.

Estimating the intake of abused methamphetamines using experimenter-administered deuterium labeled R-methamphetamine: selection of the R-methamphetamine dose.

All addictive drugs produce tolerance and addicts compensate by increasing drug exposure. Thus, the quantity of illicit drug ingested is related to the severity of addiction. Unfortunately, there are no objective methods to estimate intake for most addictive drugs. Using experimenter-administered doses of deuterium-labeled R-methamphetamine (R-[-]-MA-d3), we have developed a method to estimate the amount of abused methamphetamine intake in addicts enrolled in clinical trials. This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of R-MA in healthy adults to select a dose of R-MA-d3 to be used as a biomarker for estimation the amount of methamphetamine abuse. This was a five-session randomized, double-blind, placebo-controlled, balanced crossover study in eight subjects. Oral R-(-)-MA was dosed at 0 mg, 1 mg, 2.5 mg, 5 mg, or 10 mg; bioavailability was estimated by slow intravenous dosing (30 minutes) of 2.5 mg R-(-)-MA-d3 given with the 2.5 mg R-(-)-MA oral dose condition. Pharmacokinetic and pharmacodynamic measures were obtained. No serious adverse events occurred during the study and all doses of R-MA were well tolerated. Linear pharmacokinetics was observed within our oral dose range of 1 to 10 mg. Complete bioavailability and pharmacologic inactivity were found for all oral doses. These characteristics indicate the advantage of using a small oral R-(-)-MA-d3 dose as a biomarker to estimate exposure to abused methamphetamine. Based on these results, 5 mg R-(-)-MA-d3 has been selected as the biomarker dose in future studies. Preliminary findings from our study indicate that experimenter-administered oral R-(-)-MA-d3 may allow estimation of abused methamphetamine intake and exposure. Knowledge of the quantity of methamphetamine intake may allow better estimation of disease severity and treatment efficacy. Experience gained from this study also can be applied to the management of other drug dependence problems such as cocaine, cannabinoid, and opiate addiction.

An examination of drug craving over time in abstinent methamphetamine users.

Craving for addictive drugs may predict relapse in abstinent addicts. To assess relationships between craving and use, we examined changes in craving for methamphetamine (MA) in a sample of 865 outpatients in a multisite 16-week MA-treatment study. Craving was assessed on a 0-100 scale, and MA use was assessed by self-report and confirmed by urinalysis. We hypothesized that the magnitude of craving would decline (decay) with increased time of abstinence, and that decay would be greater for more frequent MA users, and greater for intravenous (IV) users and smokers as compared to those who used MA intranasally. Craving declined significantly as the number of weeks of consecutive abstinence increased. Rate of decay was greater for IV users and smokers as compared to both intranasal users and oral users, but not for more frequent users of MA. Rate of decay was independent of age, gender, and race/ethnicity. The trajectory to 0 (no) craving was 1 week shorter for females than males because females had significantly lower pretreatment craving scores compared to males. This study confirms that the sooner MA-dependent people are able to quit using and the longer that they are able to stay abstinent, the more likely it is that their craving for MA will decrease over time.

Methamphetamine and paranoia: the methamphetamine experience questionnaire.

Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. We administered the MEQ to 274 MA-dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = .77, p < .05 and kappa = .80, p < .05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p < .05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. (Am J Addict 2010;00:1-14).

Development of an acceptance-based coping intervention for alcohol dependence relapse prevention.

Both psychological and neurobiological findings lend support to the long-standing clinical observation that negative affect is involved in the development and maintenance of alcohol dependence, and difficulty coping with negative affect is a common precipitant of relapse after treatment. Although many current approaches to relapse prevention emphasize change-based strategies for managing negative cognitions and affect, acceptance-based strategies for preventing relapse to alcohol use are intended to provide methods for coping with distress that are fundamentally different from, though in theory complementary to, approaches that emphasize control and change. This paper describes the development of Acceptance-Based Coping for Relapse Prevention (ABCRP), a new intervention for alcohol-dependent individuals who are within 6 months of having quit drinking. Results of preliminary testing indicate that the intervention is feasible with this population; and a small uncontrolled pilot study (N = 23) showed significant (P < .01) improvements in self-reported negative affect, emotional reactivity, perceived stress, positive affect, psychological well-being, and mindfulness level, as well as a trend (P = .06) toward reduction in craving severity between pre- and postintervention assessments. The authors conclude that this acceptance-based intervention seems feasible and holds promise for improving affect and reducing relapse in alcohol-dependent individuals, warranting further research.

What did we learn from our study on sober living houses and where do we go from here?

Lack of a stable, alcohol- and drug-free living environment can be a serious obstacle to sustained abstinence. Destructive living environments can derail recovery for even highly motivated individuals. Sober living houses (SLHs) are alcohol- and drug-free living environments for individuals attempting to abstain from alcohol and other drugs. They are not licensed or funded by state or local governments and the residents themselves pay for costs. The philosophy of recovery emphasizes 12-Step group attendance and peer support. We studied 300 individuals entering two different types of SLHs over an 18-month period. This article summarizes our published findings documenting resident improvement on measures of alcohol and drug use, employment, arrests, and psychiatric symptoms. Involvement in 12-Step groups and characteristics of the social network were strong predictors of outcome, reaffirming the importance of social and environmental factors in recovery. This article adds to our previous reports by providing a discussion of implications for treatment and criminal justice systems. We also describe the next steps in our research on SLHs, which will include: (1) an attempt to improve outcomes for residents referred from the criminal justice system and (2) a depiction of how attitudes of stakeholder groups create a community context that can facilitate and hinder the legitimacy of SLHs as a recovery modality.

How do residents of recovery houses experience confrontation between entry and 12-month follow-up?

The role of confrontation in recovery has been vigorously debated. Proponents suggest confrontation can break down denial and increase motivation. Critics point to counseling studies showing confrontation harms the therapeutic alliance and increases resistance. Frequently missing in these debates is an operational definition of confrontation that can be reliably measured. The Alcohol and Drug Confrontation Scale (ADCS) is a new 72-item measure that defines confrontation as "warnings about potential harm" that might result from substance use (e.g., arrests, loss of job, loss of relationships, etc.). Previous psychometric work indicated the ADCS had acceptable reliability and validity when administered to 323 individuals entering recovery houses. Confrontation from different sources (e.g., family, friends and professionals) was generally experienced as supportive and helpful. The goals of the current study were twofold: (1) to see if the psychometric properties of the ADCS among the same sample were maintained at six and 12 month follow-up, and (2) to see if experiences and perceptions of confrontation changed over time. Despite minor variations in the factor structure between baseline and follow-up, the ADCS generally maintained good reliability and validity. At follow-up, the amount of confrontation participants received declined, but it continued to be generally experienced as supportive and helpful.

Eighteen Month Outcomes for Clients Receiving Combined Outpatient Treatment and Sober Living Houses.

One of the most frequent and frustrating challenges facing clients in outpatient treatment is finding a living environment that is free of alcohol and drugs and supportive of recovery. Sober Living Houses (SLHs) have been suggested as one potential solution (Polcin, 2009). Among other advantages, SLHs are financially self-sustaining and residents can remain there as long as they wish, provided they comply with house rules and expectations. This study examined 18-month outcomes for 55 individuals receiving outpatient treatment combined with residence in a SLH. Repeated measures analyses comparing 6-month time periods showed significant improvement on measures of alcohol and drug use, arrests, and days worked. The Addiction Severity Index (ASI) showed significant improvement on legal and employment scales. On ASI alcohol and drug scales, individuals entered SLHs with very low severity that was maintained at 18 months. Involvement in 12-step groups was associated with reductions in alcohol and drug use.

Confirmatory Factor Analysis and Test-Retest Reliability of the Alcohol and Drug Confrontation Scale (ADCS).

The addiction field lacks an accepted definition and reliable measure of confrontation. The Alcohol and Drug Confrontation Scale (ADCS) defines confrontation as warnings about the potential consequences of substance use. To assess psychometric properties, 323 individual entering recovery houses in U.S. urban and suburban areas were interviewed between 2003 and 2005 (20% women, 68% white). Analyses included test-retest reliability, confirmatory factor analysis, and measures of internal consistency. Findings support the ADCS as a reliable way of assessing two factors: Internal Support and External intensity. Confrontation was experienced as supportive, accurate and helpful. Additional studies should assess confrontation in different contexts.

Heavy Drinking among Women Receiving Intensive Motivational Interviewing: 6-Month Outcomes.

Compared to men, women with alcohol use disorders experience more severe consequences related to drinking. Intensive Motivational Interviewing (IMI) is a new 9-session version of Motivational Interviewing (MI) designed for women with alcohol use disorders. The current study reports outcomes from a randomized clinical trial of IMI compared to a single session of MI. Data were collected at baseline, 2-month, and 6-month follow-up. In addition to a standard "intent-to-treat" (ITT) analysis, we conducted disaggregated subgroup analyses of women who were heavy drinkers and a "per protocol" (PP) analysis of women in the IMI condition who attended 7-9 sessions (80% of the IMI sample). Women in both study conditions made large reductions in drinking between baseline and 2 months that were maintained at 6 months. Generalized estimating equation (GEE) models using the full sample (N = 215) did not show time by condition differences, but heavy drinkers(n = 153) receiving IMI showed significantly larger reductions in drinking at 2- and 6-month follow-up than the comparison condition. Assessment of heavy drinkers using the PP sample showed larger between condition differences favoring IMI at both follow-up time points. Results support the efficacy of IMI in terms of reducing drinking, particularly among women who are heavy drinkers.

Effects of the Psychedelic Amphetamine MDA (3,4-Methylenedioxyamphetamine) in Healthy Volunteers.

Entactogens such as 3,4-Methylenedioxymethamphetamine (MDMA, "molly", "ecstasy") appear to have unusual, potentially therapeutic, emotional effects. Understanding their mechanisms can benefit from clinical experiments with related drugs. Yet the first known drug with such properties, 3,4-Methylenedioxyamphetamine (MDA), remains poorly studied and its pharmacokinetics in humans are unknown. We conducted a within-subjects, double-blind, placebo-controlled study of 1.4 mg/kg oral racemic MDA and compared results to those from our prior similar studies with 1.5 mg/kg oral racemic MDMA. MDA was well-tolerated by participants. MDA induced robust increases in heart rate and blood pressure and increased cortisol and prolactin to a similar degree as MDMA. MDA self-report effects shared features with MDMA as well as with classical psychedelics. MDA self-report effects lasted longer than those of MDMA, with MDA effects remaining elevated at 8 h while MDMA effects resolved by 6 h. Cmax and AUC0-∞ for MDA were 229 ± 39 (mean ± SD) and 3636 ± 958 µg/L for MDA and 92 ± 61 and 1544 ± 741 µg/L for the metabolite 4-hydroxy-3-methoxyamphetamine (HMA). There was considerable between-subject variation in MDA/HMA ratios. The similarity of MDA and MDMA pharmacokinetics suggests that the greater duration of MDA effects is due to pharmacodynamics rather than pharmacokinetics.