Adaptations to Opioid Use Disorder Care During the COVID-19 Pandemic: A National Survey of Prescribers.

OBJECTIVES: Among opioid use disorder (OUD)-treating providers, to characterize adaptations used to provide medications for OUD (MOUD) and factors associated with desire to continue virtual visits post-COVID-19 pandemic. METHODS: In a national electronic survey of OUD-treating prescribers (July-August 2020), analyses restricted to X-waivered buprenorphine prescribers providing outpatient, longitudinal care for adults with OUD, quantitative and qualitative analyses of survey items and free text responses were conducted. RESULTS: Among 797 respondents, 49% were men, 57% ≥50 years, 76% White, 68% physicians. Respondents widely used virtual visits to continue prescribing existing MOUD regimens (79%), provide behavioral healthcare (71%), and initiate new MOUD prescriptions (49%). Most prescribers preferred to continue/expand use of virtual visits after COVID-19. In multivariable models, factors associated with preference to continue/expand virtual visits to initiate MOUD postpandemic were treating a moderate number of patients prepandemic (aOR = 1.67; 95%[CI] = 1.06,2.62) and practicing in an urban setting (aOR = 2.17; 95%[CI] = 1.48,3.18). Prescribing buprenorphine prepandemic (aOR = 2.06; 95%[CI] = 1.11,3.82) and working in an academic medical center (aOR = 2.47; 95%[CI] = 1.30,4.68) were associated with preference to continue/expand use of virtual visits to continue MOUD postpandemic. Prescribing naltrexone extended-release injection prepandemic was associated with preference to continue/expand virtual visits to initiate and continue MOUD (aOR = 1.51; 95%[CI] = 1.10,2.07; aOR = 1.74; 95%[CI] = 1.19,2.54). Qualitative findings suggest that providers appreciated virtual visits due to convenience and patient accessibility, but were concerned about liability and technological barriers. CONCLUSIONS: Surveyed prescribers widely used virtual visits to provide MOUD with overall positive experiences. Future studies should evaluate the impact of virtual visits on MOUD access and retention and clinical outcomes.

A Comparison of Cognitive Processing Therapy and Seeking Safety for the Treatment of Posttraumatic Stress Disorder in Veterans.

To compare the outcomes of Seeking Safety (SS) and cognitive processing therapy (CPT) in veterans with PTSD in a specialty clinic of an urban VA medical center. Retrospective chart review of electronic medical records was conducted for 420 veterans with PTSD who received treatment with either CPT (n = 227) or SS (n = 193) in group setting. 1) treatment completion rate, 2) self-reported PTSD symptom severity measured by PTSD checklist (PCL), and 3) additional mental health services received within 12 months after treatment. Data were analyzed for the 160 who had both a pre and post PCL documented in their charts. The final analysis sample included n = 94 for CPT and n = 66 for SS veterans with a mean age of 49.71[SD = 14] years, 24 women [15%]; mean baseline PCL score was 68.41 [9]. Significantly more veterans completed SS treatment (SS, 59 [89%] than CPT, 47 [50%] (p = <.001). However, PCL score decreases were significantly greater for patients who completed CPT treatment than those in SS (treatment x time interaction, 9.60 vs.4.98, respectively; difference, 4.62; t84 = 2.16; p = .02). The patients who received SS used significantly more mental health services of the PTSD clinical team than patients who completed CPT treatment (p = .01). The results of this study demonstrate the need for alternative approaches where dually diagnosed patients would not be delayed in their receipt of trauma-focused care - i.e., where treatment is initiated concurrently rather than sequentially to substance abuse treatment.

Functional activation and effective connectivity differences in adolescent marijuana users performing a simulated gambling task.

Background. Adolescent marijuana use is associated with structural and functional differences in forebrain regions while performing memory and attention tasks. In the present study, we investigated neural processing in adolescent marijuana users experiencing rewards and losses. Fourteen adolescents with frequent marijuana use (>5 uses per week) and 14 nonuser controls performed a computer task where they were required to guess the outcome of a simulated coin flip while undergoing magnetic resonance imaging. Results. Across all participants, "Wins" and "Losses" were associated with activations including cingulate, middle frontal, superior frontal, and inferior frontal gyri and declive activations. Relative to controls, users had greater activity in the middle and inferior frontal gyri, caudate, and claustrum during "Wins" and greater activity in the anterior and posterior cingulate, middle frontal gyrus, insula, claustrum, and declive during "Losses." Effective connectivity analyses revealed similar overall network interactions among these regions for users and controls during both "Wins" and "Losses." However, users and controls had significantly different causal interactions for 10 out of 28 individual paths during the "Losses" condition. Conclusions. Collectively, these results indicate adolescent marijuana users have enhanced neural responses to simulated monetary rewards and losses and relatively subtle differences in effective connectivity.

Impulsivity, attention, memory, and decision-making among adolescent marijuana users.

RATIONALE: Marijuana is a popular drug of abuse among adolescents, and they may be uniquely vulnerable to resulting cognitive and behavioral impairments. Previous studies have found impairments among adolescent marijuana users. However, the majority of this research has examined measures individually rather than multiple domains in a single cohesive analysis. This study used a logistic regression model that combines performance on a range of tasks to identify which measures were most altered among adolescent marijuana users. OBJECTIVES: The purpose of this research was to determine unique associations between adolescent marijuana use and performances on multiple cognitive and behavioral domains (attention, memory, decision-making, and impulsivity) in 14- to 17-year-olds while simultaneously controlling for performances across the measures to determine which measures most strongly distinguish marijuana users from nonusers. METHODS: Marijuana-using adolescents (n = 45) and controls (n = 48) were tested. Logistic regression analyses were conducted to test for: (1) differences between marijuana users and nonusers on each measure, (2) associations between marijuana use and each measure after controlling for the other measures, and (3) the degree to which (1) and (2) together elucidated differences among marijuana users and nonusers. RESULTS: Of all the cognitive and behavioral domains tested, impaired short-term recall memory and consequence sensitivity impulsivity were associated with marijuana use after controlling for performances across all measures. CONCLUSIONS: This study extends previous findings by identifying cognitive and behavioral impairments most strongly associated with adolescent marijuana users. These specific deficits are potential targets of intervention for this at-risk population.

Acquisition of Rater Agreement for the Stressful Life Events Schedule.

Stress has been linked to a broad range of psychopathology including alcohol and drug dependence. Recent advances in our understanding of how stress interacts with biological systems involved in addiction has generated even greater interest in stress assessment among addiction researchers. The Stressful Life Events Schedule (SLES) capitalizes on the strengths and avoids the pitfalls of self-report checklist and interview-based stress assessments. Because the SLES depends on consensus ratings of a research team, this study examined rater agreement of stressful event ratings across the first year using the SLES. Individual ratings of stressful events were compared between two experienced and three new raters. Ratings were analyzed for life events generated from interviews of 70 adolescent psychiatric inpatients and 62 healthy adolescents. Inexperienced raters, with backgrounds in addiction research, reliably rated stressful events and rater agreement improved over a year's time. Recommendations for successfully adopting the SLES for consensus rating are discussed.

Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173.

We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3'-untranslated region (3'-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective "urge to drink" and "crave for a drink," we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample sizes are needed to characterize the interactive effects of the serotonin transporter-linked polymorphic region (5'-HTTLPR)-L-allele reported in our previous study and of the rs1042173-TT genotype on cue-induced alcohol craving.

Intolerance to delayed reward in girls with multiple suicide attempts.

Impulsivity has been conceptualized as influencing the expression of suicidal behavior. Adolescence is a developmental period characterized both by a relatively high rate of suicide attempts and a high level of impulsivity. The current study examined two behavioral measures (delay reward and disinhibition) and one self-report measure of impulsivity among girls with suicide attempt histories. Girls with multiple suicide attempts performed more impulsively on measures of delayed reward, and had higher self-ratings of depression and aggression than girls with either one or no suicide attempts. The multiple attempter girls' preference for immediate gratification may directly increase vulnerability to suicidal acts in the context of distressing states or indirectly increase risk by creating poor life experience over time.

Failure to sustain prepulse inhibition in adolescent marijuana users.

BACKGROUND: Marijuana use is typically initiated during adolescence, which is a critical period for neural development. Studies have reported reductions in prepulse inhibition (PPI) among adults who use marijuana chronically, although no human studies have been conducted during the critical adolescent period. METHODS: This study tested PPI of acoustic startle among adolescents who were either frequent marijuana users or naïve to the drug (Controls). Adolescents were tested using two intensities of prepulses (70 and 85 dB) combined with a 105 dB startle stimulus, delivered across two testing blocks. RESULTS: There was a significant interaction of group by block for PPI; marijuana users experienced a greater decline in the PPI across the testing session than Controls. The change in PPI of response magnitude for users was predicted by change in urine THC/creatinine after at least 18 h of abstinence, the number of joints used during the previous week before testing, as well as self-reported DSM-IV symptoms of marijuana tolerance, and time spent using marijuana rather than participating in other activities. CONCLUSIONS: These outcomes suggest that adolescents who are frequent marijuana users have problems maintaining prepulse inhibition, possibly due to lower quality of information processing or sustained attention, both of may contribute to continued marijuana use as well as attrition from marijuana treatment.

Drinking histories in alcohol-use-disordered youth: preliminary findings on relationships to platelet serotonin transporter expression with genotypes of the serotonin transporter.

OBJECTIVE: The serotonin (5-HT) transporter (5-HTT) is thought to play a key role in the onset of alcohol use, with potential behavioral and biological mechanisms mediated by the level of 5-HT in the synapse and in cerebral spinal fluid. Although 5-HT dysregulation has been related to poor impulse control, the biological mechanism is unknown, although functional control of the serotonergic system has been shown to be regulated in part by differential expression of the 5-HTT. The gene responsible for encoding 5-HTT has a functional polymorphism at the 5'-regulatory promoter region, which results in two forms: long (L) and short (S). The LL genotype is hypothesized to play a key role in the early onset of alcohol use and may be related to poor impulse control. The objective of this pilot study is to determine whether adolescents with a current alcohol-use disorder (AUD) (N = 21) have platelet measures of the 5-HTT functioning that are related to 5-HTT genotype and poor impulse control. Specifically, we wanted to examine the relationships between the following: platelet 5-HTT and 5-HTT genotype; platelet 5-HTT parameters and age at onset, as well as duration of drinking; and 5-HTT genotype and impulse control. METHOD: Adolescents with current AUD were recruited from the community to participate in a cross-section pilot study. RESULTS: Our main findings showed significantly higher paroxetine binding (density of 5-HTT) in LL genotype versus S carriers (SS or SL genotypes); also, the LL group had a significantly earlier age at onset of drinking and longer duration of drinking, and poorer impulse control. CONCLUSIONS: These findings provide partial support for the hypothesis that, among currently drinking adolescents with an AUD, differential expression of 5-HTT may play an important role in the onset of adolescent AUD.

Impulsivity and clinical symptoms among adolescents with non-suicidal self-injury with or without attempted suicide.

This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI+SA; n=25) or without (NSSI-Only; n=31) suicide attempts. We hypothesized that adolescent with NSSI+SI would exhibit more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4-6 weeks after discharge. During hospitalization, NSSI+SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity on a reward-directed laboratory measure compared to NSSI-Only patients. In the follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI+SA group still exhibited significantly more depressive symptoms, hopelessness, and impulsivity than the NSSI-Only group. Risk assessments for adolescents with NSSI+SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well.

Can serotonin transporter genotype predict craving in alcoholism?

BACKGROUND: We hypothesize that functional control of the serotonergic system is regulated in part by differential expression of the serotonin (5-HT) transporter (5-HTT). Alcohol-dependent individuals with the LL/LS genotype (L-carriers), compared with those with the SS genotype, have a lower 5-HT neurotransmission, which we hypothesize would be associated with higher craving for alcohol among L-carriers. We hypothesize further that acute peripheral depletion of tryptophan (5-HT's precursor), while further reducing 5-HT function, might decrease auto-inhibition of 5-HT neuronal firing, thereby increasing 5-HT neurotransmission transiently and lowering alcohol craving. METHODS: We tested these hypotheses by examining whether in 34 Hispanic alcohol-dependent individuals subjective and physiological cue craving for alcohol differed by genotype, age of onset of problem drinking, and tryptophan availability. RESULTS: On subjective "urge to drink" and "crave for a drink," we found a significant (p < 0.05) main effect of genotype and cue, as well as an interaction among genotype, age of onset of problem drinking, and tryptophan depletion. For the physiological measure of pulse, there was a main effect of genotype. L-carriers had higher craving than their SS counterparts, an effect that decreased under tryptophan depletion. While craving in L-carriers increased with an earlier age of onset of problem drinking, the opposite effect was seen in those with the SS genotype. CONCLUSION: These results not only provide support for the hypothesis that alcoholics who are L-carriers have greater alcohol craving and possibly greater propensity for drinking but also propose that there is an important 5-HTT gene-by-environment interaction that alters cue craving response for alcohol.

L-Tryptophan: Basic Metabolic Functions, Behavioral Research and Therapeutic Indications.

An essential component of the human diet, L-tryptophan is critical in a number of metabolic functions and has been widely used in numerous research and clinical trials. This review provides a brief overview of the role of L-tryptophan in protein synthesis and a number of other metabolic functions. With emphasis on L-tryptophan's role in synthesis of brain serotonin, details are provided on the research uses of L-tryptophan, particularly L-tryptophan depletion, and on clinical trials that have been conducted using L-tryptophan supplementation. The ability to change the rates of serotonin synthesis in the brain by manipulating concentrations of serum tryptophan is the foundation of much research. As the sole precursor of serotonin, experimental research has shown that L-tryptophan's role in brain serotonin synthesis is an important factor involved in mood, behavior, and cognition. Furthermore, clinical trials have provided some initial evidence of L-tryptophan's efficacy for treatment of psychiatric disorders, particularly when used in combination with other therapeutic agents.

Distinctions in Behavioral Impulsivity: Implications for Substance Abuse Research.

OBJECTIVES: Researchers have clearly implicated impulsivity as having a key role in substance use disorders, and comparisons of self-report measures suggest there are measurably different components of impulsive behavior. However comparatively little research has been devoted to understanding the multidimensional nature of this construct using laboratory measures of impulsivity that may be more sensitive to tracking changes across time. Many studies have measured impulsivity, but this construct has been measured using methodologically different types of laboratory impulsivity paradigms that are often used in isolation. As a result, it is important to determine whether some of the most frequently used types of behavioral measures of impulsivity account for unique variance. METHODS: Here, we used factor analytical techniques in two studies to evaluate the independence of three of the most commonly used behavioral impulsivity paradigms. First, a factor analysis was conducted using previously collected data (n = 204), and second, data was gathered specifically to replicate and extend the results of our original analysis (n = 198). RESULTS: Both studies revealed three distinct factors, confirming our hypothesis of at least three components of impulsive behavior that can be measured by these methodological approaches. CONCLUSIONS: These findings suggest that researchers should carefully consider their selection of laboratory-behavioral impulsivity measures, and that the measure(s) selected should be related to the particular underlying processes relevant to substance use disorders and treatment success.

Adolescent Suicidal Behavior and Substance Use: Developmental Mechanisms.

Adolescent suicidal behaviors and substance use are disturbingly common. Research suggests overlap of some of the etiological mechanisms for both adolescent suicidal behavior and substance use, yet clear understanding of the complex relations between these behaviors and their causal underpinnings is lacking. A growing body of evidence and a diathesis model (Mann et al. 1999; Mann, 2003) highlight the importance of impulse control as a proximal risk factor for adolescent suicidal and substance use behaviors. This literature review extends current theory on the relationships between adolescent suicidal behavior and substance use by: (1) examining how, when, and to what extent adolescent development is affected by poor impulse control, stressful life events, substance use behavior, and biological factors; (2) presenting proposed causal mechanisms by which these risk factors interact to increase risk for suicidal behaviors and substance use; and (3) proposing specific new hypotheses to extend the diathesis model to adolescents at risk for suicide and substance use. More specifically, new hypotheses are presented that predict bidirectional relationships between stressful life events and genetic markers of 5-HT dysregulation; substance use behavior and impulsivity; and substance use behavior and suicide attempts. The importance of distinguishing between different developmental trajectories of suicidal and substance use behaviors, and the effects of specific risk and protective mechanisms are discussed. Use of new statistical approaches that provide for the comparison of latent growth curves and latent class models is recommended to identify differences in developmental trajectories of suicidal behavior and substance use. Knowledge gained from these prospective longitudinal methods should lead to greater understanding on the timing, duration, and extent to which specific risk and protective factors influence the outcomes of suicidal behavior and substance use. In turn, findings from these studies should inform researchers who conduct future treatment and prevention studies.

Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5'-HTTLPR) among healthy control subjects but not alcohol-dependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5'-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p<0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of Bmax for paroxetine binding, but not Vmax for serotonin (5-HT) uptake, was lower than that for SS subjects (p<0.05). More L-carriers than their SS counterparts had Vmax for 5-HT uptake below 200 nmol/10(7) platelets-min (p<0.05) and Bmax for paroxetine binding below 600 nmol/mg protein (p<0.06). Current drinking (drinks per day during the past 14 days) correlated positively with Km and Vmax of platelet 5-HT uptake (p<0.05) and negatively with Bmax, but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with Km and Vmax of platelet 5-HT uptake (p<0.05) and B(max), but not Kd, of paroxetine binding (p<0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.

The effects of alcohol on laboratory-measured impulsivity after L: -Tryptophan depletion or loading.

RATIONALE: Indirect evidence supports a link between serotonergic activity and individual differences in the behavioral response to alcohol, but few studies have experimentally demonstrated that an individual's biological state can influence the sensitivity to alcohol-induced behaviors. OBJECTIVE: Our purpose was to temporarily modify serotonin synthesis in healthy individuals to determine how altered biological states may interact with alcohol administration to affect impulsive behavior. MATERIALS AND METHODS: In a repeated-measures design, 18 normal controls consumed a 50-g L: -tryptophan (Trp) depleting (ATD) or loading (ATL) amino-acid beverage that temporarily decreased or increased (respectively) serotonin synthesis before receiving either a moderate dose of alcohol (0.65 g/kg) or placebo. All participants completed three impulsivity testing sessions on each of the five experimental days. Session one was a baseline session. Session two included testing after ATD-only or ATL-only. Session three included: (1) placebo after ATL (ATL+PBO); (2) placebo after ATD (ATD+PBO); (3) alcohol after ATL (ATL+ALC); (4) alcohol after ATD (ATD+ALC); and (5) Alcohol-only conditions. Impulsivity was assessed using the Immediate Memory Task (Dougherty et al., Behav Res Methods Instrum Comput 34:391-398, 2002), a continuous performance test yielding commission errors that have been previously validated as a component of impulsive behavior. RESULTS: Primary findings were that ATD-only increased impulsive responding compared to ATL-only, and ATD+ALC increased commission errors to levels higher than either the ATL+ALC or Alcohol-only conditions. CONCLUSIONS: These findings demonstrate that reduced serotonin synthesis can produce increased impulsivity even among non-impulsive normal controls, and that the behavioral effects of alcohol are, in part, dependent on this biological state.

Effects of acute topiramate dosing on methamphetamine-induced subjective mood.

Clinical studies have shown that topiramate, a sulphamate-substituted fructopyranose derivative, might be an efficacious treatment for alcohol dependence, smoking cessation within an alcohol-dependent population, and cocaine dependence. Mechanistically, topiramate's therapeutic effects have been hypothesized to be due to inhibition of cortico-mesolimbic dopamine function, the primary substrate that governs the acquisition, maintenance, and reinstatement of goal-directed behaviour towards seeking abused drugs. Predicated on this hypothesis, we tested in 10 methamphetamine-dependent individuals (three females) whether low- or high-dose (15 or 30 mg i.v.) methamphetamine-induced positive subjective effects and reinforcement can be antagonized by low- or high-dose (100 or 200 mg orally) topiramate using a placebo-controlled, cross-over, factorial design. Methamphetamine administration was associated with orderly, prototypical, and significant increases on measures of stimulation, euphoria, craving, and reinforcement; however, some dysphoric symptoms also emerged. Topiramate alone showed a non-significant trend towards mild reductions in positive mood and reinforcement; yet topiramate appeared to accentuate the appreciation of methamphetamine-induced stimulation and euphoria significantly, but not craving or reinforcement. The experimental combination of topiramate and methamphetamine appeared to be safe and well tolerated, with few adverse events. Acute dosing with up to 200 mg topiramate appears to enhance, rather than attenuate, the positive subjective effects of methamphetamine. Perhaps this indicates a partial inhibition of methamphetamine's reinforcing effects. Thus, testing chronically administered or higher doses, or both, of topiramate would be necessary to determine conclusively whether or not it can attenuate the positive subjective and reinforcing effects of methamphetamine.

Effects of topiramate on methamphetamine-induced changes in attentional and perceptual-motor skills of cognition in recently abstinent methamphetamine-dependent individuals.

Methamphetamine-dependent individuals often cite the need to maintain enhanced cognitive performance and attention as a reason for continuing or relapsing to drug-taking. Further, methamphetamine addicts might not comply with taking a potentially therapeutic medication if it had a profound effect on these cognitive processes. Topiramate, a sulfamate-substituted fructopyranose derivative, has been suggested as a putative therapeutic medication for treating methamphetamine dependence. Examination of topiramate's effects on cognitive performance and attention is a clinically and scientifically important component of understanding its potential therapeutic profile. In 10 male and female individuals who met DSM-IV criteria for methamphetamine dependence, we examined the effects of low (50 mg b.i.d.)- and high (100 mg b.i.d.)-dose topiramate - in both the presence and absence of low (15 mg)- and high (30 mg)-dose intravenous methamphetamine--on cognitive performance, attention, and concentration on the rapid visual information processing task and the digit symbol substitution test. Intravenous methamphetamine enhanced cognitive performance, attention, and concentration among recently withdrawn methamphetamine addicts--an effect that hitherto had not been well characterized. Topiramate's cognitive effects were mixed and rather paradoxical, with a tendency to improve attention and concentration both alone and in the presence of methamphetamine while worsening psychomotor retardation. No deleterious interaction occurred between topiramate and methamphetamine on any of these cognitive processes. While clinical studies with topiramate should prepare participants for possible psychomotor retardation, the cognitive effects profile observed would not likely present an important obstacle to compliance in motivated patients. Topiramate's complicated cognitive effects among methamphetamine addicts need more comprehensive examination.