Gantt P. Galloway

Psychiatric Symptoms in Methamphetamine Users

The Methamphetamine Treatment Project (MTP) offers the opportunity to examine co-occurring psychiatric conditions in a sample of 1016 methamphetamine users participating in a multisite outpatient treatment study between 1999-2001. Participants reported high levels of psychiatric symptoms, particularly depression and attempted suicide, but also anxiety and psychotic symptoms. They also reported high levels of problems controlling anger and violent behavior, with a correspondingly high frequency of assault and weapons charges. Findings continue to support the value of integrated treatment for co-occurring conditions, especially the importance of training counseling staff to handle psychotic symptoms when needed.

Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals

Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7+/-7.2 years of age), who had used methamphetamine for 15.75+/-8.4 years but were currently abstinent for 2-4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference (P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.

Attentional Control and Brain Metabolite Levels in Methamphetamine Abusers

BACKGROUND Methamphetamine abuse is associated with neurotoxicity to frontostriatal brain regions with concomitant deleterious effects on cognitive processes. METHODS By using a computerized measure of selective attention and single-voxel proton magnetic resonance spectroscopy, we examined the relationship between attentional control and brain metabolite levels in the anterior cingulate cortex (ACC) and primary visual cortex (PVC) in 36 currently abstinent methamphetamine abusers and 16 non-substance-using controls. RESULTS The methamphetamine abusers exhibited reduced attentional control (i.e., increased Stroop interference) compared with the controls (p = .04). Bonferroni-adjusted comparisons revealed that ACC levels of N-acetyl aspartate (NAA)-creatine and phosphocreatine (Cr) were lower and that levels of choline (Cho)-NAA were higher in the methamphetamine abusers compared with the controls, at the adjusted p value of .0125. Levels of NAA-Cr, but not of Cho-NAA, within the ACC correlated with measures of attentional control in the methamphetamine abusers (r = -.41; p = .01) but not in controls (r = .22; p = .42). No significant correlations were observed in the PVC (methamphetamine abusers, r = .19; p = .28, controls, r = .38; p = .15). CONCLUSIONS Changes in neurochemicals within frontostriatal brain regions including ACC may contribute to deficits in attentional control among chronic methamphetamine abusers.

A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence

Abstract: The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals. This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene (5, 20, or 40 mg) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals. Participants concomitantly received 4 sessions of a motivational enhancement therapy (with a medication compliance component) delivered from trained counselors. Although more subjects in the active medication groups terminated the study early secondary to adverse events, the rates did not differ significantly from that of placebo. The 20-mg/d group experienced more insomnia, dizziness, and confusion, while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group. Most of these symptoms were mild and improved over time. Although all subjects had a reduction in heavy drinking days, craving, γ-glutamyl transferase, and carbohydrate-deficient transferrin concentrations over the course of the study, there was no difference between the active medication and placebo groups on these measures. The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups. This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics. However, possibly because of variation among the sites or the comparatively small sample size, there was no evidence of superior efficacy outcomes with nalmefene treatment.

Craving predicts use during treatment for methamphetamine dependence: a prospective, repeated-measures, within-subject analysis.

Clinical lore dictates that craving drives the compulsive use of drugs and alcohol - the core feature of substance dependence. Yet limited research has yielded mixed results, suggesting that craving is neither necessary nor sufficient for continued use or relapse to addictive substances. To investigate the role of craving in compulsive methamphetamine use, 31 men and women in treatment for methamphetamine dependence were asked to indicate, once each week for 12 weeks, the severity of craving that they had experienced during the previous 24 h, using a 100-mm visual analog scale. In a prospective, repeated-measures, within-subject analysis, craving intensity significantly predicted methamphetamine use in the week immediately following each craving report. Craving remained a highly significant predictor in multivariate models controlling for pharmacological intervention, and for methamphetamine use during the prior week. Craving scores that preceded use were 2.7 times higher than scores that preceded abstinence. Risk of subsequent use was 2.5 times greater for scores in the upper half of the scale relative to scores in the lower half. The results obtained demonstrate that, while craving alone may be neither necessary nor sufficient to explain substance addiction, when measured prospectively in a carefully-designed study craving emerges as a salient predictive factor in continued methamphetamine use for patients in treatment for methamphetamine dependence.

Low N-acetyl-aspartate and high choline in the anterior cingulum of recently abstinent methamphetamine-dependent subjects: a preliminary proton MRS study

Studies based on animal models report that methamphetamine (MA) abuse diminishes dopamine (DA) and serotonin innervation in frontal brain regions. In this in vivo human study, we used proton magnetic resonance spectroscopy (MRS), which yields measures of N-acetyl-aspartate (NAA), a marker of living neurons, to examine frontal brain regions possibly affected by methamphetamine dependence (MD). We tested the hypothesis that MD subjects would exhibit abnormally low levels of NAA, referenced to creatine (Cr), in anterior cingulate gray matter. We further hypothesized that the primary visual cortex, which receives relatively less DA innervation than the frontal brain regions, would show normal NAA/Cr ratios in MD subjects. Subjects included nine MD men (mean+/-standard deviation (S.D.)=32.5+/-6.4 years) and nine age-matched control men (mean+/-S.D.=32.7+/-6.8 years). The MD subjects were MA-free for 4-13 weeks. Proton MRS metabolites were expressed as ratios of creatine; the absolute values of which did not distinguish controls and MD subjects. With regard to metabolite ratios, the MD men had significantly lower NAA/Cr in the cingulum (mean+/-standard error (S.E.): control=1.46+/-0.03; MD=1.30+/-0.03; Mann-Whitney P=0.01) but not in the visual cortex (mean+/-S.E.: control=1.64+/-0.06; MD=1.69+/-11; Mann-Whitney P=0.52) relative to controls. These results provide evidence for NAA/Cr deficit that is selective to the anterior cingulum, at least with respect to visual cortex, in MD subjects. The neuronal compromise that these changes reflect may contribute to the attentional deficits and dampened reward system in MD.

Ritanserin in the treatment of alcohol dependence – a multi-center clinical trial

Abstract Four hundred and twenty-three alcohol dependent subjects were enrolled into a 12-week randomized, double-blind, placebo-controlled study to determine the safety and efficacy of the 5-HT2 receptor antagonist, ritanserin (2.5 mg/day or 5 mg/day), in reducing alcohol intake and craving. All subjects received 1 week of single-blind placebo prior to randomization into the 11-week double-blind phase. Additionally, all subjects received weekly individual sessions of manual-guided cognitive-behavioral therapy. Comparing the single-blind period with endpoint, there was approximately a 23% reduction in drinks/day; 34% fall in the total number of drinking days/week; 22% decrease in drinks/drinking day; and a 37% diminution in alcohol craving for all treatment groups. All treatment groups experienced a beneficial clinical outcome as assessed by the Clinical Global Impression Scale. There was, however, no significant difference between treatment groups on any of these measures of alcohol drinking, craving, or clinical outcome. Subjects were of relatively high social functioning at baseline, and this did not change significantly during treatment. Treatment groups did not differ significantly on either medication compliance or reported adverse events. Ritanserin treatment was associated with a dose-related prolongation of subjects’ QTc interval recording on the electrocardiogram. These results suggest that alcohol dependent subjects can show marked clinical improvement within a structured alcohol treatment program. These findings do not support an important role for ritanserin in the treatment of alcohol dependence.

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.

Use patterns and self-reported effects of Salvia divinorum: An internet-based survey

BACKGROUND There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD. OBJECTIVES To characterize the reasons, methods, and reported consequences of SD use. METHODS Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. RESULTS Participants (N=500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1-250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drugs main effects were estimated to last 14.1 ± 12.8 (range 0.5-120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥ 24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety). CONCLUSIONS SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies.

A Randomized, Placebo-Controlled Trial of Sustained-Release Dextroamphetamine for Treatment of Methamphetamine Addiction

Sixty treatment‐seeking individuals with methamphetamine (MA) dependence entered a randomized, placebo‐controlled, double‐blind clinical trial of oral dextroamphetamine (d‐AMP) as a replacement therapy for MA dependence. The subjects took 60 mg sustained‐release d‐AMP for 8 weeks, during which time they received eight 50‐min sessions of individual psychotherapy. Adverse events and urine toxicology for MA were assessed two times a week. There were no serious adverse events. Urine samples containing <1,000 ng/ml of MA were classified as negative for MA. The MA‐negative scores in the d‐AMP group (3.1 ± SD 4.6) were no higher than those in the placebo group (3.3 ± SD 5.3; P > 0.05). However, withdrawal and craving scores were significantly lower in the d‐AMP group (P < 0.05 for both). Although subjects taking d‐AMP did not reduce their use of MA, the significant reductions observed in withdrawal and craving scores in this group support the need for further exploration of d‐AMP as a pharmacologic intervention for MA dependence, possibly at higher doses.