Differences in white matter connectivity between treatment-resistant and treatment-responsive subtypes of schizophrenia.

Schizophrenia is a heterogeneous disorder exhibiting variable responsiveness to treatment between individuals. Previous work demonstrated that white matter abnormalities may relate to antipsychotic response but no study to date has examined differences between first-line treatment responders (FLR) and clozapine-eligible individuals receiving first-line antipsychotics. The current study aimed to establish whether differences in white matter structure exist between these two cohorts. Diffusion-weighted images were acquired for 15 clozapine-eligible and 10 FLR participants. Measures of fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) were obtained and between-group t-tests interrogating differences in FA were conducted. To investigate the neural basis of a decrease in FA, the significant cluster from FA analysis was masked and used to obtain mean RD and AD measures for that region. Those who were clozapine-eligible had significantly lower FA in the body of the corpus callosum (p < 0.05), associated with a significant increase in mean RD compared with FLR (p < 0.001). No difference in mean AD was observed for this region. These data reveal differences in diffusion measures between FLR and those eligible for clozapine and suggest that lower FA and greater RD in the corpus callosum could exist as a biomarker of treatment resistance in people with schizophrenia.

Policy barriers to evidence-based practices in vocational rehabilitation for people with psychiatric disabilities in New Zealand.

BACKGROUND: Most working-age adults with psychiatric disabilities are not employed yet are interested in being in employment. This goal is achievable for the majority who are interested, with the help of international evidence-based practices in vocational rehabilitation. However, these practices are not widely available in developed countries. OBJECTIVE: To identify whether, and how, the availability of evidence-based vocational rehabilitation is linked to government policy. METHODS: A systematic examination of New Zealand's economic and social policy context to understand how it facilitates or hinders evidence-based vocational rehabilitation for people with psychiatric disabilities. RESULTS: The New Zealand policy context is currently hindering the availability of evidence-based vocational rehabilitation for people with psychiatric disabilities. Whilst policy reform has commenced, it has not yet translated into a purchasing framework free of policy conflicts and barriers. Consequently, the proportion of people with psychiatric disabilities not employed and not participating in the labor market is increasing. CONCLUSIONS: Adopting the policy adjustments identified could expand the availability of evidence-based vocational rehabilitation, reducing the disparity between individual vocational goals and actual labor force activity. This in turn could have national social and economic benefits through reduced welfare dependence, reduced health service utilization, and increased labor force participation.

Upright posture improves affect and fatigue in people with depressive symptoms.

BACKGROUND AND OBJECTIVES: Slumped posture is a diagnostic feature of depression. While research shows upright posture improves self-esteem and mood in healthy samples, little research has investigated this in depressed samples. This study aimed to investigate whether changing posture could reduce negative affect and fatigue in people with mild to moderate depression undergoing a stressful task. METHODS: Sixty-one community participants who screened positive for mild to moderate depression were recruited into a study purportedly on the effects of physiotherapy tape on cognitive function. They were randomized to sit with usual posture or upright posture and physiotherapy tape was applied. Participants completed the Trier Social Stress Test speech task. Changes in affect and fatigue were assessed. The words spoken by the participants during their speeches were analysed. RESULTS: At baseline, all participants had significantly more slumped posture than normative data. The postural manipulation significantly improved posture and increased high arousal positive affect and fatigue compared to usual posture. The upright group spoke significantly more words than the usual posture group, used fewer first person singular personal pronouns, but more sadness words. Upright shoulder angle was associated with lower negative affect and lower anxiety across both groups. LIMITATIONS: The experiment was only brief and a non-clinical sample was used. CONCLUSIONS: This preliminary study suggests that adopting an upright posture may increase positive affect, reduce fatigue, and decrease self-focus in people with mild-to-moderate depression. Future research should investigate postural manipulations over a longer time period and in samples with clinically diagnosed depression.

Varenicline improves motor and cognitive symptoms in early Huntington's disease.

The aim of this study was to describe the effects of varenicline, a smoking cessation aid that acts as a nicotinic agonist, on cognitive function in patients with early clinical Huntington's disease (HD) who were current smokers. Three gene-positive patients transitioning to symptomatic HD were evaluated using the Unified Huntington's Disease Rating Scale part I and III (motor and behavioral subscales) at baseline and after 4 weeks of treatment. Cognitive function was assessed using a touch screen computer-based neurocognitive test battery (IntegNeuro®). Varenicline (1 mg twice daily) significantly improved performance in executive function and emotional recognition tasks. Our case reports describe no clinically significant adverse effects and suggest that varenicline improves aspects of cognitive function in patients with early HD. A randomized controlled study is now underway.

Investigation of the effects of 'piperazine-containing party pills' and dexamphetamine on interhemispheric communication using electroencephalography.

BACKGROUND: 'Piperazine-containing party pills' were marketed and sold as legal alternatives to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. The major constituents of these 'pills' were benzylphenylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP). Despite their popularity, there is a paucity of knowledge about their central effects in humans. This study investigated their effects on human neural processing using electroencephalographic techniques. METHODS: A randomised, double-blind, placebo-controlled study investigated the effects of an acute dose of these compounds on the interhemispheric transfer of information (IHTT) using the Poffenberger task. Reaction time data were also collected. Healthy, right-handed males were given an oral dose of either BZP (n = 13) (200 mg), TFMPP (n = 15) (60 mg), a combination of BZP + TFMPP (n = 15) (100 mg/30 mg), dexamphetamine (n = 16) (20 mg), or placebo (n = 23) and tested both before and 120 min after drug administration. RESULTS: A mixed factorial repeated measures analysis of variance of absolute N160 latency and contrast analysis revealed that only TFMPP (F (1,77) = 17.30, p ≤ 0.001) significantly reduced the absolute N160 latency. Analysis of the IHTT revealed that only TFMPP (F (1,77) = 5.266, p ≤ 0.02) significantly reduced the IHTT, while BZP, BZP + TFMPP and dexamphetamine had no effect. Contrast analysis revealed that both TFMPP (F (1,77) = 17.30, p ≤ 0.001) and placebo (F (1,77) = 15.08, p ≤ 0.001) preserved the laterality of information transfer from one hemisphere to the other. Reaction time (p > 0.05) was not significantly affected by any of the drug treatments. CONCLUSIONS: The usual directional asymmetry (i.e. faster R-to-L transfer relative to L-to-R) observed in healthy control group was absent following the administration of either BZP, BZP + TFMPP or dexamphetamine. Surprisingly, lateralised hemispheric function was not affected by TFMPP. Our findings highlight how the administration of BZP, TFMPP and BZP + TFMPP leads to changes in the pattern of information transfer.

Brain drawings following traumatic brain injury (TBI) and links to illness perceptions and health outcomes - Findings from a population-based study.

OBJECTIVE: Individuals' illness perceptions predict health behaviours and influence functional outcomes. This study examined associations between a novel assessment of illness perceptions, in the form of adult's brain drawings after traumatic brain injury (TBI) and questionnaire measures of illness perceptions, quality of life and post-concussive symptoms. DESIGN: Population-based, prospective longitudinal study examining 245 adults with predominantly mild TBI with high risk of complications. MAIN OUTCOME MEASURES: Participants were asked to draw pictures of what they thought their brain looked like before injury and at baseline and one month post-injury. Drawing characteristics (height, width and percentage damage at one month) were examined in relation to each outcome of interest at six months. RESULTS: Greater damage at one month was associated with more negative illness perceptions (rs = .23), poorer mental health (rs = -.21), and more total post-concussive symptoms (rs = .27 to r = .35) at six months. The extent of damage depicted reduced over time (p < .001). No associations were found between the amount of damage drawn and injury severity, nor the height or width of drawings and injury severity or illness perceptions. CONCLUSION: Drawings post-TBI offer a simple, cost- and time-effective way to begin discussions and improve understanding of peoples' illness perceptions.

Mental health law in New Zealand.

New Zealand has an established history of mental health legislation that sits within a framework of human rights, disability and constitutional protections. We outline a brief history of mental health legislation in New Zealand since its inception as a modern state in 1840. The current legislation, the Mental Health (Compulsory Assessment and Treatment) Act 1992, defines mental disorder and the threshold for compulsory treatment. We describe its use in clinical practice and the wider legal and constitutional context which psychiatrists need to be aware of in their relationships with patients.

Acute effects of BZP, TFMPP and the combination of BZP and TFMPP in comparison to dexamphetamine on an auditory oddball task using electroencephalography: a single-dose study.

RATIONALE: Piperazine-based designer drugs such as benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been marketed and sold as legal alternatives to dexamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. When administered in combination, BZP + TFMPP have been reported to produce drug-drug synergism in rodents by stimulating the release of dopamine and serotonin. OBJECTIVES: This study was to evaluate the acute event-related potential effects of BZP, TFMPP or the combination of BZP + TFMPP compared with dexamphetamine in young healthy male adults. METHODS: A double-blind, randomised, placebo-controlled study investigated the effects of BZP, TFMPP, the combination of BZP + TFMPP, and dexamphetamine on the event-related potentials during an auditory oddball task. Healthy, right-handed males were given a single oral dose of either BZP (200 mg), TFMPP (60 mg), a combination of BZP + TFMPP (100/30 mg), dexamphetamine (20 mg) or placebo (lactose) and tested both before and 120 min after drug administration. RESULTS: A single dose of either TMFPP (t = -2.29, p = 0.03) or dexamphetamine (t = -2.33, p = 0.02) significantly reduced the P300 amplitude. A similar trend was also found in BZP. In contrast, BZP and TFMPP in combination has no effect. Neither P300 latency nor the mean reaction time was affected by any of the drug treatments. In addition, neither the P100 nor the P200 component was significantly affected following any of the drug treatments. CONCLUSIONS: A single oral dose of BZP or TFMPP, but not the combination of BZP/TFMPP, affected auditory sensory-evoked P300 potential in a manner similar to dexamphetamine.

Acute effects of the designer drugs benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) using functional magnetic resonance imaging (fMRI) and the Stroop task--a pilot study.

RATIONALE: A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. OBJECTIVES: In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. METHODS: Thirteen healthy participants aged 18-40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. RESULTS: Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. CONCLUSION: These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP's indirect effects on dopamine release via 5HT2C receptors.

Investigating the microstructural and neurochemical environment within the basal ganglia of current methamphetamine abusers.

BACKGROUND: Methamphetamine is a highly addictive psychostimulant and the medical, social, and economic consequences associated with its use have become a major international problem. Current evidence has shown methamphetamine to be particularly neurotoxic to dopamine neurons and striatal structures within the basal ganglia. A previous study from our laboratory demonstrated larger putamen volumes in actively using methamphetamine-dependent participants. The purpose of this current study was to determine whether striatal structures in the same sample of participants also exhibit pathology on the microstructural and molecular level. METHODS: Diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were carried out in current methamphetamine users (n = 18) and healthy controls (n = 22) to investigate diffusion indices and neurometabolite levels in the basal ganglia. RESULTS: Contrary to findings from previous DTI and MRS studies, no significant differences in diffusion indices or metabolite levels were observed in the basal ganglia regions of current methamphetamine users. CONCLUSIONS: These findings differ from those reported in abstinent users and the absence of diffusion and neurochemical abnormalities may suggest that striatal enlargement in current methamphetamine use may be due to mechanisms other than edema and glial proliferation.

Changes in resting EEG following methadone treatment in opiate addicts.

OBJECTIVE: This study investigated the electrophysiological activity associated with methadone maintenance treatment (MMT). METHODS: The resting EEG spectrum of beta (14.5-30 Hz), alpha (8-13 Hz), theta (4-7.5 Hz) and delta (1.5-3.5 Hz) rhythm were measured in 32 patients undertaking chronic MMT, 17 opiate users and 25 healthy volunteers. Differences in the EEG components of each group were evaluated using a repeated measures Analyses of Variance (ANOVA). Post-hoc comparisons were Bonferroni corrected. RESULTS: Our results show that either patients undertaking MMT or active opiate users exhibited a significant increase in the power of beta and theta bands relative to healthy control subjects. However, the spectral power of patients undertaking MMT fell between that of current opiate users and healthy control subjects on many regional EEG measures. There was an inverse correlation between the power of beta or theta bands and cognitive performance. CONCLUSION: The abnormal neural electrical activity present in those still using illicit opiates might be reduced following MMT. SIGNIFICANCE: The present findings provide further support for MMT of opiate dependence and demonstrates potentially positive effects of substitution treatment on brain function.

Neuropsychological performance of methadone-maintained opiate users.

Methadone maintenance treatment (MMT) has been used to treat opiate dependence since the mid-1960s. Previous studies have investigated the effects of methadone on cognitive function however the findings have been inconsistent. Some report a complete absence of deficits while others report different types of cognitive impairment. Our research aimed to investigate the effects of MMT on cognitive function by comparing the performance of patients currently enrolled in MMT (n=32) with opiate-dependent subjects (n=17) and healthy control subjects (n=25) on a computerised neuropsychological test battery. Both the patients undertaking MMT and the opiate users showed less efficient interaction between visual searching and manually connecting digits and letters during the Switching of Attention Task than the healthy control subjects (F(2,64)=3.25, p=0.05), which indicates deficits in information processing. Nevertheless, the performance of the MMT group was similar to that of healthy control subjects in all other tasks, in contrast to the group of opiate users who performed poorly when compared to healthy control subjects during tests of attention (mean difference (MD)=2.8, 95% confidence interval (CI) (0.9-4.7), p=0.001) and executive function (MD=5.9, 95% CI (1.3-10.5), p=0.007). These findings suggest that cognitive function in patients undertaking MMT is improved compared to those dependent on illicit opiates.

The effects of methylphenidate on cognitive control in active methamphetamine dependence using functional magnetic resonance imaging.

Methamphetamine (MA) dependence is associated with cognitive deficits. Methylphenidate (MPH) has been shown to improve inhibitory control in healthy and cocaine-dependent subjects. This study aimed to understand the neurophysiological effects before and after acute MPH administration in active MA-dependent and control subjects. Fifteen MA-dependent and 18 control subjects aged 18-46 years were scanned using functional magnetic resonance imaging before and after either a single oral dose of MPH (18 mg) or placebo while performing a color-word Stroop task. Baseline accuracy was lower (p = 0.026) and response time (RT) was longer (p < 0.0001) for the incongruent compared to congruent condition, demonstrating the task probed cognitive control. Increased activation of the dorsolateral prefrontal cortex (DLPFC) and parietal cortex during the incongruent and Stroop effect conditions, respectively was observed in MA-dependent compared to control subjects (p < 0.05), suggesting the need to recruit neural resources within these regions for conflict resolution. Post- compared to pre-MPH treatment, increased RT and DLPFC activation for the Stroop effect were observed in MA-dependent subjects (p < 0.05). In comparison to MPH-treated controls and placebo-treated MA-dependent subjects, MPH-treated MA-dependent subjects showed decreased activation of parietal and occipital regions during the incongruent and Stroop effect conditions (p < 0.05). These findings suggest that in MA-dependent subjects, MPH facilitated increased recruitment of the DLPFC for Stroop conflict resolution, and a decreased need for recruitment of neural resources in parietal and occipital regions compared to the other groups, while maintaining a comparable level of task performance to that achieved pre-drug administration. Due to the small sample size, the results from this study are preliminary; however, they inform us about the effects of MPH on the neural correlates of cognitive control in active MA-dependent subjects.

A benzodiazepine impairs the neurogenic and behavioural effects of fluoxetine in a rodent model of chronic stress.

Antidepressant agents such as fluoxetine have been shown to produce neurogenic effects involving transcriptional and translational changes that direct molecular and cellular plasticity. These cellular and molecular events appear necessary to mediate the therapeutic effects of fluoxetine and may be generated through the ability for fluoxetine to regulate BDNF levels. Clinically, benzodiazepines are frequently used in combination with standard antidepressants both for initial treatment and maintenance therapy, especially when comorbid anxiety is present. However, very little is known regarding the consequence of combined treatment of benzodiazepines and antidepressant on the development of clinical effect. The current study therefore examined the effect of co-administration of fluoxetine and the benzodiazepine, diazepam, on hippocampal neurogenesis in the social isolation rodent model of chronic stress. We demonstrate that 9 weeks of social isolation induces a deficit in motivational behaviour with increased anxiety as well as impairment in hippocampal neurogenesis. This was parallelled by reduced BDNF levels in the hippocampus. While treatment with fluoxetine alone for 3 weeks restored anxiety behaviour as well as progenitor cell proliferation and the generation of new hippocampal neurons, this effect was prevented by co-administration with diazepam. This suggests that co-administering benzodiazepines with antidepressants could significantly delay or prevent the cellular and behavioural improvement needed by patients. These findings indicate the need for future clinical studies designed to investigate the combined effects of benzodiazepines and antidepressants in patients.

Extended-release methylphenidate for treatment of amphetamine/methamphetamine dependence: a randomized, double-blind, placebo-controlled trial.

AIMS: To assess the efficacy of methylphenidate as a substitution therapy for amphetamine/methamphetamine dependence in Finland and New Zealand. DESIGN: Parallel-group, double-blind, randomized placebo-controlled trial. SETTING: Out-patient care. PARTICIPANTS: Amphetamine-/methamphetamine-dependent, aged 16-65 years. MEASUREMENTS: The primary outcome measure was presence/absence of amphetamine/methamphetamine in urine samples collected twice weekly. Secondary measures included treatment adherence, alterations in craving scores and self-reported use. Primary analysis was by intention-to-treat (ITT). The study drug, methylphenidate (as Concerta(®) ), was up-titrated over 2 weeks to a maximum dose of 54 mg daily and continued for a further 20 weeks. Doses were given under daily supervision at the clinics. FINDINGS: Seventy-nine participants were randomized (40 methylphenidate; 39 placebo); 76 received allocated treatment and 27 completed the trial. ITT analysis (n = 78) showed no statistically significant difference in the percentage of positive urines between the methylphenidate and placebo arms (odds ratio: 0.95, 95% confidence interval: 0.83-1.08). However, there was a significant difference (P < 0.05) between the active and placebo arms in retention, the placebo arm displaying a significantly lower retention from 6 weeks that persisted until the end of the trial. CONCLUSIONS: The trial failed to replicate earlier findings suggesting that methylphenidate was superior to placebo. The low retention rate confounded the ability to draw firm conclusions about efficacy. The higher retention rate was observed in the methylphenidate arm. Any replication of this work would need to consider alternatives to the rigid clinic attendance criteria, and consider an increased dose.

Neuropsychological assessment of distractibility in mild traumatic brain injury and depression.

Traditional neuropsychological assessments are conducted exclusively in a quiet, distraction-free environment; clients' abilities to operate under busy and distracting conditions remain untested. Environmental distractions, however, are typical for a multitude of real-life situations and present a challenge to clients with frontal-temporal brain injury. In an effort to improve ecological validity, an extension of the traditional neuropsychological assessment was developed, comprising a standardized distraction condition. This allowed cognitive functions to be tested both in the traditional setting and with exposure to a specified audio-visual distraction. The present study (n = 240) investigated how clients with mild Traumatic Brain Injury (mTBI) (n = 80), Major Depression (MDE) (n = 80), and a healthy control sample (n = 80) performed on sub-tests of the Wechsler Adult Intelligence Scale-IV and the Wechsler Memory Scale-IV both in the standard and the distraction conditions. Test effort was controlled. Significant deterioration of performance in the distraction setting was observed among clients with mTBI. In contrast the performance of a healthy control sample remained unchanged. Significant improvement of performance in the distraction setting was documented for clients with MDE. Contrary to their improved performance, depressed clients experienced the distraction setting as more distressing than the control and mTBI group.

Functional and structural brain changes associated with methamphetamine abuse.

Methamphetamine (MA) is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET) and functional and structural magnetic resonance imaging (MRI). The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

Striatal volume increases in active methamphetamine-dependent individuals and correlation with cognitive performance.

The effect of methamphetamine (MA) dependence on the structure of the human brain has not been extensively studied, especially in active users. Previous studies reported cortical deficits and striatal gains in grey matter (GM) volume of abstinent MA abusers compared with control participants. This study aimed to investigate structural GM changes in the brains of 17 active MA-dependent participants compared with 20 control participants aged 18-46 years using voxel-based morphometry and region of interest volumetric analysis of structural magnetic resonance imaging data, and whether these changes might be associated with cognitive performance. Significant volume increases were observed in the right and left putamen and left nucleus accumbens of MA-dependent compared to control participants. The volumetric gain in the right putamen remained significant after Bonferroni correction, and was inversely correlated with the number of errors (standardised z-scores) on the Go/No-go task. MA-dependent participants exhibited cortical GM deficits in the left superior frontal and precentral gyri in comparison to control participants, although these findings did not survive correction for multiple comparisons. In conclusion, consistent with findings from previous studies of abstinent users, active chronic MA-dependent participants showed significant striatal enlargement which was associated with improved performance on the Go/No-go, a cognitive task of response inhibition and impulsivity. Striatal enlargement may reflect the involvement of neurotrophic effects, inflammation or microgliosis. However, since it was associated with improved cognitive function, it is likely to reflect a compensatory response to MA-induced neurotoxicity in the striatum, in order to maintain cognitive function. Follow-up studies are recommended to ascertain whether this effect continues to be present following abstinence. Several factors may have contributed to the lack of more substantial cortical and subcortical GM changes amongst MA-dependent participants, including variability in MA exposure variables and difference in abstinence status from previous studies.

Carbohydrate reward and psychosis: an explanation for neuroleptic induced weight gain and path to improved mental health?

Evidence links dopamine release in the mid-brain to the pathophysiology of psychosis, addiction and reward. Repeated ingestion of refined carbohydrate may stimulate the same mesolimbic dopaminergic pathway, rewarding such eating behaviour and resulting in excessive food intake along with obesity. In this paper, we explore the role of dopamine in reward and psychosis, and discuss how reward pathways may contribute to the weight gain that commonly follows antipsychotic drug use, in people with psychotic illness. Our theory also explains the frequent co-occurrence of substance abuse and psychosis. From our hypothesis, we discuss the use of carbohydrate modified diets as an adjunctive treatment for people with psychosis.

Subjective effects in humans following administration of party pill drugs BZP and TFMPP alone and in combination.

The use of piperazine derivatives, colloquially named 'party pills', has been escalating in New Zealand and worldwide since their introduction in the 1990s. Benzylpiperazine (BZP) is often used alone, or can be combined with trifluoromethylphenylpiperazine (TFMPP). Taken together as an oral dose, they have been reported to produce effects similar to 3, 4-methylenedioxymethamphetamine (MDMA). While the pharmacokinetic data have recently been published, little research has been conducted on the subjective effects of these piperazines on humans. This paper outlines the subjective effects observed following oral doses of BZP (200 mg) and TFMPP (60 mg) alone, or in combination (100/30 mg) compared to placebo. Participants were asked to comment on the subjective effects of each drug using three subjective rating scales-the Addiction Center Research Inventory (ARCI), the Profile of Mood States (POMS), and the Visual Analog Scales (VAS)-before and approximately 120 min after a single dose. BZP showed significant dexamphetamine-like stimulant effects, inducing euphoria, sociability, and drug liking, whereas TFMPP induced fewer stimulant-like effects and increased anxiety, via its serotonergic effects. The combination of BZP and TFMPP induced similar subjective effects, along with well-characterized dexamphetamine- and MDMA-like effects. These subjective data allow for obvious comparisons to be made between party pill drugs and other commonly known stimulants. However, despite estimates of over 20 million doses sold in New Zealand alone and increasing seizures by the Drug Enforcement Administration in the USA, there are no published cases of dependence worldwide. The long-term effects of regular party pill use are also unknown, and create the potential for future research.