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      Illicit Stimulant Use in Humans Is Associated with a Long-Term Increase in Tremor

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          Abstract

          Use of illicit stimulants such as methamphetamine, cocaine, and ecstasy is a significant health problem. The United Nations Office on Drugs and Crime estimates that 14–57 million people use stimulants each year. Chronic use of illicit stimulants can cause neurotoxicity in animals and humans but the long-term functional consequences are not well understood. Stimulant users self-report problems with tremor whilst abstinent. Thus, the aim of the current study was to investigate the long-term effect of stimulant use on human tremor during rest and movement. We hypothesized that individuals with a history of stimulant use would exhibit abnormally large tremor during rest and movement. Tremor was assessed in abstinent ecstasy users (n = 9; 22±3 yrs) and abstinent users of amphetamine-like drugs (n = 7; 33±9 yrs) and in two control groups: non-drug users (n = 23; 27±8 yrs) and cannabis users (n = 12; 24±7 yrs). Tremor was measured with an accelerometer attached to the index finger at rest (30 s) and during flexion and extension of the index finger (30 s). Acceleration traces were analyzed with fast-Fourier transform. During movement, tremor amplitude was significantly greater in ecstasy users than in non-drug users (frequency range 3.9–13.3 Hz; P<0.05), but was unaffected in cannabis users or users of amphetamine-like drugs. The peak frequency of tremor did not significantly differ between groups nor did resting tremor. In conclusion, abstinent ecstasy users exhibit an abnormally large tremor during movement. Further work is required to determine if the abnormality translates to increased risk of movement disorders in this population.

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          Most cited references 51

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          Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming.

          Normative data stratified by three levels of age (16-59, 60-79, and 80-95 years) and three levels of education (0-8, 9-12, and 13-21 years) are presented for phonemic verbal fluency (FAS) and categorical verbal fluency (Animal Naming). The normative sample, aged 16 to 95 years, consisted of 1,300 cognitively intact individuals who resided in the community. Years of education ranged from 0 to 21. The total number of words in 1 minute for each of the letters F, A, and S was correlated r =.52 with the number of animal names generated in 1 minute. Regression analyses showed that FAS was more sensitive to the effects of education (18.6% of the variance) than age (11.0% of the variance). The opposite relationship occurred for Animal Naming, where age accounted for 23.4% of the variance and education accounted only for 13.6%. Gender accounted for less than 1% of variance for FAS and Animal Naming. The clinical utility of these norms is discussed.
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            The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy").

            The amphetamine derivative (+/-)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.
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              Physiological and pathological tremors and rhythmic central motor control.

              In recent years there has been increasing interest in oscillatory neural activity in the CNS and in the role that such activity may have in motor control. It is thought that physiological tremor may be a manifestation in the periphery of such central oscillatory activity and that some pathological tremors are the result of derangement of these oscillators. This review re-evaluates both early and recent studies on physiological and pathological tremors and other peripheral oscillations in order to gain a new perspective on the nature and function of their central progenitors. This approach, namely using tremor as a 'window' into the function of central oscillations, is particularly suited to human investigations because of the obvious limitations of direct central recording. It is argued that physiological tremor is likely to be multifactorial in origin, with contributions not only from CNS 10-Hz range oscillatory activity, but also from motor unit firing properties, mechanical resonances and reflex loop resonances. Different origins are likely to dominate under different conditions. While some pathological tremors appear to arise as a distortion of central or peripheral components of physiological tremor, others arise de novo, such as the pathological oscillation of 3- to 6-Hz parkinsonian tremor. CNS oscillations outside the 10-Hz range are also found to modulate limb activity in normal individuals, and oscillatory activity exists in other motor systems such as eye movements. Finally, it is shown how studies of peripheral oscillations may help develop hypotheses on the role of CNS oscillations in motor control, including the proposed 'binding' function of synchronized oscillations and the possibility that motor signals could be coded by frequency of modulating oscillation as well as by synaptic connectivity.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2012
                18 December 2012
                : 7
                : 12
                Affiliations
                [1 ]School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
                [2 ]Sansom Institute, University of South Australia, Adelaide, South Australia, Australia
                University of Toronto, Canada
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: GT JW. Performed the experiments: GT SF JK. Analyzed the data: GT SF JK. Wrote the paper: GT SF JK JW.

                Article
                PONE-D-12-26037
                10.1371/journal.pone.0052025
                3525545
                23272201

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Pages: 9
                Funding
                This work was supported by the Clive and Vera Ramaciotti Foundation (Establishment Grant, ID 2974/2010), National Health and Medical Research Council of Australia (GT holds a Career Development Award; ID 627003), and University of South Australia (GT holds a RsearchSA Fellowship, SF held an Australian Postgraduate Award, and JK held a South Australia Rural Health Scholarship). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Anatomy and Physiology
                Neurological System
                Central Nervous System
                Motor Systems
                Nervous System Physiology
                Neuroscience
                Neurophysiology
                Motor Systems
                Motor Systems
                Medicine
                Anatomy and Physiology
                Neurological System
                Motor Systems
                Mental Health
                Psychiatry
                Substance Abuse
                Neurology
                Movement Disorders
                Neuropharmacology

                Uncategorized

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