Active clinical trials for "Amphetamine-Related Disorders"

Illicit use of the psychostimulant "Ecstasy" (3,4-methylenedioxymethamphetamine, MDMA) is considered a major public health issue. In Switzerland, MDMA and congeners are - after cannabis and cocaine - number three in the ranking of the most popular illicit drugs. Worldwide, Ecstasy is estimated to be even the second most popular illicit drug, used by millions of regular users. On the basis of animal data, it is likely that MDMA at high or cumulative doses damages serotonin (5-HT) neurons in the human brain. However, because of a multitude of methodological problems and a limited number of studies conducted in human subjects, no firm conclusions can yet be established whether chronic MDMA exposure produces a long lasting 5-HT deficiency syndrome, with consequent neuropsychiatric risks. To further address the putative neurotoxicity of MDMA in the human brain, we propose that novel functional assays of serotonergic neurotransmission may be useful to clarify this issue. We suggest that a 5-HT challenge study using positron emission tomography (PET) in conjunction with the 5-HT releaser dexfenfluramine [(+)FEN] may test the functional integrity of the 5-HT system in the living human brain. Specifically, in a placebo-controlled study, the 5-HT release capacity of serotonergic neurons shall be investigated by assessing [18F]-altanserin binding to 5-HT2A receptors following (+)FEN challenge in former and continuing MDMA users, and age and sex-matched MDMA-naïve controls. (+)FEN is a potent serotonin releaser without relevant affinity for 5-HT, dopamine (DA) or norepinephrine (NE) receptors, and devoid of acute adverse effects in man. This makes (+)FEN an ideal pharmacological probe to explore functional integrity of serotonin neurotransmission. A second aim of our investigation is to detect possible impairments of cognitive functions and to study their relationship to serotonin neurotransmission as indexed by PET. In the course of the neuroimaging study, the investigators therefore also measure cognitive (e.g. attention, visual and working memory, learning, executive function) and affective functions (e.g. anxiety, impulsivity), suspected to be altered due to chronic MDMA use. Using correlational analyses, the investigators aim to determine if circumscribed regions of altered 5-HT function are associated with specific impairments in cognitive and/or behavioural parameters. We hypothesize that (+)FEN-evoked 5-HT release will discernibly alter availability of 5-HT2A receptors to [18F]-altanserin, with a pattern revealing the spatially heterogeneous vulnerability of 5-HT innervations to MDMA. The investigators predict that [18F]-altanserin volume of distribution (DV) will decline following (+)FEN challenge to a lesser extent in current MDMA users compared to MDMA-naïve control subjects. On the basis of animal data and recent neuroimaging studies in humans, the investigators hypothesize that functional recovery in former MDMA users will be manifest by a normalization or overshoot of the 5-HT release capacity. Our methodology will allow us to quantitatively assess serotonergic functions in the living human brain. The novel combination of (+)FEN-induced release of 5-HT from intracellular storage vesicles and subsequent PET assessment of competitively altered [18F]-altanserin binding at postsynaptic 5-HT2A receptors will provide a more direct biological marker of in vivo serotonin function than has been hitherto available. By applying this new pharmacological challenge/PET neuroimaging approach to groups of current and former users of MDMA, the investigators shall be able to gain important new insight in the debated functional consequences of MDMA use, especially concerning the controversy about the reversibility of 5-HT changes following cessation of MDMA use. Successful completion of this project should have useful implications for public education and harm reduction with respect to MDMA use, and may also facilitate the development of possible treatment options for chronic MDMA users.

The purpose of this study is to determinate the effect of a pre-treatment with centrally acting alpha2-receptor agonist clonidine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that clonidine will attenuate the subjective and cardiovascular response to MDMA.

The purpose of this study is to determinate the effect of a pre-treatment with the combined serotonin (5-HT) and norepinephrine (NE) transport blocker duloxetine on the pharmacodynamics and pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"). The investigators hypothesize that duloxetine will attenuate the subjective and cardiovascular response to MDMA.

The proposed study will evaluate the tolerability, acceptability and potential efficacy of minocycline for the treatment of co-occurring opioid and amphetamine-type stimulant (ATS) dependence. In the proposed clinical trial, all patients will first discontinue illicit opioid and ATS and be inducted onto buprenorphine maintenance treatment (BMT) in the inpatient ward at the department of psychiatry before beginning to receive minocycline. Tolerability and acceptability will be evaluated by assessing the rates of patient retention during treatment, patient satisfaction with treatment and adverse effects during treatment. The potential efficacy of minocycline will be evaluated with regard to the primary outcome measure: reductions in ATS use , based on urine toxicology testing and self-report. Secondary outcome measures include retention, reduction in HIV risk behaviors and improvements in functional status.

Addiction to amphetamine is characterized by alternating phases of intoxication and short abstinence, followed by recurrent drug-craving episodes which result in distress and relapse. Addiction involves a number of neurotransmission systems, including the endocannabinoid system (ECBS). It has been demonstarted that cannabidioids can have physiological, anxiolytic and neuroprotective properties. It has been shown to have multiple therapeutic properties for treating anxiety, schizophrenia and interestingly cannabinoids have been shown to be potentially helpful in treating addiction, due to their effects on various neuronal circuits involved in this disorder. The investigators overall hypothesis is that cannabinoids are an interesting pharmacological contender to decrease amphetamine craving and treat amphetamine addiction.

The purpose of this study is to assess the interactions between intravenous methamphetamine and aripiprazole.

Patients treated for methamphetamine dependence have high rates of relapse, and no pharmacotherapy has yet been demonstrated to be efficacious. Modafinil (d, l-2-[(diphenylmethyl)sulfinyl]acetamide) is a novel wake- and vigilance-promoting agent that is chemically and pharmacologically dissimilar to CNS stimulants. It is well tolerated and has low abuse liability compared to CNS stimulants. Modafinil is FDA approved for a variety of sleep disorders, may relieve methamphetamine withdrawal symptoms, improves cognitive function, has been shown to reduce cocaine use in dependent users, and is safe when coadministered with intravenous methamphetamine. We will conduct a randomized dose ranging clinical trial of modafinil to establish its safety and efficacy as a pharmacotherapy for methamphetamine dependence.

The purpose of this study is to assess the potential interactions between intravenous methamphetamine and oral selegiline.

The purpose of this study is to evaluate tolerability, acceptability and potential efficacy of 4 months of maintenance treatment with Mirtazapine as compared to placebo for patients with co-occurring amphetamine-type stimulant and opioid dependence (COATS) receiving buprenorphine maintenance treatment (BMT) in Kota Bharu.

In this parallel group clinical pharmacology laboratory experiment, we will assess pharmacodynamic interactions (with a focus on cardiovascular effects) of a 15 mg intravenous methamphetamine dose and single oral doses of reserpine (0.5 and 1.0 mg) or placebo.