-
Laeknabladid May 2024MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy... (Review)
Review
MDMA is a potential novel treatment for post-traumatic stress disorder (PTSD). Our goal is to review current knowledge on MDMA and its use in MDMA-assisted psychotherapy for PTSD. Literature searches were done on PubMed, Web of Science and Google Scholar and references reviewed in identified articles. MDMA-assisted therapy for PTSD usually consists of a few preparatory sessions before two or three sessions where one or two oral doses of MDMA are given along with supportive psychotherapy. The therapy is delivered in the presence of two therapists for about eight hours each time. In addition, the patient receives up to 9 integrative sessions in due course. This use of MDMA as a part of psychotherapy for PTSD is proposed to lessen the psychological distress that often arises in the processing of traumatic events to facilitate the treatment process and reduce the risk of drop-out. Recent studies indicate that MDMA-assisted psychotherapy reduces PTSD symptoms and is generally well tolerated. These studies are necessary if this MDMA-assisted treatment is to be approved by licensing authorities. There is an urgent need for new effective treatments for PTSD and for comparisons between this MDMA-assisted psychotherapy and currently approved psychotherapies with and without MDMA-use.
Topics: Humans; Stress Disorders, Post-Traumatic; Treatment Outcome; Psychotherapy; N-Methyl-3,4-methylenedioxyamphetamine; Hallucinogens; Combined Modality Therapy
PubMed: 38713560
DOI: 10.17992/lbl.2024.05.793 -
Advances in Pharmacology (San Diego,... 2024The availability of monoamine neurotransmitters in the brain is under the control of dopamine, norepinephrine, and serotonin transporters expressed on the plasma... (Review)
Review
The availability of monoamine neurotransmitters in the brain is under the control of dopamine, norepinephrine, and serotonin transporters expressed on the plasma membrane of monoaminergic neurons. By regulating transmitter levels these proteins mediate crucial functions including cognition, attention, and reward, and dysregulation of their activity is linked to mood and psychiatric disorders of these systems. Amphetamine-based transporter substrates stimulate non-exocytotic transmitter efflux that induces psychomotor stimulation, addiction, altered mood, hallucinations, and psychosis, thus constituting a major component of drug neurochemical and behavioral outcomes. Efflux is under the control of transporter post-translational modifications that synergize with other regulatory events, and this review will summarize our knowledge of these processes and their role in drug mechanisms.
Topics: Humans; Amphetamine; Biological Transport; Dopamine; Neurotransmitter Agents; Protein Processing, Post-Translational
PubMed: 38467478
DOI: 10.1016/bs.apha.2023.10.003 -
The Journal of Neuroscience : the... Oct 2023Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the...
Prevailing frameworks propose that a key feature of attention-deficit/hyperactivity disorder (ADHD) is lower motivation. An important component of motivation is the willingness to engage in cognitively or physically effortful behavior. However, the degree to which effort sensitivity is impaired in ADHD has rarely been tested, and the efficacy of stimulant medication in ameliorating any such impairments is unclear. Here, we tested 20 individuals with ADHD (11 males, 9 females) who were managed with amphetamine-based medication (dexamfetamine, lisdexamfetamine), and 24 controls (8 males, 16 females). Individuals with ADHD were tested over two counterbalanced sessions, ON and OFF their usual amphetamine-based medication. In each session, participants performed an effort-based decision-making task, in which they were required to choose how much cognitive or physical effort they were willing to engage in return for reward. Our results revealed three main findings. First, individuals with ADHD had lower motivation relative to controls to invest effort in both the cognitive and physical domains. Second, amphetamine increased motivation uniformly across both domains. Finally, the net effect of amphetamine treatment was to mostly restore motivation across both domains of effort relative to healthy controls. These data provide clear evidence for a heightened sensitivity to both cognitive and physical effort in ADHD, and reveal the efficacy of amphetamine-based drugs in restoring effort sensitivity to levels similar to controls. These findings confirm the existence of reduced motivational drive in ADHD, and more broadly provide direct causal evidence for a domain-general role of catecholamines in motivating effortful behavior. A core feature of attention-deficit/hyperactivity disorder (ADHD) is thought to be a heightened aversion to effort. Surprisingly, however, the degree to which effort sensitivity is impaired in ADHD has rarely been tested. More broadly, the relative efficacy of catecholamines in motivating the investment of cognitive and physical effort is unclear. We tested 20 individuals with ADHD ON and OFF amphetamines, and compared their behavior on an effort-based decision-making task to 24 controls. When tested OFF medication, the ADHD group was less cognitively and physically motivated than controls. However, amphetamines led to a comparable increase in motivation across both domains. This demonstrates the efficacy of catecholamines in facilitating domain-general effort, and highlights the broader potential of such drugs to treat disorders of motivation.
Topics: Male; Female; Humans; Attention Deficit Disorder with Hyperactivity; Motivation; Amphetamines; Lisdexamfetamine Dimesylate; Catecholamines; Central Nervous System Stimulants
PubMed: 37666665
DOI: 10.1523/JNEUROSCI.0982-23.2023 -
PloS One 2023Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
Studies that examined the effect of amphetamine or caffeine on spatial working memory (SWM) and verbal working memory (VWM) have used various tasks. However, there are no studies that have used spatial span tasks (SSTs) to assess the SWM effect of amphetamine and caffeine, although some studies have used digit span tasks (DST) to assess VWM. Previous reports also showed that increasing dopamine increases psychosis-like experiences (PLE, or schizotypy) scores which are in turn negatively associated with WM performance in people with high schizotypy and people with schizophrenia. Therefore, the present study aimed to examine the influence of d-amphetamine (0.45 mg/kg, PO), a dopamine releasing stimulant, on SST, DST, and on PLE in healthy volunteers. In a separate study, we examined the effect of caffeine, a nonspecific adenosine receptor antagonist with stimulant properties, on similar tasks.
METHODS
Healthy participants (N = 40) took part in two randomized, double-blind, counter-balanced placebo-controlled cross-over pilot studies: The first group (N = 20) with d-amphetamine (0.45 mg/kg, PO) and the second group (N = 20) with caffeine (200 mg, PO). Spatial span and digit span were examined under four delay conditions (0, 2, 4, 8 s). PLE were assessed using several scales measuring various aspects of psychosis and schizotypy.
RESULTS
We failed to find an effect of d-amphetamine or caffeine on SWM or VWM, relative to placebo. However, d-amphetamine increased a composite score of psychosis-like experiences (p = 0.0005), specifically: Scores on Brief Psychiatric Rating Scale, Perceptual Aberrations Scale, and Magical Ideation Scale were increased following d-amphetamine. The degree of change in PLE following d-amphetamine negatively and significantly correlated with changes in SWM, mainly at the longest delay condition of 8 s (r = -0.58, p = 0.006).
CONCLUSION
The present results showed that moderate-high dose of d-amphetamine and moderate dose of caffeine do not directly affect performances on DST or SST. However, the results indicate that d-amphetamine indirectly influences SWM, through its effect on psychosis-like experiences.
CLINICAL TRIAL REGISTRATION NUMBER
CT-2018-CTN-02561 (Therapeutic Goods Administration Clinical Trial Registry) and ACTRN12618001292268 (The Australian New Zealand Clinical Trials Registry) for caffeine study, and ACTRN12608000610336 for d-amphetamine study.
Topics: Humans; Dextroamphetamine; Caffeine; Healthy Volunteers; Dopamine; Australia; Amphetamine; Double-Blind Method
PubMed: 37440493
DOI: 10.1371/journal.pone.0287538 -
Sante Publique (Vandoeuvre-les-Nancy,... 2024Sexual and gender diverse individuals (SGDI) report higher usage of methamphetamine in sexual contexts. They face difficulties making sense of their experiences and...
CONTEXT
Sexual and gender diverse individuals (SGDI) report higher usage of methamphetamine in sexual contexts. They face difficulties making sense of their experiences and being heard in services. Peer researchers (individuals with lived experience) were involved in a participatory study on methamphetamine consumption.
OBJECTIVES
1) To describe the opportunities and challenges of involving peer researchers in all stages of the research process; 2) To discuss how this involvement could address the epistemic injustice experienced by SGDI who practice chemsex.
METHODOLOGY
The peer-researcher participatory process was documented through a journal and meeting notes, which were analyzed through the framework of epistemic injustice. This notion refers to the mechanisms that prevent the knowledge of a person or group from being heard and considered legitimate.
RESULTS
The contribution of peer researchers was highly valued and raised questions. Their in-depth knowledge facilitated data analysis and guided knowledge dissemination, promoting the transformation of current services. Their presence also helped to establish relationships of trust with the study population.
DISCUSSION
This connection with the study population can create expectations for services that may require a significant level of involvement from researchers. The team’s commitment to improving services can generate a mistaken perception of a lack of objectivity.
Topics: Humans; Substance-Related Disorders; Sexual Behavior; Methamphetamine
PubMed: 38360772
DOI: No ID Found -
Expert Review of Neurotherapeutics 2023Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with symptoms that may persist in up to 90% of adults diagnosed during childhood and... (Review)
Review
INTRODUCTION
Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with symptoms that may persist in up to 90% of adults diagnosed during childhood and continue to cause significant impairment throughout the lifespan. In the United States (US), amphetamine and methylphenidate formulations have been available to treat ADHD for several decades. Only one nonstimulant, atomoxetine, was available for the treatment of ADHD in adults until recently. In April 2022, a second nonstimulant, viloxazine extended-release (VLX-ER), became available in the US for the treatment of adult ADHD. Efficacy was previously established in placebo-controlled trials in children and adolescents.
AREAS COVERED
VLX-ER is a norepinephrine reuptake inhibitor with serotonin activity. The efficacy in adults, adverse event profile, pharmacokinetics, drug-drug interactions, and metabolism of VLX-ER are reviewed.
EXPERT OPINION
Despite the availability of effective pharmacological treatments for ADHD, many patients discontinue treatment in less than 1 year. Stimulants are effective in more than 80% of patients; however, some may have difficulty tolerating them. Although there were no head-to-head studies, the effect size of VLX-ER in an adult efficacy trial was lower than has been shown for stimulants. Nevertheless, the approval of VLX-ER adds another effective ADHD treatment option for adults.
Topics: Adolescent; Child; Humans; Adult; United States; Attention Deficit Disorder with Hyperactivity; Viloxazine; Delayed-Action Preparations; Propylamines; Atomoxetine Hydrochloride; Methylphenidate; Central Nervous System Stimulants; Amphetamine; Attention
PubMed: 37846759
DOI: 10.1080/14737175.2023.2265068 -
Cell Reports. Medicine Jan 2024Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and...
Craving is central to methamphetamine use disorder (MUD) and both characterizes the disease and predicts relapse. However, there is currently a lack of robust and reliable biomarkers for monitoring craving and diagnosing MUD. Here, we seek to identify a neurobiological signature of craving based on individual-level functional connectivity pattern differences between healthy control and MUD subjects. We train high-density electroencephalography (EEG)-based models using data recorded during the resting state and then calculate imaginary coherence features between the band-limited time series across different brain regions of interest. Our prediction model demonstrates that eyes-open beta functional connectivity networks have significant predictive value for craving at the individual level and can also identify individuals with MUD. These findings advance the neurobiological understanding of craving through an EEG-tailored computational model of the brain connectome. Dissecting neurophysiological features provides a clinical avenue for personalized treatment of MUD.
Topics: Humans; Methamphetamine; Craving; Electroencephalography; Brain
PubMed: 38151021
DOI: 10.1016/j.xcrm.2023.101347 -
Drug and Alcohol Review Sep 2023Methamphetamine use is a public health concern that has been associated with comorbid mental health problems. We aim to better understand the relationship between... (Meta-Analysis)
Meta-Analysis Review
ISSUES
Methamphetamine use is a public health concern that has been associated with comorbid mental health problems. We aim to better understand the relationship between methamphetamine use and depression by: (i) systematically reviewing and meta-analysing the risks of depression by methamphetamine use; and (ii) investigating the risk of unmeasured confounding.
APPROACH
A systematic review and meta-analysis were conducted following PRISMA guidelines. EMBASE, PsycINFO and PubMed were searched to identify human studies reporting on the association between methamphetamine or amphetamine use and depressive outcomes. The data were summarised narratively and meta-analysed, stratified by cross-sectional and longitudinal estimates. Unmeasured confounding was assessed by E-values analyses.
KEY FINDINGS
From the 6606 studies that came up from the search, 14 eligible studies were included in the narrative review and had data for meta-analysis. A significant association was found between any use of methamphetamine and any depression outcomes in cross-sectional (odds ratio [OR] = 1.66 [95% confidence interval [CI] 1.34, 2.05]) and longitudinal estimates (OR = 1.18 [95% CI 1.08, 1.28]). People with a methamphetamine use disorder had significantly higher odds of depression than those without (OR = 2.80 [95% CI 1.40, 5.90]). The E-values ranged from 1.28 to 6.30 for cross-sectional studies and from 2.37 to 3.21 for longitudinal studies.
CONCLUSION
Based on limited data, people who used methamphetamine have higher odds of depression than people who do not. There were mostly a low to moderate risk of unmeasured confounding in the longitudinal study results. Future longitudinal studies conducted using causal framework methods are warranted.
Topics: Humans; Depression; Methamphetamine; Longitudinal Studies; Cross-Sectional Studies; Comorbidity
PubMed: 37126460
DOI: 10.1111/dar.13670 -
Acta Neurobiologiae Experimentalis Dec 2023Methamphetamine (METH) is a highly addictive psychostimulant known for its profound impact on the nervous system. Chronic METH use leads to neurotoxicity characterized... (Review)
Review
Methamphetamine (METH) is a highly addictive psychostimulant known for its profound impact on the nervous system. Chronic METH use leads to neurotoxicity characterized by various molecular and structural alterations in the brain. This review article primarily aims to elucidate the mechanisms underlying METH‑induced neurotoxicity. METH's mechanism of action involves the inhibition of dopamine, serotonin, and norepinephrine reuptake, resulting in altered synaptic function. Prolonged METH exposure triggers oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, impaired axonal transport, autophagy, and programmed cell death, ultimately contributing to neurotoxicity. These neurotoxic effects manifest as increased neuronal firing rate, disruptions in intracellular ion balance (Ca2+ and Na+), energy production imbalances, and excessive reactive oxygen species production. The blood‑brain barrier is compromised, leading to structural, functional, and neurochemical alterations, particularly in the fronto‑striatal circuit. While our comprehensive review addresses these intricate molecular and structural changes induced by METH, we also examined the latest therapeutic strategies designed to mitigate neurotoxicity. Our investigation sheds light on the critical need to comprehend the complex pathways underlying METH‑induced neurotoxicity and develop effective treatment approaches.
Topics: Humans; Methamphetamine; Neurotoxicity Syndromes; Central Nervous System Stimulants; Inflammation; Apoptosis
PubMed: 38224280
DOI: 10.55782/ane-2023-2488 -
Journal of Analytical Toxicology Jun 2024Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the...
Illegal amphetamine is usually composed of a racemic mixture of the two enantiomers (S)- and (R)-amphetamine. However, when amphetamine is used in medical treatment, the more potent (S)-amphetamine enantiomer is used. Enantiomer-specific analysis of (S)- and (R)-amphetamine is therefore used to separate legal medical use from illegal recreational use. The aim of the present study was to describe our experience with enantiomer-specific analysis of amphetamine in urine and oral fluid, as well as blood, and examine whether the distribution of the two enantiomers seems to be the same in different matrices. We investigated 1,722 urine samples and 1,977 oral fluid samples from prison inmates, and 652 blood samples from suspected drugged drivers, where prescription of amphetamine was reported. Analyses were performed using ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS). The enantiomer separation was achieved by using a chiral column, and results from the method validation are reported. Samples containing <60% (S)-amphetamine were interpreted as representing illegal use of amphetamine. The distribution of the two enantiomers was compared between different matrices. In urine and oral fluid, the mean amount of (S)-amphetamine was 45.2 and 43.7%, respectively, while in blood, the mean amount of (S)-amphetamine was 45.8%. There was no statistically significant difference in the amount of (S)-amphetamine between urine and oral fluid samples and between urine and blood samples, but the difference was significant in blood compared to oral fluid samples (P < 0.001). Comparison of urine and oral fluid between similar populations indicated that enantiomers of amphetamine can be interpreted in the same way, although marginally higher amounts of (R)-amphetamine may occur in oral fluid. Oral fluid, having several advantages, especially during collection, could be a preferred matrix in testing for illegal amphetamine intake in users of medical amphetamine.
Topics: Humans; Amphetamine; Saliva; Stereoisomerism; Substance Abuse Detection; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Central Nervous System Stimulants
PubMed: 38706158
DOI: 10.1093/jat/bkae038