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Biomedicine & Pharmacotherapy =... May 2023Methamphetamine (METH) is one of the psychostimulants most widely abused in the world. METH abuse can lead to severe neurotoxicity. The blood-brain barrier (BBB) is a... (Review)
Review
Methamphetamine (METH) is one of the psychostimulants most widely abused in the world. METH abuse can lead to severe neurotoxicity. The blood-brain barrier (BBB) is a natural barrier separating the central nervous system (CNS) from the peripheral blood circulation, which can limit or regulate the exchange of toxic substances, molecules, ions, etc., to maintain the homeostasis of CNS. Long-term or high dose abuse of METH can cause structural or functional abnormalities of the BBB and increase the risk of neurodegenerative diseases. In this review, we discussed the mechanisms of METH-induced BBB dysfunction, summarized the risk factors that could exacerbate METH-induced BBB dysfunction, and introduced some potential therapeutic agents. It would provide an important basis and direction for the prevention and treatment of BBB dysfunction induced by METH.
Topics: Humans; Blood-Brain Barrier; Central Nervous System Stimulants; Methamphetamine; Amphetamine-Related Disorders; Neurotoxicity Syndromes
PubMed: 37002574
DOI: 10.1016/j.biopha.2023.114478 -
International Review of Neurobiology 2022Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs... (Review)
Review
Experimentation with psychoactive drugs is often initiated in the peri-adolescent period, but knowledge of differences in the outcomes of peri-adolescent- vs adult-initiated exposure is incomplete. We consider the existing animal research in this area for (meth)amphetamines. Established for a number of phenotypes, is lower sensitivity of peri-adolescents than adults to acute effects of (meth)amphetamines, including neurotoxic effects of binge-level exposure. More variable are data for long-term consequences of peri-adolescent exposure on motivational and cognitive traits. Moreover, investigations often exclude an adult-initiated exposure group critical for answering questions about outcomes unique to peri-adolescent initiation. Despite this, it is clear from the animal research that (meth)amphetamine exposure during the peri-adolescent period, whether self- or other-administered, impacts brain motivational circuitry and cognitive function, and alters adult sensitivity to other drugs and natural rewards. Such consequences occurring in humans have the potential to predispose toward unfortunate and potentially disastrous family, social and livelihood outcomes.
Topics: Adolescent; Animals; Brain; Cognition; Humans; Methamphetamine; Models, Animal
PubMed: 34801166
DOI: 10.1016/bs.irn.2021.06.011 -
The Western Journal of Medicine Apr 1999During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has... (Review)
Review
During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.
Topics: Amphetamine-Related Disorders; Cardiovascular System; Central Nervous System; Central Nervous System Stimulants; Humans; Methamphetamine
PubMed: 10344175
DOI: No ID Found -
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 -
Biological Psychiatry Jun 2019Disruptions in the decision-making processes that guide action selection are a core feature of many psychiatric disorders, including addiction. Decision making is...
BACKGROUND
Disruptions in the decision-making processes that guide action selection are a core feature of many psychiatric disorders, including addiction. Decision making is influenced by the goal-directed and habitual systems that can be computationally characterized using model-based and model-free reinforcement learning algorithms, respectively. Recent evidence suggests an imbalance in the influence of these reinforcement learning systems on behavior in individuals with substance dependence, but it is unknown whether these disruptions are a manifestation of chronic drug use and/or are a preexisting risk factor for addiction.
METHODS
We trained adult male rats on a multistage decision-making task to quantify model-free and model-based processes before and after self-administration of methamphetamine or saline.
RESULTS
Individual differences in model-free, but not model-based, learning prior to any drug use predicted subsequent methamphetamine self-administration; rats with lower model-free behavior took more methamphetamine than rats with higher model-free behavior. This relationship was selective to model-free updating following a rewarded, but not unrewarded, choice. Both model-free and model-based learning were reduced in rats following methamphetamine self-administration, which was due to a decrement in the ability of rats to use unrewarded outcomes appropriately. Moreover, the magnitude of drug-induced disruptions in model-free learning was not correlated with disruptions in model-based behavior, indicating that drug self-administration independently altered both reinforcement learning strategies.
CONCLUSIONS
These findings provide direct evidence that model-free and model-based learning mechanisms are involved in select aspects of addiction vulnerability and pathology, and they provide a unique behavioral platform for conducting systems-level analyses of decision making in preclinical models of mental illness.
Topics: Animals; Behavior, Addictive; Decision Making; Male; Methamphetamine; Models, Psychological; Rats; Reinforcement, Psychology
PubMed: 30737015
DOI: 10.1016/j.biopsych.2018.12.017 -
Addiction Science & Clinical Practice Aug 2023We examined acceptability of and preferences for potential medications for treating methamphetamine use disorder (MUD) among people who use methamphetamine and examined...
INTRODUCTION
We examined acceptability of and preferences for potential medications for treating methamphetamine use disorder (MUD) among people who use methamphetamine and examined how benefits and drawbacks of methamphetamine use affect perceived acceptability and preferences.
METHODS
We conducted qualitative interviews as part of a larger study in 2019-2020. The interview assessed patterns of substance use (including methamphetamine), benefits and drawbacks of methamphetamine use, and interest in a medication to treat MUD. Analysis used an inductive thematic approach, guided by three primary questions: (1) would participants be interested in taking a potential medication for MUD?; (2) what effects would they would like from such a medication?; and (3) what would their ideal treatment route and schedule be (e.g. daily pill, monthly injection)?.
RESULTS
We interviewed 20 people reporting methamphetamine use in the past 3 months (10 from Reno, Nevada, USA and 10 from Rio Arriba County, New Mexico, USA). Seven used exclusively methamphetamine, while thirteen used other substances in addition to methamphetamine. Most were enthusiastic about a potential medication to treat MUD. Of those who were not interested (n = 5), all indicated no current concerns about their methamphetamine use. Perceived functional benefits of methamphetamine use (i.e., energy, counteracting opioid sedation, and improved social and emotional wellbeing) informed preferences for a replacement-type medication that would confer the same benefits while mitigating drawbacks (e.g., psychosis, hallucinations, withdrawal). Opinions on preferred dosing varied, with some preferring longer acting medications for convenience, while others preferred daily dosing that would align with existing routines.
CONCLUSION
Participants were excited about a potential for a medication to treat MUD. Their preferences were informed by the functional role of methamphetamine in their lives and a desire to maintain the stimulant effects while mitigating harms of illicit methamphetamine. Treatment outcomes that emphasize functioning and wellbeing, rather than abstinence, should be explored.
Topics: Humans; Methamphetamine; Qualitative Research; Analgesics, Opioid; Emotions
PubMed: 37587515
DOI: 10.1186/s13722-023-00401-1 -
Chemical & Pharmaceutical Bulletin 2023We have developed a fluorescence detection-liquid chromatography (HPLC-FL) method that involves sample pretreatment by solid-phase dispersive extraction (SPDE) and...
We have developed a fluorescence detection-liquid chromatography (HPLC-FL) method that involves sample pretreatment by solid-phase dispersive extraction (SPDE) and solid-phase fluorescence derivatization for the simple and rapid analysis of methamphetamine (MA) in urine. This method uses a reversed-phase polymeric solid-phase gel to clean up analytes in SPDE, followed by fluorescence derivatization with 9-fluorenylmethyl chloroformate (FMOC) in the solid-phase. The optimal conditions for SPDE and solid-phase fluorescence derivatization were obtained when J-SPEC PEP was used as the solid-phase gel and 0.5 mmol/L FMOC in 50 mmol/L borate buffer solution (pH 10) was used as the fluorescence derivatization reagent. The recovery experiment of MA in urine yielded a clean chromatogram with no interfering peaks, demonstrating the validity of our method; the recoveries were 83.6% when spiked at a low concentration level (100 ng/mL) and 80.7% when spiked at a high concentration level (1000 ng/mL). Compared with the conventional liquid-phase method, the reaction product (FMOC-MA) of solid-phase fluorescence derivatization had higher stability. Reaction rate constants were calculated by changing the temperature conditions, and physicochemical parameters, including activation energy and activation entropy involved in the degradation reaction, were obtained from the Arrhenius plot and analyzed thermodynamically. Taken together, our results suggest that the HPLC-FL method with SPDE and solid-phase fluorescence derivatization for sample pretreatment provides a simple and rapid means of analyzing MA in urine samples.
Topics: Methamphetamine; Chromatography, High Pressure Liquid; Chromatography, Liquid
PubMed: 36596509
DOI: 10.1248/cpb.c22-00216 -
Tidsskrift For Den Norske Laegeforening... May 2013Since the summer of 2010, there has been an epidemic of deaths related to paramethoxymethamphetamine (PMMA) in Norway. We present a review of the pharmacology and... (Review)
Review
BACKGROUND
Since the summer of 2010, there has been an epidemic of deaths related to paramethoxymethamphetamine (PMMA) in Norway. We present a review of the pharmacology and toxicology of the substance.
MATERIAL AND METHOD
The review is based on a literature search in the databases PubMed, Ovid and MEDLINE. A discretionary selection was made of relevant articles.
RESULTS
Paramethoxymethamphetamine and paramethoxyamphetamine (PMA) are two so-called designer amphetamines which appear from time to time on the illegal narcotics market in many countries. They are frequently sold as ecstasy or amphetamine, often mixed with amphetamine or methamphetamine. The substances, known on the street as «Death», have potent serotonergic effects and are associated with significant toxicity. Many deaths have been reported worldwide, even after intake of an «ordinary user dose». The narcotic effect is not very pronounced and the onset is slow, which may lead to unintentional overdosing.
INTERPRETATION
In cases of severe intoxation that are apparently related to intake of amphetamine or ecstasy, PMMA/PMA intoxation should be suspected.
Topics: Amphetamines; Designer Drugs; Hallucinogens; Humans; Methamphetamine; Norway; Poisoning
PubMed: 23652145
DOI: 10.4045/tidsskr.12.0417 -
European Journal of Pharmacology Jun 2011We have previously reported that selective blockade of brain dopamine D(3) receptors by SB-277011A significantly attenuates cocaine self-administration and...
We have previously reported that selective blockade of brain dopamine D(3) receptors by SB-277011A significantly attenuates cocaine self-administration and cocaine-induced reinstatement of drug-seeking behavior. In the present study, we investigated whether SB-277011A similarly inhibits methamphetamine self-administration and methamphetamine-induced reinstatement to drug-seeking behavior. Male Long-Evans rats were allowed to intravenously self-administer methamphetamine (0.05 mg/kg/infusion) under fixed-ratio 2 (FR2) or progressive-ratio (PR) reinforcement conditions, and some rats were tested for methamphetamine-induced reinstatement of drug-seeking behavior after extinction of self-administration. The effects of SB-277011A on each of these methamphetamine-supported behaviors were then tested. Acute intraperitoneal (i.p.) administration of SB-277011A failed to alter methamphetamine self-administration under FR2 reinforcement, but significantly lowered the break-point for methamphetamine self-administration under PR reinforcement. SB-277011A also significantly inhibited methamphetamine-triggered reinstatement of extinguished drug-seeking behavior. Overall, these data show that blockade of dopamine D(3) receptors by SB-277011A attenuates the rewarding and incentive motivational effects of methamphetamine in rats, supporting the development of selective dopamine D(3) antagonists for the treatment of methamphetamine addiction.
Topics: Animals; Binding, Competitive; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Male; Methamphetamine; Nitriles; Rats; Receptors, Dopamine D3; Self Administration; Tetrahydroisoquinolines
PubMed: 21466803
DOI: 10.1016/j.ejphar.2011.02.046 -
Missouri Medicine 2022Methamphetamine use is increasing in the U.S. and in Missouri, as are the number of deaths associated with its use. Many systemic and mental health issues are associated... (Review)
Review
Methamphetamine use is increasing in the U.S. and in Missouri, as are the number of deaths associated with its use. Many systemic and mental health issues are associated with methamphetamine use or methamphetamine use disorder (MUD). Given the range of health issues associated with methamphetamine use or MUD, a collaborative approach to the care of patients can improve outcomes. This article provides an overview of a collaborative approach to caring for patients using or have used methamphetamine, from the perspective of the primary care, behavioral and dental clinician.
Topics: Humans; Methamphetamine; Missouri; Patient Care; Patients
PubMed: 36588648
DOI: No ID Found