Effects Of Methamphetamine Research Articles

Manifestation of Psychosis and Impairments of Executive Functions Emphasize the Interaction of Psychological and Neurological Dysfunctions in People Who Use Methamphetamine

Aim: Cumulative evidence has demonstrated the neurotoxic effect of methamphetamine (Meth) on the central nervous system. Meth can induce psychotic symptoms and impairments of cognitive abilities, including executive function (EF). Method: In this study, we hypothesized the interaction of the neurotoxic effects of Meth on psychotic symptoms and EF performances. The Stroop test evaluated the EF performances, Go/No-Go task, one-back test (OBT), and Wisconsin Card Sorting Test (WCST) in people who use Meth with psychosis (MWP) and without psychosis (MWOP) compared with healthy control participants. Result: The results showed that MWOP and MWP exhibited EF deficits in attention, working memory, and initial conceptualization. Moreover, a deficit in inhibition was observed in MWOP, while poorer processing speed and cognitive flexibility were found in MWP. Conclusion: The correlation between psychotic symptoms and poor EF performances was observed in MWP. These findings underline the interaction of the mechanistic neurotoxic effect of Meth to induce psychological and neurological dysfunctions in people who use Meth.

Construction of a macrophage-tropic subtype C HIV-1 mGreenLantern reporter virus for studies on HIV-1 replication and the impact of methamphetamine.

HIV-1 subtype C viruses are responsible for 50% of global HIV burden. However, nearly all currently available reporter viruses widely used in HIV research are based on subtype B. We constructed and characterized a replication competent HIV-1 subtype C reporter virus expressing mGreenLantern. mGreenLantern sequences were inserted in-frame with nef ATG in HIV-1 IndieC1 . As controls, we employed HIV-1 IndieC1 , HIV-1 ADA, and HIV-1 NLAD8-GFP-Nef viruses. HIV-1 IndieC1-mGreenLantern (HIV-1 IndieC1-mGL ) exhibited characteristics of the parental HIV-1 IndieC1 virus, including its infectivity in TZMbl reporter cells and replication competence in macrophages. To further characterize HIV-1 IndieC1-mGL virus, we tested its responsiveness to CCL2 levels, a characteristic feature of subtype B HIV-1 that is missing in subtype C. CCL2 immunodepletion inhibited the production of HIV-1 ADA and HIV-1 NLAD8-GFP-Nef as expected, but not that of HIV-1 IndieC1-mGL as previously reported. We also tested the effect of Methamphetamine, as its effect is mediated by NF-κB and since subtype C viruses carry an additional copy of NFκB. We found that methamphetamine increased the replication of all viruses tested in macrophages, however, its effect was much more robust for HIV-1 IndieC1 and HIV-1 IndieC1-mGL . Our studies established that HIV-1 IndieC1-mGL retains all the characteristics of the parental HIV-1 IndieC1 and can be a useful tool for HIV-1 subtype C investigations.

Examining the Cardioprotective Effects of Aerobic Exercise Combined with Crocin or Berberine on Methamphetamine-Induced Heart Damage in Female Rats

Background: While the harmful effects of methamphetamine abuse on the heart are well-known, the solutions to deal with these damages are not well-known. Objectives: This study aimed to investigate whether aerobic exercise combined with supplements such as Crocin and Berberine can potentially protect against methamphetamine-induced changes in the heart tissue of female rats. Methods: Forty-two female rats were randomly assigned into seven groups (n = 6). The groups included healthy control, methamphetamine, methamphetamine + exercise, methamphetamine + Crocin, methamphetamine + Berberine, methamphetamine + exercise + Crocin, and methamphetamine + exercise + Berberine group. Methamphetamine (10 mg/kg) was injected intraperitoneally over five days. The animals were administered Crocin via intraperitoneal injection at 40 mg/kg during a four-week withdrawal period. At the same time, Berberine was dissolved in drinking water at 100 mg/kg concentration. The aerobic training consisted of running at 25 m/min for 30 minutes. A light microscope was used to observe the structural changes. Data analysis was performed using non-parametric Kruskal-Wallis and Mann-Whitney U tests by SPSS 26, with a significance level of 5%. Results: The results of the study indicate that methamphetamine use causes hyperemia, inflammation, and histopathological damage in the heart cells and tissue (P = 0.001). The combination of exercise with Crocin significantly eliminated methamphetamine-induced heart tissue damage (P = 0.001) and improved cardio-respiratory endurance compared to control (P = 0.004) and methamphetamine (P = 0.01) groups. The combination of aerobic exercise with Berberine removed methamphetamine-induced heart cell damage (P = 0.001), and improved cardio-respiratory endurance compared to control (P = 0.024) and methamphetamine (P = 0.05) groups. In addition, all intervention groups showed a significant reduction in hyperemia and inflammation compared to the methamphetamine group (P = 0.001). Conclusions: A combination of exercise with either Crocin or Berberine supplements demonstrated potential benefits in mitigating some of the harmful structural effects of methamphetamine and improving cardio-respiratory endurance.

Impact of HIV-1 tat protein on methamphetamine-induced inhibition of vesicular monoamine transporter2-mediated dopamine transport and methamphetamine conditioned place preference in HIV-1 tat transgenic mice

Perturbation of dopamine transmission has been implicated as a contributing factor in HIV-1 associated neurocognitive disorders with concurrent methamphetamine (METH) abuse. We have demonstrated that the HIV-1 protein, transactivator of transcription (Tat), decreases dopamine transport through inhibition of vesicular monoamine transporter2 (VMAT2). This study determined the effects of Tat protein on METH-inhibited VMAT2 function and METH-conditioned place preference (CPP). In vitro exposure of isolated mouse whole brain vesicles to recombinant Tat1-86 or METH displayed a concentration-dependent inhibition of the vesicular [3H]Dopamine uptake, in which a combination of Tat and METH induced a greater reduction of dopamine uptake compared to Tat or METH alone. In vivo, the maximal velocity (Vmax) of vesicular [3H]Dopamine uptake was decreased in inducible Tat transgenic (iTat-tg) mice harvested after treatment with either 21-day doxycycline (Dox) or 14-day METH (3 mg/kg, i.p., daily), whereas these mice treated with both Dox and METH displayed an additive reduction of the Vmax compared to either Tat or METH alone. Moreover, Dox-induced Tat expression increased METH-CPP in an exposure-dependent manner, with iTat-tg mice demonstrating a 2.3-fold potentiation of METH-CPP compared with Tat null control mice upon administration of Dox for 14 days. Furthermore, a 7-day administration of Dox reinstated extinguished METH-CPP. Collectively, these results suggest a synergistic effect of Tat protein and METH on inhibition of VMAT2-mediated DA transport, potentially contributing to potentiation of METH-CPP in iTat-tg mice.

Dopamine D3 receptor mediates natural and methamphetamine rewards via regulating the expression of miR-29c in the nucleus accumbens of mice

The dopamine D3 receptor (D3R), principally confined to the nucleus accumbens (NAc), is involved in regulating natural and drug rewards; however, the molecular mechanisms underlying the associated process remain unclear. Earlier research has reported the concurrent influence of D3R and miR-29c expressed in the NAc on methamphetamine (METH)-induced reward behaviors and microglial activation, hinting at regulatory roles in reward processing. Herein, we performed viral manipulation-mediating D3R/miR-29c overexpression and inhibition in the whole NAc in male D3R knockout and wild-type mice to investigate this potential relationship. Behavioral responses to the rewarding stimuli were assessed using sucrose preference score, METH-induced locomotor sensitization, and METH-induced conditioned place preference tests. Overall, we observed a notable decrease in the behavioral response to sucrose and METH in D3R-deficient mice, accompanied by the downregulation of miR-29c expression in the NAc. Diminished responses to those rewarding stimuli in D3R-deficient mice primarily stemmed from the reduction of GSK3β activity and subsequent down-regulation of miR-29c in the NAc. Microglial activation in the NAc mediates the effect of D3R-miR-29c deficiency on the reward effects of sucrose and METH. Pharmacological suppression of microglial activity rescued the reduced response in mice lacking D3R-miR-29c in the NAc. Overall, this study revealed the mechanism by which D3R regulates both natural and drug rewards via miR-29c in the murine NAc, highlighting the role of the NAc D3R-miR-29c pathway as a critical regulator of rewards, and providing new insights into the role of NAc D3R-miR-29c in encoding rewarding experiences.

Ultra-low doses of methamphetamine suppress 5-hydroxytryptophan-induced head-twitch response in mice during aging.

The head-twitch response (HTR) in mice is considered a behavioral assay for activation of 5-HT 2A receptors in rodents. It can be evoked by direct-acting 5-HT 2A receptor agonists such as (±)-2,5-dimethoxy-4-iodoamphetamine, 5-hydroxytryptamine precursors [e.g. 5-hydroxytryptophan (5-HTP)], and selective 5-hydroxytryptamine releasers (e.g. d -fenfluramine). The nonselective monoamine releaser methamphetamine by itself does not produce the HTR but can suppress both (±)-2,5-dimethoxy-4-iodoamphetamine- and d -fenfluramine-evoked HTRs across ages via concomitant activation of the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors. Currently, we investigated: (1) the ontogenic development of 5-HTP-induced HTR in 20-, 30-, and 60-day-old mice; (2) whether pretreatment with ultra-low doses of methamphetamine (0.1, 0.25, and 0.5 mg/kg, intraperitoneally) can suppress the frequency of 5-HTP-induced HTR at different ages; and (3) whether the inhibitory serotonergic 5-HT 1A or adrenergic α 2 receptors may account for the potential inhibitory effect of methamphetamine on 5-HTP-induced HTR. In the presence of a peripheral decarboxylase inhibitor (carbidopa), 5-HTP produced maximal frequency of HTRs in 20-day-old mice which rapidly subsided during aging. Methamphetamine dose-dependently suppressed 5-HTP-evoked HTR in 20- and 30-day-old mice. The selective 5-HT 1A -receptor antagonist WAY 100635 reversed the inhibitory effect of methamphetamine on 5-HTP-induced HTR in 30-day-old mice, whereas the selective adrenergic α 2 -receptor antagonist RS 79948 failed to reverse methamphetamine's inhibition at any tested age. These findings suggest an ontogenic rationale for methamphetamine's inhibitory 5-HT 1A receptor component of action in its suppressive effect on 5-HTP-induced HTR during development which is not maximally active at a very early age.

Optimizing Brain-Computer Interfaces for Methampetamine Use Disorder through Quantitative Electroencephalography (QEEG) and Transcranial Doppler Analysis: Article Review

A Brain-Computer Interface (BCI) is a system that allows a person to control external devices using only their brain activity. It works by translating brain signals into commands that can be understood by a computer. Several lines of evidence demonstrated the deleterious effect of methamphetamine (MA) on neurological and psychological functions. The use of amphetamines, such as MA, is associated with cerebrovascular complications such as cerebrovascular accidents (CVA) ,hemorrhage, hypoxic damage and vasculitis. Interestingly, while changes to cerebral blood flow (CBF) in response to acute amphetamine exposure have been reported. Transcranial Color Doppler (TCCD) is a non-invasive medical imaging technique that uses ultrasound waves to measure blood flow velocity in the major arteries of the brain, specifically within the circle of Willis. The research paper you referenced explores the use of TCCD as a potential measurement modality for BCIs. Quantitative electroencephalogram (qEEG) is a powerful tool for understanding brain function qEEG can reveal specific brain wave patterns associated with drug addiction, potentially providing insights into the neurobiological mechanisms underlying cravings, withdrawal symptoms, and relapse risk in Methamphetamine User Disorder (MUD). There is growing research interest in using Transcranial dopller as a measurement modality for BCIs.Here are some of the key considerations for using Transcranial doppler in BCIs: Mental Tasks, signal processing and classification, accuracy and reliability. Transcranial doppler provides information about blood flow in specific arteries but lacks detailed spatial information about brain activity. These patterns could vary depending on the type of drug, the severity of addiction, and individual differences. Transcranial doppler in measuring middle cerebral artery (MCA) blood flow velocity parameters (peak systolic velocity (PSV) and mean flow velocity (MFV)). qEEG can help researchers investigate the complex interplay between addiction and other brain disorders, like depression or anxiety. Characteristic qEEG in drugs addiction Increased Theta (4-8 Hz) and delta (1-4 Hz) brain waves are often associated with sleep and relaxation. However, research has shown that individuals with drug addiction may have increased theta and delta activity, particularly in the frontal and temporal regions of the brain. Altered Beta (13-30 Hz) brain waves are generally associated with wakefulness, alertness, and cognitive processing. Studies have observed both increases and decreases in beta activity in individuals with drug addiction, depending on the type of drug, the stage of addiction, and the specific brain regions being examined. The results of this research have important practical implications for building an diagnostic and functional assement with a better understanding of an using technology.

Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse.

Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach. 38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument. Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body. It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.

The Effects of Subchronic Methamphetamine Administration on the NLRP3 Inflammasome, Memory Function, and Hippocampal Morphology

Background: While it is established that addictive doses of methamphetamine correlate with inflammation-mediated neurotoxic pathways, the extent of toxicity resulting from subchronic administration at lower doses remains uncertain. Objectives: This study aimed to investigate the subtle effects of daily subchronic methamphetamine (MA) administration on neuroinflammatory processes, cognitive dimensions, gene expression, and hippocampal morphology. Methods: The experimental study employed a longitudinal design with three groups (G1B, G2B, G3B) receiving methamphetamine (5 mg/kg, intraperitoneally, once daily) for 1, 2, or 3 weeks, respectively. Corresponding control groups (G1A, G2A, G3A) received 0.2 mL of normal saline. Spatial learning, novel object recognition, and passive avoidance tests were conducted to assess spatial, recognition, and fear avoidance memories. Hippocampal morphology was evaluated using Nissl staining, and the expressions of NLRP3, ASC, and caspase-1 genes were measured as markers of neuroinflammation. Results: Statistical analyses, including one-way and two-way ANOVA, showed that subchronic low-dose administration of MA led to significant activation of the inflammasome (NLRP3, ASC, and caspase-1), which may have resulted in pyramidal cell death in the hippocampus. The hippocampal structure in the CA1 region was completely disrupted. Spatial memory and passive avoidance learning were impaired in the MA groups, while recognition memory remained unaffected. Conclusions: The findings suggest that prolonged administration of 5 mg/kg of methamphetamine may be associated with significant inflammasome activation, pyramidal cell death, and mild cognitive decline. Contrary to previous evidence, even lower doses of methamphetamine taken over an extended period could be neurotoxic.

Single-cell RNA-seq Reveals that Methamphetamine Inhibits Liver Immunity with Involvement of Dopamine Receptor D1.

Methamphetamine (METH) is a highly addictive psychostimulant that causes physical and psychological damage and immune system disorder, especially in the liver that contains a significant number of immune cells. Dopamine, a key neurotransmitter in METH addiction and immune regulation, plays a crucial role in this process. Here, we developed a chronic METH administration model and conducted single-cell RNA sequencing (scRNA-seq) to investigate the effect of METH on liver immune cells and involvement of dopamine receptor D1 (DRD1). Our findings reveal that chronic exposure to METH induces immune cell identity shifts from Ifitm3+Macrophage (Mac) and Ccl5+Mac to Cd14+Mac, and from Fyn+CD4+T effector (Teff), CD8+T, and natural killer T cells (NKT) to Fos+CD4+T and Rora+ group 2 innate lymphoid cells (ILC2), along with suppression of multiple functional immune pathways. DRD1 is implicated in regulating certain pathways and identity shifts among the hepatic immune cells. Our results provide valuable insights into development of targeted therapies to mitigate METH-induced immune impairment.

The role of heterodimers formed by histamine H3 receptors and dopamine D1 receptors on the methamphetamine-induced conditioned place preference

RationaleThe rewarding effect of Methamphetamine (METH) is commonly believed to play an important role in METH use disorder. The altered expression of dopamine D1 receptor (D1R) has been suggested to be essential to the rewarding effect of METH. Notably, D1R could interact with histamine H3 receptors (H3R) by forming a H3R-D1R heteromer (H3R-D1R). ObjectivesThis study was designed to specifically investigate the involvement of H3R-D1R in the rewarding effect of METH. MethodsC57BL/6 mice were treated with intraperitoneal injections of a selective H3R antagonist (Thioperamide, THIO; 20 mg/kg), an H1R antagonist (Pyrilamine, PYRI; 10 mg/kg), or microinjections of cytomegalovirus (CMV)-transmembrane domain 5 (TM5) into the nucleus accumbens (NAc). The animal model of Conditioned Place Preference (CPP) was applied to determine the impact of H3R-D1R on the rewarding effect of METH. ResultsMETH resulted in a significant preference for the drug-associated chamber, in conjunction with increased H3R and decreased D1R expression in both NAc and the ventral tegmental area (VTA). THIO significantly attenuated the rewarding effect of METH, accompanied by decreased H3R and increased D1R expression. In contrast, pyrilamine failed to produce the similar effects. Moreover, the inhibitory effect of THIO on METH-induced CPP was reversed by SKF38393, a D1R agonist. Furthermore, SCH23390, a D1R antagonist, counteracted the ameliorative effect of SKF38393 on THIO. Co-immunoprecipitation (CO-IP) experiments further demonstrated the specific interaction between H3R and D1R in METH CPP mice. The rewarding effect of METH was also significantly blocked by the interruption of CMV-transmembrane domain 5 (TM5), but not CMV-transmembrane domain 7 (TM7) in NAc. ConclusionThese results suggest that modulating the activity of H3R-D1R complex holds promise for regulating METH use disorder and serves as a potential drug target for its treatment.

Locomotion changes in methamphetamine and amphetamine withdrawal: a systematic review.

Despite extensive preclinical research over the years, a significant gap remains in our understanding of the specific effects of methamphetamine (METH) and amphetamine (AMPH) withdrawal. Understanding these differences could be pivotal to unveiling the unique pathophysiology underlying each stimulant. This may facilitate the development of targeted and effective treatment strategies tailored to the specific characteristics of each substance. Following PRISMA guidelines, this systematic review was conducted to examine alterations in spontaneous locomotor activity, specifically horizontal activity, in animals experiencing withdrawal from extended and repeated administration of AMPH or METH. Original articles were retrieved from four electronic databases, supplemented by a review of the references cited in the published papers. A total of thirty-one full-length articles (n = 31) were incorporated in the analysis. The results indicated that six studies documented a significant increase in horizontal activity among animals, seven studies reported decreased locomotion, and eighteen studies (8 AMPH; 10 METH) reported no significant alterations in the animals' locomotor activity. Studies reporting heightened locomotion mainly employed mice undergoing withdrawal from METH, studies reporting diminished locomotion predominantly involved rats undergoing withdrawal from AMPH, and studies reporting no significant changes in horizontal activity employed both rats and mice (12 rats; 6 mice). Drug characteristics, routes of administration, animal models, dosage regimens, duration, and assessment timing seem to influence the observed outcomes. Despite more than 50% of papers enlisted in this review indicate no significant changes in the locomotion during the stimulant withdrawal, the unique reactions of animals to withdrawal from METH and AMPH reported by some underscore the need for a more nuanced understanding of stimulant withdrawal.

ChemsexPH: The association between chemsex, HIV status and adherence to antiretroviral therapy among men who have sex with men in the Philippines.

Chemsex, the use of psychotropic drugs before or during sexual intercourse, is associated with various HIV risk factors, including condomless sex and reduced adherence to pre-exposure prophylaxis or antiretroviral therapy (ART). In the Philippines, there are still limited studies exploring the associations between chemsex, HIV status and ART adherence. This study aims to compare recent and lifetime chemsex engagement in association with self-reported HIV status among Filipino men who have sex with men (MSM). We further explored the association between chemsex and ART adherence among people living with HIV engaged in chemsex. A cross-sectional online survey of 479 Filipino MSM was conducted from 3 August to 1 December 2019. Demographic profiles, sexual behaviours, drug use, history of sexually transmitted infections (STIs), chemsex engagement and HIV status were collected and analysed. Bivariable and multivariable logistic regression were employed to assess the association between self-reported HIV status and chemsex engagement. Among the 479 respondents, Filipino MSM engaged in drug use and chemsex were generally older compared to those not engaged in drug use and chemsex (average age 31-33 vs. 29 years old; p<0.05). Methamphetamine was the most common drug for people who reported using drugs. An HIV-positive status was associated with recent chemsex engagement (aOR = 5.18, p<0.05) and a history of STIs (aOR = 2.09, p<0.05). The subgroup analysis showed that 79% (166/200) of persons living with HIV were adherent to ART. There was no significant association found between chemsex and ART adherence in the logistic regression analyses. Chemsex behaviour, particularly recent chemsex engagement, is significantly associated with self-reported HIV status. The emerging data on MSM engaged in chemsex require integration of a more person-centred, comprehensive and robust harm reduction programmes into the existing combination prevention strategies in the country. Health education for Filipino MSM engaged in chemsex should prioritize raising awareness about methamphetamine effects and overdose risks, alongside proper medical management.

Augmentation of intracranial self-stimulation induced by amphetamine-like drugs in Period circadian regulator 2 knockout mice is associated with intracellular Ca2+ levels

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.

The Subjective Sexual Effects of Intravenous Methamphetamine Use in Women

Purpose: This study aimed to identify the sexual effects of methamphetamine on female users and determine the factors that encourage continued use of this substance. Methods: This structured interview study was approved by the Institutional Review Board at Louisiana State University Health Shreveport. The research participants were female volunteers that reported either currently or previously using methamphetamine. One study team member conducted all the interviews similarly to reduce variability between interviews. This individual was a doctorate-level addiction specialist to ensure the integrity and value of the data collection. All interviews were conducted in private offices at the Council on Alcoholism and Drug Abuse of Northwest Louisiana (CADA) facility in Bossier City, LA, between January 25, 2013, and October 7, 2014. Each volunteer provided informed consent to participate in the study. The specialist asked study subjects open-ended questions, and each conversation lasted approximately one hour. The specialist started each interview with an inquiry regarding the participant’s experiences with methamphetamine. The interviewer would particularly ask about the activities in which that participant would become involved immediately after using methamphetamine. The research subject was given time to discuss any sexual effects of using this stimulant without any prompting by the interviewer. If the study participant did not broach this topic during the interview, the specialist would ask them, “How does methamphetamine make you feel?” This “trigger” question was developed with the primary objective of the study in mind, which was identifying the sexual effects of methamphetamine use on females. Descriptive statistical analysis was performed on the data collected from the interviews. Results: Fifty-six interviews were conducted over 1.5 years. The mean age of the research subjects was determined to be 34.5 (± 10.2; range: 18 to 56). The entire study population was comprised of white females. Fifty (90%) of the study subjects utilized methamphetamine through the intravenous route. Most of these intravenous users (96%) had smoked, snorted, or ingested the substance prior to injecting the substance. Forty-four (88%) of the research participants who engaged in intravenous methamphetamine use reported feeling sexual arousal and an immediate sensation of pleasure indistinguishable from that attributed to orgasm when they injected the substance. The methamphetamine had to be of “sufficient amount and of better quality,” according to these subjects, to elicit this effect. None of the individuals interviewed reported a feeling similar to orgasm when they smoked or snorted methamphetamine. Many subjects stated that they engaged in intravenous methamphetamine use as frequently as every two hours to keep experiencing the sexual response, even if they still felt intoxicated. Twelve (21%) of the subjects reported being directed towards intravenous methamphetamine use by other females describing the sexual effects. Twenty-three (47%) of the participants recounted immediate “vapors,” which were described as “cough” or “taste” of the drug. None of the subjects said they had previously shared the sexual component of their experience with methamphetamine use with medical providers. All participants recounted disinhibition regarding sex but not social interactions. They also declared indifference to the consequences of high-risk sexual behavior and unsafe use of needles. Four subjects admitted avoiding hospital settings because they feared their methamphetamine use would be discovered. Conclusion: Female study participants who currently use or previously used methamphetamine reported a sexual response to intravenous use of the substance. Females who use methamphetamine were drawn toward intravenous use for the sexual experience, and those who use intravenous methamphetamine increase the frequency of use to reexperience the sexual response. These findings indicate that the sexual effects attributed to intravenous methamphetamine may contribute to its ongoing and recurrent use.

Methamphetamine and REM sleep deprivation interact to affect behavioral performance in adult and adolescent rats

Drug addiction may result in sleep problems. Importantly, sleep deprivation (SD) is known as an important risk factor for relapse to drug abuse as SD mimics the effects of psychostimulants on dopamine system of the brain. Moreover, aging may affect sleep and drug addiction. This study, therefore, set out to assess the effects of methamphetamine (METH) and REM sleep deprivation (RSD) on locomotor activity, anxiety-like behavior and spatial memory in adult and adolescent rats. Adult and adolescent male Wistar rats received a neurotoxic METH regimen; four subcutaneous injections of 6 mg/kg, at 2 h intervals. Five days later, the animals underwent a 48-h RSD episode using the multiple platforms method. They were then examined using the open field (OF), elevated plus maze (EPM) and Y-maze tasks. We found that the METH and RSD paradigms showed synergistic effects to increase locomotion and risk-taking behavior in both adult and adolescent animals, while only adolescent rats revealed RSD-induced anxiety-like behavior. Moreover, adolescent animals revealed greater sensitization for vertical activity following METH plus RSD episode. In addition, METH and RSD paradigms revealed synergistic effects to impair spatial working memory, but neither METH nor RSD alone affected performance of animals in the Y-maze task. Our findings may indicate that there are important relationships between METH and RSD to induce hyperlocomotion, risk-taking behavior and spatial memory impairment, particularly in adolescent animals. Moreover, it seems that adolescent rats may be more susceptible to anxiety-like behavior and hyperlocomotion than adults.

Review of natural antioxidant plants to overcome the neurotoxic effects of methamphetamine

Background: Methamphetamine (METH) is a psychostimulant substance known for its substantial abuse potential and neurotoxic properties. METH is a second-line drug in certain conditions such as Attention Deficit Hyperactivity Disorder (ADHD), severe obesity, or narcolepsy. Objective: This study aims to compare natural plant antioxidants to overcome neurotoxicity caused by methamphetamine. Method: The authors used a literature review method and collected articles from "PubMed", "Google Scholar", "ScienceDirect", "Scopus" from 2010 - 2023 without excluding old works that are often cited and trusted using the terms “Methamphetamine”, “Neurotoxicity”, “Ipomoea batatas L.”, “Scutellaria baicaleinsis Georgi ”, “Cinnamomum cassia”, “Laurus nobilis L.”, “Aronia melanocarpa”, “Tripterygium wilfordii Hook. f.”, “Gingko biloba L.”, "Centella asiatica (L.)", "Curcuma longa Linn.", "Brassia oleracea L." as inclusion criteria. Result: Several reviewed natural antioxidant plants exhibit pathways and substantial evidence from both in vivo and in vitro studies addressing methamphetamine-induced neurotoxicity. However, Aronia melanocarpa demonstrates a superior LD50 profile, making it the safest choice for consumption. Conclusion: Aronia melanocarpa had the highest LD50 value at 5 g/kg of body weight. Further research is needed to investigate the efficacy of Aronia melanocarpa in addressing methamphetamine-induced neurotoxicity.

Methamphetamine and carbon monoxide co-toxicity: an unusual case report and literature review

BackgroundComprehending the toxic effects of substances co-detected in bodily fluids presents a formidable challenge. The combined toxic effect of carbon monoxide and methamphetamine remains a rarely discussed issue within the realm of scholarly literature. The main objective of this research is to delve into the potential intricacies of death mechanisms, unraveling the profound impact of both CO and methamphetamine on the heart.Case presentationThe cause and mechanism of death of a young man with toxic levels of CO–Hb and low-dose methamphetamine in his bloodstream were discussed in conjunction with the literature in this study. Methamphetamine levels of 30 ng/mL (0.03 mg/L) and 25.8% CO–Hb were detected in the blood of a 25-year-old individual who was found dead and without any disease.ConclusionsAlthough the amounts of methamphetamine and CO–Hb in the blood were not in the deadly range, it was determined that death occurred as a result of the combined action of these substances. In the present case, it was considered that death occurred as a result due to the combined cardiac effect of methamphetamine and CO, before the lethal blood CO level was reached.

Toxic Effects of Methamphetamine on Reproductive Systems, Embryo Development, and Newborns: An Evidence-Based Review.

Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.

Inhibition of GSDMD-dependent pyroptosis decreased methamphetamine self-administration in rats

It is widely believed that the activation of the central dopamine (DA) system is crucial to the rewarding effects of methamphetamine (METH) and to the behavioral outcomes of METH use disorder. It was reported that METH exposure induced gasdermin D (GSDMD)-dependent pyroptosis in rats. The membrane pore formation caused by METH-induced pyroptosis may also contribute to the overflow of DA into the extracellular space and subsequently increase the DA levels in the brain. The present study firstly investigated whether the membrane pore information induced by GSDMD-dependent pyroptosis was associated with the increased DA levels in the ventral tegmental area (VAT) and nucleus accumbens (NAc) of rats self-administering METH and SY-SH5Y cells treated by METH. Subsequently, the effect of pore formation blockade or genetic inhibition of GSDMD on the reinforcing and motivational effect of METH was determined in rats, using the animal model of METH self-administration (SA). METH exposure significantly increased the activity of NLRP1/Cas-1/GSDMD pathway and the presence of pyroptosis, accompanied by the significantly increased DA levels in VTA and NAc. Moreover, intraperitoneal injections of disulfiram (DSF) or microinjection of rAAV-shGSDMD into VTA/NAc significantly reduced the reinforcing and motivational effect of METH, accompanied by the decreased level of DA in VTA and NAc. The results provided novel evidence that METH-induced pyroptosis could increase DA release in VTA and NAc via the NLRP1/Cas-1/GSDMD pathway. Additionally, membrane pores or GSDMD blockade could significantly reduce the reinforcing and motivational effect of METH. In conclusion, blocking GSDMD and membrane pore formation could be a promising potential target for the development of agents to treat METH use disorder.