Methamphetamine Dependence Research Articles

Does Topiramate Add-On Enhance the Response to the MATRIX Program in Individuals with Methamphetamine Use Disorder? A Double-Blinded Randomized Placebo-Controlled Trial

Background: Methamphetamine dependence significantly impacts individuals and society. Treating methamphetamine use disorder is challenging due to limited evidence on effective pharmacotherapies and their interaction with nonpharmacologic interventions. This study evaluated the efficacy of topiramate compared to placebo in treating methamphetamine use disorder among participants in a Matrix program. Methods: Participants were recruited from the Addiction Center of Iran Psychiatric Hospital between January 2020 and June 2023 and randomly assigned to receive either topiramate or a placebo for 12 weeks, alongside Matrix program sessions. Blinding was maintained for participants, personnel, outcome assessors, and statisticians. Main outcomes included craving, desire to use, positive urine amphetamine toxicology rates, and depression severity. Craving was assessed using the Visual Analog Scale (VAS) and the Substance Craving Questionnaire–brief (SCQ-B). The desire to use was evaluated with the Addiction Severity Index (ASI), while depression severity was measured using the Beck Depression Inventory. Data analysis utilized IBM SPSS Statistics® 20.0, employing various statistical tests for comparison. Results: Both groups exhibited improvement in craving as per VAS scores (p=0.007), with greater reduction in the topiramate group; however, no significant difference was found between groups (p=0.06). The negative urine toxicology rates showed no significant difference (Hazard ratio=1.15, 95% CI: 0.75, 1.78). Depression scores decreased in both groups without significant between-group differences (p=0.78). Conclusion: The findings do not support the efficacy of topiramate in enhancing outcomes within a Matrix program for individuals with methamphetamine use disorder.

Mindfulness-based relapse prevention targeting psychological craving and trait mindfulness in young Chinese women with methamphetamine dependence: a randomized controlled trial.

We recruited 58 MA-dependent young adult females from a compulsory isolation drug rehabilitation center in Sichuan Province and randomly divided them into an MBRP group (n = 29) and a control group (n = 29) according to their degree of psychological craving. The MBRP group received 2 hours of MBRP training twice a week for 4 weeks, alongside routine treatment at the drug rehabilitation center. Meanwhile, the control group solely received routine treatment at the drug rehabilitation center without any additional interventions. The assessment was conducted before and immediately after the intervention, with the Compulsive Drug Use Scale (OCDUS) used to assess craving and the Five-Factor Mindfulness Scale (FFMQ) used to assess trait mindfulness. Also, a "mental feedback monitoring balance" instrument was used to assess concentration and relaxation during some training sessions. This randomized trial was conducted to evaluate the effectiveness of decreasing psychological craving and increasing trait mindfulness. At baseline, there were no significant differences in total or dimension scores for FFMQ or OCDUS between the two groups (all P > 0.05). After the intervention, the repeated measures ANOVA showed a significant time main effect on changes in observing, non-judging, and non-reacting scores (all P < 0.05), and a significant interaction effect between time and group on both FFMQ total score and OCDUS score (P < 0.01 or P < 0.05). Mental feedback monitoring indicated significant improvement in concentration and relaxation after breath meditation exercises (P < 0.05 or P < 0.001). Additionally, the MBRP group showed improved relaxation during the body scan exercise (P < 0.01). MBRP training can improve the trait mindfulness of MA addicts and reduce psychological cravings effectively.

Psychometric validation of the Chinese Version of the stimulant relapse risk scale (SRRS) in patients with methamphetamine use disorder

BackgroundEvaluating the risk of relapse is a pivotal step in the treatment of patients with methamphetamine use disorder (MUD). The 30-item Stimulant Relapse Risk Scale (SRRS) was originally developed in Japan to meet the demand. This study examined the reliability, validity, and factor structure of the Chinese version of the SRRS for patients with MUD.Methods247 patients with MUD self-rated the Chinese version of the SRRS. Cronbach’s alpha coefficients and inter-item correlation analysis were used to assess the internal consistency reliability. Construct validity was determined through confirmatory factor analysis (CFA), and concurrent validity was examined using the visual analogue scale (VAS) for drug craving and the severity of dependence scale (SDS). We followed the participants for 1 year and assessed the predictive validity based on the correlation of the scores of the Chinese version of the SRRS with the relapse rate within 3, 6, and 12 months of follow-up.ResultsCFA revealed satisfactory model fit estimates for the 22-item Chinese version of the SRRS that consisted of four subscales. The four-factored 22-item Chinese version of the SRRS had adequate internal consistency with Cronbach’s alphas ranging from 0.76 to 0.92. The 22-item Chinese version of the SRRS scores were significantly correlated with the VAS and SDS scores as well as the relapse rate within 3, 6, and 12 months, indicating good concurrent and predictive validity of this scale. The receiver operating characteristic curve revealed a cutoff score of 40 could discriminate between participants with (SDS score ≥ 4) and without (SDS score < 4) methamphetamine dependence (area under the curve = 0.71, p < 0.01).ConclusionsThe 22-item Chinese version of the SRRS that consists of four subscales is a valid and reliable instrument to assess the relapse risk in patients with MUD.

Impulsiveness, suicide, and aggression in a sample of patients with disorders of methyl amphetamine use.

Research has showed a link between patients with methamphetamine dependence and the risk of impulsiveness, aggression, and the risk of suicide. But, this link has not been studied in patients abusing methamphetamine, and it is unknown how impulsiveness, aggression, and the risk of suicide affect them. This cross-sectional study included 130 adult patients diagnosed with the disorder of the use of amphetamine, methamphetamine, cannabinoids, alcohol, other substances, and polysubstance admitted in the Addiction Department for Mental Health. Participants were interviewed for detailed psychiatric history using a structured questionnaire comprising of structured clinical interview for diagnosis I, Arabic version of the Barratt Impulsiveness Scale-11 (BIS), Beck Scale for Suicidal Ideation for the evaluation of suicidal ideation and behavior, and the Aggression and Hostility scale for adolescents and youth. SPSS was used for data analysis; Initial analysis included descriptive statistics: frequencies and percentages for categorical variables and mean and standard deviation for continuous variables. Chi-square test/Fisher's exact test assessed for association between categorical variables, whereas one-way analysis of variance (ANOVA)/ Kruskal-Wallis test was used to compare continuous variables. Patients who used methamphetamine either alone (23%) or with polysubstance (42.6%) were associated with higher suicidal risk than patients who did use other substances than methamphetamine (36.1%). A comparison of the three groups on impulsivity, showed significant difference regarding total scores, motor preservation, and non-planning self-control. No significant differences found between three groups on the aggression scores. There was a higher rate of impulsivity and suicidal risk in patients with methamphetamine dependence in comparison to dependence on other substances, while there was no difference with regard to aggression between patients with methamphetamine dependence and those dependent on other substances. This finding raises the issue of methamphetamine use disorder as a new substance of dependence.

Neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence.

Abuse of methamphetamine has aroused concern worldwide. Stimulant use and sexual behaviours have been linked in behavioural and epidemiological studies. Although methamphetamine-related neurofunctional differences are reported in previous studies, only few studies have examined neurofunctional changes related to methamphetamine and sexual cues in methamphetamine dependence from short- to long-term abstinence. Neurofunctional changes were measured using a cue-reactivity task involving methamphetamine, sexual, and neutral cues in 20 methamphetamine abusers who were evaluated after a short- (1 week to 3 months) and long-term (10-15 months) abstinence. Five brain regions mainly involved in the occipital lobe and the parietal lobe were found with the group-by-condition interaction. Region-of-interest analyses found higher sexual-cue-related activation than other two activations in all five brain regions in the long-term methamphetamine abstinence group while no group differences were found. Negative relationships between motor impulsivity and methamphetamine- or sexual-cue-related activations in the left middle occipital gyrus, the superior parietal gyrus and the right angular gyrus were found. The findings suggested that methamphetamine abstinence may change the neural response of methamphetamine abusers to methamphetamine and sexual cues, and the neurofunction of the five brain regions reported in this study may partly recover with long-term methamphetamine abstinence. Given the use and relapse of methamphetamine for sexual purposes, the findings of this study may have particular clinical relevance.

Proteomic Landscape Associated with Cognitive Impairment in Individuals with Long-term Methamphetamine Dependence.

Methamphetamine (METH) is a highly addictive drug that directly affects the central nervous system. METH use not only harms the user's health but also poses risks and costs to society. Prolonged METH dependence has been shown to impair cognition, which may be the primary factor in impulsive drug-seeking behaviors and high relapse rates. However, the molecular mechanisms underlying METH addiction and METH-induced cognitive decline remain poorly understood. To illuminate the potential molecular mechanisms underpinning METH addiction, we compared serum protein expression levels between 12 long-term METH users and 12 healthy controls using label-free quantitative proteomics. Bioinformatic analyses were conducted to determine functional networks and protein-protein interactions. In total, 23 differentially expressed proteins were identified between the two groups. The differentially expressed proteins were related to cognitive dysfunction, neuroinflammation, immune impairment, metabolic disturbances, and calcium binding and regulation. These 23 proteins may underpin the multi-system damage induced by chronic METH exposure. Our findings provide novel insights into the molecular basis of METH addiction and inform potential prevention and treatment strategies for individuals with METH dependence.

The impact of methamphetamine use and dependence: A systematic review on the cognitive-behavioural implications for road safety

Methamphetamine (MA) users are over-represented in vehicle crash statistics but under-represented in the road safety research literature. This systematic review evaluates the current research base relating to MA use and its associated cognitive-behavioural outcomes; and aims to discuss the implications that these findings may have towards driving and future road safety research directions. Following PRISMA guidelines, a literature search was conducted on research studies using six different databases. Inclusion criteria were acute and chronic MA use in humans, with outcome variables relating to cognitive performance, behavioural tendencies, or psychopathology. Primary exclusion criteria included outcomes that were not directly translatable to road safety outcomes (e.g., health) or very specific samples that may have confounded the effects of MA use (e.g., prisoners). In total, 101 publications met the criteria for inclusion in the review. The literature showed that firstly, acute use (but not abuse) of MA may lead to cognitive enhancements, although these findings are not likely translatable to real-world use. Secondly, evidence suggested that chronic MA use is associated with cognitive impairments, self-regulatory difficulties, and increased aggression, suggesting that MA users may be at a significantly increased risk on the road, in a variety of domains. In addition, chronic MA use has been linked to a range of psychological issues (e.g., psychosis; anxiety; depression), which may exacerbate the negative cognitive-behavioural effects of MA. Finally, abstinence from MA was shown to reduce the aversive impacts of chronic MA use, although cognitive improvements have been demonstrated to take much longer, compared to behavioural and psychopathology conditions. The limitations associated with the current MA literature base were evaluated and methodological suggestions were made for future research to better understand the effect of MA use patterns on driving performance and behaviour.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine-induced gut microbiota dysbiosis.

Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum, has potential health-promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA-induced CPP and hyperactivity. Interestingly, LBP improved MA-induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum, Gordonibacter, and Ileibacterium. MA exposure induced the co-occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short-chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA-induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

BackgroundDrug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese.MethodsA total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping.ResultsBoth single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction.ConclusionsThese findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Epigenome-wide association study on methamphetamine dependence.

Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.

The role of orexin receptors within the CA1 area in the acquisition and expression of methamphetamine place preference

Treatment of Methamphetamine (METH) use disorder has become a crucial public health issue. The orexin system manipulation has provided promising evidence to attenuate addictive-like behaviors. This study explored the role of the orexin 1 receptor and orexin 2 receptor (OX1R and OX2R) in the CA1 area of the hippocampal formation in the acquisition and expression of METH-induced place preference. Animals were subjected to bilateral administration of different dosages (1, 3, 10, and 30 nmol/0.5 μl DMSO per side) of a selective OX1R antagonist, SB334867, or selective OX2R antagonist, TCS OX2 29 into the CA1 area throughout the conditioning phase or once on the post-conditioning phase in separate control and experimental groups. Behavioral data revealed that both OX1R (10 nmol; P < 0.01 and 30 nmol; P < 0.001) and OX2R (10 nmol; P < 0.05 and 30 nmol; P < 0.001) antagonism during the conditioning phase could block the formation of METH place preference dose-dependently. In addition, intra-CA1 microinjection of SB334867 on the post-conditioning phase attenuated the expression of METH place preference in a dose-dependent manner (3 nmol; P < 0.05, 10 nmol; P < 0.01 and 30 nmol; P < 0.001) whereas intra-CA1 administration of TCS OX2 29 only at the highest dosage (30 nmol) declined the expression of METH place preference (P < 0.01). It was also indicated that the suppressive effects of orexin receptor blockade on the METH-seeking behavior in the CA1 area were anatomically specific to this area. These findings support the possibility of targeting the orexin system to develop novel and successful pharmacological options for the treatment of METH dependence.

Model-based and model-free mechanisms in methamphetamine use disorder.

People with methamphetamine use disorder (MUD) struggle to shift their behaviour from methamphetamine-orientated habits to goal-oriented choices. The model-based/model-free framework is well suited to understand this difficulty by unpacking the computational mechanisms that support experienced-based (model-free) and goal-directed (model-based) choices. We aimed to examine whether 1) participants with MUD differed from controls on behavioural proxies and/or computational mechanisms of model-based/model-free choices; 2) model-based/model-free decision-making correlated with MUD symptoms; and 3) model-based/model-free deficits improved over six weeks in the group with MUD. Participants with MUD and controls with similar age, IQ and socioeconomic status completed the Two-Step Task at treatment commencement (MUD n = 30, Controls n = 31) and six weeks later (MUD n = 23, Controls n = 26). We examined behavioural proxies of model-based/model-free decisions using mixed logistic regression, and their underlying mechanisms using computational modelling. At a behavioural level, participants with MUD were more likely to switch their choices following rewarded actions, although this pattern improved at follow up. At a computational level, groups were similar in their use of model-based mechanisms, but participants with MUD were less likely to apply model-free mechanisms and less likely to repeat rewarded actions. We did not find evidence that individual differences in model-based or model-free parameters were associated with greater severity of methamphetamine dependence, nor did we find that group differences in computational parameters changed between baseline and follow-up assessment. Decision-making challenges in people with MUD are likely related to difficulties in pursuing choices previously associated with positive outcomes.

The association between neuropsychiatric effects of substance use and occurrence of endoplasmic reticulum and unfolded protein response: A systematic review

IntroductionThis systematic review aimed to assess the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response (UPR) through comprehensive electronic search of existing literature and review of their findings. MethodsA comprehensive electronic literature search was carried out on research articles published between 1950 to July 2023 through major databases, such as Scopus, Web of Science, Google Scholar, PubMed, PsycINFO, EMBASE, Medline and Cochrane Library. ResultsA total of 21 research articles were selected for review, which were comprised of sixteen animal studies, four human studies and one study on postmortem human brain samples. The selected studies revealed that alcohol, methamphetamine, cocaine, opioid and kratom exposures contributed to neuropsychiatric effects: such as decline in learning and memory function, executive dysfunction, alcohol, methamphetamine, opioid, and kratom dependence. These effects were associated with activation and persistent of ER stress and UPR with elevation of BiP and CHOP expression and the direction of ER stress is progressing towards the PERK-eIF2α-ATF4-CHOP pathway and neuronal apoptosis and neurodegeneration at various regions of the brain. In addition, regular kratom use in humans also contributed to elevation of p-JNK expression, denoting progress of ER stress towards the IRE1-ASK1-JNK-p-JNK pathway which was linked to kratom use disorder. However, treatment with certain compounds or biological agents could reverse the activation of ER stress. ConclusionsThe neuropsychiatric effects of alcohol, methamphetamine, cocaine, opioid and kratom use may be associated with persistent ER stress and UPR.

Association Analysis of a GSTP1 Functional Polymorphism with Methamphetamine Dependence and Associated Symptoms in a Multiethnic Malaysian Population

Methamphetamine (METH) is a psychostimulant that is highly addictive and has been widely linked to the adverse effect on brain. METH-induced oxidative stress can be effectively protected by glutathione S-transferases (GSTs). Genetic polymorphism of GST gene family may affect the susceptibility of METH users to its dependence and associated symptoms. Therefore, this study investigated the association of a functional single nucleotide polymorphism rs1695 of GSTP1 gene with METH-induced symptoms and dependence in a Malaysian population, including Malay, Chinese, Kadazan-Dusun, and Bajau ethnic groups. Genotyping for GSTP1 rs1695 polymorphism from 230 METH-dependent male subjects and 232 healthy male controls was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP). For statistical analyses, the χ2 test and Fisher’s were performed in this research. The results showed a significant difference between GSTP1 rs1695 polymorphism and METH dependence in the Malay and Chinese populations. Our findings suggest that the GSTP1 rs1695 polymorphism may have possibility to methamphetamine dependence in the Malay and Chinese populations but not in other ethnicities. Furthermore, the Malay ethnic group who carried the -105G allele might have a protective role for METH-induced mania.

Methamphetamine (MA) use and MA-induced psychosis are associated with increasing aberrations in the compensatory immunoregulatory system, interleukin-1α, and CCL5 levels

There are only a few studies reporting on the immunological profiles of methamphetamine (MA) use, MA dependency, or MA-induced psychosis (MAP). This study measured M1 macrophage, T helper (Th)-1, Th-2, growth factor, and chemokine profiles, as well as the immune inflammatory response system (IRS) and compensatory immunoregulatory system (CIRS) in peripheral blood samples from patients with MA use (n = 51), MA dependence (n = 47), and MAP (n = 43) in comparison with controls (n = 32). We discovered that persistent MA use had a robust immunosuppressive impact on all immunological profiles. The most reliable biomarker profile of MA use is the combination of substantial CIRS suppression and a rise in selected pro-inflammatory cytokines, namely CCL27 (CTACK), CCL11 (eotaxin), and interleukin (IL)-1α. In addition, MA dependency is associated with increased immunosuppression, as demonstrated by lower stem cell factor levels and higher IL-10 levels. MAP is related to a significant decrease in all immunological profiles, particularly CIRS, and an increase in CCL5 (RANTES), IL-1α, and IL-12p70 signaling. In conclusion, long-term MA use and dependency severely undermine immune homeostasis, whereas MAP may be the consequence of increased IL-1α – CCL5 signaling superimposed on strongly depleted CIRS and Th-1 functions. The widespread immunosuppression established in longstanding MA use may increase the likelihood of infectious and immune illness or exacerbate disorders such as hepatitis and AIDS. Furthermore, elevated levels of CCL5, CCL11, CCL27, IL-1α, and/or IL-12p70 may play a role in the peripheral (atherosclerosis, cutaneous inflammation, immune aberrations, hypospermatogenesis) and central (neuroinflammation, neurotoxic, neurodegenerative, depression, anxiety, and psychosis) side effects of MA use.

Blockade of the orexin-2 receptors within the ventral tegmental area facilitates the extinction and prevents the reinstatement of methamphetamine-seeking behavior

Repeated use of methamphetamine (METH) causes severe effects on the central nervous system, associated with an increased relapse rate. The orexinergic system is highly implicated in the reward circuitry and may be a promising target for treating psychostimulant dependency. The present study aimed to investigate the involvement of the orexin system, mainly the orexin-2 receptors (OX2R) in the ventral tegmental area (VTA) in the extinction and reinstatement of METH-seeking behavior using a conditioned place preference (CPP) paradigm. To this end, animals received METH (1 mg/kg; sc) for a 5-day conditioning period. Then, in the first set of experiments, different groups of rats were given intra-VTA TCS OX2 29 (1, 3, 10, or 30 nmol/0.3 μl DMSO) as an OX2R antagonist over a 10-day extinction period. In another experiment, after the extinction period, a different set of animals received a single dose of TCS OX2 29 (1, 3, 10, or 30 nmol) before the priming dose of METH (0.25 mg/kg; sc) on the reinstatement day. The results revealed that TCS OX2 29 (10 and 30 nmol) remarkably facilitated the extinction of rewarding properties of METH (P < 0.001 for both doses). Furthermore, TCS OX2 29 (3, 10, or 30 nmol) significantly suppressed the METH-induced reinstatement (3 nmol; P < 0.05, 10 nmol; P < 0.01, and 30 nmol; P < 0.001). In conclusion, the current study revealed that the orexinergic system, specifically the VTA OX2R, is involved in METH-seeking behaviors and that manipulation of this system can be considered a potential therapeutics in treating METH dependency.

Targeted magnetic resonance imaging (tMRI) of small changes in the T1 and spatial properties of normal or near normal appearing white and gray matter in disease of the brain using divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences.

This review describes targeted magnetic resonance imaging (tMRI) of small changes in the T1 and the spatial properties of normal or near normal appearing white or gray matter in disease of the brain. It employs divided subtracted inversion recovery (dSIR) and divided reverse subtracted inversion recovery (drSIR) sequences to increase the contrast produced by small changes in T1 by up to 15 times compared to conventional T1-weighted inversion recovery (IR) sequences such as magnetization prepared-rapid acquisition gradient echo (MP-RAGE). This increase in contrast can be used to reveal disease with only small changes in T1 in normal appearing white or gray matter that is not apparent on conventional MP-RAGE, T2-weighted spin echo (T2-wSE) and/or fluid attenuated inversion recovery (T2-FLAIR) images. The small changes in T1 or T2 in disease are insufficient to produce useful contrast with conventional sequences. To produce high contrast dSIR and drSIR sequences typically need to be targeted for the nulling TI of normal white or gray matter, as well as for the sign and size of the change in T1 in these tissues in disease. The dSIR sequence also shows high signal boundaries between white and gray matter. dSIR and drSIR are essentially T1 maps. There is a nearly linear relationship between signal and T1 in the middle domain (mD) of the two sequences which includes T1s between the nulling T1s of the two acquired IR sequences. The drSIR sequence is also very sensitive to reductions in T1 produced by Gadolinium based contrast agents (GBCAs), and when used with rigid body registration to align three-dimensional (3D) isotropic pre and post GBCA images may be of considerable value in showing subtle GBCA enhancement. In serial MRI studies performed at different times, the high signal boundaries generated by dSIR and drSIR sequences can be used with rigid body registration of 3D isotropic images to demonstrate contrast arising from small changes in T1 (without or with GBCA enhancement) as well as small changes in the spatial properties of normal tissues and lesions, such as their site, shape, size and surface. Applications of the sequences in cases of multiple sclerosis (MS) and methamphetamine dependency are illustrated. Using targeted narrow mD dSIR sequences, widespread abnormalities were seen in areas of normal appearing white matter shown with conventional T2-wSE and T2-FLAIR sequences. Understanding of the features of dSIR and drSIR images is facilitated by the use of their T1-bipolar filters; to explain their targeting, signal, contrast, boundaries, T1 mapping and GBCA enhancement. Targeted MRI (tMRI) using dSIR and drSIR sequences may substantially improve clinical MRI of the brain by providing unequivocal demonstration of abnormalities that are not seen with conventional sequences.

Increased AGE-RAGE axis stress in methamphetamine abuse and methamphetamine-induced psychosis: Associations with oxidative stress and increased atherogenicity.

Methamphetamine (MA)-induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE-RAGE stress or whether the latter is associated with MIP. This case-control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE-RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE-RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA-induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE-RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE-RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE-RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity.

Rats have low motivation to self-administer oral methamphetamine across increasing response requirements

Methamphetamine (METH) is a psychostimulant drug that has become increasingly popular in recent years, with overdose deaths more than doubling during the second half of the 2010s. As methamphetamine use disorder rates continue to increase, finding effective treatment strategies to decrease METH dependence is important. Animal studies are well-suited for studying the neurobiological mechanisms underlying addiction-like behaviors. Although individuals can ingest METH orally, few studies have examined oral METH self-administration in animals. Mice show decreased responding for oral METH as the response requirement increases across sessions. The purpose of the current study was to determine if rats show a similar decrease in motivation to earn oral METH across increasing response requirements. Sixteen Sprague Dawley rats were trained to emit a response in an aperture to receive a 0.1-ml METH solution (40 mg/l) according to an FR 1 schedule. The FR requirement increased across sessions to a terminal FR 10. Responses for METH decreased significantly when an FR 10 schedule was used. These results suggest that rats, similarly to mice, have low motivation to self-administer oral METH.

A New Protocol of Methamphetamine Dependence Treatment with Taper-Up-Off Treatment of Opium Tincture, a New Hope to Cure the Methamphetamine Addiction

Methamphetamine is a neurotoxic drug and highly addictive stimulant, which causes a significant psychological dependence in use disorder and potential brain damage even in the first use disorder. Despite decades of research, no approved pharmacotherapy is available for methamphetamine (METH) use disorder, and behavioral therapies are faced with a great lack of long-term recovery and a high rate of relapse. Opium tincture is air-dried Papaver somniferum latex, formulated for oral administration. The present study aimed to evaluate the effectiveness of the new protocol for taper up-off method of opium tincture used for treatment of methamphetamine addiction in Iran, for more than 10 years. In the present study, the effectiveness of the Opium tincture taper-up-off treatment method for methamphetamine dependence called “Dezhakam step time (DST) for methamphetamine” was assessed. We used data collected via the “Congress 60” a nongovernmental organization in Iran, dedicated to addiction treatment with the DST method, from Jan 2018 until December 2020. We evaluated the treatment safety, success, and relapse rate in methamphetamine dependents treated in the “Congress 60” organization with the DST for methamphetamine method. All subjects were tested using Urine drug monitoring for both opioid and methamphetamine use after the treatment period and during the next two years as a follow-up. Findings revealed 89 percent of successful treatments for methamphetamine dependence and only 11 percent of substance abuse relapses in two years follow up. Also, less than one percent of the subjects that finished the treatment program abused opioids in two years follow up. Findings suggest the safety and effectiveness of the Opium tincture taper-up-off method in the treatment of methamphetamine dependence. The findings of the study may help to a better understanding of a safe potential novel method for methamphetamine dependence treatment and its effects on psychological dependence on psychostimulants.