-
The International Journal of... Aug 2021Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine...
BACKGROUND
Synthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])-presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.
METHODS
The present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.
RESULTS
Each training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.
CONCLUSIONS
These findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.
Topics: Alkaloids; Animals; Behavior, Animal; Benzodioxoles; Central Nervous System Stimulants; Discrimination Learning; Interoception; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Propiophenones; Psychotropic Drugs; Pyrrolidines; Saimiri; Synthetic Cathinone
PubMed: 33909067
DOI: 10.1093/ijnp/pyab017 -
Neuroscience and Biobehavioral Reviews Oct 2016Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by... (Review)
Review
Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse.
Topics: Amphetamine-Related Disorders; Cognition; Humans; Memory Disorders; Methamphetamine; Self Administration
PubMed: 27450578
DOI: 10.1016/j.neubiorev.2016.07.020 -
Scientific Reports Mar 2022Cue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these phenomena develop and...
Temporally dynamic neural correlates of drug cue reactivity, response inhibition, and methamphetamine-related response inhibition in people with methamphetamine use disorder.
Cue-induced drug craving and disinhibition are two essential components of continued drug use and relapse in substance use disorders. While these phenomena develop and interact across time, the temporal dynamics of their underlying neural activity remain under-investigated. To explore these dynamics, an analysis of time-varying activation was applied to fMRI data from 62 men with methamphetamine use disorder in their first weeks of recovery in an abstinence-based treatment program. Using a mixed block-event, factorial cue-reactivity/Go-NoGo task and a sliding window across the task duration, dynamically-activated regions were identified in three linear mixed effects models (LMEs). Habituation to drug cues across time was observed in the superior temporal gyri, amygdalae, left hippocampus, and right precuneus, while response inhibition was associated with the sensitization of temporally-dynamic activations across many regions of the inhibitory frontoparietal network. Methamphetamine-related response inhibition was associated with temporally-dynamic activity in the parahippocampal gyri and right precuneus (corrected p-value < 0.001), which show a declining cue-reactivity contrast and an increasing response inhibition contrast. Overall, the declining craving-related activations (habituation) and increasing inhibition-associated activations (sensitization) during the task duration suggest the gradual recruitment of response inhibitory processes and a concurrent habituation to drug cues in areas with temporally-dynamic methamphetamine-related response inhibition. Furthermore, temporally dynamic cue-reactivity and response inhibition were correlated with behavioral and clinical measures such as the severity of methamphetamine use and craving, impulsivity and inhibitory task performance. This exploratory study demonstrates the time-variance of the neural activations undergirding cue-reactivity, response inhibition, and response inhibition during exposure to drug cues, and suggests a method to assess this dynamic interplay. Analyses that can capture temporal fluctuations in the neural substrates of drug cue-reactivity and response inhibition may prove useful for biomarker development by revealing the rate and pattern of sensitization and habituation processes, and may inform mixed cue-exposure intervention paradigms which could promote habituation to drug cues and sensitization in inhibitory control regions.
Topics: Conditioning, Psychological; Craving; Cues; Humans; Magnetic Resonance Imaging; Male; Methamphetamine; Substance-Related Disorders
PubMed: 35246553
DOI: 10.1038/s41598-022-05619-8 -
Tidsskrift For Den Norske Laegeforening... Oct 2011
Topics: Arrhythmias, Cardiac; Central Nervous System Stimulants; Hallucinogens; Humans; Illicit Drugs; Male; Methamphetamine; N-Methyl-3,4-methylenedioxyamphetamine; Seizures
PubMed: 22016127
DOI: 10.4045/tidsskr.11.0950 -
Fa Yi Xue Za Zhi Dec 2021To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal...
OBJECTIVES
To investigate the inhibitory effect of cholecystokinin octapeptide (CCK-8) binding to cholecystokinin 2 receptor (CCK2R) on methamphetamine (METH)-induced neuronal apoptosis, and to explore the signal transduction mechanism of β-arrestin 2 in CCK-8 inhibiting METH-induced neuronal apoptosis.
METHODS
SH-SY5Y cell line was cultured, and HEK293-CCK1R and HEK293-CCK2R cell line were constructed by lentivirus transfection. Small interfering RNA (siRNA) was used to knockdown the expression of β-arrestin 2. Annexin Ⅴ-FITC/PI staining and flow cytometry were used to detect the apoptotic rate of cells, and Western blotting was used to detect the expression of apoptosis-related proteins.
RESULTS
The apoptosis of SH-SY5Y cells was induced by 1 mmol/L and 2 mmol/L METH treatment, the number of nuclear fragmentation and pyknotic cells was significantly increased, and the expression of apoptosis-related proteins Bax and cleaved caspase-3 were increased. CCK-8 pre-treatment at the dose of 0.1 mmol/L and 1 mmol/L significantly reversed METH-induced apoptosis in SH-SY5Y cells, and inhibited cell nuclear fragmentation, pyknosis and the changes of apoptosis-related proteins induced by METH. In lentivirus transfected HEK293-CCK1R and HEK293-CCK2R cells, the results revealed that CCK-8 had no significant effect on METH-induced changes of apoptosis-related proteins in HEK293-CCK1R cells, but it could inhibit the expression level of apoptosis-related proteins in HEK293-CCK2R cells induced by METH. The inhibitory effect of CCK-8 on METH-induced apoptosis was blocked by the knockdown of β-arrestin 2 expression in SH-SY5Y cells.
CONCLUSIONS
CCK-8 can bind to CCK2R and exert an inhibitory effect on METH-induced apoptosis by activating the β-arrestin 2 signal.
Topics: Apoptosis; Central Nervous System Stimulants; HEK293 Cells; Humans; Methamphetamine; Sincalide
PubMed: 35243844
DOI: 10.12116/j.issn.1004-5619.2021.310206 -
Drug and Alcohol Review Jan 2023Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to... (Meta-Analysis)
Meta-Analysis Review
ISSUES
Cessation of methamphetamine use may result in a characteristic withdrawal syndrome, no medication has been approved for this indication. This systematic review aims to assess the efficacy of pharmacotherapy for methamphetamine withdrawal, the first comprehensive meta-analysis since 2008.
APPROACH
MEDLINE (1966-2020), CINAHL (1982-2020), PsychINFO (1806-2020) and EMBASE (1947-2020) were systematically searched. Studies were included if they were randomised controlled trials (RCT) investigating pharmacological treatments for methamphetamine withdrawal, reviewing outcomes of treatment discontinuation, mental health outcomes, withdrawal symptoms (including craving) and patient safety. The relative risk (RR) and weighted mean difference (MD) were used to meta-analyse dichotomous and continuous data respectively, with 95% confidence intervals. Risk of bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments were conducted.
KEY FINDINGS
Nine RCTs of six medications (n = 242 participants) met inclusion criteria, however, only six trials of four medications (n = 186) could be meta-analysed. Mean sample size across studies was 27 participants, and 88% of participants were male. The quality of evidence in this review varies from low to very low on GRADE assessments. Amineptine may reduce discontinuation rates (RR 0.22, 95% confidence interval [CI] 0.07, 0.72, p = 0.01), and improve global state (MD -0.49, 95% CI -0.80, -0.17), compared with placebo, however, this medication is no longer approved. No other medications improved any domain when compared with placebo. Due to lack of reporting safety profiles could not be established.
CONCLUSIONS
There is insufficient evidence to indicate any medication is effective for the treatment of methamphetamine withdrawal. The poor quality of the evidence indicates a need for better powered, high-quality trials.
Topics: Male; Humans; Female; Substance Withdrawal Syndrome; Methamphetamine; Randomized Controlled Trials as Topic
PubMed: 35862266
DOI: 10.1111/dar.13511 -
Molecules (Basel, Switzerland) Dec 2021The host-guest interactions of cucurbit[7]uril (CB[7]) as host and amphetamine (AMP), methamphetamine (MET) and their enantiomeric forms (S-form and R-form) as guests...
The host-guest interactions of cucurbit[7]uril (CB[7]) as host and amphetamine (AMP), methamphetamine (MET) and their enantiomeric forms (S-form and R-form) as guests were computationally investigated using density functional theory calculations with the recent D4 atomic-charge dependent dispersion corrections. The analysis of energetic, structural and electronic properties with the aid of frontier molecular orbital analysis, charge decomposition analysis (CDA), extended charge decomposition analysis (ECDA) and independent gradient model (IGM) approach allowed to characterize the host-guest interactions in the studied systems. Energetic results indicate the formation of stable non-covalent complexes where R-AMP@CB[7] and S-AMP@CB[7] are more stable thermodynamically than R-MET@CB[7] and S-MET@CB[7] in gas phase while the reverse is true in water solvent. Based on structural analysis, a recognition mechanism is proposed, which suggests that the synergistic effect of van der Waals forces, ion-dipole interactions, intermolecular charge transfer interactions and intermolecular hydrogen bonding is responsible for the stabilization of the complexes. The geometries of the complexes obtained theoretically are in good agreement with the X-ray experimental structures and indicate that the phenyl ring of amphetamine and methamphetamine is deeply buried into the cavity of CB[7] through hydrophobic interactions while the ammonium group remains outside the cavity to establish hydrogen bonds with the portal oxygen atoms of CB[7].
Topics: Amphetamine; Biosensing Techniques; Bridged-Ring Compounds; Density Functional Theory; Hydrogen Bonding; Imidazoles; Methamphetamine; Molecular Structure; Thermodynamics
PubMed: 34946564
DOI: 10.3390/molecules26247479 -
The Western Journal of Emergency... Feb 2023Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency...
INTRODUCTION
Methamphetamine use is on the rise with increasing emergency department (ED) visits, behavioral health crises, and deaths associated with use and overdose. Emergency clinicians describe methamphetamine use as a significant problem with high resource utilization and violence against staff, but little is known about the patient's perspective. In this study our objective was to identify the motivations for initiation and continued methamphetamine use among people who use methamphetamine and their experiences in the ED to guide future ED-based approaches.
METHODS
This was a qualitative study of adults residing in the state of Washington in 2020, who used methamphetamine in the prior 30 days, met criteria for moderate- to high-risk use, reported recently receiving care in the ED, and had phone access. Twenty individuals were recruited to complete a brief survey and semi-structured interview, which was recorded and transcribed prior to being coded. Modified grounded theory guided the analysis, and the interview guide and codebook were iteratively refined. Three investigators coded the interviews until consensus was reached. Data was collected until thematic saturation.
RESULTS
Participants described a shifting line that separates the positive attributes from the negative consequences of using methamphetamine. Many initially used methamphetamine to enhance social interactions, combat boredom, and escape difficult circumstances by numbing the senses. However, continued use regularly led to isolation, ED visits for the medical and psychological sequelae of methamphetamine use, and engagement in increasingly risky behaviors. Because of their overwhelmingly frustrating experiences in the past, interviewees anticipated difficult interactions with healthcare clinicians, leading to combativeness in the ED, avoidance of the ED at all costs, and downstream medical complications. Participants desired a non-judgmental conversation and linkage to outpatient social resources and addiction treatment.
CONCLUSION
Methamphetamine use can lead patients to seek care in the ED, where they often feel stigmatized and are provided little assistance. Emergency clinicians should acknowledge addiction as a chronic condition, address acute medical and psychiatric symptoms adequately, and provide positive connections to addiction and medical resources. Future work should incorporate the perspectives of people who use methamphetamine into ED-based programs and interventions.
Topics: Adult; Humans; Methamphetamine; Motivation; Emergency Service, Hospital; Qualitative Research; Violence
PubMed: 36976607
DOI: 10.5811/westjem.2022.12.58396 -
Neuropsychopharmacology : Official... Feb 2012The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about... (Review)
Review
The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition. Included in the discussion are findings from studies that have assessed the acute and long-term effects of methamphetamine on several domains of cognition, including visuospatial perception, attention, inhibition, working memory, long-term memory, and learning. In addition, relevant neuroimaging data are reviewed in an effort to better understand neural mechanisms underlying methamphetamine-related effects on cognitive functioning. In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures. More importantly, however, the clinical significance of these findings may be limited because cognitive functioning overwhelmingly falls within the normal range when compared against normative data. In spite of these observations, there seems to be a propensity to interpret any cognitive and/or brain difference(s) as a clinically significant abnormality. The implications of this situation are multiple, with consequences for scientific research, substance-abuse treatment, and public policy.
Topics: Amphetamine-Related Disorders; Attention; Cognition; Cognition Disorders; Humans; Memory, Long-Term; Methamphetamine
PubMed: 22089317
DOI: 10.1038/npp.2011.276 -
Substance Abuse Treatment, Prevention,... Jul 2023The high rate of treatment failure is a common problem in the treatment of methamphetamine use. Therefore, the aim of this research is to identify the most common causes...
OBJECTIVE
The high rate of treatment failure is a common problem in the treatment of methamphetamine use. Therefore, the aim of this research is to identify the most common causes of relapse in methamphetamine users.
METHOD
This is a qualitative study and of content analysis type. Information was collected using purposeful sampling and through semi-structured interviews and focus group discussions. The statistical population consisted of all people with the methamphetamine-use disorder in 2022 who were in the abstinence phase and participated in the meetings of the Narcotics Anonymous (NA) Center of Bojnord. Theoretical sampling continued until data saturation. A total of 10 one-on-one interviews were conducted, each lasting between 45 to 80 min. Additionally, two focus group interviews were conducted with six members in each group, lasting between 95 to 110 min and data saturation was achieved through these interviews. Data analysis was done using the content analysis method (Sterling). Recoding and Holsti's method were used to measure reliability; validity was then calculated through content validity assessment.
FINDINGS
The results of the thematic analysis showed that laps and relapse factors were identified and categorized into 5 organizing themes, including negative emotional states, positive emotional states, negative physical states, interpersonal factors, and environmental factors, consisting of 39 basic themes.
RESULT
Identifying the risk factors leading to laps and relapse in methamphetamine users and increasing the knowledge in this field can lay the groundwork for preventive therapeutic interventions in this community.
Topics: Humans; Methamphetamine; Reproducibility of Results; Amphetamine-Related Disorders; Qualitative Research; Recurrence
PubMed: 37420278
DOI: 10.1186/s13011-023-00548-9