-
The International Journal on Drug Policy Jun 2024In the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with...
INTRODUCTION
In the United States, methamphetamine use is increasing and the context of its use has changed, with reports of illicitly manufactured fentanyl being mixed with methamphetamine (either deliberately or inadvertently). We explore risk-mitigating actions taken by people who use drugs to protect their health when using methamphetamine in that context.
METHODS
We conducted qualitative interviews with 48 adults (18+) who used methamphetamine in the past three months at two sites in Nevada, USA and two sites in New Mexico, USA. Interviews were recorded, transcribed, and analyzed using thematic analysis.
RESULTS
Respondents described two rationales for employing harm reduction strategies. First, to prevent harm from methamphetamine containing illicit fentanyl, and second, to maintain their general wellbeing while using methamphetamine. Regarding methamphetamine containing illicit fentanyl, our findings highlight how respondents employ primary strategies like buying from trusted sources and secondary strategies such as spotting and selective use of harm reduction tools (i.e., fentanyl test strips) to reduce risks. To maintain their general wellbeing, participants reduced their use of methamphetamine as reasonably as possible, and used other substances like marijuana and alcohol alongside methamphetamine to counter the unwanted side effects of methamphetamine (i.e., hallucinations and paranoia). Use of these harm reduction strategies varied within situational and social contexts, and respondents usually developed these strategies based on their lived experiences.
CONCLUSION
Our findings uniquely demonstrate that people who use methamphetamine prioritize community driven, trust-based strategies within their social networks to mitigate risks in a fentanyl-contaminated drug environment. Additionally, our results indicate that harm reduction behaviors are influenced by multilevel risk environments, which include social, physical, economic, and political factors. Overall, these results highlight the potential for targeted interventions at the network level, which are responsive to complexities and shifts in drug market dynamics- such as illicit fentanyl in methamphetamine.
Topics: Humans; Fentanyl; Methamphetamine; Harm Reduction; Adult; Female; Male; Amphetamine-Related Disorders; Drug Contamination; Middle Aged; Young Adult; New Mexico; Nevada; Illicit Drugs; Qualitative Research; Interviews as Topic
PubMed: 38761461
DOI: 10.1016/j.drugpo.2024.104456 -
Medical Care Jul 2024Methamphetamine detoxification before entering formal and longer term treatment may have a positive impact on treatment retention and success. Understanding geographic...
INTRODUCTION
Methamphetamine detoxification before entering formal and longer term treatment may have a positive impact on treatment retention and success. Understanding geographic distribution of methamphetamine specialty detox services and differential access by race/ethnicity is critical for establishing policies that ensure equitable access across populations.
METHODS
We used the Mental health and Addiction Treatment Tracking Repository to identify treatment facilities that offered any substance use detoxification in 2021 (N=2346) as well as the census block group in which they were located. We sourced data from the US Census Bureau to identify the percentage of a census block group that was White, Black, and Hispanic. We used logistic regression to model the availability of methamphetamine-specific detox, predicted by the percentage of a block group that was Black and Hispanic. We adjusted for relevant covariates and defined state as a random effect. We calculated model-based predicted probabilities.
RESULTS
Over half (60%) of detox facilities offered additional detox services specifically for methamphetamine. Sixteen states had <10 methamphetamine-specific detox facilities. The predicted probability of methamphetamine-specific detox availability was 60% in census block groups with 0%-9% Black residents versus only 46% in census block groups with 90%-100% Black residents, and was 61% in census block groups with 0%-9% Hispanic residents versus 30% in census block groups with 90%-100% Hispanic residents.
CONCLUSIONS
During an unprecedented national methamphetamine crisis, access to a critical health care service was disproportionately lower in communities that were predominately Black and Hispanic. We orient our findings around a discussion of health disparities, residential segregation, and the upstream causes of the systematic exclusion of minoritized communities from health care.
Topics: Humans; United States; Methamphetamine; Health Services Accessibility; Amphetamine-Related Disorders; Hispanic or Latino; Substance Abuse Treatment Centers; Ethnicity; Black or African American; White People; Racial Groups; Male; Female
PubMed: 38761164
DOI: 10.1097/MLR.0000000000002013 -
Journal of Environmental Management Jun 2024Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely...
Efficient degradation of venlafaxine using intimately coupled high-active crystal facets exposed TiO and biodegradation system: Kinetic studies, biofilm stress behavior and transformation mechanism.
Intimately coupled photocatalysis and biodegradation (ICPB) system is a potential wastewater treatment technology, of which TiO-based ICPB system has been widely studied. There are many ways to improve the degradation efficiency of the ICPB process, but no crystal facet engineering method has been reported yet. In this work, a new ICPB system coated with NaF-TiO exposing high energy facets was designed to degrade biorecalcitrant psychotropic drug - venlafaxine (VNF). Initially, the TiO crystal surface was modified with NaF, resulting in the formation of NaF-TiO with a 14.4% increase in the exposure ratio of (001). The contribution rate of ·OH was increased by 9.5%, and the contribution rate of h was increased by 33.2%. Next, NaF-TiO was loaded onto the surface of the sponge carrier, and then the ICPB system was constructed after about 15 days of biofilm formation. After the ICPB system was acclimated with VNF, the removal rate of COD decreased significantly (the lowest was 62.7%), but that of ammonia nitrogen remained at 50.5 ± 6.0% and the extracellular polymeric substance (EPS) secretion increased by 84.1 mg/g VSS. According to the high throughput results, at the phylum level, Proteobacteria and Chloroflexi together maintain the nitrogen removal capability and structural stability of the ICPB system. The relative abundance of Bacteroidota was significantly increased by 14.2%, suggesting that there may be some correlation between Bacteroidota and certain metabolites of the anti-depressant active ingredients. At the genus level, the Thauera (3.1%∼11.5%) is the major bacterial group that secretes EPS, protecting biofilm against external influences. Most of the changes in microorganisms are consistent with the decontamination properties and macroscopic appearance of EPS in the ICPB system. Finally, the degradation efficiency of ICPB system for VNF was investigated (92.7 ± 3.8%) and it was mostly through hydroxylation and demethylation pathways, with more small molecular products detected, providing the basis for biological assimilation of VNF. Collectively, the NaF-TiO based ICPB system would be lucrative for the future degradation of venlafaxine.
Topics: Venlafaxine Hydrochloride; Biofilms; Titanium; Biodegradation, Environmental; Kinetics; Water Pollutants, Chemical; Wastewater; Catalysis
PubMed: 38759549
DOI: 10.1016/j.jenvman.2024.121159 -
Applied Health Economics and Health... Jul 2024This study evaluated, in a Swedish setting, the cost effectiveness of fenfluramine (FFA) as an add-on to standard of care (SoC) for reducing seizure frequency in Dravet...
OBJECTIVE
This study evaluated, in a Swedish setting, the cost effectiveness of fenfluramine (FFA) as an add-on to standard of care (SoC) for reducing seizure frequency in Dravet syndrome, a severe developmental epileptic encephalopathy.
METHODS
Cost effectiveness of FFA+SoC compared with SoC only was evaluated using a patient-level simulation model with a lifetime horizon. Patient characteristics and treatment effects, including convulsive seizures, seizure-free days and mortality, were derived from FFA clinical trials. Resource use and costs included cost of drug acquisition, routine care and monitoring, as well as ongoing and emergency resources. Quality of life (QoL) estimates for patients and their caregivers were derived from clinical trial data. Robustness was evaluated by one-way sensitivity analysis, probabilistic sensitivity analysis and scenario analyses.
RESULTS
Lifetime cost of FFA+SoC was ~3 million SEK per patient compared with ~1.5 million SEK for SoC only. FFA+SoC generated 15% more QALYs than SoC only (21.2 vs 18.5 over a lifetime), resulting in an incremental cost-effectiveness ratio (ICER) of ~540,000 SEK. Moreover, FFA+SoC had a higher probability of being cost effective than SoC only from a willingness-to-pay threshold of 710,000 SEK. Results remained generally consistent across scenario analyses, with only few exceptions (exclusions of carer utility or FFA effect on sudden unexpected death in epilepsy).
CONCLUSION
Due to better seizure control, FFA is a clinically meaningful add-on therapy and was estimated to be a cost-effective addition to current SoC for patients with this rare disease in Sweden at a willingness-to-pay threshold of 1,000,000 SEK.
Topics: Humans; Sweden; Epilepsies, Myoclonic; Cost-Benefit Analysis; Fenfluramine; Female; Male; Standard of Care; Quality-Adjusted Life Years; Anticonvulsants; Adult; Adolescent; Child; Quality of Life; Young Adult; Cost-Effectiveness Analysis
PubMed: 38758509
DOI: 10.1007/s40258-024-00886-0 -
Ecotoxicology and Environmental Safety Jul 2024Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest...
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
Topics: Animals; Methamphetamine; Male; Gastrointestinal Microbiome; Mice; Testis; Reproduction; Spermatozoa; Mice, Inbred C57BL; Central Nervous System Stimulants; Fecal Microbiota Transplantation
PubMed: 38754198
DOI: 10.1016/j.ecoenv.2024.116457 -
International Immunopharmacology Jun 2024The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that...
The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and β-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca levels, phosphorylation levels of CaMK, PLCβ1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.
Topics: Animals; Rats; Mast Cells; Cell Degranulation; Mice; Humans; Hypersensitivity; Receptors, G-Protein-Coupled; Anti-Allergic Agents; Cytokines; p-Methoxy-N-methylphenethylamine; Male; Phellodendron; Cell Line, Tumor; Nerve Tissue Proteins; Mice, Inbred BALB C; NF-kappa B; Signal Transduction; Receptors, Neuropeptide
PubMed: 38744172
DOI: 10.1016/j.intimp.2024.112256 -
Journal of the Science of Food and... May 2024The excessive salt intake associated with Douchi has become a topic of controversy. Addressing this concern and enhancing its market competitiveness necessitates the...
BACKGROUND
The excessive salt intake associated with Douchi has become a topic of controversy. Addressing this concern and enhancing its market competitiveness necessitates the application of salt reduction fermentation in Douchi. Therefore, to promote the application of salt reduction fermentation in Douchi, a comprehensive study was undertaken aiming to investigate the differences in biogenic amines, volatile compounds and non-volatile compounds in Douchi with varying salt content.
RESULTS
The findings unequivocally demonstrate that salt hampers the formation of metabolites in Douchi. As the salt content increased, there was a significant decrease (P < 0.05) in the levels of total acid, amino-type nitrogen and free amino acids in Douchi. Notably, when the salt content exceeded 80 g kg, there was a substantial reduction (P < 0.05) in putrescine, lactic acid and malic acid levels. Similarly, when the salt content surpassed 40 g kg, β-phenethylamine and oxalic acid levels exhibited a significant decline (P < 0.05). Furthermore, the results of E-nose and principal component analysis based on headspace solid phase microextraction gas chromatography-mass spectrometry revealed notable discrepancies in the volatile compound content between Douchi samples with relatively low salt content (40 and 80 g kg) and those with relatively high salt content (120, 160 and 200 g kg) (P < 0.05). By employing partial least squares discriminant analysis, eight distinct volatile compounds, including o-xylene, benzaldehyde and 1-octen-one, were identified. These compounds exhibited higher concentrations in Douchi samples with relatively low salt content (40 and 80 g kg). The sensory results showed that Douchi samples with lower salt content exhibited higher scores in the soy sauce-like and Douchi aroma attributes.
CONCLUSION
In conclusion, this study significantly enhances our understanding of the impact of salt on metabolites in Douchi and provides invaluable insights for the development of salt reduction fermentation in this context. © 2024 Society of Chemical Industry.
PubMed: 38738583
DOI: 10.1002/jsfa.13574 -
Chirality May 2024Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms...
Among different substance classes, New Psychoactive Substances (NPS) comprise chiral amphetamines for stimulant and empathic effects. There is little knowledge in terms of clinical studies about possibly different effects of the two enantiomers of novel amphetamine derivatives. For this reason, there is a big demand for enantioseparation method development of this new substance class. Regarding gas chromatography, cyclodextrins proved to be effective for enantioseparation of NPS. In our attempt, an Astec® Chiraldex™ G-PN column containing 2,6-di-O-pentyl-3-propionyl-γ-cyclodextrin and a Lipodex™ D column containing heptakis-(2,6-di-O-pentyl-O-acetyl)-β-cyclodextrin as chiral selector served as stationary phases in a Shimadzu GCMS-QP2010 SE system. Because of the special coating, maximum temperature is limited to 200 °C isothermal or 220 °C in programmed mode. To ensure detection, trifluoroacetic anhydride (TFAA) was used to increase sample volatility. As a result, 35 amphetamines were tested as their TFAA-derivatives. A screening method with a temperature gradient from 140 °C to 200 °C at a heating ramp of 1 °C per minute and final time of 5 min, showed baseline separation for seven and partial separations for 16 trifluoro acetylated amphetamines using the Chiraldex™ G-PN column. Six baseline and nine partial separations were observed with the Lipodex™ D column, respectively.
Topics: Stereoisomerism; Amphetamines; Chromatography, Gas; Cyclodextrins; Temperature; Gas Chromatography-Mass Spectrometry
PubMed: 38736271
DOI: 10.1002/chir.23676 -
Journal of the American Academy of... May 2024Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a...
Youth today are burdened by significant mental health challenges. In 2022, 25% of adolescents aged 12 to 17 years experienced a mental illness, with 20% experiencing a depressive episode, 12.5% reporting serious thoughts of suicide, and 17% meeting criteria for a substance use disorder. Close to 5% of adolescents experience posttraumatic stress disorder. Impairing psychiatric symptoms remain present in upwards of 40% of adolescents after receiving existing mental health services, so it is necessary to identify additional and more effective treatment options. We propose there is an acceptable benefit-to-risk calculation that supports trialing classic serotonergic psychedelics (eg, psilocybin) and phenethylamine compounds with empathogenic and entactogenic range of effects (eg, 3,4-methylenedioxymethamphetamine [MDMA]) in combination with psychotherapy among select adolescents aged 16 to 17 years. Specifically, we propose testing these treatments among adolescents aged 16 to 17 years who are experiencing treatment-resistant manifestations of psychiatric disorders (ie, multiple failed trials of current evidence-based treatments) or psychiatric disorders that are in line with the current evidence base for adults as determined, for example, by the breakthrough designation of the US Food and Drug Administration for a particular psychedelic medicine (eg, psilocybin for major depressive disorder, MDMA for posttraumatic stress disorder).
PubMed: 38734406
DOI: 10.1016/j.jaac.2024.03.021 -
Progress in Neuro-psychopharmacology &... Jul 2024Methamphetamine (METH) is a major health problem without effective pharmacological treatment. Cannabidiol (CBD), a component of the Cannabis sativa plant, is believed to...
Methamphetamine (METH) is a major health problem without effective pharmacological treatment. Cannabidiol (CBD), a component of the Cannabis sativa plant, is believed to have the potential to inhibit drug-related behavior. However, the neurobiological mechanisms responsible for the effects of CBD remain unclear. Several studies have proposed that the suppressing effects of CBD on drug-seeking behaviors could be through the modulation of the dopamine system. The hippocampus (HIP) D1-like dopamine receptor (D1R) is essential for forming and retrieving drug-associated memory. Therefore, the present study aimed to investigate the role of D1R in the hippocampal CA1 region on the effects of CBD on the extinction and reinstatement of METH-conditioned place preference (CPP). For this purpose, different groups of rats over a 10-day extinction period were administered different doses of intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl, Saline) as a D1R antagonist before ICV injection of CBD (10 μg/5 μl, DMSO12%). In addition, a different set of animals received intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl) before CBD injection (50 μg/5 μl) on the reinstatement day. The results revealed that the highest dose of SCH23390 (4 μg) significantly reduced the accelerating effects of CBD on the extinction of METH-CPP (P < 0.01). Furthermore, SCH23390 (1 and 4 μg) in the reinstatement phase notably reversed the preventive effects of CBD on the reinstatement of drug-seeking behavior (P < 0.05 and P < 0.001, respectively). In conclusion, the current study revealed that CBD made a shorter extinction period and suppressed METH reinstatement in part by interacting with D1-like dopamine receptors in the CA1 area of HIP.
Topics: Animals; Methamphetamine; Cannabidiol; Extinction, Psychological; Male; Receptors, Dopamine D1; Benzazepines; Rats, Wistar; Rats; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Hippocampus; Dopamine Antagonists; CA1 Region, Hippocampal
PubMed: 38729234
DOI: 10.1016/j.pnpbp.2024.111025