Neurobiology, Clinical Presentation, and Treatment of Methamphetamine Use Disorder: A Review.
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ABSTRACT: Importance
The prevalence of and mortality associated with methamphetamine use has doubled during the past 10 years. There is evidence suggesting that methamphetamine use disorder could be the next substance use crisis in the United States and possibly worldwide.Observation
The neurobiology of methamphetamine use disorder extends beyond the acute effect of the drug as a monoaminergic modulator and includes intracellular pathways focused on oxidative stress, neurotoxic and excitotoxic effects, and neuroinflammation. Similarly, the clinical picture extends beyond the acute psychostimulatory symptoms to include complex cardiovascular and cerebrovascular signs and symptoms that need to be identified by the clinician. Although there are no pharmacologic treatments for methamphetamine use disorder, cognitive behavioral therapy, behavioral activation, and contingency management show modest effectiveness.Conclusions and relevance
There is a need to better understand the complex neurobiology of methamphetamine use disorder and to develop interventions aimed at novel biological targets. Parsing the disorder into different processes (eg, craving or mood-associated alterations) and targeting the neural systems and biological pathways underlying these processes may lead to greater success in identifying disease-modifying interventions. Finally, mental health professionals need to be trained in recognizing early cardiovascular and cerebrovascular warning signs to mitigate the mortality associated with methamphetamine use disorder.
SUBMITTER: Paulus MP
PROVIDER: S-EPMC8098650 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAn emerging public health threat of methamphetamine/opioid co-use is occurring in North America, including increases in overdoses related to concomitant methamphetamine/opioid use. This presents a potential risk to established treatments for opioid use disorder (i.e., medications for opioid use disorder [MOUD]). To date, few studies have examined the impact of methamphetamine use on MOUD-related outcomes, and no studies have synthesized data on MOUD retention.MethodsA scoping review was undertaken to examine the impact of methamphetamine use on MOUD retention. All original published research articles were searched in Embase, MEDLINE, PsychINFO, CINAHL, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Cochrane Protocols, and Google scholar databases. Data were extracted into a standardized data extraction chart. Findings were presented narratively.ResultsAll eight included studies demonstrated an increased likelihood of treatment discontinuation or dropout among patients enrolled in MOUD who used methamphetamine. The frequency of methamphetamine use was also associated with MOUD dropout, in that those who used methamphetamine more often were more likely to discontinue MOUD. The definitions and measurements of MOUD retention varied considerably, as did the magnitude of effect size.ConclusionsResults indicate that methamphetamine use has an undesirable impact on MOUD retention and results in an increased risk of treatment discontinuation or dropout. Strategies to identify concurrent methamphetamine use among individuals engaging in MOUD and educate them on the increased risk for dropout should be undertaken. Further research is needed to understand how MOUD retention among patients with concomitant opioid and methamphetamine use can be improved.
| S-EPMC10433668 | biostudies-literature
Project description:BackgroundThe transition from methamphetamine (MA) casual use (MCU) to compulsive use is enigmatic as some MA users can remain in casual use, but some cannot. There is a knowledge gap if gut microbiota (GM) play a role in differing MCU from MA use disorder (MUD). We aimed to investigate the clinical features and GM differences between individuals with MCU and MUD.MethodWe recruited two groups of MA users -MCU and MUD - and matched them according to age and body mass index (n=21 in each group). Participants were accessed using the Semi-Structured Assessment for Drug Dependence and Alcoholism, and their fecal samples were undergone 16S ribosomal DNA sequencing. We compared the hosts' clinical features and GM diversity, composition, and structure (represented by enterotypes) between the two groups. We have identified differential microbes between the two groups and performed network analyses connecting GM and the clinical traits.ResultCompared with the casual users, individuals with MUD had higher incidences of MA-induced neuropsychiatric symptoms (e.g., paranoia, depression) and withdrawal symptoms (e.g., fatigue, drowsiness, and increased appetite), as well as stronger cravings for and intentions to use MA, and increased MA tolerance. The GM diversity showed no significant differences between the two groups, but four genera (Halomonas, Clostridium, Devosia, and Dorea) were enriched in the individuals with MUD (p<0.05). Three distinct enterotypes were identified in all MA users, and Ruminococcus-driven enterotype 2 was dominant in individuals with MUD compared to the MCU (61.90% vs. 28.60%, p=0.03). Network analysis shows that Devosia is the hub genus (hub index = 0.75), which is not only related to the counts of the MUD diagnostic criteria (ρ=0.40; p=0.01) but also to the clinical features of MA users such as reduced social activities (ρ=0.54; p<0.01). Devosia is also associated with the increased intention to use MA (ρ=0.48; p<0.01), increased MA tolerance (ρ=0.38; p=0.01), craving for MA (ρ=0.37; p=0.01), and MA-induced withdrawal symptoms (p<0.05).ConclusionOur findings suggest that Ruminococcus-driven enterotype 2 and the genera Devosia might be two influential factors that differentiate MA casual use from MUD, but further studies are warranted.
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Project description:Introduction and aimsAs South Africa, especially the Western Cape Province, faces an epidemic of methamphetamine use disorder, therapeutic approaches suited to the South African context are needed. This secondary analysis assessed retention and methamphetamine abstinence outcomes in response to an 8-week pilot contingency management (CM) intervention trial of neural correlates of methamphetamine abstinence, exploring sociodemographic and clinical differences between responders and non-responders.Design and methodsResearch participants provided thrice-weekly monitored urine samples, which were analysed by qualitative radioimmunoassay. The primary outcome for this analysis was therapeutic response, defined as abstinence from methamphetamine (?23 of 24 possible methamphetamine-negative urine samples).ResultsData from 30 adults living in Cape Town, South Africa (34?±?6.1?years of age, mean age?±?SD, 21 men) were included. Sixty-three percent (12 men) were responders. In bivariate comparisons, baseline measurements showed fewer responders reported monthly household income ?25?000+ South African Rand (ZAR; ~USD $1880; vs. ZAR <?25?000) than non-responders (15.8% vs. 63.6%; P = 0.007). Furthermore, responders had higher median years of education (12 vs. 10; Kruskal-Wallis ?2 = 4.25, DF = 1, P = 0.039) and lower median body mass index than non-responders (19 vs. 24; Kruskal-Wallis ?2 = 6.84, P = 0.008).Discussion and conclusionsTherapeutic response in this study were comparable to those obtained with CM for methamphetamine use disorder in North America and Europe. Our findings suggest that CM may be a useful component of treatment strategies to boost retention and continuous abstinence from methamphetamine in Cape Town, South Africa. Larger efficacy studies are needed in this setting.
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Project description:The experience of craving via exposure to drug-related cues often leads to relapse in drug users. This study consolidated existing empirical evidences of cue reactivity to methamphetamine to provide an overview of current literature and to inform the directions for future research. The best practice methodological framework for conducting scoping review by Arkey and O'Malley was adopted. Studies that have used a cue paradigm or reported on cue reactivity in persons with a history of methamphetamine use were included. Databases such as Medline, EMBASE, PsycINFO and CINAHL were searched using key terms, in addition to citation check and hand search. The search resulted in a total of 32 original research articles published between 2006 to 2020. Three main themes with regard to cue reactivity were identified and synthesized: (1) effects of cue exposure, (2) individual factors associated with cue reactivity, and (3) strategies that modulate craving or reactivity to cues. Exposure to methamphetamine-associated cues elicits significant craving and other autonomic reactivity. Evidence suggests that drug cue reactivity is strongly associated with indices of drug use and other individual-specific factors. Future studies should focus on high quality studies to support evidence-based interventions for reducing cue reactivity and to examine cue reactivity as an outcome measure.
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Project description:There have been dramatic changes worldwide in the attitudes toward and consumption of recreational and medical cannabis. Cannabinoid receptors, which mediate the actions of cannabis, are abundantly expressed in brain regions known to mediate neural processes underlying reward, cognition, emotional regulation and stress responsivity relevant to addiction vulnerability. Despite debates regarding potential pathological consequences of cannabis use, cannabis use disorder is a clinical diagnosis with high prevalence in the general population and that often has its genesis in adolescence and in vulnerable individuals associated with psychiatric comorbidity, genetic and environmental factors. Integrated information from human and animal studies is beginning to expand insights regarding neurobiological systems associated with cannabis use disorder, which often share common neural characteristics with other substance use disorders, that could inform prevention and treatment strategies.
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Project description:Methamphetamine use disorder is a chronic relapsing condition associated with substantial mental, physical, and social harms and increasing rates of mortality. Contingency management and psychotherapy interventions are the mainstays of treatment but are modestly effective with high relapse rates, while pharmacological treatments have shown little to no efficacy. Psilocybin-assisted psychotherapy is emerging as a promising treatment for a range of difficult-to-treat conditions, including substance use disorders; however, no studies have yet been published looking at psilocybin-assisted psychotherapy in the treatment of methamphetamine use disorder. Here we review the rationale for psilocybin-assisted psychotherapy as a potential treatment for this indication, and describe practical considerations based on our early experience designing and implementing four separate clinical trials of psilocybin-assisted psychotherapy for methamphetamine use disorder.
| S-EPMC10043240 | biostudies-literature
Project description:The number of people diagnosed with opioid use disorder has skyrocketed as a consequence of the opioid epidemic and the increased prescribing of opioid drugs for chronic pain relief. Opioid use disorder is characterized by loss of control of drug taking, continued drug use in the presence of adverse consequences, and repeated relapses to drug taking even after long periods of abstinence. Patients who suffer from opioid use disorder often present with cognitive deficits that are potentially secondary to structural brain abnormalities that vary according to the chemical composition of the abused opioid. This review details the neurobiological effects of oxycodone, morphine, heroin, methadone, and fentanyl on brain neurocircuitries by presenting the acute and chronic effects of these drugs on the human brain. In addition, we review results of neuroimaging in opioid use disorder patients and/or histological studies from brains of patients who had expired after acute intoxication following long-term use of these drugs. Moreover, we include relevant discussions of the neurobiological mechanisms involved in promoting abnormalities in the brains of opioid-exposed patients. Finally, we discuss how novel strategies could be used to provide pharmacological treatment against opioid use disorder.
| S-EPMC9090195 | biostudies-literature
Project description:Although stimulant dependence is highly heritable, few studies have examined genetic influences on methamphetamine dependence. We performed a candidate gene study of 52 SNPs and pretreatment methamphetamine use frequency among 263 methamphetamine dependent Hispanic and Non-Hispanic White participants of several methamphetamine outpatient clinical trials in Los Angeles. One SNP, rs7591784 was significantly associated with pretreatment methamphetamine use frequency following Bonferroni correction (p < 0.001) in males but not females. We then examined rs7591784 and methamphetamine urine drug screen results during 12 weeks of outpatient treatment among males with treatment outcome data available (N = 94) and found rs7591784 was significantly associated with methamphetamine use during treatment controlling for pretreatment methamphetamine use. rs7591784 is near CREB1 and in a linkage disequilibrium block with rs2952768, previously shown to influence CREB1 expression. The CREB signaling pathway is involved in gene expression changes related to chronic use of multiple drugs of abuse including methamphetamine and these results suggest that variability in CREB signaling may influence pretreatment frequency of methamphetamine use as well as outcomes of outpatient treatment. Medications targeting the CREB pathway, including phosphodiesterase inhibitors, warrant investigation as pharmacotherapies for methamphetamine use disorders.
| S-EPMC5053101 | biostudies-literature
Project description:BACKGROUND AND AIMS:No effective pharmacotherapy for methamphetamine (MA) use disorder has yet been found. This study evaluated sustained-release methylphenidate (MPH-SR) compared with placebo (PLA) for treatment of MA use disorder in people also undergoing behavioral support and motivational incentives. DESIGN:This was a randomized, double-blind, placebo-controlled design with MPH-SR or PLA provided for 10 weeks (active phase) followed by 4 weeks of single-blind PLA. Twice-weekly clinic visits, weekly group counseling (CBT) and motivational incentives (MI) for MA-negative urine drug screens (UDS) were included. SETTING:Treatment sites were in Los Angeles, California (LA) and Honolulu, Hawaii (HH), USA. PARTICIPANTS:A total of 110 MA-dependent (via DSM-IV) participants (LA?=?90; HH?=?20). MEASUREMENTS:The primary outcome measure is self-reported days of MA use during the last 30 days of the active phase. Included in the current analyses are drug use (UDS and self-report), retention, craving, compliance (dosing, CBT, MI), adverse events and treatment satisfaction. FINDINGS:No difference was found between treatment groups in self-reported days of MA use during the last 30 days of the active phase (P?=?0.22). In planned secondary outcomes analyses, however, the MPH group had fewer self-reported MA use days from baseline through the active phase compared with the PLA group (P?=?0.05). The MPH group also had lower craving scores and fewer marijuana-positive UDS than the PLA group in the last 30 days of the active phase. The two groups had similar retention, other drug use, adverse events and treatment satisfaction. CONCLUSIONS:Methylphenidate may lead to a reduction in concurrent methamphetamine use when provided as treatment for patients undergoing behavioral support for moderate to severe methamphetamine use disorder, but this requires confirmation.
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Project description:BackgroundThe use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.MethodsWe conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.ResultsA total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.ConclusionsAmong adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).
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