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PubMed2026

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans↗

PubMed2026

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize γ-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants ≤ 12 weeks postpartum with ≥ 4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving ≥ 80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p > 0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans↗

PubMed2026

New Horizons in the Development of Treatments for Substance Use Disorders.

Substance use disorders (SUDs) are a major public health problem in the United States and cause substantial morbidity and mortality. There are meaningful gaps in the available SUD treatment options, and the development of new therapies is urgently needed. While medications with U.S. Food and Drug Administration approval are available for alcohol, nicotine, and opioid use disorders, there are no approved pharmacotherapies for cannabis, cocaine, or methamphetamine use disorders. Behavioral treatments for SUDs have significant limitations in effectiveness and accessibility, and there is a need for the development of both new behavioral treatment options and new models of treatment delivery. The next generation of treatments for SUDs will likely come from a diverse set of interventions, including new drug classes, new technologies, and new methods of delivery.

Humans↗

PubMed2026

Brain network alterations underlying cue reactivity and craving in abstinent methamphetamine users: a systematic review of functional MRI findings.

BACKGROUND: Methamphetamine use disorder (MUD) is marked by intense craving and high relapse risk, often triggered by drug-related cues. Functional magnetic resonance imaging (fMRI) provides key insight into the neural basis of this cue reactivity, implicating large-scale brain networks for reward, motivation, and control. Yet, findings remain inconsistent across studies due to differences in task design, abstinence duration, and participant characteristics. OBJECTIVE: This systematic review synthesises evidence on how abstinence influences brain network alterations underlying cue reactivity and craving in methamphetamine users, integrating task-based and resting-state fMRI findings within leading neurobiological models of addiction. METHODS: A systematic search of PubMed, Scopus, Web of Science, and Ovid was conducted up to August 10, 2025, following PRISMA 2020 guidelines. Eligible fMRI studies examined cue reactivity or craving in abstinent methamphetamine users. Data were extracted on activation, connectivity, and brain-behaviour associations, and synthesised narratively. RESULTS: Task-based studies revealed heightened activation across reward, salience, and control networks during cue exposure, which diminished as parietal and executive control systems re-engaged with longer abstinence. Resting-state findings showed disrupted intrinsic connectivity among default mode, salience, and frontoparietal networks, reflecting persistent imbalances linked to craving and use severity. CONCLUSION: fMRI evidence shows that MUD is marked by network-level disruption linking reward, salience, and control systems. Task-based findings reveal strong cue reactivity in reward circuits, while resting-state data show persistent imbalance among default mode and control networks. With abstinence, partial restoration of network integrity emerges, highlighting both vulnerability and opportunities for targeted, recovery-based interventions.

Humans↗

PubMed2025

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p < 5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p > 0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans↗

PubMed2026

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's κ. Agreement was rated as strong where measures were ≥ 0.50, moderate where agreement was 0.30-0.49, and weak where < 0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans↗

PubMed1979

Frequency of use or abuse of amphetamine-related drugs.

A survey was done on over 10,000 urine samples from the Los Angeles County Probation Department and methadone maintenance programs to determine the frequency of use of eight sympathomimetic amine drugs including amphetamine, methamphetamine, ephedrine, mephentermine, phendimetrazine, beta-phenethylamine, phenmetrazine, and phentermine. As expected, the frequency of use of amphetamine was relatively high followed by phentermine, ephedrine, and methamphetamine. The extensive use of ephedrine and phentermine may warrant testing for these drugs on a more routine basis in drug monitoring programs.

Amphetamines↗

PubMed1975

Mononeuropathy multiplex as a complication of amphetamine angiitis.

A patient who abused multiple drugs developed a rapidly progressive mononeuropathy multiplex, which appeared to respond to corticosteroid therapy with partial resolution. Intravenous methamphetamine had been used almost exclusively from the fourth month prior to the onset of symptoms. Biopsy material revealed a necrotizing angiitis involving medium and small sized arteries, capillaries, and venules, typical of a hypersensitivity-type angiopathy, rather than the previously reported polyarteritis nodosa-type lesions secondary to illicit drugs. The apparent response to corticosteroids suggests that these agents might be useful in the treatment of some complications of drug abuse.

Adolescent↗

PubMedDate not supplied

Patterns of drug use among methadone maintenance patients in Los Angeles county.

Any evaluation of the effectiveness of methadone maintenance programmes in rehabilitating heroin addicts is inherently complex and subject to varied interpretations, both scientific and philosophical. From a scientific perspective, it is necessary to accumulate sufficient factual data to validate any hypothetical conclusions. A retrospective survey of drug-use patterns among the methadone maintenance population of Los Angeles County was undertaken in an effort to provide some such information. Over 5,000 urine samples from 730 paitients were analysed for eleven drugs over a two-month period in 1975. Over 23 per cent of these samples were found positive for a drug other than methadone and 80 per cent of these positives were attributed to illicitly used drugs. The opiates (codeine and morphine) comprised almost 74 per cent of the drugs found while barbiturates and amphetamine and/or methamphetamine contributed 16 per cent and 10 per cent to the total, respectively.

Adult↗

PubMed1977

Effects of 1694 and other dopaminergic agents on circling behavior.

One hour after the administration of 40 mg/kg of amineptine chlorydrate (1694) the HVA concentration in the striatum was increased but the concentrations of DA, NA, 5HT and 5-HIAA in the striatum, cortex, thalamus-hypothalamus and pons-midbrain of rats were not significantly altered. Unilateral lesioning at the level of the entopeduncular nucleus in cats and rats resulted in spontaneously occurring ipsiversive circling behavior in the two species. However circling was more sustained in cats than in rats. Apomorphine, d-amphetamine, methamphetamine, L-dopa and piribedil (ET-495) exaggerated the ipsiversive circling. 1694 (amineptine chlorydrate), a new agent, was comparatively more active than L-dopa and ET-495 and less active than apomorphine, d-amphetamine and methamphetamine. Although in higher doses (30--40 mg/kg), 1694 caused increased exploratory activity it was not associated with any stereotypy. Its biochemical and pharmacological effects are comparable to those of d-amphetamine and methamphetamine. Removal of the contralateral (with respect to the side of the entopeduncular lesion) motor cortex in the lesioned cat abolished spontaneous and drug-induced circling movements. The results of this and of previous studies support the idea that these dopaminergic agents act on the striopallidal system of the intact side which is no longer properly counterbalanced by the corresponding system of the lesioned side. Although this experimental model is useful to determine the degree of dopaminergic activity of various chemical agents it does not duplicate the motor disorders encountered in parkinsonism which are associated with a decreased concentration of dopamine.

Animals↗

PubMed1978

A survey of drug use among probationers in the Los Angeles area in 1976.

The results are presented from the analysis of 10,000 urine specimens from Los Angeles County probationers in early 1976 for the following drugs: amphetamine, methamphetamine, allylbarbital, amobarbital, butabarbital, pentobarbital, phenobarbital, secobarbital, morphine, codeine, methadone, primary metabolite of methadone, cocaine, benzoylecgonine, propoxyphene, norpropoxyphene, methaqualone, and phencyclidine. Over 27% of the urine samples analyzed were positive for at least one drug. Opiates were found to be the most widely used drugs, but multiple drug use was also quite common.

California↗

PubMed1979

The significance of drug analysis of sweat in respect to rapid screening for drug abuse.

Morphine and methamphetamine, which are excreted in the sweat, are detected by the use of routine serological and physicochemical techniques for urinary examinations. Screening for drug abuse can be done with the same accuracy of that of urine. Rapid excretion of the drug via kidney (within one day) is followed by a slow but steady excretion of the sweat gland. Methamphetamine given orally in a dose of 10 mg is excreted in the sweat at a constant rate (1.4 microgram/ml). No significant difference of the amount excreted by both systems is found. Alveolar lining seems to prevent the elimination of the volatile methamphetamine via respiration. Not only narcotics and stimulants, but also many alkaloids and barbituarates are excreted in the sweat and detected quantitatively by the same principles. The toxicological analysis of the sweat promises a new scope of forensic investigation.

Forensic Medicine↗

PubMed1975

Amphetamine stereotypy: the influence of environmental factors and prepotent behavioral patterns on its topography and development.

This report describes a series of experiments, all of which demonstrate a strong contribution of the behavioral pattern manifested at the time of initial amphetamine injection to the topography and development of the stereotypy that develops with chronic amphetamine intoxication. These initial behavioral patterns reflect (i) learned behaviors, (ii) species-specific behaviors, (iii) behaviors associated with amphetamine arousal, and (iv) novel behaviors reflecting unique environmental circumstances prevailing at the time of administration. In an experiment using eight dogs administered amphetamine in a situation which allowed interaction between the animals, the behavioral stereotypies that developed were comprised of the social interaction patterns ongoing at the time of initial drug effects. Experiments with rats have demonstrated that the configuration of the enclosure in which they are injected influences the initial behavioral reactions to amphetamine and thus modifies the stereotypy. In experiments with cats pressing a lever to self-administer amphetamine, investigatory behavior at the lever-press operandi becomes incorporated as does the learned behavior response into the stereotypy. The behavioral patterns originally associated with amphetamine arousal eventually supersede the learned response component of the stereotypy. Finally, monkeys incorporate components of the initial behaviors associated with amphetamine administration into a wider range of stereotype patterns over months of chronic intoxication, and eventually the stereotypy may evolve into a specific dyskinesia involving movements of the original behavioral component.

Animals↗

PubMed1979

[Neuropharmacological studies on drug dependence (I). Effects due to the difference in strain, sex and drug administration time on physical dependence development and characteristics of withdrawal signs in CNS-affecting drug dependent rats (author's transl)].

We studied the influence of differences in strain, sex and drug administration time on physical dependence of morphine and phenobarbital in rats and also whether or not pole climbing avoidance is useful as an indicator of physical dependence. We then compared the behavioral characteristics seen with morphine-dependence with those of other CNS-affecting drugs. Withdrawal signs involving weight loss in morphine and phenobarbital groups were different in JCL-Wistar, SLC-Wistar, JCL-Sprague Dawley and HOS-Donryu strain rats. Withdrawal signs in males were generally more marked than in females. Withdrawal signs due to the difference of drug administration time were different with the sex and/or kinds of drugs. After administration of morphine-type and barbiturate-type drugs, withdrawal signs of sedation and weight loss, also excitability together with weight loss appeared 24 and 40 hours later, respectively. These signs were generally greatly increased by antagonist-induced withdrawal. Abrupt withdrawal of methamphetamine and cocaine caused no withdrawal signs. Rectal temperature was unchanged on abrupt withdrawal in the case of each drug, though temperatures did decrease with morphine-type drugs, and increased with phenobarbital and chlordiazepoxide groups, on antagonist-induced withdrawal. Inhibition of the avoidance was mild with the abrupt withdrawal of morphine, codeine, phenobarbital chlordiazepoxide and cocaine, but was marked on antagonist-induced withdrawal of morphine and codeine.

Animals↗

PubMed2026

Implementation factors shaping British Columbia's drug decriminalization pilot: A systematic review with narrative synthesis.

BACKGROUND: In January 2023, British Columbia (BC) became the first Canadian province to implement a legally sanctioned drug decriminalization policy, removing criminal penalties for adults possessing 2.5 g or less of opioids, cocaine, methamphetamine, and MDMA. Introduced as a three-year pilot, it aimed to reframe substance use as a public health issue, reduce stigma, and improve health and social service engagement. Criminal penalties were reintroduced for drug possession in most public spaces in May 2024, and the pilot ended in January 2026. Its termination has been interpreted as policy failure; this review aimed to examine how the pilot was implemented in practice and to identify factors that shaped its operationalization and early implementation-relevant outcomes. METHODS: We conducted a systematic review with narrative synthesis of peer-reviewed literature examining implementation-relevant aspects of BC's decriminalization pilot. Six databases were searched (January-February 2026) for studies published May 31, 2022-February 1, 2026. The protocol was registered in PROSPERO (CRD420251271694). RESULTS: Twenty-seven studies were included. Four cross-cutting implementation barriers were identified: pilot design features, public and cross-sector communication gaps, limited frontline training, and insufficient funding and infrastructure. Design features included the 2.5 g possession threshold, misalignment with real-world drug use patterns; the three-year timeframe, which constrained system-level effects; and the May 2024 amendment, which introduced additional instability. The pilot was implemented without commensurate investment in harm reduction, treatment, or housing infrastructure, within already constrained systems. CONCLUSION: BC's decriminalization pilot suggests the effects of legal reform are shaped by implementation context. Early outcomes may reflect design features, institutional readiness, and system capacity rather than legal change alone; longer-term impacts remain uncertain. Future reforms should align legal change with coordinated implementation, operational guidance, public communication, and adequate service infrastructure.

British Columbia↗