-
Nature Communications Jul 2023Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to...
Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence. Here we show that amphetamine, by dysregulating Netrin-1/DCC signaling, triggers ectopic growth of mesolimbic dopamine axons to the prefrontal cortex, only in early-adolescent male mice, underlying a male-specific vulnerability to enduring cognitive deficits. In adolescent females, compensatory changes in Netrin-1 protect against the deleterious consequences of amphetamine on dopamine connectivity and cognitive outcomes. Netrin-1/DCC signaling functions as a molecular switch which can be differentially regulated by the same drug experience as function of an individual's sex and adolescent age, and lead to divergent long-term outcomes associated with vulnerable or resilient phenotypes.
Topics: Female; Mice; Male; Animals; Amphetamine; Dopamine; Netrin-1; DCC Receptor; Axons
PubMed: 37419977
DOI: 10.1038/s41467-023-39665-1 -
Current Problems in Cardiology Aug 2023There is limited evidence demonstrating whether cannabis, cocaine, amphetamine, or other stimulants use contributes to heart failure (HF) readmissions. We used the... (Review)
Review
There is limited evidence demonstrating whether cannabis, cocaine, amphetamine, or other stimulants use contributes to heart failure (HF) readmissions. We used the National Readmissions Database years 2016-2018 to identify patients with HF with and without substance use disorder (SUD) (defined as a composite of cannabis, cocaine, or other stimulant use disorders). The main outcome was to assess the risk of 30-day readmissions in HF patients with and without SUD. Of 978,217 HF hospitalizations that met the inclusion criteria, 34,717 (3.5%) had concomitant SUD. HF patients with SUD had significantly higher hazard for 30-day all-cause readmissions (adjusted hazard ratio [aHR] 1.16 [1.12-1.21]; P < 0.01) compared to HF patients without SUD. In conclusion, HF patients with SUD have an elevated risk of 30-day all-cause readmissions, mainly driven by cocaine and other stimulant disorders. Screening for substance use in hospitalized HF patients as well as timely referral for treatment are important to prevent HF readmissions.
Topics: Humans; Patient Readmission; Cocaine; Cannabis; Amphetamine; Substance-Related Disorders; Heart Failure
PubMed: 35346722
DOI: 10.1016/j.cpcardiol.2022.101189 -
Journal of Clinical Psychopharmacology
Topics: Humans; Central Nervous System Stimulants; Methamphetamine; Amphetamine-Related Disorders
PubMed: 37930197
DOI: 10.1097/JCP.0000000000001755 -
Addiction (Abingdon, England) Feb 2024There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
There is currently no standard of care for pharmacological treatment of amphetamine-type stimulant (ATS) use disorder (ATSUD). This systematic review with meta-analysis (PROSPERO CRD42022354492) aimed to pool results from randomized placebo-controlled trials (RCTs) to evaluate efficacy and safety of prescription psychostimulants (PPs) for ATSUD.
METHODS
Major indexing sources and trial registries were searched to include records published before 29 August 2022. Eligible studies were RCTs evaluating efficacy and safety of PPs for ATSUD. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Risk ratio (RR) and risk difference were calculated for random-effect meta-analysis of dichotomous variables. Mean difference and standardized mean difference (SMD) were calculated for random-effect meta-analysis of continuous variables.
RESULTS
Ten RCTs (n = 561 participants) were included in the meta-analysis. Trials studied methylphenidate (n = 7), with daily doses of 54-180 mg, and dextroamphetamine (n = 3), with daily doses of 60-110 mg, for 2-24 weeks. PPs significantly decreased end-point craving [SMD -0.29; 95% confidence interval (CI) = -0.55, -0.03], while such a decrease did not reach statistical significance for ATS use, as evaluated by urine analysis (UA) (RR = 0.93; 95% CI = 0.85-1.01). No effect was observed for self-reported ATS use, retention in treatment, dropout following adverse events, early-stage craving, withdrawal and depressive symptoms. In a sensitivity analysis, treatment was associated with a significant reduction in UA positive for ATS (RR = 0.89; 95% CI = 0.79-0.99) after removing studies with a high risk of bias. In subgroup analyses, methylphenidate and high doses of PPs were negatively associated with ATS use by UA, while higher doses of PPs and treatment duration (≥ 20 weeks) were positively associated with longer retention.
CONCLUSIONS
Among individuals with amphetamine-type stimulant use disorder, treatment with prescription psychostimulants may decrease ATS use and craving. While effect size is limited, it may increase with a higher dosage of medications.
Topics: Humans; Central Nervous System Stimulants; Methylphenidate; Substance-Related Disorders; Amphetamines; Prescriptions; Randomized Controlled Trials as Topic
PubMed: 37880829
DOI: 10.1111/add.16347 -
Naunyn-Schmiedeberg's Archives of... Jul 2024Central stimulatory and hallucinogenic drugs of abuse like amphetamine and most congeners of amphetamine can have cardiac harmful effects. These cardiac side effects can... (Review)
Review
Central stimulatory and hallucinogenic drugs of abuse like amphetamine and most congeners of amphetamine can have cardiac harmful effects. These cardiac side effects can lead to morbidities and death. In this paper, we review current knowledge on the direct and indirect effects of these amphetamine congeners on the mammalian heart-more specifically, the isolated human heart muscle preparation. In detail, we address the question of whether and how these drugs affect cardiac contractility and their mechanisms of action. Based on this information, further research areas are defined, and further research efforts are proposed.
Topics: Humans; Heart; Animals; Central Nervous System Stimulants; Myocardial Contraction; Amphetamine; Hallucinogens
PubMed: 38340182
DOI: 10.1007/s00210-024-02983-2 -
Advances in Pharmacology (San Diego,... 2024The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological...
The synthetic cathinones are man-made compounds derived from the naturally occurring drug cathinone, which is found in the khat plant. The drugs in this pharmacological class that will be the focus of this chapter include mephedrone, MDPV, methcathinone and methylone. These drugs are colloquially known as "bath salts". This misnomer suggests that these drugs are used for health improvement or that they have legitimate medical uses. The synthetic cathinones are dangerous drugs with powerful pharmacological effects that include high abuse potential, hyperthermia and hyperlocomotion. These drugs also share many of the pharmacological effects of the amphetamine class of drugs including methamphetamine, amphetamine and MDMA and therefore have high potential to cause damage to the central nervous system. The synthetic cathinones are frequently taken in combination with other psychoactive drugs such as alcohol, marijuana and the amphetamine-like stimulants, creating a situation where heightened pharmacological and neurotoxicological effects are likely to occur. Despite the structural features shared by the synthetic cathinones and amphetamine-like stimulants, including their actions at monoamine transporters and receptors, the effects of the synthetic cathinones do not always match those of the amphetamines. In particular, the synthetic cathinones are far less neurotoxic than their amphetamine counterparts, they produce a weaker hyperthermia, and they cause less glial activation. This chapter will briefly review the pharmacology and neurotoxicology of selected synthetic cathinones with the aim of delineating key areas of agreement and disagreement in the literature particularly as it relates to neurotoxicological outcomes.
Topics: Humans; Synthetic Cathinone; Methamphetamine; Amphetamine; Central Nervous System Stimulants
PubMed: 38467489
DOI: 10.1016/bs.apha.2023.12.001 -
Harm Reduction Journal Jul 2023Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose...
BACKGROUND
Opioid and methamphetamine co-use is increasing across the USA with overdoses involving these drugs also rising. West Virginia (WV) has led the US in opioid overdose death rates since at least 2013 and rising co-use of methamphetamine with opioids has played a greater role in deaths over the last 5 years.
METHODS
This study used rapid ethnography to examine methods and motivations behind opioids and methamphetamine co-use from the viewpoint of their consumers. Participants (n = 30) were people who injected heroin/fentanyl also using methamphetamine who participated in semi-structured interviews.
RESULTS
We found multiple methods of co-using opioids and methamphetamine, whether alternately or simultaneously and in varying order. Most prioritized opioids, with motives for using methamphetamine forming three thematic categories: 'intrinsic use', encompassing both inherent pleasure of combined use greater than using both drugs separately or for self-medication of particular conditions; 'opioid assisting use' in which methamphetamine helped people manage their existing heroin/fentanyl use; and 'reluctant or indifferent use' for social participation, reflecting methamphetamine's low cost and easy availability.
CONCLUSIONS
Methamphetamine serves multiple functions among people using opioids in WV. Beliefs persist that methamphetamine can play a role in preventing and reversing opioid overdose, including some arguments for sequential use being protective of overdose. 'Reluctant' uptake attests to methamphetamine's social use and the influence of supply. The impact on overdose risk of the many varied co-use patterns needs further investigation.
Topics: Motivation; Methamphetamine; Heroin; West Virginia; Fentanyl; Heroin Dependence; Interviews as Topic; Self Medication; Pleasure; Social Interaction; Health Knowledge, Attitudes, Practice; Humans; Male; Female; Adult
PubMed: 37438812
DOI: 10.1186/s12954-023-00816-8 -
BMJ Mental Health Apr 2024Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent...
BACKGROUND
Use of psychostimulants and relative drugs has increased worldwide in treatment of attention-deficit hyperactivity disorder (ADHD) in adolescents and adults. Recent studies suggest a potential association between use of psychostimulants and psychotic symptoms. The risk may not be the same between different psychostimulants.
OBJECTIVE
To assess whether amphetamine or atomoxetine use is associated with a higher risk of reporting symptoms of psychosis than methylphenidate use in adolescents and adults, particularly in patients with ADHD.
METHODS
Using VigiBase, the WHO's pharmacovigilance database, disproportionality of psychotic symptoms reporting was assessed among adverse drug reactions related to methylphenidate, atomoxetine and amphetamines, from January 2004 to December 2018, in patients aged 13-25 years. The association between psychotic symptoms and psychostimulants was estimated through the calculation of reporting OR (ROR).
FINDINGS
Among 13 863 reports with at least one drug of interest, we found 221 cases of psychosis with methylphenidate use, 115 with atomoxetine use and 169 with a prescription of an amphetamine drug. Compared with methylphenidate use, amphetamine use was associated with an increased risk of reporting psychotic symptoms (ROR 1.61 (95% CI 1.26 to 2.06)]. When we restricted the analysis to ADHD indication, we found a close estimate (ROR 1.94 (95% CI 1.43 to 2.64)). No association was found for atomoxetine.
CONCLUSION
Our study suggests that amphetamine use is associated with a higher reporting of psychotic symptoms, compared with methylphenidate use.
CLINICAL IMPLICATIONS
The prescription of psychostimulants should consider this potential adverse effect when assessing the benefit-risk balance.
Topics: Adult; Humans; Adolescent; Amphetamine; Methylphenidate; Atomoxetine Hydrochloride; Central Nervous System Stimulants; Psychotic Disorders; Drug-Related Side Effects and Adverse Reactions
PubMed: 38609318
DOI: 10.1136/bmjment-2023-300876 -
Drug and Alcohol Dependence Jul 2023Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs.... (Review)
Review
BACKGROUND
Nicotine is commonly co-used with other psychostimulants. These high co-use rates have prompted much research on interactions between nicotine and psychostimulant drugs. These studies range from examination of illicitly used psychostimulants such as cocaine and methamphetamine to prescription psychostimulants used to treat attention deficit hyperactivity disorder (ADHD) such as methylphenidate (Ritalin™) and d-amphetamine (active ingredient of Adderall™). However, previous reviews largely focus on nicotine interactions with illicitly used psychostimulants with sparse mention of prescription psychostimulants. The currently available epidemiological and laboratory research, however, suggests high co-use between nicotine and prescription psychostimulants, and that these drugs interact to modulate use liability of either drug. The present review synthesizes epidemiological and experimental human and pre-clinical research assessing the behavioral and neuropharmacological interactions between nicotine and prescription psychostimulants that may contribute to high nicotine-prescription psychostimulant co-use.
METHODS
We searched databases for literature investigating acute and chronic nicotine and prescription psychostimulant interactions. Inclusion criteria were that participants/subjects had to experience nicotine and a prescription psychostimulant compound at least once in the study, in addition to assessment of their interaction.
RESULTS AND CONCLUSIONS
Nicotine clearly interacts with d-amphetamine and methylphenidate in a variety of behavioral tasks and neurochemical assays assessing co-use liability across preclinical, clinical, and epidemiological research. The currently available research suggests research gaps examining these interactions in women/female rodents, in consideration of ADHD symptoms, and how prescription psychostimulant exposure influences later nicotine-related outcomes. Nicotine has been less widely studied with alternative ADHD pharmacotherapy bupropion, but we also discuss this research.
Topics: Female; Humans; Nicotine; Central Nervous System Stimulants; Methylphenidate; Attention Deficit Disorder with Hyperactivity; Dextroamphetamine; Prescriptions
PubMed: 37216808
DOI: 10.1016/j.drugalcdep.2023.109906 -
Attention-Deficit/Hyperactivity Disorder Medications and Work Disability and Mental Health Outcomes.JAMA Network Open Mar 2024Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD...
IMPORTANCE
Individuals with attention-deficit/hyperactivity disorder (ADHD) often have comorbid psychiatric conditions. Relatively little is known about how specific ADHD medications are associated with overall treatment outcomes among these patients.
OBJECTIVE
To investigate the association of the use of specific ADHD medications with hospitalization outcomes and work disability among adolescents and adults with ADHD.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide register-based cohort study identified individuals (aged 16-65 years) with ADHD from Swedish nationwide registers of inpatient health care, specialized outpatient health care, sickness absence, and disability pension during the years 2006 to 2021. Data analysis was performed from November 2022 to August 2023.
EXPOSURE
Use of specific ADHD medications.
MAIN OUTCOMES AND MEASURES
The main outcome measure was psychiatric hospitalization, and secondary outcomes were suicide attempt and/or death by suicide, nonpsychiatric hospitalization, and work disability (ie, sickness absence or disability pension). The risk of outcomes between use vs nonuse periods of ADHD medications was compared in a within-individual design, where a person acts as their own control, and was analyzed with stratified Cox models.
RESULTS
A total of 221 714 persons with ADHD were included in the study cohort (mean [SD] age, 25.0 [11.2] years; 120 968 male individuals [54.6%]). Methylphenidate was the most commonly used ADHD medication (151 837 individuals [68.5%]), followed by lisdexamphetamine (78 106 individuals [35.2%]) during the follow-up (mean [SD], 7.0 [4.7] years). The following medications were associated with a decreased risk of psychiatric hospitalization: amphetamine (adjusted hazard ratio [aHR], 0.74; 95% CI, 0.61-0.90), lisdexamphetamine (aHR, 0.80; 95% CI, 0.78-0.82), ADHD drug polytherapy (aHR, 0.85; 95% CI, 0.82-0.88), dexamphetamine (aHR, 0.88; 95% CI, 0.83-0.94), and methylphenidate (aHR, 0.93; 95% CI, 0.92-0.95). No associations were found for modafinil, atomoxetine, clonidine, and guanfacine. Decreased risk of suicidal behavior was associated with the use of dexamphetamine (aHR, 0.69; 95% CI, 0.53-0.89), lisdexamphetamine (aHR, 0.76; 95% CI, 0.68-0.84), and methylphenidate (aHR, 0.92; 95% CI, 0.86-0.98). None of the medications was associated with increased risk of nonpsychiatric hospitalization; instead, use of amphetamine, lisdexamphetamine, polytherapy, dexamphetamine, methylphenidate, and atomoxetine were associated with decreased risk of nonpsychiatric hospitalization. The results regarding work disability were significant only for the use of atomoxetine (aHR, 0.89; 95% CI, 0.82-0.97), especially among adolescents and young adults aged 16 to 29 years, (aHR, 0.82; 95% CI, 0.73-0.92).
CONCLUSIONS AND RELEVANCE
In this nationwide cohort study of adolescents and adults with ADHD, the use of ADHD medication was associated with fewer hospitalizations for both psychiatric and nonpsychiatric morbidity and lower suicidal behavior.
Topics: Adolescent; Young Adult; Humans; Male; Adult; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Cohort Studies; Lisdexamfetamine Dimesylate; Methylphenidate; Amphetamine
PubMed: 38506810
DOI: 10.1001/jamanetworkopen.2024.2859