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Experimental and Clinical... Oct 2017Adolescent nicotine exposure has been shown to lead to further psychostimulant use in adulthood. Previous preclinical research in rats has shown that environmental...
Adolescent nicotine exposure has been shown to lead to further psychostimulant use in adulthood. Previous preclinical research in rats has shown that environmental enrichment may protect against drug abuse vulnerability. The current study was designed to examine whether environmental enrichment can block the ability of adolescent nicotine exposure to increase d-amphetamine self-administration in adulthood. Male Sprague-Dawley rats were raised in either enriched conditions (ECs) or isolated conditions (ICs) and then injected with saline or nicotine (0.4 mg/kg, sc) for 7 days during adolescence. In adulthood rats were allowed to self-administer d-amphetamine under a fixed ratio (FR; 0, 0.006, 0.01, 0.02, 0.06, and 0.1 mg/kg/infusion) and progressive ratio (PR; 0, 0.006, 0.06, and 0.1 mg/kg/infusion) schedule of reinforcement. Nicotine-treated IC rats self-administered more d-amphetamine at 0.006, 0.01, and 0.02 mg/kg/infusion doses compared with their saline-treated IC counterparts regardless of the schedule maintaining behavior. This effect of nicotine was reversed in EC rats on a fixed ratio schedule. These findings indicate that environmental enrichment can limit the ability of adolescent nicotine exposure to increase vulnerability to other psychostimulant drugs, such as d-amphetamine. (PsycINFO Database Record
Topics: Animals; Central Nervous System Stimulants; Dextroamphetamine; Dose-Response Relationship, Drug; Male; Nicotine; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration
PubMed: 29048188
DOI: 10.1037/pha0000137 -
Harm Reduction Journal Oct 2017As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing... (Review)
Review
As postsecondary students' use of "study drugs" becomes more popular with increasingly reported negative effects on health and academic performance, failing prohibitionist policies to reduce consumption, and ambiguity in literature towards best practices to address this population, we present a literature review that seeks effective solutions educational institutions can apply to improve outcomes for students who use drugs. Motivations for use, effects of the substances, an analysis of efforts to control use from educational institutions, and suggestions on promoting most effective outcomes based on harm reduction, are described. Theory, quantitative, and qualitative works from systematic reviews, cohort studies, and epidemiological assessments are examined on the "study drugs" methylphenidate, dextroamphetamine, and amphetamine, also known as Adderall, Ritalin, Focalin, and Concerta. There is a focus on postsecondary students ages 18-25 in North America. Results show important risk factors for drug use including low perceived self-efficacy or enjoyment in courses, poor accommodation of special needs, reliance on external validation, having a low GPA, and experiencing a mental health issue. There is much misconception on the health and academic effects of these drugs in literature, among students, and on online knowledge sources. We suggest these drugs do not improve GPA and learning, while they might temporarily increase memory, but with detrimental negative health effects. Campaigns that address underlying factors of use can be most successful in mitigating harms.
Topics: Academic Success; Adolescent; Adult; Amphetamines; Central Nervous System Stimulants; Dexmethylphenidate Hydrochloride; Female; Harm Reduction; Humans; Male; Methylphenidate; Motivation; Prescription Drug Misuse; Risk Factors; Students; Substance-Related Disorders; Young Adult
PubMed: 28985738
DOI: 10.1186/s12954-017-0194-6 -
Pharmacology, Biochemistry, and Behavior May 2021It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However,...
BACKGROUND
It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However, recreational drug use sometimes occurs in the absence of positive subjective effects, suggesting that other factors contribute. Here, we examine the extent to which the direct subjective effects of amphetamine, a commonly misused stimulant, predict subsequent choice of the drug vs placebo.
METHODS
Healthy adults (N = 112) participated in a five-session amphetamine choice study. On the first four sessions, participants sampled either 20 mg d-amphetamine or placebo in color-coded capsules two times each. On the fifth session, they chose which color (d-amphetamine or placebo) they preferred. We examined the choice of drug vs placebo in relation to demographic characteristics, baseline mood states, personality and subjective and cardiovascular responses to acute administration of the drug.
RESULTS
Eighty-one participants chose amphetamine (Choosers) while 31 chose placebo (Non-choosers). Overall, amphetamine produced typical stimulant-like effects on subjective questionnaires, and it elevated heart rate and blood pressure vs placebo. Choosers reported greater positive mood, elation and stimulant-like effects following amphetamine compared to Non-choosers. The Choosers also exhibited a greater increase in systolic blood pressure, but not heart rate. The groups did not differ on demographic characteristics, mood states before drug administration or personality.
CONCLUSIONS
These findings support the idea that pleasurable subjective responses to amphetamine, including positive mood, elation, and stimulant-like effects influence behavioral choice of the drug.
Topics: Adult; Affect; Arousal; Blood Pressure; Central Nervous System Stimulants; Choice Behavior; Dextroamphetamine; Female; Healthy Volunteers; Heart Rate; Humans; Male; Personality; Recreational Drug Use; Young Adult
PubMed: 33675838
DOI: 10.1016/j.pbb.2021.173158 -
Progress in Neuro-psychopharmacology &... Jun 2021Reduction in direct social contact with peers during early adolescence is thought to be a risk factor for an increase in depressive symptoms, but there is still no clear...
Reduction in direct social contact with peers during early adolescence is thought to be a risk factor for an increase in depressive symptoms, but there is still no clear evidence to suggest early behavioral manifestations and their association with the later outcome of social distancing during this period. To address this question, we used social isolation paradigm in peripubertal rats as the rodent model of adolescence. The litter was an experimental unit. On postnatal day 29, each litter gave group-housed and single-housed males, which were reared and tested one week and two weeks thereafter. Psychomotor/emotional response to novelty in exploration-based tasks, behavioral and neuronal responses to the drug reward (D-amphetamine), motivation/hedonic behavior, physiological and response to physiological stress were examined. Social isolation in peripubertal rats manifested through: hyper-reactivity/agitation and the state anxiety/risk-taking at an early stage; reduced behavioral response to D-amphetamine and altered neural processing of this stimulus, at a later stage; consummatory hypohedonia that deepened over time without changing the motivation to eat; unchanged body weight gain and resting blood corticosterone, cortisol and glucose levels over time; altered blood biochemistry (silenced corticosterone and increased glucose) due to overnight fasting only at an early stage. Our results highlight that the outcome of reduced direct social contact with peers during peripuberty is dynamic, with the cluster of atypical early symptoms that evolve into the syndrome that is delicate for assessment through routinely measurable behavior and biomarkers of stress, but with progressive consummatory hypohedonia and unaffected motivation to eat as stable marks.
Topics: Animals; Corticosterone; Dextroamphetamine; Emotions; Exploratory Behavior; Male; Motor Activity; Prefrontal Cortex; Rats; Rats, Wistar; Sexual Maturation; Social Isolation; Stress, Psychological
PubMed: 33238164
DOI: 10.1016/j.pnpbp.2020.110186 -
Addiction Biology Jul 2021Prescription stimulants, such as d-amphetamine or methylphenidate are used to treat suffering from attention-deficit hyperactivity disorder (ADHD). They potently release...
Prescription stimulants, such as d-amphetamine or methylphenidate are used to treat suffering from attention-deficit hyperactivity disorder (ADHD). They potently release dopamine (DA) and norepinephrine (NE) and cause phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 in the striatum. Whether other brain regions are also affected remains elusive. Here, we demonstrate that d-amphetamine and methylphenidate increase phosphorylation at Ser845 (pS845-GluA1) in the membrane fraction of mouse cerebellum homogenate. We identify Bergmann glial cells as the source of pS845-GluA1 and demonstrate a requirement for intact NE release. Consequently, d-amphetamine-induced pS845-GluA1 was prevented by β1-adenoreceptor antagonist, whereas the blockade of DA D1 receptor had no effect. Together, these results indicate that NE regulates GluA1 phosphorylation in Bergmann glial cells in response to prescription stimulants.
Topics: Animals; Central Nervous System Stimulants; Cerebellum; Dextroamphetamine; Male; Methylphenidate; Mice; Norepinephrine; Phosphorylation; Phosphotransferases; Receptors, Dopamine D1
PubMed: 33368923
DOI: 10.1111/adb.12995 -
Frontiers in Psychiatry 2021Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the...
Opioids and stimulants are often used in combination for both recreational and non-recreational purposes. High-efficacy mu opioid agonists generally increase the behavioral effects of stimulants, whereas opioid receptor antagonists generally attenuate the behavioral effects of stimulants; however, less is known regarding the interactions between stimulants and opioids possessing low to intermediate efficacy at the mu receptor. The purpose of this study was to examine the role of an opioid's relative efficacy at the mu receptor in altering the behavioral effects of dextro(-)amphetamine. To this end, opioids possessing a range of relative efficacy at the mu receptor were examined alone and in combination with cumulative doses of -amphetamine on a test of open-field, locomotor activity in male rats. Levorphanol, buprenorphine, butorphanol, nalbuphine, (-)-pentazocine, (-)-metazocine, (-)-cyclazocine, (-)-NANM, and nalorphine increased the locomotor effects of -amphetamine in either an additive or greater-than-additive manner according to an effect-additive model. Only the selective, high-efficacy kappa agonist, spiradoline, and the non-selective opioid receptor antagonist, naloxone, failed to increase the effects of -amphetamine under the conditions examined. These data indicate that opioids possessing a large range of relative efficacy at the mu receptor, including those possessing very low relative efficacy, significantly increase the locomotor effects of -amphetamine.
PubMed: 35069292
DOI: 10.3389/fpsyt.2021.790471 -
Current Neuropharmacology 2020To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
OBJECTIVE
To systematically review the literature on the therapeutic use of amphetamine, lisdexamfetamine and methylphenidate in elderly population with and without dementia.
METHODS
We conducted two researches on the PubMed, Scopus and Embase using the keywords ("elderly") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine") and then ("Alzheimer" OR "dementia") AND ("amphetamine" OR "methylphenidate" OR "lisdexamfetamine").
RESULTS
Twenty-nine papers met all the eligibility criteria. The results are encouraging as 81.5% of the studies showed clinical improvement of the investigated condition.
CONCLUSION
Amphetamines and methylphenidate are probably effective strategies for different conditions in the elderly population. However, further studies are needed to provide more robust evidence on efficacy, dosage and safety for this population.
Topics: Aged; Amphetamine; Dementia; Depressive Disorder, Major; Humans; Lisdexamfetamine Dimesylate; Methylphenidate
PubMed: 31660835
DOI: 10.2174/1570159X17666191010093021 -
PloS One 2022Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based...
INTRODUCTION
Methamphetamine (MA) use disorder is an important public health concern. MA withdrawal is often the first step in ceasing or reducing use. There are no evidence-based withdrawal treatments, and no medication is approved for the treatment of MA withdrawal. Lisdexamfetamine (LDX) dimesilate, used in the treatment of attention deficit hyperactivity disorder and binge eating disorder has the potential as an agonist therapy to ameliorate withdrawal symptoms, and improve outcomes for patients.
METHODS
A single arm, open-label pilot study to test the safety and feasibility of LDX for the treatment of MA withdrawal. Participants will be inpatients in a drug and alcohol withdrawal unit, and will receive a tapering dose of LDX over five days: 250mg LDX on Day 1, reducing by 50mg per day to 50mg on Day 5. Optional inpatient Days 6 and 7 will allow for participants to transition to ongoing treatment. Participants will be followed-up on Days 14, 21 and 28. All participants will also receive standard inpatient withdrawal care. The primary outcomes are safety (measured by adverse events, changes in vital signs, changes in suicidality and psychosis) and feasibility (the time taken to enrol the sample, proportion of screen / pre-screen failures). Secondary outcomes are acceptability (treatment satisfaction questionnaire, medication adherence, concomitant medications, qualitative interviews), retention to protocol (proportion retained to primary and secondary endpoints), changes in withdrawal symptoms (Amphetamine Withdrawal Questionnaire) and craving for MA (visual analogue scale), and sleep outcomes (continuous actigraphy and daily sleep diary).
DISCUSSION
This is the first study to assess lisdexamfetamine for the treatment of acute MA withdrawal. If safe and feasible results will go to informing the development of multi-centre randomised controlled trials to determine the efficacy of the intervention.
Topics: Alcoholism; Amphetamine-Related Disorders; Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Double-Blind Method; Humans; Lisdexamfetamine Dimesylate; Methamphetamine; Pilot Projects; Substance Withdrawal Syndrome; Treatment Outcome
PubMed: 36190973
DOI: 10.1371/journal.pone.0275371 -
Journal of Neurochemistry Aug 2015Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant...
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by poor attention, impulse control and hyperactivity. A significant proportion of ADHD patients are also co-morbid for other psychiatric problems including mood disorders and these patients may be managed with a combination of psychostimulants and anti-depressants. While it is generally accepted that enhanced catecholamine signalling via the action of psychostimulants is likely responsible for the cognitive improvement in ADHD, other neurotransmitters including acetylcholine and histamine may be involved. In the present study, we have examined the effect of lisdexamfetamine dimesylate (LDX), an amphetamine pro-drug that is approved for the treatment of ADHD on acetylcholine and histamine efflux in pre-frontal cortex and hippocampus alone and in combination with the anti-depressant s-citalopram. LDX increased cortical acetylcholine efflux, an effect that was not significantly altered by co-administration of s-citalopram. Cortical and hippocampal histamine were markedly increased by LDX, an effect that was attenuated in the hippocampus but not in pre-frontal cortex when co-administered with s-citalopram. Taken together, these results suggest that efflux of acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially influenced by the co-administration of s-citalopram. Attention deficit hyperactivity disorder (ADHD) is characterized by poor attention, impulse control and hyperactivity. Some ADHD patients are also co-morbid for mood disorders and may be managed with psychostimulants (e.g. lisdexamfetamine, LDX) and anti-depressants (e.g. s-citalopram). LDX increased the efflux of acetylcholine and histamine, neurotransmitters involved in cognitive function, which were differentially influenced when co-administered with s-citalopram. Acetylcholine and histamine may be involved in the therapeutic effects of LDX and are differentially affected by the co-administration of s-citalopram.
Topics: Acetylcholine; Animals; Antidepressive Agents, Second-Generation; Attention Deficit Disorder with Hyperactivity; Citalopram; Dextroamphetamine; Drug Therapy, Combination; Hippocampus; Histamine Release; Lisdexamfetamine Dimesylate; Male; Microdialysis; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Treatment Outcome
PubMed: 25946513
DOI: 10.1111/jnc.13157 -
Neuropsychopharmacology Reports Mar 2020To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults. (Randomized Controlled Trial)
Randomized Controlled Trial
A phase 1, randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics of single and multiple doses of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adult subjects.
AIM
To assess safety, tolerability, and pharmacokinetics of lisdexamfetamine dimesylate in Japanese and Caucasian healthy adults.
METHODS
A phase 1, double-blind, randomized, placebo-controlled, single- and multiple-dose study in Japanese and Caucasian subjects. Subjects received lisdexamfetamine 20 mg or placebo on Day 1, then lisdexamfetamine 20 mg/d (Days 4-8), 50 mg/d (Days 9-13), 70 mg/d (Days 14-18), or matching placebo. Pharmacokinetic parameters for lisdexamfetamine and d-amphetamine were estimated by noncompartmental analysis.
RESULTS
Fifteen Japanese and 19 Caucasian subjects were enrolled and randomized. The lisdexamfetamine and d-amphetamine plasma concentration-time curves were similar for both ethnic groups following single and multiple doses. Mean area under the concentration-time curves for d-amphetamine were higher (by 11%-15%) in Japanese than Caucasian subjects following multiple dosing of lisdexamfetamine. Mean bodyweight was 17% lower in Japanese than Caucasian subjects. Weight-corrected means for oral clearance were similar in both ethnic groups, with no unexpected accumulation of d-amphetamine. Lisdexamfetamine was generally well tolerated by both ethnic groups, with no serious adverse events reported. The 10/12 Japanese and 11/16 Caucasian subjects who received lisdexamfetamine completed the study; two Japanese and three Caucasian subjects discontinued due to adverse events. Most adverse events were of mild severity.
CONCLUSION
Pharmacokinetics were generally similar for Japanese and Caucasian subjects; the minor differences observed were likely due to bodyweight differences in the two ethnic groups. Lisdexamfetamine was generally well tolerated. Adverse events were consistent with the established safety profile of lisdexamfetamine and were similar in both ethnic groups.
Topics: Adolescent; Adult; Asian People; Central Nervous System Stimulants; Double-Blind Method; Female; Healthy Volunteers; Humans; Japan; Lisdexamfetamine Dimesylate; Male; Middle Aged; Treatment Outcome; White People; Young Adult
PubMed: 31765110
DOI: 10.1002/npr2.12082