https://www.healio.com/psychiatry/journals/psycann/1976-12-6-12/{806b8887-c02e-40c8-a228-57f1cdb2bdba}/the-stress-of-life.pdf

The stress of life

Vision for Transformation Strengths: The SHSIP describes a holistic transformation plan and ensures connections between various plan components. The State’s Plan seeks to reward health care providers for better care, smarter spending, and healthier people through higher quality, instead of quantity of services by utilizing valuebased purchasing across public and private payers. The SHSIP provides a well-detailed description of the proposed value-based models of care through the Patient-Centered Medical Home (PCMH) model, resulting in the statewide implementation of Accountable Health Communities (AHCs). The SHSIP outlines a long-term vision of building and expanding the PCMH model into a Community Centered Health Homes (CCHHs) model, which will focus on prevention and collaboration with other communitybased organizations. Another strength identified is the amount of existing PCMHs operating within the State. The SHSIP provides a course of action to assist non-PCMH practices to become nationally certified, as well as, goals for a single, statewide PCMH model to be used by all providers and payers within the state. The implementation of the AHCs will be key in addressing social determinants of health within various communities and seems to align well with the PCMH goals. This focus on population and community health will enable the State to make a broader impact and support the long-term goal of moving towards a CCHH model. The focus on the improvement of clinical, behavioral, and oral health care within the urban, rural, and frontier communities is well aligned and consistent with the SIM goals and the overall Triple Aim initiative. Figure 18: Driver Diagram clearly shows how the State plans to achieve the Triple Aim by 2020.

Department of health & human services

The serotonin syndrome is a potentially life-threatening drug reaction that may result from therapeutic medication use, self-poisoning, or interactions between drugs.

/pdf/the-serotonin-syndrome-52b0yisqua.pdf

The serotonin syndrome.

Impulsivity as a vulnerability marker for substance-use disorders: Review of findings from high-risk research, problem gamblers and genetic association studies

The amphetamine derivative (±)-3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is a popular recreational drug among young people, particularly those involved in the dance culture. MDMA produces an acute, rapid enhancement in the release of both serotonin (5-HT) and dopamine from nerve endings in the brains of experimental animals. It produces increased locomotor activity and the serotonin behavioral syndrome in rats. Crucially, it produces dose-dependent hyperthermia that is potentially fatal in rodents, primates, and humans. Some recovery of 5-HT stores can be seen within 24 h of MDMA administration. However, cerebral 5-HT concentrations then decline due to specific neurotoxic damage to 5-HT nerve endings in the forebrain. This neurodegeneration, which has been demonstrated both biochemically and histologically, lasts for months in rats and years in primates. In general, other neurotransmitters appear unaffected. In contrast, MDMA produces a selective long-term loss of dopamine nerve endings in mice. Studies on the mechanisms involved in the neurotoxicity in both rats and mice implicate the formation of tissue-damaging free radicals. Increased free radical formation may result from the further breakdown of MDMA metabolic products. Evidence for the occurrence of MDMA-induced neurotoxic damage in human users remains equivocal, although some biochemical and functional data suggest that damage may occur in the brains of heavy users. There is also some evidence for long-term physiological and psychological changes occurring in human recreational users. However, such evidence is complicated by the lack of knowledge of doses ingested and the fact that many subjects studied are or have been poly-drug users.

The Pharmacology and Clinical Pharmacology of 3,4-Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

Three groups of young people (aged 19-30 years) were compared: 15 regular ecstasy users who had taken MDMA (3,4-methylenedioxymethamphetamine) on ten or more occasions; 15 novice ecstasy users who had taken MDMA on fewer than ten previous occasions; and 15 controls who had never taken MDMA. Each subject completed a cognitive test and mood scale battery four times: an initial drug-free baseline, at a Saturday night dance/club (on-drug), then 2 days later, and 7 days later. On the Saturday night, regular ecstasy users took an average of 1.80 MDMA tablets, novice users took 1.45 MDMA tablets, while controls mostly drank alcohol. The consumption of cannabis and cocaine at the club was similar across groups. All three groups reported positive moods at the dance club (on-drug), although there were borderline trends (P < 0.10) for less sadness/depression in the MDMA subgroups. However 2 days afterwards, the ecstasy users felt significantly more depressed, abnormal, unsociable, unpleasant, and less good tempered, than the controls. Cognitive performance on both tasks (verbal recall, visual scanning) was significantly reduced on-MDMA. Memory recall was also significantly impaired in drug-free MDMA users, with regular ecstasy users displaying the worst memory scores at every test session. This agrees with previous findings of memory impairments in drug-free ecstasy users. Animal data have shown that MDMA can generate long-term serotonergic neurodegeneration in various brain areas, including the hippocampus. The cognitive deficits in drug-free recreational ecstasy users, suggest that MDMA may also be neurotoxic in humans.

/pdf/ecstasy-mdma-effects-upon-mood-and-cognition-before-during-3kqnn5446t.pdf

Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance.

MDMA (3,4-methylenedioxymethamphetamine) or ‘Ecstasy’ was scheduled as an illegal drug in 1986, but since then its recreational use has increased dramatically. This review covers 15 years of research into patterns of use, its acute psychological and physiological effects, and the long-term consequences of repeated use. MDMA is an indirect monoaminergic agonist, stimulating the release and inhibiting the reuptake of serotonin (5-HT) and, to a lesser extent, other neurotransmitters. Single doses of MDMA have been administered to human volunteers in double-blind placebo-controlled trials, although most findings are based upon recreational MDMA users. The ‘massive’ boost in neurotransmitter activity can generate intense feelings of elation and pleasure, also hyperactivity and hyperthermia. This psychophysiological arousal may be exacerbated by high ambient temperatures, overcrowding, prolonged dancing and other stimulant drugs. Occasionally the ‘serotonin syndrome’ reactions may prove fatal. In the days after Ecstasy use, around 80% of users report rebound depression and lethargy, due probably to monoaminergic depletion. Dosage escalation and chronic pharmacodynamic tolerance typically occur in regular users. Repeated doses of MDMA cause serotonergic neurotoxicity in laboratory animals, and there is extensive evidence for long-term neuropsychopharmacological damage in humans. Abstinent regular Ecstasy users often display reduced levels of 5-HT, 5-HIAA, tryptophan hydroxylase and serotonin transporter density; functional deficits in learning/memory, higher cognitive processing, sleep, appetite and psychiatric well-being, and, most paradoxically, ‘loss of sexual interest/pleasure’. These psychobiological deficits are greatest in heavy Ecstasy users and may reflect serotonergic axonal loss in the higher brain regions, especially the frontal lobes, temporal lobes and hippocampus. These problems seem to remain long after the recreational use of Ecstasy has ceased, suggesting that the neuropharmacological damage may be permament. Copyright © 2001 John Wiley & Sons, Ltd.

Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research

https://psy.swansea.ac.uk/staff/parrott/p-and-sisk-and-turnerd-and-adep-2000.pdf

Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users.

The ring-substituted amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) or ‘‘Ecstasy’’ is widely used a recreational drug. It stimulates the release and inhibits the reuptake of serotonin (5-HT) and other neurotransmitters such as dopamine to a lesser extent. The acute boost in monoamine activity can generate feelings of elation, emotional closeness, and sensory pleasure. In the hot and crowded conditions of raves/dances, mild versions of the serotonin syndrome often develop, when hyperthermia, mental confusion, and hyperkinesia predominate. Rest in a cooler environment generally reverses these problems, although they can develop into medical emergencies, which occasionally prove fatal. This acute serotonergic overactivity is exacerbated by the high ambient temperatures, overcrowding (aggregate toxicity), and use of other stimulant drugs. The on-drug experience is generally followed by negative moods, with 80–90% of weekend Ecstasy users reporting ‘midweek blues’, due probably to monoaminergic depletion. Single doses of MDMA can cause serotonergic nerve damage in laboratory animals, with repeated doses causing extensive loss of distal axon terminals. Huether’s explanatory model for this 5-HT neurotoxicity will be briefly described. There is an increasing body of evidence for equivalent neuropsychobiological damage in humans. Abstinent regular Ecstasy users often show: reduced cerebrospinal 5-HIAA, reduced density of 5-HT transporters, blunted response to a fenfluramine challenge, memory problems, higher cognitive deficits, various psychiatric disorders, altered appetite, and loss of sexual interest. Functional deficits may remain long after drug use has ceased and are consistent with serotonergic axonal loss in higher brain regions. D 2002 Elsevier Science Inc. All rights reserved.

https://www.erowid.org/archive/rhodium/pharmacology/PBB-71-837.pdf

Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity.

Cognitive task performance was assessed in three groups of young people: 10 regular users of 3,4methylenedioxymethamphetamine (MI)MA) who had taken 'ecstasy' 10 times or more; 10 novice MDMA users who had taken'ecstasy'one to nine times; and 10 control subjects who had never taken MDMA. A computerized battery of cognitive tasks (Cognitive Drug Research system) was undertaken on a day when subjects were drug free. Performance on the response speed and vigilance measures (simple reaction time, choice reaction time, number vigdlnnce), was similar across the three subgroups. However on immediate word recall and delayed word recall, both groups of MDMA users recalled significantly less words than controls. Animal research has shown that MDMA can lead to serotonergic neurodegeneration, particularly in the hippocampus and frontal cortex. Although the design of this study was far from ideal, these data are consistent with other findings of memory decrements in recreational MDMA users, possibly caused by serotonergic neurotoxicity.

Andrew C. Parrott

Papers

Ecstasy (MDMA) effects upon mood and cognition: before, during and after a Saturday night dance.

Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research

Psychobiological problems in heavy 'ecstasy' (MDMA) polydrug users.

Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity.

Cognitive performance in recreational users of MDMA or 'ecstasy': evidence for memory deficits