Amphetamine usage in adolescents
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Transcript of Amphetamine usage in adolescents
Heidi ChodorowiczHLTH 471April 2nd, 2013
Amphetamine Usage in Adolescents
Introduction
History
Usage – adolescents
Pharmacokinetics
Immediate effects
Pharmacodynamics
Prolonged effects/Neurotoxicity
Discussion
Overview
Introduction: Chemical structure
1. Unsubstituted phenyl ring,
2. 2-C side chain
3. An a-methyl group
4. A primary amino group
Methamphetamine (METH) “Crystal meth”
No amino group (just NH)
Methylphenidate “Ritalin”Chain substituted
Methylenedioxymethamphetamine(MDMDA) “Ecstasy”
Ring substituted
Tyramine & Mescaline Non a-methylated not always
considered an amphetamine
Variations
Used for 1000s of years as plant products: Ephedra China, Middle East, IndiaKhat Kenya, Simalia, Yemen
1887 :Nagajoshi Nagai – first isolated ephedrineLazăr Edeleanu – first synthesized amphetamine
Pharm use1927 by: Gordon Alles stimulant
Illicit drug usage jumped 1950-1970Declined after cocaine Increases Ritalin
History
Adolescent usage
Paglia-Boak, Adlaf & Man, 2011
Profressor Mielke briefly mentioned research with a colleague at WLU: peak in MDMA usage after the
nightclub, Beta opened
Correlation between night clubs/“rave space” with MDMA etc.
Lifetime prevalence of illicit drugs: UK Clubbers:52-81% vs. 12% of 16-29 yr olds
Drugs and Clubs
Measham, 2004
Amphetamine: Oral (slow release Px), IV
Methamphetamine: Oral, IV, or inhalation
MDMA Oral, insufflation (snort)
Lipophilic, therefore:
Metabolized in liver: deamination and hydroxylation: Slow, half-life ≥7 -32 hrs Detection: 24-72 hrs
Pharmacokinetics
Crosses BBB
Psychological: Heightened alertness, concentration, arousal Reduced fatigue, increased energy _______________
Grandosity, self-confidence/esteem, sociability
Behavioural: Locomotor activation, Steroptypy (repetitive movement, posture, or
utterance)
Clinical: Narcolepsy, ADHD, Body weight management
Immediate Effects
Euphoria
Milesi-Hallé et al, 2005
Despite similar concentrations of drug in the body
Lower magnitude of locomotor activity in adolescents
Adolescent differences
Zombeck JA, Gupta T & Rhodes JS. (2009)
Competitive agonists to transporters, increase:1. Dopamine (DA)
2. Serotonin (5-HT)
3. Norepinephrine (NE)
Inhibit:Vesiculart monoamine
transporters (VMAT)Monoamine Oxidases (MAO)
Overarching effects:Stimulate the _____________
nervous system
Pharmacodynamics
For all three transporters, transport was saturablewith increasing neurotransmitter concentration
Verrico, Miller,& Madras, 2007
Sympathetic
System
Neuron origin Neuron Innervation Functions modulated
DA Substantia nigra of midbrain, ventral tegmentum of midbrain
Cortex and parts of limbic system
Motor control, reward centers pleasure, addicition
5-HT Raphe nuclei, midline of brain stem
Most of brain, spinal cord Pain/locomotion, sleep-wake cycle, mood, emotional behaviours
NE Locus coerulus of pons
Cerebreal cortex, thalamus, hypothalamus, olfactory bulb, cerebellum, midbrain, spinal cord
Attention, arousal, sleep cycles, learning, memory, anxiety, pain, mood
Brain Systems affected
Long term/high dose effects
Psychological Physical
Serotonin syndromePsychosomatic disorders, Psychomotor agitation, Paranoia,Amphetamine psychosis
Tachycardia,Hypertension,Hyperthermia,Seizures,Urinary retentionIntracranial hemorrhage, Myocardial infarction, hyponatremia,Death
Significant, and likely permanent overall damage to the brain
King et al, 2010: Adolescents METH usage is inversely correlated with neuropsychological functioning (dose-response):Executive functioningAbstract, non-verbal reasoning
Dzietko et al, 2010: Adolescents of child bearing age: single injections results in damage to the following areas of neonatal rat brains: cortex, septum, thalamus, hypothalamus and the cornu ammonis
Neurotoxicity
Decrease density of Basal Ganglia: Caudate nucleus: -23%,-24% Putamen: -25%-16%
Larger decreases in PD Caudate Nucleus: -47% Putamen: -68%
Reductions in density:Loss of DA fibresLoss of DATsDecreased expression of tyrosine
hydroxylase
Neurotoxicity: DA
McCann, 1998
Clinical trial comparing monkeys treated with MDMA 7 years prior, 2 weeks prior, and a controlSignificant damage to 5-HT
axons at 2 weeksSome 5-HT recovery:
Seldom complete Not in all brain regions
MDMA permanent apoptotic damage to fine serotonergic axons
Neurotoxicity: 5-HT
Caudate nucleus 5-HT immunoreactive axons:Control, 2 weeks post mdma, 7 yrs post mdma
Hatzidimitriou, McCann, & Ricaurte, 1999
AMPH use decreases NE over time
DA loss more significant with NE loss and meth, than meth alone
NE loss: Enhance neurotoxic damage Decrease the threshold for
neurotoxicity to nigrostriatal DA neurons
Neurotoxicity: NE
Fornai et al, 1996
Mice: locomotor sensitization to amphetamine after a single injectionAdolescent mice: higher magnitude
of sensitization
Accelerate dependence courses: shorter time: first use addiction
Adolescents &Addiction risk
Kameda S.R. et al. (2011).
Varied usage profiles, lower comparatively
Immediate effects, prolonged excretion
General catecholamine agonists: DA, 5-HT, NE
Can cause permanent death of neurons, addiction, and sudden death in users
Further research: mechanisms behind neurodegenerative damage
Summary
Questions & Discussion