Medical Effects and Consequences of Use

Jennifer Lowry, MD American College of Medical Toxicology Associate Professor, Pediatrics University of Missouri-Kansas City Children’s Mercy – Kansas City, MO

ACMT / BIA Meth Lab Working Group

Clandestine Meth Labs 2015 The Faces of Meth How Did We Get There?

Clandestine Meth Labs 2015 2.5 Years Later Objectives

l Where Meth Works l Routes of Abuse l Phases and Patterns of Abuse l Short Term and Long Term Effects

Clandestine Meth Labs 2015 What is Methamphetamine?

● Methamphetamine is a central nervous system stimulant. ● It interferes with neurotransmission. ● It increases the release of the neurotransmitters dopamine, norepinephrine and serotonin.

Clandestine Meth Labs 2015 Toxicokinetics / dynamics

● Methyl group is key – is a metabolite of methamphetamine – Greater CNS penetration – ~10X Longer duration of action than amphetamine

H H

N N CH3 H

CH3 CH3 Methamphetamine Amphetamine Clandestine Meth Labs Pseudoephedrine 2015 Why People Use Meth

Dopamine is manufactured in nerve cells within the ventral tegmental area and is released in the nucleus accumbens and the frontal cortex.

Clandestine Meth Labs 2015 What Happens in the Brain l Dopamine – Responsible for enjoyment/pleasure – Responsible for reinforcement l Frontal Cortex – Behavior l Movement – Substantia Nigra

Clandestine Meth Labs 2015 Medicinal Use

l Started with benzadrine (amphetamine) l Military use - Pervitin l Methedrine (Methamphetamine)

l Now is a Schedule II agent

Clandestine Meth Labs 2015 Oral Administration

● Oral forms – The prescribed form ● Onset 20-60 min

Clandestine Meth Labs Desoxyn2015 (methamphetamine) Intranasal methamphetamine

● Sniffed powder ● Onset of action: 5-10 min

Clandestine Meth Labs 2015 Crystal Meth (aka Ice)

● Inhalational form ● Onset of action: Less than 2 min

Clandestine Meth Labs 2015 Intravenous Administration

● Onset of action: Less than 2 min

Clandestine Meth Labs 2015 What It Feels Like To Use Meth l Rush (5-30 min) - due to adrenal gland release of epinephrine putting the body into “fight or flight” mode and the explosive release of dopamine; – effects are tachycardia, increased metabolism, hypertension, palpitations; euphoria likened to the intensity of 10 orgasms (sexual rush) l High (4-16 hrs) - follows the rush and sometimes called the shoulder; feelings of aggression and “heightened intellect” Clandestine Meth Labs 2015 Short-term Effects of Meth Abuse

● Increased wakefulness and physical activity and decrease appetite. ● A brief, intense sensation, or rush, is reported by those who smoke or inject methamphetamine. ● Oral ingestion or snorting produces a long-lasting high instead of a rush. ● Both the rush and the high are believed to result from the release of very high levels of the neurotransmitter dopamine into areas of the brain that regulate feelings of pleasure.

Clandestine Meth Labs 2015 Meth Use Patterns

● Low intensity – Casual use / often task-oriented – Tend to swallow or snort – Not addicted ● Binge – Psychological dependence – May develop – Tolerance during binges (2 - 15 days) – “Speed Runs” Clandestine Meth Labs – Develop Medical Problems2015 A binge goes through several stages l Binge (2-15 days) - continuation of the high but due to tolerance larger doses required to achieve same intensity until no rush or high felt; physical and mental hyperactivity l Tweaking - at the end of the binge when nothing will take away the feelings of emptiness and dysphoria; often alcohol and heroin used during this time to ease the bad feelings; Irritable, psychotic symptoms, paranoid, violence more likely Clandestine Meth Labs – Myoclonic, jerking 2015movements When the binge is over

● Crash (1-3 days) – Follows binge or long period of high-intensity use – Suffers from sleep deprivation and neurotransmitter washout – Similar to other stimulants (cocaine) l Post-binge – relatively normal – Physical and psychological state slightly deteriorated compared to pre-binge – May depend on length of usage

Clandestine Meth Labs 2015 When the binge is over

● Withdrawal (30-90 days) – No acute, immediate symptoms. Psychological element strongest – Depression (suicidal), lethargy, drug craving – Relieved by return to drug use

Clandestine Meth Labs 2015 Volkow et al. J of Neuroscience 2001;21:9414-18. Meth Use Patterns (cont)

● High intensity – Psychological and physical dependence – Tend to smoke or inject l Rush – Entire life aimed at preventing crash -->Life dysfunction

Clandestine Meth Labs 2015 High Intensity Use

● Extreme Weight Loss (50-100 lbs.), Malnutrition ● Belligerence, Aggression, Violence ● Toxic Psychosis – Paranoia – Hallucinations – Hysteria – Sleep Deprivation ● Multiple medical complications ● e.g. Stroke, Heart Failure

Clandestine Meth Labs 2015 Classes of Clinical Effects

Early – during binge Late – at the end l Adrenaline excess l Adrenaline Depletion – Tachycardia – Lethargy – Hypertension – Unresponsive – Tachypnea – Normal vital signs – Dilated pupils – Depression – Psychomotor

agitationClandestine Meth Labs 2015 l Hyperthermia

Depends on Route

Chronicity of Use

Clandestine Meth Labs 2015 Abstinence

● Anergia: – Decreased energy.

● Anhedonia: – Inability to experience pleasure, boredom: – in contrast to the intense euphoria of the drug experience, sharpens the users dissatisfaction with the current state.

Clandestine Meth Labs 2015 Abstinence

● Craving: – Endogenous: ● "comes from within" or background craving, feelings of dysphoria. – Environmentally Cued: ● Craving stimulated by objects, persons and situations associated with prior use

Clandestine Meth Labs 2015 Clandestine Meth Labs 2015 Clinical Features of Sympathomimetic Toxicity l Vitals l Cardiovascular – Tachycardia – MI – Hypertension – Dysrhythmias – Fast Respiratory Rate – Necrotizing Angiitis – Hyperthermia – Aortic Dissection

l l Neurological Pulmonary – Wheezing – Stroke – Chemical Pneumonia – Seizures – Pulmonary edema – TremorsClandestine Meth Labs 2015 Clinical Features of Symptomatic Meth Patients l Musculoskeletal l Psychiatric – Muscle Spasms – Tremors – Rigidity – Aggressiveness – Rhabdomyolysis – Paranoia – Confusion l Psychiatric – Hallucinations – Insomnia – Psychosis – Anxiety – Impulsive

– IrritabilityClandestine Meth Labs 2015 Clinical Features of Symptomatic Meth Patients l Skin l Gastrointestinal – Sweating – N/V – Lesions – Diarrhea – Formication – Malnourished l Mouth l Genito-urinary – Dry mouth – STDs (HIV) – Bruxism – Dehydration – Extensive tooth – Renal Failure decay – Rhabdomyolysis Clandestine Meth Labs 2015 Other Meth Related Problems

– Smoking-Related – IV-Related – Trauma – Medico-legal – Lab / Chemical Exposures

Clandestine Meth Labs 2015 Long-term Effects of Meth Abuse

● Addiction ● Tolerance for methamphetamine ● Violent behavior, anxiety, confusion, and insomnia ● Psychotic features ● Physical Appearance

Clandestine Meth Labs 2015 Specific to Methamphetamine l Cardiovascular – Stroke (Hypertension, Tachycardia, Vasculitis) – Cardiomyopathy (Infarction, Catecholamine Use) – MI, arrhythmias less likely l Neurologic – Acute psychosis – Kindling Effect – Seizures Less Likely – Movement Disorders Clandestine Meth Labs l Neuropsychiatric Changes2015

Clandestine Meth Labs 2015 Clandestine Meth Labs 2015 Clandestine Meth Labs 2015 The Faces of Meth

Clandestine Meth Labs 4 YEARS LATER 2015 The Faces of Meth

Clandestine Meth Labs 2015 3 MONTHS LATER Chronic Effects

Clandestine Meth Labs 2015 Meth & Pregnancy

● Methamphetamine use and/or abuse during pregnancy can be fatal to the mother and result in spontaneous abortion of the fetus. ● Methamphetamine has been shown to cause placental vasoconstriction and interfere with placental monoamine transporters. ● Neonatal drug withdrawal symptoms requiring treatment have been reported.

Clandestine Meth Labs 2015 Summary

l Meth is a stimulant drug whose abuse has both acute and chronic effects l Various use patterns are known (low / high intensity, tweaking, etc.) l Acute effects are generally due to adrenergic excess l Adrenergic depletion in the crash phase l Chronic effects involve neurologic, psychiatric, and dental deterioration plus much more

Clandestine Meth Labs 2015 Questions?

Clandestine Meth Labs 2015