Psychomotor Stimulants

Naturally occuring sources

ephedrine

cathinone (khat)

cocaine

What is the baseline for non-cocaine stimulants that is still used in traditional Chinese medications and is found in tea?

Mah Huang

other names for ephedrine

ephedra, mah huang

What is a type of cathinone?

methcathinone (cat)

bath salt precursor

North/East African

Other name for cocaine

erythroxylum coca

Synthetic occurring sources

amphetamines

methamphetamine

methylphenidate

Types of amphetamines

D

L

DL

D Amphetamine

dexadrine

L amphetamine

levo amphet

DL amphetamine

adderall and benzadrine (bennies)

What is sudafed?

synthetic ephedrine

synthetic NS effects

precursor to meth

other names for methamphetamines

crystal, ice, crystal meth

other name for methylphenidate

ritalin

Where did cocaine use originate?

Columbia (2500 BC)

Columbian History of cocaine

included in Aztec creation myths

sacredd to Incas

made from coca leaf (ertyhroxylum coca)

History of cocaine

isolated in 1860 (Albert Neiman)

used by Freud, Sherlock Holmes

first local anesthetic

ingredient in many drinks (e.g. coca cola)

Harrison Narcotic Act of 1914

Harrison Narcotic Act of 1914

limited use to doctors for medicinal use only

History of amphetamines

ephedrine used in China for 5000 years (ma huang)

medical use during WWII (by AMA)

weight reduction use, antidepressant, stimulant

historical use of ephedrine (China)

asthma treatment

Amphetamine was ________ in 1887 and used as a _________ substitute in late 1920s

synthesized; ephedrine

what was developed as a competitor for amphetamine

methylphenidate

current use of amphetamines

narcolepsy and hyperactivity (e.g. ADHD) treatment

amphetamine admin & absorption

poorly from digestive system, slow release

high potency when injected or inhaled (e.g. snort)

cocaine admin & absorption

coca leaves chewed

inhaled as a salt

smoked

freebase (basic, increases bioavailbility)

crack

cocaine mixed with baking soda

distribution

crosses blood-brain barrier

concentrated in spleen, kidneys, brain

amphetamine excretion

excreted in urine, sweat, saliva

decomposes into active metabolites

amphetamine half life

16-34 hours

cocaine half life

40 minutes

monoamines

dopmine, norepinephrine, epinephrine, serotonin

general stimulant effects on monoamine synapses

weakens vesicular monamine transporters (VMAT)

blocks reuptake of dopamine (effect on nigro-striatal and mesolimbic symptoms)

amphetamine effects on monoamine synapses

leaking of NTs from vesicles into synaptic clefts

increases amount of NT released in response to action potentials

are amphetamines rewarding?

no

cocaine effects on monoamine synapses

blocks reuptake of dopamine (no leaking caused)

blocks ion channels in membranes (aka blocks pain receptors) —> inhibits firings

cocaine can act as a local __________

anesthetic

effects of D & L amphetamines on the body

increases heart rate and BP

vasodilation

bronchodilation

headaches, dry mouth, stomach disturbances, weight loss

D & L amphetamines stimulate the _________ nervous system

sympathetic

meth (amphetamine) effects on body

stimulates CNS and deactivates sympathetic NS = highly rewarding and high abuse potential

amphetamine effects on sleep

causes insomnia

can stimulants induce psychotic effects?

yes, but only in those who are predisposed

What drug is the #1 cause of a psychotic break?

alcohol

effects on behavior

euphoria, energy

DA blockers do not cause euphoria

punding

possible psychosis

comedown is correlated with low cortical activity

punding

fidgeting

acute tolerance

cannot achieve first high again in the same session

cocaine is fast-acting so requires frequent admin

what reverses a stimulant overdose?

benzos

amphetamine psychosis

formication

paranoid schizophrenia

violence (impulsivity and irritability)

what can contribute to development of amphetamine psychosis

very high dosage

low sleep

formication

feeling of bugs crawling out from under skin

sensory effects

increases visual acuity

slight improvement in auditory and visual flicker fusion

effects on performance

counteracts fatigue

increases vigilance and attention

increases oxygen intake and blood flow (increases athletic performance)

improve clock test

low dose effects on unconditioned behavior

increases spontaneous locomotor and exploratory activity

decrease food and water consumption

high dose effects on unconditioned behavior

start to show increased sniffing and other stereotyped behaviors like automutilation

decrease food and water consumption

automutilation in animals

bite off tail

overgroom until sore

automutilation in humans

biting nails

picking skin

amphetamine dissociation

animals trained under the influence cannot remember what they learned once effects have worn off

psychomotor stimulants (can/cannot) be discriminated from saline

can

discrimination/generalization of stimulants

generalize cocaine and amphetamines

what types of tolerance are associated with stimulants

acute

chronic

acute tolerance

keep administering but do not get higher

NS effects are still observed which could lead to fatal overdoses

What is a slang term for acute tolerance to amphetamines

coke-out

chronic tolerance

appetite, heart, BP effects become tolerated with repeated admin

sensitization

stereotyped behaviors and psychosis

withdrawal symptoms

depression (monoamine-related, long-term)

insomnia

suicidal ideation

decreased decision-making & planning

What causes the decision-making and planning symptom of withdrawal?

lower dorsolateral-prefrontal activation

guilt birds

physical stimulation but depression (no sleep)

cocaine admin

orally, snorted, injected, smoked

cocaine is a ______ drug

social (sporadic use)

speed ball

stimulants and opioids combined

amphetamine administration

usually sporadically used for specific tasks

peak user/speed freak

run and crash cycle of amphetamine use

also observed in non-humans

use drug (run) for days then sleep (crash) for days

self-admin in nonhumans (monkeys)

usage enhanced by stress and experience with stimulants and other substances

use until convulse and then use again

if supply is limited then admin is more regular

what is the most reinforcing drug

cocaine

direct harmful effects

treat hyperactivity in children (methylphenidate) but effects are non-specific and cause concerns regarding diagnosis

direct harmful effects of cocaine

mild jaundice/liver disease

inflammation and ulceration of mucous membranes in the nose

harmful effects of crack

crack babies

dependent syndrome

why is crack more common than cocaine?

less expensive

rapid onset (but short-lived effects)

direct harmful effects of amphetamine

restlessness, excessive talking, confusion, dizziness

insomnia

paranoid psychotic behavior (chronic use)

increased BP, stroke, heart attack

depression, suicide, lethargy (cessation of use)

possible neurotoxic effect on brain in parts associated with dopamine atrophy

indirect effects

hepatitis, HIV/AIDS

violence

high death rate

contamination

effects on reproduction

enhances sexual activity (high risky behaviors, chemsex)

disruption in sexual activity (chronic use)

cocaine overdose

muscle weakness and respiratory depression (large doses)

lethal (depending on route of admin) —> cardiac issues

caine reaction

caine reaction

intial excitement followed by severe headaches, nausea, and convulsions that could result in cardiac failure and death

how to treat a cocaine overdose

benzodiazepam

treatment types

detox

positive reinforcement (better than teaching just abstinence)

drug therapy

substitution therapies

positive reinforcement therapy

counselling

contingency management (gifts/rewards)

what can increase the risk of relapse

priming

sensitization

drug therapy treatment

antidepressants

modafinil

modafinil

sleep suppressant

mild stimulant without stimulant effects

not very effective

substitution therapies

methylphenidate (not very successful in cocaine abusers)