Psychostimulants Flashcards
Psychostimulants are Sympathomimetics which means they…
mimic the effects of sympathetic nervous system
6 Types of psychostimulants
Ephedrine Amphetamine Methylphenidate Methamphetamine Cocaine Cathinone
Ephedra can be split into two categories:
ephedrine and pseudoephedrine
Ephedra was first used as a
Nasal Decongestant (Sudafed) Also used for weight loss, increased energy, etc.
How strong are Ephedra effects?
Mild by comparison to other psychostimulants
Other names for Amphetamines
Benzedrine, Adderall (Racemic mixture), Vyvanse, “speed”, d-amphetamine (handedness).
Aside: optical isomers (D and L), aka enantiomers, racemic mixtures
Amphetamines history
Synthesized in 1887
Used extensively during WWII (with methamphetamine too)
Amphetamines can be used for:
congestion, narcolepsy, weight loss, ADHD, “performance enhancement”
Methamphetamine is also known as
Desoxyn, “Crystal Meth”
What is methamphetamine used for?
ADHD and nasal congestion
Methamphetamine and addiction
Very high addiction potential
Stimulant psychosis frequent with high doses - Hallucinations, similar to schizophrenia, mimics dopamine
Methylphenidate also known as:
Ritalin, Concerta, “kiddie coke’
Methylphenidate vs. amphetamine
Similar effects but methylphenidate’s are weaker and shorter-lasting
Methylphenidate is used as:
Often the preferred childhood ADHD prescription
Problem: short lasting
Cathinones also known as:
Khat (Catha edulis), bath salts (synthetic khat)
Laws on cathinones
Usually really hard to regulate and khat is seen as a danger to society
Cathinones addiction and harm
Khat is relatively benign but treated like a menace
Bath salts decidedly lass benign (bc synthetic)
Cocaine history
Derived from the coca plant
Coca used for ages, chewing
Cocaine instrumental use
Anesthetic, analgesic, and blood vessel constrictors
Cocaine preparation
what is synthetic?
Base paste -> convert it into salt (synthetic process) cocaine salt is which people snore -> base - other synthetic process which turns cocaine into crack cocaine
Method of Administration cocaine
Salt: insufflated, injected Free base (crack cocaine): inhaled
How did cocaine shape psychology’s history?
Uber Coca - book by Freud
Sigmund Freud - cocaine lover!
Synthetic danger
Ephedra, khat and coca
vs.
Methamphetamine, synthetic cathinones, cocaine
The synthetic drugs are more potent and dangerous
Route of administration matters?
It has profound effects: insufflation, inhalation and injection are more dangerous
Biotransformation
Two types
a. Active metabolites
b. Metabolites that result from polydrug use
Pharmacokinetics
How a substance moves through the body
What are metabolites that result from polydrug use?
Substances that form due to drug mixing. Unique from drug mixing. (ex.: cocaethylene)
Eliminates / Half-lives
what does it mean?
When Half of the molecules have been eliminated from the body
Half life Amphetamines
10-11 hours
Half life Methylphenidate
2 hours
Half life Cathinones
1.5 hours
Half life Cocaine
1 hour
What do psychostimulants do in synapse?
They increase dopamine function in synapse bind to transporters which are related to reuptake (are not dopamine agonists)
amphetamine in synapse
amphetamines are reversers.
They bind to vesicle transporters and pushes the dopamine to terminal
They also binds to the membrane and reverse the flow of dopamine in the reuptake transporters. - it flows towards the site.
Why is amphetamine so addictive?
It causes dopamine to be artificially released
Your body reacts
Cocaine in synapse
Causes a larger than usual dopamine release
Makes the vesicular molecules work more efficiently (Pack up NTs - dopamine - more frequently)
Therefore more dopamine is released when an action potential is fired
Also binds to reuptake transporters and blocks its effects
What are the effects of Psychostimulants on the levels of nucleus accumbens dopamine?
Psychostimulants increase by 100x times the baseline of natural dopamine release! Especially methamphetamine.
Psychostimulants affect more than just dopamine. They also usually affect…
multiple other monoamine systems
What transportations systems do psychostimulants affect?
DAT - Dopamine transporters
NET - Norepinephrine transporters
SERT - Serotonin transporters
What do the monoamine transporters that psychostimulants affect have in common?
They are all very similar (similar structure) transporters of dopamine and norepinephrine
They mimic the sympathetic system
Pharmacological effects of psychostimulants
On the Sympathetic system!
Increased heart rate, blood vessel constriction, airway relaxation, pupil dilation, inhibited digestion, increased body temp, tooth decay, psychosis, hallucination, increased motor activity, agitation euphoria, improved sense of wellbeing, alertness and energy.
Dangerous sodium channel blocking effects
Behavioral effects of psychostimulants
Low doses
Low doses of psychostimulants increase purposeful behaviour (Effects for ADHD for example)
Behavioral effects of psychostimulants
High doses
increase purposeless behaviour like stereotypy or Punding for humans
Stereotypy/ Punding
Stereotypy - species specific behaviours (rat do things like grooming)
Punding - Stereotypy but in Humans (we usually pick our skin, sort things)
Drug discrimination studies on rats
Training - A sober animal presses one lever = reward
Same animal but high if they press the same sober lever, they don’t get the reward. Other lever = reward
Experiment - A second drug. Which lever does the rat press? This is used to measure similar subjective effects. (Is the drug more similar to sobriety or drug 1?) If drug 1 is similar to the experimental drug, the rat will press the high lever
Subjective effects of psychostimulants
Lower doses
Increased sense of alertness
Sense of energy
Sense of well-being (all self reported)
Subjective effects of psychostimulants
High doses
Rush/euphoria
Dangerous sodium channel blocking effects
Adverse effects of psychostimulant use
Cardiovascular dysfunction Pulmonary dysfunction “Meth mouth” Psychostimulant-induced psychosis Formication Some evidence for neuron damage
Cardiovascular dysfunction due to psychostimulant use
High disease: cocaine is a Na+ channel blocker
Plus increased sympathetic NS output
Pulmonary dysfunction in psychostimulant use is due to
due to prolonged stress of body to breathe more
“Meth mouth” in psychostimulant use happens due to
poor dental hygiene, inhaling = damage to gums, dry mouth, more inclined to drinking sugary drinks.
What is psychostimulant-induced psychosis :
Hallucinations, formication, delusions (info processing), thought and speech are disorganized - same as positive symptoms of schizophrenia
Formication
somatosensory hallucinations of “bugs crawling your skin”
Does a mother using psychostimulants make her babies addicted and prone to using? AKA developmental effects
not actually true. Prediction of drug use was due to socioeconomic status.
Tolerance in psychostimulants is
Tolerance is stronger for the reinforcing effects of the drug (people become tolerant to the pleasure)
and Occurs more often with continuous drug use
Sensitization in psychostimulants
Addicts become more sensitized to effects like stereotypy (which can be associated with intermittent drug use) and Cravings/ incentive sensitization (more motivated to seek the drug)
Incentive sensitization
when a person becomes more sensitized to wanting the drug, craving
Two big predictors of addiction in psychostimulants
Route of administration (more exposure to drugs) and polydrug use (prolongs and enhances the effects, more dangerous)
Women are ____ likely to have a psychostimulant addiction
more
Metabolism and addiction
High metabolism = predictor for addiction
The higher the drug metabolism, the more enzymes are effective at breaking down drugs, if it clears faster, the person uses more.
Who experiences the negative effects of psychostimulants the most? What does that mean?
People with C1021T polymorphism - slower rate of dopamine into norepinephrine = effects of psychostimulants are more unpleasant = less inclined to addiction.
Addiction directly related to ________________________.
dopamine release onto nucleus accumbens
If NAcc is blocked…
many addiction processes are blocked.
Two primary phases of recovery in psychostimulants
Detoxification
Relapse
Pharmacological Treatments for psychostimulant addiction
Disulfiram Modafinil Tricyclic antidepressants Anticonvulsant drugs Vaccine?
ADHD Key symptoms
extreme inattention, hyperactivity, impulsivity
What psychostimulants are mostly used for ADHD?
amphetamine and methylphenidate
Dopamine ADHD Hypothesis
ADHD is driven by low dopamine function
The Yerkes-Dodson curve
at low levels of arousal = performance low, intermediate arousal = high performance and interest, high levels of arousal = performance drops again.
The Yerkes-Dodson curve in ADHD people
People with ADHD sit extremely left of the curve, “always bored”, low level of arousal/ motivation.
Why do psychostimulants work for people with ADHD?
ADHD people have low levels of arousal/ motivation. This is why psychostimulants work.
Yerkes-dodson curve in PreFrontal Cortex catecholamines
Pre-frontal cortex has targets for norepinephrine and dopamine.
Catecholamine levels go up in PFC: we go from quiet (low firing rate in PFC) to alert (high firing) to stressed (PFC quiet). Curve.
Long-term effects of psychostimulants use in ADHD
psychostimulants use may have a “normalizing effect” on brain development in ADHD
ADHD has developmental effects on the brain that medication attenuates with no effects to weight/heart.
Drug diversion
Unfortunate pressure onto people with a condition to sell needed meds - pressure person with ADHD to sell their prescriptions
Instrumental use of ADHD medication
Low doses.
Cognitive: improvements with attention, working memory, consolidation, long-term memory, inhibitory control, “goals-directed behaviour”
Physical performance: benefits to endurance, alertness
Weight loss initially
But High dose leads to performance impairments (person becomes too stressed)
Nootropics
Smart drugs, cognitive enhancers
Only exist modestly: amphetamine, methylphenidate, modafinil, caffeine, nicotine
