Psychostimulants (& ADHD/catecholamines) Flashcards
Psychostimulants
These mimic the sympathetic nervous system, elevate mood, and increase energy and stamina. They are both commonly used for medicinal purposes as well as commonly used as stimulants.
“Psychostimulant” and “stimulant” are different words for the same thing. Many psychostimulants are classified as sympathomimetics.
Six general categories of psychostimulants
Ephedrines, pseudoephedrines, amphetamines, methamphetamines, methylphenidates, cathinones
Ephedra
Plant with ephedrine and pseudophedrine. Used as a decongestant (Sudafed). Also used for weight loss, increased energy, etcetera. Is a relatively mild stimulant in comparison to many others.
Banned in the USA in 2004, but not in Canada. Can be found in supplement stores.
Amphetamines
Comes in forms like: Adderall, Vyvanse (inactive prodrug converted in body), Benzedrine (amphetamine inhaler). All have similar effects but have different half lifes, different ways they metabolize, etcetera.
Used extensively in WWII to help soldiers stay awake and alert.
Useful in congestion, narcolepsy, weight loss, ADHD, chronic pain, “performance enhancement.”
Narcolepsy is a disorder of hypersomnolence/sleepiness.
Aside: Amphetamines contain optical isomers dextroamphetamine (D) and/or levoamphetamine (L). A mixture of the both is called a racemic mixture.
Methamphetamine
Similar to amphetamines. Also known as Desoxyn (uncommonly, Desoxyn can be obtained by prescription) or on the streets, “crystal meth.”
Highly addictive, and detrimental to habitual users. Stimulant psychosis frequent with high doses.
Stimulant psychosis is stimulant-induced psychosis. Psychosis involves hallucinations, delusions and/or paranoia.
Methylphenidate
AKA Ritalin, Concerta, first line treatment for children with ADHD due to the fact it is shorter-lasting and weaker than amphetamines. This has its cons as well as children may have to take multiple doses per day.
Also used in adults with ADHD.
Cathinones
The plant Catha edulis, or khat, is a benign cathinone stimulant. If khat is synthesized into a drug like ‘bath salts,’ it becomes more powerful and less benign.
‘Bath salts’ are taken by ingestion/inhalation.
They’re called bath salts, because that’s what the synthetic product is marketed as to find a loophole in laws.
Cocaine
Derived from the coca plant, which has been used historically.
Can also be used as an anaesthetic, analgesic (pain reliever), and constricts blood vessels. Blocks action potentials (voltage gated sodium channels are blocked) thus brain doesn’t send certain signals to the body.
Cocaine salt is insufflated (snorted) and injected, the free. base (crack) inhaled. The free base is called crack because it makes a crackling noise when smoked through a crack pipe.
Can also be used legally in dental work.
Sigmund Freud wrote many of his concepts under the influence of ____.
Cocaine. Freud even wrote a book called Über Coca as a ‘love letter’ to cocaine. Freud also did not believe cocaine was addictive.
Are synthetic drugs typically more or less potent/concentrated than the plants they come from?
Synthetic drugs are typically more potent than than the plants they come from.
Intravenous, insufflation, inhalation
Least to most efficient way to get drug effects
Inhalation -> Intravenous -> Insufflation (Peak effect MUCH faster in insufflation than other two methods.
Polydrug Use
Taking two different drugs that metabolize in the body to form more effective active metabolites.
Eg. Cocaine + alcohol (aka ethanol) = cocaethylene, which has a longer half-life than cocaine
Cocaine action mechanisms
Blocks dopamine transporters (DAT) from reuptaking dopmine, thus more dopamine proliferates within the brain.
Half-life of amphetamines
10-11 hours
Half-life of methylphenidate
2 hours
Half-life of cathinones
1.5 hours
Half-life of cocaine
1 hour
Low doses of psychostimulants increase ____ behaviour while higher doses increase ____ behaviour.
Low doses: Increase purposeful behaviour
High doses: Increase purposeless behaviour
Stereotypy/Punding
(Purposeless) Repetitive motor movement: Scratching, skin picking, etc.
This increases with higher doses of psychostimulants.
Cocaine biomechanisms
Cocaine displaces vesicular dopamine/pushes dopamine out into synaptic cleft, as well as blocks dopamine’s reuptake.
DAT
Dopamine transporter
Affected by psychostimulants (increase in dopamine).
NET
Norepinephrine transporter
Usually affected by psychostimulants (increase in norepinephrine).
SERT
Serotonin transporter
Usually affected by psychostimulants (increase in serotonin).
Physiological effects of psychostimulants
Name as many as you remember
Increased heart rate, blood vessel constriction, airway relaxation, digestion inhibition, pupil dialation, increased body temperature, dry mouth
Subjective effects of psychostimulants
Name as many as you remember
Increased energy, euphoria, increased alertness, improved sense of well-being, anxiety, agitation
Animal Experiments
Vehicle pretreatment, training drug pretreatment, test drug pretreatment
- Vehicle pretreatment: Inject a rat with placebo/saline, teach it to press a lever for food.
- Training pretreatment: Inject the rat with a comparative drug to the one you want to test, see its behaviour of lever pressing.
- Test pretreatment: Inject the rat with the new drug, see its behaviour of lever pressing.
Adverse effects of psychostimulant use
Name as many as you remember
- Cardiovascular dysfunction (especially in high doses of cocaine, a Na+ channel blocker)
- Pulmonary dysfunction
- “Meth mouth”/tooth decay from reduced salivation (and secondarily, poorer dental habits)
- Psychostimulant-induced psychosis
- Formication (hallucination of bugs underneath one’s skin)
- Tactile hallucinations common in high doses of meth
- Neuron damage (possibly)
- Developmental disorders (when individuals use stimulants while pregnant)
Sensitization vs tolerance of potent psychostimulants
When do they occur, and what specific effects do each of them have
Tolerance: Occurs more often with continuous drug use, more pronounced for the reinforcing effects of the drug (eg. euphoria).
Sensitization: More stereotypy (even with intermittent use), cravings, and incentive sensitization (addictive properties) with repeated use
Are men or women more likely to have a psychostimulant addiction?
Women
Possibly due to societal reasons? Eg. Stimulants for weight loss
What are two primary predictors of addiciton?
In the sense of how the drug itself is used rather than the person’s environment
Route of administration (eg. oral less addictive than sufflation) and polydrug use
Polymorphism gene
Decreases susceptibility to psychostimulant addiction.
This gene makes dopamine less likely to get converted into norepinephrine, thus more dopamine stays dopamine when someone takes a stimulant. This build-up reduces the positive feelings/effects from psychostimulants and increases aversive effects.
Cue-induced reinstatement
Cues increase craving of drugs in withdrawal periods. Thus mental cues (environments, seeing the drug, etc.) can activate physical cravings.
Cocaine cravings increase over time of withdrawal, until about 6 months after quitting.
What is likely to cause transition from recreational to chronic use
The more access an animal has to drugs, the more likely they are to administer the drug for themselves. They then begin to escalate their intake.
This may be why people get addicted after multi-day drug binges/benders.
Two primary phases of recovery
Detoxification, relapse
Disulfiram
Used for treatment of psychostimulant (and alcohol) addiction. Disulfiram prevents the conversion of dopamine to norepinephrine and causes averse effects when taking stimulants/reduces pleasurable effects.
Sometimes this will not work, as people will often go off disulfiram instead of going off the psychostimulant.
Modafinil
Part of drug-replacement therapy. Modafinil is a psychostimulant with lesser effects than many addictive psychostimulants.
Sometimes will not work as Modafinil itself has abuse potential.
Tricyclic antidepressants (for treating drug addiction)
Reduces the psychological effects of withdrawal. Treating the depression that comes with psychostimulant withdrawal can increase the likelihood of the person being able to come off the addictive drug.
Anticonvulsant drugs
Theoretically will dampen excitability from psychostimulants. Not necessarily effective, but some evidence of efficacy.
Psychostimulant vaccines
Vaccines meant to reduce usage of a psychostimulant (recently, used for cocaine addicts). Shows short term promise but effects seem to diminish in the long term.
Attention deficit / hyperactivity disorder (ADHD)
Define ADHD and recall the theory of what ADHD is driven by.
Symptoms: Extreme inattention, hyperactivity (in some), impulsivity. Diagnosed in about 1/10th of individuals aged 4-17 (USA). First-line treatment is psychostimulants, as theoretically, ADHD is driven by low dopamine function.
Catecholamines
Hormones/neurotransmitters made by the adrenal glands & released into the body. An umbrella term of sorts for epinephrine, norepeniphrine and dopamine.
Catecholamines are a sub-class of monoamines.
Yerkes-Dodson Curve
Models the relationship between stress and task performance. Proposes one reaches their peak level of performance with an intermediate level of stress/arousal (intermediate depending on the person).
The curve is seen in pre-frontal cortex (PFC) monoamines. More catecholamines, more alertness. High amount of catecholamines = stress/shuts off the PFC.
Psychostimulant use may have a ____ on brain development in ADHD
“normalizing effect”
Psychostimulants generally have been shown to have far more positive than negative effects on individuals with ADHD.
Brain anatomy
High levels of catecholamines can suppress the ____
Prefrontal cortex
Drug diversion
Transfer of prescription drugs to someone they’re not intended for (eg. someone on ADHD meds selling their medication to someone else)
Nootropics
Another word for “smart drugs” or “cognitive enhancers.” The only nootropics that evidently work are psychostimulants (caffeine, nicotine, etc.). No evidential support for putative (supposed) nootropics (ginseng, gingko, omega-3s).
