Controlled stimulants Flashcards
In general, what effects do stimulants have? (5)
- Heighten mood
- Increase alertness
- Decrease fatigue
- Grandiosity
- Risk can feel more rewarding
Controlled stimulants (4)
cocaine, amphetamines, Ritalin and Adderall
Coca leaf
The coca leaf has mild stimulating properties when absorbed in the mouth. Used in South America- Bolivia, Ecuador, Argentina, and Peru. Indigenous populations in these regions chewed the coca leaf for its mild stimulating properties. It has religious, medical, and social uses. An individual coca leaf doesn’t contain a lot of cocaine. The content in synthetic cocaine is much higher
Cocaine in 16th century South America
Spanish conquistadors arrived in South America during the 16th century, and at this time they took control over access to the coca leaf. Used the coca leaf to “pay” enslaved Incas. They believed it made them work harder and longer- since it was a stimulant. At this time- the Spanish were devout Catholics- they did not export the drug and considered it a vice. They also discouraged European use
The coca leaf in Europe
In the 19th century, there were a lot of different scientific discoveries- scientists started discovering the properties of different plants. As European naturalists started to explore South America, they began to study the properties of the Coca leaf. In the 1850s, European scientists were able to isolate the active agent in coca, and they developed cocaine. Scientists began looking for therapeutic and medical uses for this drug
Freud and cocaine
Freud started his career as a neurologist and was interested in neurological disorders. He has become well known for several contributions to psychology, like psychoanalysis. Many of his first writings were on therapeutic applications of cocaine- he initially thought cocaine was a miracle drug (wrote the book “On Coca”)
“On Coca”
The book written by Freud. He proposed that cocaine could be used as a local anesthetic, and as a treatment for depression, indigestion, asthma, neuroses, syphilis, morphine addiction, and alcoholism. He also considered it an aphrodisiac
The first documented addiction to cocaine
Ernst von Fleischl-Marxow- friend of Freud. He was a physician who investigated electrical activity of nerves and the brain. He became addicted to morphine due to chronic pain, and Freud suggested he use cocaine to treat his addiction. Cocaine only sort of worked- tolerance formed very quickly as he was taking large amounts of IV cocaine daily (1g/day). Marxow began to exhibit bizarre behavior, like paranoid delusions and formication syndrome (feeling like bugs are crawling on or under the skin).
Cocaine use in the 1880s
Cocaine was widely available and part of popular culture- not a lot of taboos surrounding it. Physicians prescribed it- cocaine revolutionized surgery as an anesthetic. It was available in OTC medicines as well as in coca wine and Coca-cola. Cocaine was featured in Sherlock Holmes, and Jekyll and Hyde was written while Stevenson was using cocaine for tuberculosis. Other famous users included Thomas Edison, Jules Verne, Czar Nicholas of Russia, and President Ulysses Grant
After the 1880s, when did beliefs regarding cocaine begin to shift?
By the end of the 19th century. At this point, cocaine psychosis was fairly common- erratic behavior, delusions. There were also many overdose deaths and issues with dependency. Beliefs and attitudes began to shift. In 1914, the Harrison Narcotic Act was passed it was a law to control opiates and cocaine. This led to reduction in use (for now)
Ephedra sinica
A shrub that was used in traditional Chinese medicine for more than 5000 years. In 1885, Ephedrine was naturally derived from Ephedra sinica. This compound was a stimulant of the sympathetic nervous system that was used to treat asthma and was more stable than epinephrine.
Chen and Schmidt
Researchers that discovered that ephedrine was highly similar to epinephrine, because it was also a stimulant of the sympathetic nervous system. It was originally used to treat asthma and was more stable than epinephrine. It is a derivative of amphetamines.
Lazar Edeleanu
Romanian chemist that synthesized what is now known as amphetamine in 1887.
Gideon Alles
Los Angeles chemist that discovered and published the physiological effects of amphetamines. Amphetamines are less expensive and easier to manufacture than ephedrine
Amphetamines
Amphetamine, methamphetamine, and dextroamphetamine are synthetic stimulants. They had medical uses in the 1920s, but also have a high potential for abuse.
Medical uses of amphetamines (4)
In the 1920s:
1. Cold and sinus problems
2. Obesity
3. Narcolepsy
4. Pep pills- give energy
Were used by soldiers on both sides of world war 2
Symptoms of prolonged use of cocaine and amphetamines (5)
- Suppress appetite
- Prevent sleep
- “Speed freaks”- people can go without food or sleep for multiple days
- Formication symptoms (“speed bugs”)
- Stimulant psychosis
Stimulant psychosis
Can be caused by prolonged use of cocaine and amphetamines. Paranoid delusions and disorientation- similar to the positive symptoms of schizophrenia
Cocaine use in the 1970s
In the 1970s, cocaine became a “prestige” drug- demand for the drug increased. People started to see many of the original problems that occurred in the 1880s. It was used by celebrities, pro athletes, and the wealthy
How was cocaine typically administered in the 1970s?
Usually administered in small doses and intranasally. This method of administration seemed to create less problems than IV use at the time, but this wasn’t exactly an accurate belief
Crack cocaine
In 1986, crack cocaine started to infiltrate neighborhoods (not the high prestige neighborhoods). It is freebased cocaine- cocaine is heated until it vaporizes. Inhaled vapors reach the brain very quickly, and has a very short delay between CS and US, increasing the potential for addiction
Effects of crack cocaine (3)
- Short duration (10-20 minutes)- high is very intense and more pleasurable than IV injection
- The low is equally intense
- Long term use causes paranoia, anger, anxiety/panic, deep depression, convulsions, hallucinations
The war on drugs (1980s)- crack vs cocaine
“Just say no”- the movement criminalized possession rather than just drugs, making a drug user by definition a criminal. While cocaine had been considered a prestige drug in the 70s, crack was cheaper, and therefore disproportionately impacted poor neighborhoods and African American and Latino communities
Disparities in sentencing during the war on drugs
In 1988, possession of 500 gs of cocaine= minimum 5 years, while possession of 5 gs of crack= minimum 5 years. This was in place until the Fair Sentencing Act in 2010
Methamphetamine (meth)
Street names include ice, crystal, and crank. It was initially manufactured on the West Coast and Hawaii in the early 1990s. By 2005, labs were common on the East Coast. Although use rates are in decline, meth is still a problem in many pockets of the country
Meth use is most prevalent with which groups?
Meth use is typically seen in very rural, poor areas of the country- easier to manufacture in rural areas. Also used in urban areas by gay or bi men- this is because meth is seen as a party drug and can enhance sexual prowess. However, long term meth use can also interfere with HIV prevention medications
Complications of long term meth use (8)
- Seizures/convulsions
- Cardiovascular collapse- meth can be very toxic to the body
- Paranoia (can be accompanied by violent behavior)
- Deterioration of teeth due to smoking
- Formication, skin sores due to skin picking
- Extreme weight loss due to appetite suppression and the effects of the stimulant
- Due to tooth decay, weight loss, and skin picking, many people undergo drastic changes in appearance even after a few months of use
- Erectile dysfunction over the long term
During which decade was meth considered a fad?
The 1990s
What predicts which drugs a person will use?
Parenting matters until around age 12, and then friends predict behavior after that- the drugs your friend group are using predict what drugs a person will use.
With stimulants, how does method of administration matter to addiction?
Some methods of administration allow people to experience the effects of the drug even faster and make them more at risk for addiction. Intranasal administration- effects occur within 10-15 minutes. IV injection- 30 seconds. Crack or crystal meth are smoked- onset is even faster. The US with these drugs is very intense and powerful, and the less time between the CS and US, the more likely it is that a person will develop addiction. IV and inhalation administration peaks and dies off very quickly. Snorting and oral administration have less potential for addiction- take longer to peak and longer to die off
Duration of cocaine effects vs amphetamine effects
Cocaine is metabolized rapidly (20-80 minutes), while with amphetamines, the effects last 4-12 hours. The US is extreme, intense, and powerful
Pharmacokinetics of stimulants
Both cocaine and amphetamines affect the monoamine neurotransmitters- they block reuptake of dopamine, norepinephrine, and serotonin. The blocking of these neurotransmitters can result in negative effects in the long term. Amphetamines also increase the release of dopamine and norepinephrine
Monoamine neurotransmitters (4)
- Norepinephrine
- Dopamine
- Serotonin
- Epinephrine- did not cover this one in class
How do the pharmacokinetics of amphetamines differ from those of cocaine?
Amphetamines also increase the release of dopamine and norepinephrine
Negative impact of cocaine and amphetamines blocking the reuptake of monoamines (2)
- Long term- depletion of monoamines
- Cocaine blues- users may find that it is difficult to experience pleasure. This occurs over time with repeated use- dopamine receptors decrease
Pharmacodynamics of cocaine in the PNS (3)
- Powerful local anesthetic-no longer used for surgery but derivatives are used
- Causes inhibition and numbness to local nerves
- Vasoconstrictor- causes an incision to bleed less
Pharmacodynamics of cocaine in the CNS (4)
- Powerful psychostimulant
- Highly reinforcing
- Increases synaptic action of dopamine, norepinephrine, and serotonin
- Blocks reuptake, also acts as an agonist at the receptor- can change amount of neurotransmitter released
Both cocaine and amphetamines hijack the
Mesolimbic dopaminergic pathway- they chemically activate the reward system
How does cocaine act at the synapse?
Cocaine blocks transporter reuptake of the monoamines. When there are more monoamines, the NTs keep binding to the receptors and stimulate the reward mechanisms
Pharmacodynamics of amphetamines
This category of drugs has 3 different mechanisms at the synapse:
1. Blocks and reverses transporter reuptake of monoamines
2. Blocks enzymes that degrade monoamines
3. Blocks transporter that fills vesicles with monoamines
This results in a lot more neurotransmitters in the synaptic cleft for a longer period of time
Stimulants
Sympathomimetic drugs- mimic activity of the sympathetic nervous system. The physiological effects of many stimulants are very similar at low-moderate doses
Stimulants cause an increase in
Heart rate, blood pressure, respiration, blood flow to large muscle groups and brain- can put intense strain on the cardiovascular system over time.
Anorectic effects of stimulants
Suppression of appetite- this is one of the reasons that these drugs were prescribed for weight loss. Didn’t work in the long term due to tolerance
Behavioral effects of stimulants (3)
- Feelings of elation, increased talkativeness, alertness and arousal
- Insomnia
- Increases confidence and decreases inhibition.
Why aren’t cocaine and amphetamines good study drugs?
These stimulants increase confidence and decrease inhibition. However, they don’t increase advanced problem solving or reasoning. They give you the energy to quickly write a 10 page paper, but the paper won’t necessarily be good. People have trouble differentiating between good and bad decisions
Effects of stimulants on physical performance
Stimulants enhance physical performance on a variety of tasks. They enhance physical endurance and cause an increase in strength. These drugs also increase resistance to boredom and fatigue, which is why stimulants are sometimes used as study drugs
How do stimulants impact cognitive performance?
Speed up performance on several cognitive tasks. However, there is a speed-accuracy trade off. You may answer a question more quickly and confidently, but that doesn’t mean you’re more likely to answer accurately. Seems to impair ability to learn complex concepts
Effects of stimulants at low-moderate doses (6)
- Increase in heart rate, blood pressure, respiration, blood flow- mimics activation of SNS
- Anorectic effects
- Elation, talkativeness, enhanced alertness, confidence and arousal
- Physical endurance, enhanced strength, resistance to boredom and fatigue
- Speeds up cognitive performance
- Sexual prowess- increase desire in some users but results in decreased performance
Acute effects of stimulants at high doses (2)
- Psychotic states
- Significantly increased risk of overdose
Stimulant induced psychosis
Paranoid delusions are the most common symptom. People also exhibit compulsive stereotyped behavior- rocking, hair pulling, chain smoking, fidgeting with things. Stimulant induced psychosis can be treated with antipsychotics
Symptoms of stimulant overdose
convulsions, seizures, respiratory collapse, heart attack
Prenatal exposure to stimulants- history
Used to create a public sense of hysteria- the idea that a population of people will grow up experiencing deficits from crack. Not good to expose babies to stimulants and there are still many risks, but this epidemic of issues still did not materialize
Women to take stimulants while pregnant are at risk for (3)
Higher risk of- fetal death, miscarriage, premature labor
Effects on children whose mothers took stimulants while pregnant
Lower birth weight, abnormal arousal, seizures, enhanced startle response- this startle response is also observed in children whose mothers smoked tobacco. All seem to be short lived when controlling for other maternal factors. Intellectual deficits seem to endure- attributed to the environment, primarily. The prenatal environment continues postnatally since the stressors experienced during pregnancy generally continues. These children did not have an increased risk of addiction in the future. Trimester, amount, and duration of use matters
Inattentive symptoms of ADHD (5)
- Careless mistakes
- Difficulty focusing
- Forgetfulness/losing things
- Difficulty staying on task/following instructions
- Organization problems
Hyperactive symptoms of ADHD (6)
- Fidgeting/restlessness/trouble sitting still
- Trouble stopping themselves from X (calling out an answer, interrupting)
- Excessive talking/movement
- Acting without thinking
- Trouble waiting in line/for your turn
- Reduced inhibition to risk
3 presentations of ADHD
- Primarily inattentive
- Primarily hyperactive- usually diagnosed in young boys
- Combined type
Diagnosis of ADHD
For an ADHD diagnosis, at least 6 symptoms have to be present for 6 months. These behaviors are not age appropriate and impair normal functioning. They also cannot be the result of other problems. There is a lot of variation in terms of what normal ADHD looks like
Prevalence rates of ADHD
Among ages 3-17, 6-16%
How many people with ADHD take a stimulant medication?
38-81% are taking a stimulant medication- medication is usually not recommended for children younger than 6. Behavioral interventions (for the individual and the family) should accompany medication
People with ADHD are more likely to have problems with (6)
- Accidents and injuries
- Job loss and divorce
- Higher risk of addiction/substance use disorders
- Emotional regulation
- Sense of time/timing
- Excessive risk taking behavior
Why does ADHD need to be treated?
People with ADHD make up a large proportion of the population. They may have issues with work, school, or relationships, and are more likely to be affected by accidents or injuries. More likely to have issues with substance use, especially stimulants- might be self medicating
Conduct disorder
Lack of empathy, aggression, emotional outbursts- stimulants might not be recommended for this group, SSRIs can be used instead
Comorbidity of ADHD
64% of these individuals meet the criteria for another disorder. Other co-occurring disorders include behavior or conduct disorders, anxiety, depression, autism spectrum disorder, and Tourette syndrome
Current treatment model for ADHD
Multimodal treatment-medication helps to manage symptoms. Behavioral therapy also helps manage day to day tasks. It includes skills and strategies to minimize impairment and social skills training
Chemical differences in ADHD brains
lower levels of dopamine and norepinephrine
In ADHD, structural differences are observed in (3)
- Prefrontal cortex
- Basal ganglia
- Cerebellum
Prefrontal cortex function
inhibition, self regulation, planning, working memory
Basal ganglia function
learning, reinforcement, punishment, motivated responding, learning associations between ideas
Cerebellum function
involved in timing, coordination. A network between the PFC and cerebellum regulates other systems
ADHD structural differences in the prefrontal cortex
The prefrontal cortex matures at a slower pace in ADHD. It takes 7.5 years in neurotypical brains, but 10.5 years in ADHD brains. MRIs show decreased prefrontal-limbic blood flow. There is also a pattern of disrupted activity and connectivity
Roles of the PFC in working memory (3)
- Manipulating information in your mind
- Regulating attention, organization, planning
- Self monitor and changing behavior
How are ADHD brains physically different from neurotypical brains?
ADHD brains have overall delayed brain growth relative to neurotypical brains. They have a smaller right prefrontal cortex and cerebellum. There are also abnormalities in the basal ganglia related to reward and learning.
Abnormalities in the basal ganglia in ADHD
The caudate nucleus and globus pallidus are smaller. The basal ganglia contains a high density of dopamine receptors, so these abnormalities affect reward and learning
What is the frontostriatal circuit?
Includes the ventral and dorsal anterior cingulate, which control affective and cognitive components of executive control. Also includes portions of the basal ganglia and the nucleus accumbens
Abnormalities in the frontostriatal circuit in ADHD
In ADHD there are abnormalities in the frontostriatal circuits which extend to the amygdala and cerebellum.
Fronto-cerebellar circuit
This circuit is involved in temporal processing. It includes the prefrontal cortex, basal ganglia, and cerebellum. These brain regions are closely connected in cognition and learning. In ADHD, there may be reduced connectivity between the PFC and cerebellum, resulting in a variety of symptoms depending on the region that is impacted. Fronto-cerebellar circuit abnormalities might represent a distinct subtype of ADHD
Delayed PFC growth causes
Problems with executive functioning- like attending to irrelevant information or stopping yourself from doing something
Problems with the basal ganglia causes
Issues with delaying reward
Cerebellum dysfunction is associated with
Difficulty predicting when events are likely to occur, problems with timing, and circadian dysfunction.
In the PFC and BG, symptoms of ADHD are linked with which neurotransmitters?
Dopamine and norepinephrine. These neurotransmitters are linked to reward and pleasure. When a person is anticipating a pleasurable event, like the end of class, dopamine increases.
Delayed reinforcement gradient
Change in learning due to delay between key stimuli or responses, and reinforcement. Reinforcement is most effective when it is immediate, so this delay makes it less effective. In ADHD, a reinforcer loses its value quickly, which makes it difficult to change behavior. Only short sequences of responses can be reinforced due to the short critical window in which behavior can be reinforced. Children tend to respond better to immediate rewards over delayed rewards and only show learning when rewards are received immediately and frequently.
Dynamic developmental theory of ADHD
Hypothesizes that there is a dysfunction of dopamine transmission in the frontal-limbic circuits. This dysfunction is responsible for a steeper delay of reinforcement gradient due to lower tonic (baseline) levels of dopamine. This model proposes that due to the steep delay of reinforcement, there is a critical window during which reinforcement of behavior can occur in individuals with ADHD.
Tonic vs phasic phase
Tonic phase is the baseline state of the levels of a hormone or neurochemical. Phasic phase occurs during a stressful event
Reinforcement in the brain of someone with ADHD
Due to the delayed reinforcement gradient, immediate reinforcement is very rewarding, and delayed reinforcement is very weak. This causes problems for people with ADHD, because our society tends to reward delayed gratification.
Psychostimulants in ADHD
Psychostimulants are first line treatment for ADHD (tried first) and are used in combination with therapy. Includes Adderall and Ritalin- they both inhibit dopamine reuptake
Psychostimulant mechanisms (3)
- Inhibit dopamine reuptake
- Upregulate dopamine and norepinephrine activity
- Increase PFC activity and down regulate some BG activity
Optimal response curve
The prefrontal cortex requires a proper level of catecholamines (dopamine and norepinephrine) for optimal function. When the dopamine/NE level is too low, people can experience drowsiness and ADHD symptoms, like distraction and poor impulse control. When the dopamine level is too high due to an excessive dose of the stimulant, people can experience stress, elevated arousal, and hyperfixation on irrelevant stimuli. The optimal response curve depicts the amount of the stimulant that allows the person to be optimally treated- focused, organized, and flexible
Ritalin
Generic name is methylphenidate. Ritalin is fast acting and peaks 2 hours after administration. It inhibits the reuptake of dopamine and norepinephrine and therefore increases its concentration in the CNS.
Adderall
Generic name is amphetamine. It is longer acting and peaks 3-7 hours after administration. It increases norepinephrine and dopamine in CNS by multiple mechanisms
Adderall mechanisms (4)
- Blocks reuptake
- Inhibits auto receptors
- Increase NT release
- Increase number of postsynaptic receptors
What happens if someone with a neurotypical brain takes ADHD drugs?
People with ADHD have underaroused brains, and stimulants may help with increasing arousal. The symptoms of ADHD may be due to seeking new stimuli to stimulate their brain- looks like hyperactivity and inattention on the outside. Since there’s less dopamine between the neurons, you need a bigger response to get it flowing. Using these drugs in neurotypical brains pushes someone to a bad spot in the optimal response curve
How are ADHD drugs different from cocaine or methamphetamine?
Administration differs substantially- using illicit drugs is much more risky than using a prescribed drug to treat a problem. Cocaine and methamphetamine are typically taken in increasing doses over time. They are used recreationally and people can develop tolerance. The methods of administration are different- the illicit drugs are inhaled, injected, or snorted. Also, illicit drugs are often mixed with other things and you can’t be sure you’re getting a precise dose
Administration of ADHD medications (4)
- Typically taken in measured and precise doses, which are monitored and updated as needed
- Use is instrumental and specific (1 tablet in the AM and after lunch)
- Via transdermal patch, oral administration, extended release
- Peak is not as high and occurs over longer periods of time- reduces craving and withdrawal
Benefits of ADHD drugs (6)
There is a strong base of evidence for the effectiveness of these drugs.
1. Increased academic achievement
2. Decreased absenteeism at school- teaches tend to respond to the kids better and removes some stigma in the classroom
3. Reduced risk of emergency administration at the hospital for injury/trauma
4. Lower risk of depression and anxiety
5. Decreased substance abuse
6. Measurable and significant benefits in children, adolescents, and adults
Adverse effects of stimulant medications with proper use (6)
- Decreased appetite- slower physical growth in children
- Sleep disturbances- trouble falling asleep or trouble with deep sleep- can be helped with a careful dosing schedule
- Stomach aches
- Drowsiness
- Increased emotionality
- Increased blood pressure and pulse
Monitoring while on ADHD medication
Children and adolescents are monitored carefully while on medication- height and weight compared to peers, blood pressure and heart rate monitored regularly, prescreen children for other risk factors prior to medication. Some kids also have treatment interruptions/medication holidays. There is not a significant association between these drugs and cardiovascular events
Which group of people is more likely to abuse ADHD drugs?
People with comorbidities (like conduct disorder) are more likely to abuse the stimulants or distribute them to friends
Do ADHD drugs increase risk of addiction?
No. There is a significantly reduced risk of SUD when people with ADHD are given proper medical treatment. When people have their ADHD treated, there is also a reduction in self medicating behaviors
