Addiction & Brain Flashcards
1
Q
What are neurones?
A
- The building blocks of the central nervous system (CNS)
- Responsible for receiving, processing and transmitting information throughout the body
- Roughly 86 billion in the human brain
- Responsible for cognition, sensory processing, motor control & coordination
2
Q
What are neurotransmitters?
A
- Chemical messengers that transmit signals between neurons to other neurons across a synaptic cleft
- Presynaptic neurone – synaptic cleft – postsynaptic neurone
- Neuropeptides: (subset of neurotransmitters) typically more complex and have longer lasting effects compared to traditional neurotransmitters
3
Q
Classic neurotransmitters: 4 examples
A
- Dopamine - cocaine (reward/excitement)
- Noradrenalin – cocaine (alertness/excitement)
- Serotonin - MDMA (happiness/love)
- Acetylcholine- nicotine (focus/memory)
4
Q
Drugs & Synaptic transmission
A
- Agonist: typically involves binding to a receptor and activating it (mimicking a neurotransmitter)
- Antagonist: typically involves binding to a receptor and not activating it (blocking a neurotransmitter)
- Autoreceptors: these allow the neuron to self-regulate releasing or not-releasing, so things don’t get flooded (homeostasis)
5
Q
Evidence of neurochemicals in addiction:
(Gerra et al 2000)
A
- PRL = prolactin (pituitary hormone)
- Fenfluramine promotes 5-HT release (used clinically to treat obesity, here to test 5-HT function, 5-HT regulates PRL)
- Long term: the drug itself is no longer present, but long-term effects are found
- Issues: little dose knowledge from MDMA users (only 100% in animal studies), people tend to underreport doses
6
Q
Evidence of stress in addiction:
(Miczek & Mutschler 1996)
A
- Rats trained to respond for cocaine or food reward
- ‘Social stress’ = 60 mins as an intruder in the cage of a resident rat (protected from attack by a wire mesh)
- Issues: cause and effect issues
- Results: rats sought out cocaine over food once in a stressful situation
- Suggests selective effects of social stress on cocaine-reinforced responding
- Clinical reports suggest role of stressful life events in relapse, but these are correlational. Controlled animal studies can show cause and effect
7
Q
What are catecholamines?
A
Catecholamines:
- They are psychomotor stimulants (e.g. dopamine, noradrenaline, serotonin, acetylcholine)
- Neurotransmitters and hormones derived from the amino acid tyrosine
- They play key roles in the body’s stress response, regulation of the blood pressure, heart rate, and various metabolic processes
- Tyrosine has something to do with dopamine synthesis
8
Q
Hacking catecholamines
A
- A = potential to bond at receptor site
- B = full agonist
- C = antagonist (drug attaches but no response triggered)
- Cocaine: inhibits DA & NA transporters
- Amphetamines: increased DA & NA release
- Risperidone: blocks DA receptors (used in bipolar/ schizophrenia treatments)
- Ritalin: blocks DA & NA uptake (i.e. ADHD)
9
Q
Indirect agonist: 2
A
(Bloomfield et al 2016)
- THC promotes DA release through cannabinoid receptors
- Long term DA system dulling
(Reigel et al 2007)
- Same results
- They are interacting with the systems that interact with dopamine levels
9
Q
What is reserpine?
A
- General catecholamine antagonist
- Inhibits VMAT, a protein responsible for moving them into vesicles
- Test: injected rabbits with the drug
- Results: quite dramatic behavioural effects that follow their manipulations when we interfere with these process (e.g. become lethargic)
10
Q
Dopamine pathways: 4 types
A
- Neural circuits through which dopamine travels to regulate various physical and psychological functions
- These pathways are critical for processes like movement, reward, motivation, emotion, and hormonal control
- A) mesocortical
- B) mesolimbic
- C) nigrostriatal
- D) tuberoinfundibular
11
Q
Dopamine pathway: Mesocortical
A
- Regulates cognition, decision-making, emotion, and social behaviour
- Originates in the ventral tegmental area (VTA) but projects to the prefrontal cortex
- Dysfunction or underactivity is associated with negative systems or schizophrenia and cognitive impairments
- Drugs = target the mesocortical dopamine pathway that primarily aim to modulate dopamine activity in the prefrontal cortex
- These drugs are used to address cognitive dysfunction, ADHD, depression, and schizophrenia
12
Q
Dopamine pathway: Mesolimbic
A
- Involved in reward, motivation and the feeling of pleasure
- This pathway plays a central role in reinforcing behaviours and the development of addiction
- Originates in the ventral tegmental area (VAT) and projects to the nucleus accumbens and other limbic areas (e.g. amygdala & hippocampus)
- Overactivity in this pathway is linked to addiction, positive symptoms of schizophrenia and other disorder’s involving reward processing
- Drugs = target the mesolimbic dopamine pathway primarily aim to modulate dopamine activity in the rewards and motivation system of the brain
- These drugs are commonly used to trat schizophrenia, addiction, depression, and Parkinson’s disease
- High dopamine in the mesolimbic pathway = psychosis, addiction, mania
- Low dopamine in the mesolimbic pathway = depression, anhedonia, apathy
13
Q
Dopamine pathway: Nigrostriatal
A
- Controls movement and motor planning by facilitating the interaction between the basal ganglia and other motor control systems
- Starts in the substantia nigra and projects to the striatum (caudate nucleus and putamen)
- Degeneration of neurons in this pathway is a hallmark of Parkinson’s disease, leading to tremors, rigidity, and bradykinesia
- Overactivity can contribute to involuntary movements seen in conditions like tardive dsykinesia
- Drugs = crucial for motor control and used for Parkinson’s disease, drug-induced movement disorders, and Huntington’s disease
- Low dopamine = Parkinson’s, drug induced
- Excess dopamine = tardive dyskinesia, Huntington’s chorea
14
Q
Dopamine pathway: Tuberoinfundibular
A
- Regulates in the secretion of prolactin from the anterior pituitary gland, playing a role in hormonal control
- Originates in the hypothalamus and projects to the pituitary gland
- Dysfunction can result in hyperprolactinemia, leading to symptoms such as infertility, sexual dysfunction and galafactorrhea (milk production)
- Drugs = DA acts as a prolactin antagonist
- Increase prolactin = infertility, menstrual irregularities decreased libido
- Decreased prolactin = rare and usually not clinically significant unless in conditions like hypopituitarism
15
Q
How do we target drugs?
A
- DA has multiple receptors (e.g. multiple locks work for the same key)
- Some activate easily (D3), and others less so (D1)
- Some excite the neuron (D1-like), while others calm in down (D2-like)
- Location in different regions (e.g. D1 is key for motivation and movement, while D3 is more involved in addiction and impulse control)
16
Q
Beyond drugs: 2 studies
A
(Giros et al 1996)
- From birth, not CRISPA edited
- Heterozygous = 1 deletion
- Homozygous = double deletion
- ABOVA shows double deletion = more active. The dopamine transporter would usually remove the dopamine
- An animal under treatment to become more hyperactive will respond by wanting more of that treatment, suggesting its rewarding and showing addicting potential
(Xu, Guo, Vorhees & Zhang 2000)
- Mutant mice lacking D1 receptors are insensitive to cocaine which increased locomotor activity in the wild-type but not the knockout mice
17
Q
Patterns of drug use: Past
A
According to earlier British Crime Surveys (BCS):
- In 1996, around 30% of adults had tried illegal drugs at some point in their lives
- In 1998, this increased slightly to around 32%
- By 2000, it was around 33% (1 in 3 adults)
18
Q
Patterns of drug use: Now
A
- UK: 38% of adults aged 16-59 have tried drugs
- USA: the national survey on drug use and health 2022 reports that over 50% of adults aged 12+ have tried an illicit drug at some point in their lives
- UK 2024: 8.8% of adults (16-59) reported using drugs
- USA 2022: 17.3% of Americans 12+ using illegal drugs
19
Q
Key facts of drug use
A
- Drug use is relatively stable overtime
- Most illicit drug isn’t daily
- Most drug use is by younger people
- Most drug use is by less affluent people
- Most drug use is by men
- Use patterns vary by drug and age
- PCP (e.g. angel dust a dissociative anaesthetic)
- Salvia (herb in Mexico that produces hallucinogenic experiences)
20
Q
Exposure models: Key features
A
- Most models of addiction are exposure models
- All people are at risk of becoming addicted to drugs given sufficient exposure
- Drugs interact with and change the brain
- Brain changes create continued motivation to use the drug
- Models differ in their explanation as to what sort of changes drugs produce in the brain and what sort of motivation drives subsequent drug use
- Focus on withdrawal
21
Q
Withdrawal: key features
A
- Addicts continue to use the drug to avoid withdrawal
- The initial high exhausts the reward/pleasure regions of the brain and once the drug wears off the user goes into withdrawal (VERY aversive)
- A form of negative reinforcement
22
Q
Withdrawal model issues: Relapse
A
- Stopping drugs under medical supervision does not necessarily result in long term abstinence
- Drug users often relapse despite having undergone supervised withdrawal from drugs
- Wikler (1948) proposed that withdrawal can be triggered by external cues
- Environmental stimuli such as the addict’s bedroom is consistently paired with withdrawal
- Through pavlovian conditioning, stimuli enter learned associations to become triggers for withdrawal symptoms
- Subsequent exposure to these cues is then sufficient to elicit withdrawal and thereby precipitate relapse
- Thus, conditioned withdrawal can explain relapse following primary withdrawal
- Anecdotal reports from relapsed drug users suggest things are not always as predicted e.g. by contexts in which withdrawal had occurred most frequently
- People can associate cues with outcomes over a delay or a trace (lingering effect of drugs)
23
Q
Withdrawal model issues: can’t all be aversive
A
- Midbrain dopamine cells increase activity when humans or animals detect or consume both natural rewards (food, water, sex) and drugs of abuse (nicotine, cocaine, heroin)
- Suggest that drugs of abuse hijack the brain substrate for reward/pleasure and are consumed because drug taking is positively reinforcing
24
Q
Opponent process model
A
- Initial positive experience – positively reinforcing drug use
- Subsequent negative experience – where the body attempts to restore balance, leading to a negative effect (withdrawal)
- With repeated use – the initial positive effects become weaker (tolerance) and the negative effects become stronger
- CREATES A CYCLE OF ADDICTION
- Solomon & Corbit (1973) – sky divers feel a mixture of fear and pleasure but after multiple jumps they start to be less afraid and more excited (relates to drug use – pleasure decreases & withdrawal increases overtime)
25
Q
Tolerance: 2 types
A
- Pharmacodynamic tolerance: this occurs when the drug’s effects at the cellular or receptor level become less pronounced
- Pharmacokinetic tolerance: this arises when the body becomes more efficient at metabolising or eliminating the drug (e.g. drinking)
26
Q
Conditioned tolerance: Siegel (1983)
A
- High heroin dose given to heroin tolerant rats
- Deaths by environment (Novel – 96%, Usual – 64%)
- Environmental cues associated with drug taking can elicit a ‘drug opposite’ response
- Drug opposite response may be aversive, and motivate drug taking to alleviate this state (negative reinforcement
27
Q
Positive condition: Hogwarth et al (2010)
A
- Data consistent with hypothesis drug cues prime drug taking by reminding the addict of the positive appetitive qualities of the drug (not by eliciting an aversive state)
28
Q
Exposure vs susceptibility models
A
- Exposure models – addiction is caused by the drug and the neurological changes it promotes (withdrawal, opponent process)
- Susceptibility models – addiction is caused due to individual vulnerabilities such as genetic, psychological to environmental factors (more people are more susceptible to drugs than others & not everyone becomes an addict)
29
Q
Susceptibility factors: 3 main factors
A
- Age – peak time with drugs is typically from late teens to early 20s
- Sex - men are more susceptible to drugs
- Genetics – research suggests that 40-60% of addiction vulnerability is hereditary.
Specific genes affect how individuals respond to substances and their likelihood of developing addictive behaviours (e.g. fewer dopamine receptors or increased metabolism). BIG issues with nature vs nurture - Other factors include drug availability, broken home, mental health of parents, failure at school & role modelling (BUT problems with disentangling cause and effect)
30
Q
Susceptibility factors: Tarter et al (2003)
A
- Longitudinal study with children from age 10 to 19
- Split into high and low-risk groups
- Matched across household income, parent education, parent use, etc
- Concluded that ‘Neurobehavioral disinhibition’ was greater in the high-risk group and predicted illicit drug use
31
Q
Neurobehaviour disinhibition
A
- a composite source of (difficult temperament, ADHD, depression, low cognitive function). Those at risk of drug abuse show disorganised behaviour, possibly stemming from abnormality in the frontal cortex, causing poor decision making
- Phineas gage (1823-1860): accident cause a large railroad spike to impale his head, causing a SEVERE frontal lesion. Become unreliable at work, showed callous regard. Preserved some intellectual function (e.g. memory), but planning ability become very poor. Became an alcoholic and hyper-sexual
- Conclusion: suggest PFC associated functions, such and decision making, long-term thinking, self-control, impulsivity and risk-taking tendencies influence addiction behaviour
32
Q
Iowa gambling task & risky decision making
A
- 4 decks of cards with a goal to win money
- Participants told all cards result in some level of reward
- Occasionally, choosing a card causes them to lose some money
- A & B are ‘bad decks’, C & D are ‘good decks’ but they are rigged
- Most people can figure it out that the cards are rigged but addicts can’t figure this out
- Bechara et al (2000) – patients with PFC lesions do worse than normal because they opt for high immediate gains despite higher future loses
- Deakin et al (2004) – general impression is that maturity increases over age until 20/25. Suggest the susceptibility for drug use amongst younger people might be due to PFC underdevelopment
- In the Iowa gambling task, who frequently selects the high reward desks despite the net loss of points include (with frontal lesions, in adolescence, ADHD, schizophrenia, drug addicts)
33
Q
Cause and effect: risky decisions, drug use and PFC damage
A
- Risky decision making seen in high-risk children before any drug use
- Risk decision making predicted the onset and magnitude of drug use
- Suggests PFC damage is a major susceptibility factor for becoming a drug user
- several aspects of risk decision making can predict drug use (reward hypersensitivity, reward hyposensitivity, punishment insensitivity, faulty error detection)
34
Q
Punishment insensitivity: clinical relevance
A
DSM drug dependence criteria:
1. continued use of drugs even though known to cause trouble with family/friends
2. job troubles because of drug use
3. continued use of drugs even though known to cause health problem
- Test: trained rats to give themselves coke then put them through withdrawal. reintroduced coke and provided a cue that previously predicted coke delivery, some relapsed. introduced a small experiment punishment (small shock) for relapsed rats
- Results: some animals keep wanted the coke EVEN WHEN paired with a shock
35
Q
Error detection: control vs drug addicts
A
- addicts may have full knowledge of the adverse consequences of their drug taking, but just not able to sue this knowledge to correct their behaviour
- event related potentials (ERP) used to measure the responses of cocaine addicts to errors in their performance
- Flanker test: cocaine addicts showed a reduced frontal activity in response to errors and less post-error improvement in performance
- suggests that addicts may have less knowledge of the adverse consequences of their behaviour, and so less ability to use this knowledge to modify their behaviour
- controls show sensitivity in the PFC when they make an error, but coke addicts don’t
36
Q
Cannabis background facts
A
- Produced from the weedlike plant: Cannabis Sativa (Hemp)
- Uses: rope, cloth, paper, seeds used for oil, birdfeed
- Psychoactive agent: Tetrahydrocannabinol (THC)
- Found in all parts of the plant, but concentrated in the sticky resin secreted the flowering tops of female plants
- Over 70 other non-psychoactive agents including Cannabidiol (CBD)
37
Q
Cannabis forms: 4 forms
A
- Marijuana: dried and crumbled leaves, small stems, flowering tops of the plant. Usually smoked in joints, pipes, bongs. THC content varies
- Sinsemilla: pollination prevented, potency
- Hashish (solid): prepared from resin. Potency varies with concentration
- Hash oil: reduced alcoholic extract. Single drop placed in a joint
38
Q
What is the pharmacology of cannabis?
A
- Typical joint contains approx. 0.5-1 gram of cannabis
- A joint with 1g of cannabis, 4% THC content, contains 40mg of THC
- THC content in of samples analysed in 1995 contain 4& THC, raising to average of 15% in 2015
- Burning marijuana results in vaporisation of THC where its readily absorbed through the lungs into blood plasma
- Only about 20% of original THC is absorbed into lungs but this figure could be increases by breath holding
- After peak levels reached, concentration fails (half-life of about 20-30 hrs, metabolism in liver and fat storage)
39
Q
What is the administration effects of cannabis?
A
- Route of administration has a substantial effect
- Blood plasma levels of THC following smoking vs oral consumption
- Oral consumption: ingestion – metabolism in liver – absorbed into blood plasma (slower effects relative to smoking, effect is more sustained)
40
Q
Cannabinoid receptor
A
- Cannabis receptor = CB1
- Agonist = THC
- Antagonist = SR141716
- Cannabis receptors activate in areas consistent with behavioural effects (e.g. hippocampus which is associated with spatial memory)
41
Q
Antagonist effects: Huestis et al (2001)
A
- Effects of marijuana attenuated by treatment of CB1 antagonist (SR141716)
- Two groups: placebo control and SR141716 group
- Results: responses recorded over next hour. Ratings of drug effect and increase in heart rate
42
Q
Endocannabinoid system and the effects of CB1 knockout
A
- Neurotransmitter = AEA & ANA
- Effects of CB1 antagonist (Richardson et al 1988) SR141716 induces hyperalgesia (increased pain sensitivity) and endocannabinoids reduce responsiveness to pain
Effects of CB1 knockout –
1. Varvel & Lichtman (2002) normal acquisition of spatial learning and impaired reversal learning
2. Marsicano et al (2002) normal fear conditioning, impaired extinction and a deficit in unlearning/ new learning
43
Q
Acute behavioural and physiological effects of cannabis
A
- Behavioural effects (Iversen 2000)
1. The ‘buzz’ – tingling sensations, dizziness
2. The ‘high’ – feelings of euphoria, exhilarant ‘giggles’
3. The ‘stoned’ – feelings of calm, dreamlike, slowing the perceptions of time, changes in sociability
(Psychopathology: paranoia, anxiety, panic (most likely in 1st time users)) - Physiological effects
1. Increased blood flow
2. Increase in heart rate
3. Increase in hunger (e.g. induced by THC and abolished by CB1 antagonist)
44
Q
What are the cognitive deficits of cannabis?
A
- Oral THC administration impairs verbal memory
- Psychomotor functions affected; makes driving dangerous
- Cognitive tolerance in heavy users
- Dose dependent (low doses have relatively few effects)
- Task dependant (if the task demand is high = impaired performance)
45
Q
Rewarding effects of cannabinoids (Tanda et al. 2000): 5 phases
A
- Phase 0: intravenous cocaine → lever press
- Phase 1: extinguished with saline
- Phase 2: intravenous THC → lever press
- Phase 3: Effect abolished with CB1 antagonist
- Phase 4: intravenous THC → lever press
46
Q
Conditioned place preference: Valjent & Maldonado (2000)
A
- Conditioned place preference with THC in mice and only works if mice are pre-exposed to THC in home cages
- First experience = aversive then rewarding
47
Q
Age of initiation of cannabis
A
- Most widely used illicit drug in UK & US (4.6%, 14 million in US)
- Age of initial use peaks at 17 years old (Brooks et al 1999)
- Cannabis could be the gateway drug to trying other drugs
- Risk factors: family disturbances, drug use by family/peers, school performance, age of onset (Gruber & Pope 2002)
48
Q
Tolerance & Dependence in cannabis
A
- Tolerance = needing a greater dose to achieve the same effect
- Mixed result in human studies: tolerance observed following repeated administration of marijuana or pure THC (Compton et al 1990), same ‘high’ in infrequent users relative to frequent users (Lindgren et al 1981)
- Animal studies more consistent: daily injections of THC over 3 weeks ad showed progressive reduction in CB1 receptor density and activity and some brain areas totally desensitized in 3 weeks (Breivogel et all 1999) - Dependence = difficulty stopping taking Cannabis, cravings and withdrawal symptoms
- Abstinence triggers anxiety, depression, sleep disturbance irritability. Resemble nicotine withdrawal symptoms. Worst in first 2 weeks and can last for over a month (Budney et al 2003)
- Animal studies: early studies found no effect of drug withdrawal, but THC has a long half-life, thus may still be present in system. Precipitated withdrawal when rats were given THC injections twice a day and then given SR141716. Showed symptoms of hyperactivity, shaking, face rubbing and scratching (Aceto et al 1996)
- Possibly consequence of rats being stressed as found increases corticotrophin-releasing hormone (CRH) in precipitated withdraw rats (de Fonseca 1997)
49
Q
Treatment of cannabis use disorder
A
- Cognitive behavioural therapy (CBT) pp’s rewarded with vouchers for providing cannabis-free urine samples
- Significant relapse (Moore & Budney 2003)
- Withdrawal symptoms may be released by oral consumptions of THC (Haney e al 2004)
- Useful in the sort-term, difficult to achieve long-term abstinence
50
Q
Behavioural effects of cannabis: Lynsky & Hall (2000)
A
- Chronic cannabis use associated with poor education performance
- More negative attitudes about school, poorer grades, increased absenteeism
- Amotivational syndrome: apathy = aimlessness, lack of productivity, long-term planning and motivation
- (Fergusson et al 2003) regular cannabis use early in life predicts poor school performance and drop-out rates
51
Q
Cognitive effects of cannabis: Solowij et al (2002)
A
- Cognitive deficits in long term users
- Standardised tests of learning, memory and attention
- Long-term user deficient 1 & 7 days after exposure
- (Pope et al 2001) no difference between heavy users and controls after 28 days of abstinence, cognitive deficits linked to recent use (reversible overtime)
52
Q
What are some health effects of cannabis
A
- Higher concentrations of carcinogens in cannabis smoke than tobacco
- More tar and carbon monoxide/ joint than a cigarette
- Cardiovascular/Cerebrovascular disorders
- Immune system (Cabreal & Pettit, 1998): THC suppresses immune function & increase risk of viral and bacterial infection
- Reproductive function (Smith & Asch, 1987): Smoking in women suppresses luteinizing hormone release (but can be tolerated) & Reduced sperm count in men (but only in heavy users)
53
Q
Clinical applications of cannabis
A
- Can be tracked back to hundreds/thousands of years
- Identification of THC = manufacture of synthetic compound
- Dronabinol = antiemetic for chemotherapy patients
- Nabilone = appetite stimulant on AIDS patients
- Cannabis also used for treatment of chronic pain (multiple sclerosis, spinal cord injury, glaucoma)
- Limited widespread use and has side effects
- Joints more effective than synthetics
- HU-211 (a cannabinoid that doesn’t activate CB1 receptors) = no side effects, undergoing clinical traits
54
Q
Caffeine background facts
A
- Sources of caffeine include coffee, tea, chocolate and energy/carbonated drinks
- 80-90% of people consume regularly
- Average adult daily intake = 200-400 mg
- One cup of coffee = 80-100 mg
55
Q
What is the pharmacology of caffeine?
A
- Caffeine absorbed through the gastrointestinal tract in about 30-60 minutes
- Plasma half-life of around 4 hours, but usually topped up (people have a rising concentration in blood plasma throughout day)
- Caffeine converted to metabolites by the liver (95% excreted in urine, 2-5% in faeces, rest through saliva)
- Caffeine acts primarily by blocking adenosine receptors in the brain
56
Q
What are some behavioural effects of caffeine?
A
- Caffeine has a biphasic effect in rats and mice (low dose-stimulus = higher locomotor activity & high dose-reversed = lower locomotor activity)
- Low to intermediate doses results in a variety of positive subjective effects (increased alertness, reduced tension, reduced reaction tie)
- Enhance sports performance (significant benefits to muscle strength, power and endurance)
- Disruption to sleep: Particularly in older adults and when consumed within 6 hours before going to sleep
- Negative effects at higher doses (>400mg; Nehlig, 2010) Tension, Jitteriness, Anxiety, Panic disorder patients may be hypersensitive = panic attacks
57
Q
Tolerance & Dependence in caffeine
A
- Tolerance to subjective effects of caffeine (Griffiths & Mumford (1995)): heavy drinkers can consume coffee before bed
- Abstinence → Withdrawal symptoms (Griffiths et al., 1990): Even in >100mg/day drinkers (1 cup a day). Causes: Headache, drowsiness, fatigue, impaired concentration & psychomotor performance. Withdrawal effects last a few days of consecutive abstinence but will dissipate
58
Q
What are some health effects of caffeine?
A
- Little to no risk to healthy, non-pregnant adults
- Acute consumption effects for non-consumers (van Dam et al., 2020): Causes: increased blood pressure, respiratory rate & water excretion
- Risk to pregnancy: Association with infant birth weight (Qian et al., 2020, James, 2021), Dose-dependent increase in risk of stillbirths (Greenwood et al., 2014), Prenatal exposure is associated with developmental effects such as childhood obesity, Current guideline <200mg per day
59
Q
Harms associated with drugs: alcohol
A
- Development of drug harm scale:
- A) experts assign score (0-3) for each parameter
- B) parameters are averaged to yield overall harm score
- Alcohol is harder to accidently overdose compared to other drugs
- Highly addictive
- Liver problems, cancers
60
Q
Harmfulness of different drugs compared to alcohol: old findings
A
- Alcohol is lower on the scale compared to heroin and cocaine but higher than LSD and ketamine
61
Q
Harms associated with drugs compared to alcohol: improved criteria and weighting
A
- 16 criteria (9 in 2007 study)
- Scores from 0-100 (0-3 in 2007 study)
- Differential weighting of criteria to indicate their different importance
- Results: alcohol came out on top as the most harmful drug as even though its harm to self was lower than cocaine, its harm to others was much greater
62
Q
Selected aspects of the psychopharmacology of alcohol: acute vs chronic consumption
A
- Primary neuropharmacological targets of alcohol
- Acute psychological effects of alcohol:
a) Decreased anxiety
b) Impaired memory
c) Directly ‘rewarding’ effects - Psychological effects of chronic alcohol consumption:
a) Neuropharmacological adaptations, withdrawal symptoms and alcohol dependence
b) sever and chronic cognitive deficits due to brain shrinkage
63
Q
Primary neuropharmacological targets of alcohol in the brain
A
- Complex neuropharmacology:
- Nonspecific effects (interactions with lipid bilayer, mainly at higher concentrations)
- Specific effects (interaction with ligand-gated ion channels and voltage-gated ion channels, at concentrations within range achieved by common alcohol consumption)
- First hit: Neurotransmitter receptors (GABA-A etc) and voltage-gated ion channels = cascade of synaptic events involving many neurotransmitters
- Overall, acute alcohol tends to dampen neural activity
- Other factors effected: sex drive, mood, social cues
64
Q
Alcohol-induced reduction in tension and anxiety
A
- View that alcohol reduces tension/ anxiety is a contributor to abuse is widely held
- Like classical anxiolytics, such as benzodiazepines, alcohol acts as indirect agonist at GABA-A receptors, i.e. enhances the response of the major inhibitory neurotransmitter GABA
- Alcohol relatively consistently reduces measures of anxiety in rats
65
Q
Beer drinking in rats reduces anxiety: the findings
A
- Rats who had more alcohol approached the cat odour more readily – showing that alcohol makes them less anxious
- Rats don’t typically like open spaces/heights as they can be easily caught by predators but once given alcohol, this anxiety was reduced
66
Q
Alcohol-induced memory loss (‘amnesia’)
A
- Alcohol interferes with memory, especially with the encoding of new information into long-term declarative memory
- It can range from little memory lapses to ‘black outs’
67
Q
Possible mechanisms of alcohol-induced amnesia: State-dependence
A
- Info learnt in a drugged state, may be remembered better if tested in a comparable drugged state, then in a non-drugged state
- Alcohol has been shown to render some aspects of declarative memory state dependent
- Memory retrieval in a word-association test was especially reduced when they learnt the memory drunk, and were told to recall it sober
- However, state-dependency appears to account mainly for little memory lapses as blackouts seem to be due to other mechanisms
68
Q
Possible mechanisms of alcohol-induced amnesia: Selective interference with hippocampal memory mechanisms
A
- Alcohol mainly interferes with encoding of new declarative info, like damage to the hippocampus
- Thus, interference with hippocampal synaptic mechanisms of memory may contribute to amnesia
- E.g. alcohol disrupts the induction of hippocampal long-term potentiation (LTP), an activity-dependent long-lasting increase in synaptic strength and a candidate physiological mechanism of memory
69
Q
Meso-corticolimbic dopamine system and reward
A
- Rewards activate meso-corticolimbic dopamine transmission
- Alcohol increased dopamine transmission
70
Q
Chronic excessive alcohol use can lead to alcohol dependence
A
- Neuropharmacological adaptations to repeated and chronic alcohol use contribute to dependence
- Long-term compensatory change in neural mechanisms in response to chronic excessive alcohol, which are opposed to acute effects of alcohol
- These contribute to: tolerance (i.e. in response to repeated alcohol use) & chronic psychological changes when sober
71
Q
What is withdrawal hyperexcitability?
A
- Altered balance between excitatory and inhibitory neurotransmission in response to chronic alcohol
- Decreased GABA-A receptor function
- Increased glutamate receptor stimulation and function
- Symptoms: seizures, tremor, anxiety, alcohol craving & excitotoxic brain damage
72
Q
Reduced dopamine transmission during withdrawal
A
- Reduced nucleus accumbens dopamine during withdrawal
- Reduced spontaneous activity of dopaminergic neurons in the VTA
- Withdrawal symptoms increase after each dose administered
73
Q
Severe cognitive impairments and brain shrinkage associated with chronic excessive alcohol consumption
A
- Wernicke-Korsakoff Syndrome: caused by thiamine deficiency, most commonly in association with alcoholism
- Wernicke Syndrome: acute stage, characterised by ophthalmoplegia (paralysis of eye muscles), confusion, ataxia
- Korsakoff Amnesia: remains after treatment of acute Wernicke Syndrome if thiamine deficiency lasted too long and causes impairment in forming new declarative memory, severe brain ‘shrinkage’, especially striking degeneration of the mammillary bodies
- Cognitive deficits and brain shrinkage in ‘uncomplicated’ alcoholics
- Even alcoholics without WKS, may present with deficits in sensori-motor and executive functions, learning and memory and show marked front-cerebellar brain damage
74
Q
Opioids: key facts
A
- Narcotic analgesics (i.e. drugs that cause a reduction of pain) without anaesthesia (loss of all sensation), but promote a sense of relaxation and sleep and at overdoses lead to coma and death
- A) opiates – an extract of the opium poppy plant and substances directly derived from opium
- B) related semisynthetic and synthetic compounds
- C) endogenous peptides acting on the same receptors, the opioid receptors
75
Q
Physiological and psychological effects of opioids
A
- Analgesia (no pain)
- Constipation
- Adrenal gland – reduce cortisol and affects immune/ stress responses
- Brain neurons – emotions, pleasure, respiratory depression, stress
- Decreased blood pressure, reduced sex drive
- Withdrawals of opioids cause the opposite effect of acute action of opioids
76
Q
Molecular structure of opiates and related compounds, and relationship to physiological effects
A
- Morphine has more added acetyl-groups = crosses blood-brain barrier more quickly and strong high (euphoria)
- In the brain, heroin is converted to morphine
- Codeine has less analgesic, but also less side effects/ addictive but still very potent cough suppression
77
Q
Opioid use and misuse
A
- Long history of medial use (reducing pain, coughing) and recreational use (euphoria); nowadays, medical use is strictly regulated, and recreational use is illegal
- Opioids are highly addictive
- Opioids are the main cause of drug-related deaths in the UK
- The opioid codeine can be brought without prescription in UK pharmacies
78
Q
Opioid overdose
A
- Can be treated by injection with the opioid antagonist naloxone
- Hypothermia, respiratory depression, absent or hypoactive bowel sounds
78
Q
Opioid receptors:
A
- There are also peripheral opioid receptors, including on peripheral nerve endings and in the gastrointestinal tract
- Opioid receptors are G-protein-coupled receptors
- Activation of opioid receptors tends to inhibit neural activity or neurotransmitter release of the neurons carrying the opioid receptor
- A) postsynaptic inhibition opens potassium channels
- B) axoaxonic inhibition closes calcium channels
- C) presynaptic autoreceptors reduce transmitter release
78
Q
Opioids: Pain
A
- An unpleasant sensory and emotional experience associated with actual or potential tissue damage
- Nociception: the neural process of encoding noxious stimuli (i.e. stimuli causing tissue damage)
- Chronic pain: pain that lasts or recurs for longer than 3 months, can be symptom or disease in itself (i.e. with no clear relation to tissue damage) – affects about 20% of people worldwide
- Pain is the leading cause of disability in the UK
78
Q
Pain pathways
A
- Ascending: Primary sensory neurons in dorsal root ganglion – neuron in dorsal horn of spinal cord - thalamus – cortex (first pain with adelta fibres to somatosensory cortex & second pain with C fibres to other cortical areas
- Descending: pathways originate in midbrain regions, including periaqueductal grey, and INHIBIT pain processing
78
Q
Opioids inhibit pain processing
A
- Opioids disinhibit a descending pain pathway that inhibits pain
- Opioids inhibit the ascending pain pathway
- Important in inhibiting acute pain but little evidence that they can inhibit chronic pain
78
Q
How may opioids increase dopamine release within the nucleus accumbens?
A
- Disinhibition of dopaminergic neurons in the VTA:
- Opioids stimulate opioid receptors of GABA neurons, inhibiting GABA release by these neurons, thereby allowing an increase of dopaminergic VTA neurons
- Opioids can increase NAC dopamine release via mu-opioid receptors in the VTA
- Opioids with preferential action on kappa-receptors can act presynaptically on dopamine terminals in NAC to reduce dopamine release
79
Q
Measuring the rewarding properties of opioids
A
- Reward = something we and other animals work for
- Measure how many times the rat presses the leaver to get the drug administration
80
Q
Opioids and ‘pleasure’
A
- Distinction between reward and pleasure/liking – how much a subject works for reward may not directly reflect the ‘liking’ induced by the reward, but rather ‘wanting’ of or ‘desire’ for the reward
- Facial expressions to sweet or bitter tastes as measures of ‘liking’
- Nucleus accumbens shell: stimulation of opioid receptors increases ‘liking’, whereas stimulation of dopamine receptors reduces ‘liking’
81
Q
Opioid dependence
A
- Neuropharmacological adaptations to repeated opioid use contribute to dependence:
- Tolerance in response to repeated use leads to reduced acute effects (which may lead the user to increase dose or take a stronger opioid)
- Long-term compensatory changes in neural mechanisms in response to repeated opioid use led to withdrawal symptoms
- Compensatory changes are opposed to acute opioid effects
82
Q
Prescription opioids may initiate users to heroin abuse and dependence
A
- Since the late 90s early 2000s, heroin dependent patients in the US have mainly initiated opioid abuse with a prescription opioid
- More recently, with reduction in supply of prescription opioids, heroin again gains in importance at initiating drug
83
Q
Treatments of opioid dependence
A
- Detoxification, usually assisted by substitution with a long-acting opioid drug (methadone or buprenorphine), which has lower highs and less pronounced withdrawal symptoms
- Maintenance with methadone or buprenorphine
- Reduces mortality from overdose and other causes
- However, substitution drugs have adverse effects, too, and interfere with normal life; the partial agonist buprenorphine may have reduced adverse effects compared to methadone, but high-quality evidence that this significantly improves patients’ life is lacking
- Treatment for full abstinence with opioid antagonist (e.g., with naloxone): antagonist will make opioid administration ineffective; typically, very low adherence and requires highly motivated patients
84
Q
What are hallucinogens?
A
- Induce an altered state of consciousness, characterized by distortions of perception, hallucinations or visions, ecstasy, dissolution of self-boundaries and the experience of union with the world
- Referred to as ‘psychedelics’ (mind revealing)
- Classical hallucinogens: include plant-derived substances (i.e. magic mushrooms) and synthetic drugs, such as LSD. Agonists at serotonin, especially 5-HT2A receptors. Altered state of consciousness is primary effect
- Dissociative anaesthetics: are synthetic drugs, such as ketamine. Produce anaesthesia at higher doses and altered states of consciousness at lower doses (e.g. feeling of floating). Non-competitive NMDA receptor antagonists
84
Q
Comparisons of classical hallucinogen and dissociative anaesthetic
A
- Five-dimensional altered states of consciousness rating scale
- ‘Oceanic boundlessness’ referring to positively experiences loss of ego boundaries
- ‘Anxious ego-disintegration’ including thought disorder and loss of self-control
- ‘Visionary restructuralization’ referring to perceptual alterations
- ‘Acoustic alterations’ including hypersensitivity to sound and auditory hallucinations
85
Q
Importance of ‘set’ and ‘setting’ in determining subjective experience induced by hallucinogenic drugs
A
- Psychopharmacological actions of hallucinogenic drugs may be less predictable than those of other drugs
- Hallucinogen effects are heavily dependent on the user’s expectation and the environment (e.g. expectations and environments that would foster religious r spiritual experiences increase the probability of the drug producing such an effect)
- The individual’s response to repeated administration of the same drug and dose may vary
86
Q
Hallucinogens: historical background
A
- Natural hallucinogens have been used for millennia and were often as part of rituals
- plant-derived hallucinogens and LSD entered Northen American and European mainstream culture in the first half of the 20th century
- PCPA developed anaesthetic in mid 1950s, ketamine synthesized as safer alternative in 1962 – still used as anaesthetic in humans and animals
- There was interest by researchers in understanding hallucinogenic drug actions and to exploit them clinically (using them to reveal mechanisms of altered states of consciousness in neuropsychiatric disorders or for therapy)
- On the other hand, especially the classical hallucinogens became associated with 1960s counterculture and were made illegal
- Ketamine approved as depression treatment in US in 2019
87
Q
Ecstasy (MDMA)
A
- MDMA is an amphetamine with strong effects on serotonin transmission
- Has stimulant properties; increases alertness and energy
- Has hallucinogenic-like properties: increases sociability and talkativeness and induces an altered state of consciousness with emotional and sensual overtones
- Has been suggested for use in psychotherapy, but has also become notorious for use in the rave scene and ecstasy-related deaths
88
Q
Use of hallucinogens and MDMA: current trends
A
- Proportion of 16–59-year-olds using:
A) LSD – 0.4%
B) Magic mushrooms – 0.4%
C) Ketamine – 0.8%
89
Q
Harmfulness of hallucinogenic drugs and MDMA
A
- Expert assessment of harms to user and to others
- Apart from potential distress caused by the subjective experiences induced by classical hallucinogenic drugs, these drugs cause otherwise virtually no physical harm and no dependence
- Ecstasy and dissociative anaesthetics (PCP, ketamine) can cause dependence and cause neurodegeneration, although it is debated if typical recreational usage and doses cause neurodegeneration
- Ecstasy-related deaths: about 130 in England, Wales and Scotland in 2017; may be related to overheating and dehydration
90
Q
Severe legal restrictions on hallucinogens and MDMA
A
- UK drug regulations: 3 classes (A, B & C) to determine the penalties for offences such as supply, production and possession of a controlled drug
- Five schedules regulate the clinical use of controlled substances and their storage and labelling requirements
91
Q
Classical hallucinogens: Indoleamine & Phenethylamine
A
- Indoleamine and phenethylamine hallucinogens activate serotonin receptors and 5HT2A receptor activation is main contributor to their psychological effects
- High affinity to serotonin receptors, especially 4HT2A and C receptors subtypes
- Primary neuropharmacological mechanism is stimulation of 5HT receptors
- Evidence supports that stimulation of 5HT2A receptors is critical for main psychological effects
92
Q
Serotonin system and 5HT2A receptors
A
- Serotonergic raphe nuclei in the midbrain innervate large parts of the brain, including many cortical and subcortical forebrain regions
- 5HT2A receptors are G protein-coupled receptors; their activation mainly has stimulatory effects on the neuron (increased transmitter release/ activity)
- 5HT2A receptor activation may stimulate excitatory neurons, including in the prefrontal cortex, which may be critical for the hallucinogenic effects
- In animal studies, behavioural effects of classical hallucinogens are blocked by selective 5HT2A receptor antagonist
93
Q
MDMA (‘ecstasy’) with serotonin
A
- Stimulates serotonin release and some of MDMA’s subjective effects are mediated by 5HT2A receptors
- Also stimulates dopamine release, including in nucleus accumbens, which is thought to contribute to stimulant and rewarding/ reinforcing properties
94
Q
Dissociative anaesthetics
A
- Primary neuropharmacological mechanism is blockade of the channel pore of the NMDA-type glutamate receptor (non-competitive NMDA receptor antagonist)
- One idea is that NMDA receptor blockade increases neural excitation in many brains, including cortical, areas by ‘disinhibition’ (i.e. reducing the activity of inhibitory neurons). This may be a key factor in the psychological effects of dissociative anaesthetics
- NMDA receptor antagonists also stimulate prefrontal cortex and nucleus accumbens dopamine release, and this effect may be mediated by increased neural excitation in cortical regions
95
Q
Prefrontal cortical activation: a common neural mechanism for hallucinogenic drug effects?
A
- See brain activation pattern by PET scan measurements
- Synaptic model of neural effects to show serotonin to A receptors (excitiary effects)
- Reported reduced rather than increase cortical activation following psilocybin, using fMRI
96
Q
Adverse effects of dissociate anaesthetics and MDMA
A
- Dependence: Evidence from animal models and humans supports that both dissociative anaesthetics (ketamine, PCP) and MDMA can cause dependence, although the potential for dependence may be weaker than with other drugs of abuse (amphetamines, opioids, alcohol, nicotine)
- This may partly be mediated by the increased meso-corticolimbic dopamine release caused by these drugs
- Neurodegeneration: Studies in animal models have long shown that non-competitive NMDA receptor antagonists, including PCP, ketamine and MDMA cause neurodegeneration (MDMA-induced neurodegeneration is selective to serotonergic neurons)
- For MDMA, there is evidence that recreational usage of the drug also damages serotonergic neurons in humans
- ‘Ketamine bladder’/ ketamine-induced ulcerative cystitis (thickening of bladder wall and low bladder capacity), kidney dysfunction and ‘k-cramps’ (intense abdominal pain) have also been reported in chronic ketamine users
97
Q
MDMA-induced damage of serotonergic neurons
A
- Meta–Analysis of neuroimaging studies investigating serotonin transporter (SERT) expression in different brain regions
- SERT expression was decreased in MDMA users in multiple brain regions, including parietal, temporal, occipital, cingulate cortices, thalamus and hippocampus
- Participants were heavy MDMA users, so impact of moderate MDMA use remains to be examined!
98
Q
Hallucinogen/MDMA treatment of neuropsychiatric disorders
A
- Long-standing interest in use of hallucinogens and MDMA for psychotherapy, but properly controlled clinical trials have only started recently (2000-2010) because of the strict legal regulations of hallucinogens
- Classical hallucinogen/MDMA-assisted psychotherapy:
- Drug is used on one or a few occasions during psychotherapy sessions to overcome obstacles to successful psychotherapy and to facilitate a therapeutic experience
- Ongoing research on psilocybin/LSD for substance-abuse, severe depression and cancer anxiety & MDMA for PTSD and alcohol-dependence
- Limitations: small samples, often open-label or no placebo
- Careful clinical supervision required because of potential for ‘bad trips’
- MDMA toxicity for serotonergic neurons is of concern, although therapeutic effects of MDMA reported at substantially lower doses than those that have been shown to cause neurotoxicity
99
Q
Background and history: Cocaine
A
- White, crystalline powder derived from coca leaves
- An intense, euphoria-producing stimulant drug with strong addictive potential
- Principle coca-growing regions of South America
- Origins of consumption: Minors for traditional use to reduced hunger/ pain to help them endure harsh working conditions. Economic impact and cultural significance. Major international row in Bolivia for the right to chew coca leaves
- Original formular of Coca-Cola contained cocaine derived from coca leaves
100
Q
Methods of ingestion for cocaine: 3 ways
A
- Snorting: Leads to a high lasting 15-30 minutes but can cause severe nasal damage, including loss of smell and chronic nosebleeds
- Smoking: Results in a rapid, intense high lasting 5-10 minutes, with risks of severe respiratory issues and higher addiction potential
- Injecting: Produces an immediate, intense high but carries risks of overdose, infections, and disease transmission through needle sharing
101
Q
Neural mechanisms of cocaine
A
- Different routes of ingestion
- Cocaine inhibits transporter to increase synaptic levels and can also block nerve conduction by inhibition Na+ channels, local anaesthetic
- Dopamine reuptake transporters are blocked by cocaine, this results in increased dopamine in the synaptic cleft, leading to behavioural symptoms of cocaine use
- Microinjections to nucleus accumbens increase locomotor activity
102
Q
Chronic and recreational use for cocaine: behavioural, anatomical & neurological
A
- Behavioural: Restlessness, Confusion and disorientation, Paranoia and irritability, Insomnia, Social withdrawal
- Anatomical: Heart Damage. Blood Clots, Lung Diseases, Sinus Damage, Organ Stress
- Neurological: Dopamine System Disruption: Cocaine increases dopamine levels in the brain, leading to feelings of euphoria. Over time, this can disrupt the brain’s reward system, making it difficult to experience pleasure without the drug and contributing to addiction. Cognitive Decline: Users may experience problems with attention, memory, and executive functions, which can persist even after stopping cocaine use. Reduced Gray Matter Volume, White Matter damage, Shrinkage of the Prefrontal Cortex
103
Q
Treatment strategies for cocaine
A
- Antidepressants most prescribed
- Dopamine based substances that can reduce the euphoric effects of cocaine or reduce cravings during withdrawal
- Other therapies: CM, CBT, TCs
104
Q
Background and history: Amphetamines
A
- Amphetamines re a synthetic psychostimulant that’s chemical structure is like the neurotransmitter dopamine
- E.g. MDMA, meth, speed, ecstasy, molly
- Can be described for a range of medical conditions by doctors
- Similar chemical compounds that are naturally occurring have been consumed for more than 5000 years across the world
- Ephedra now banned appetite suppressant (used for asthma in 1920s)
- Led to search for synthetic substitute (amphetamine inhaler) and later marked for narcolepsy
- Obetrol was a popular diet pill in America in the 1950/1960s
105
Q
Methods of ingestion and effects: Amphetamines
A
- Recreational drugs are taken orally and takes up to 30 mins for effects to occur
- Due to half like of the drug (7-30hrs) users typically experience a longer high than users of drugs such as cocaine
- Has many medica properties and it’s used to treat and range of psychological conditions
- As a reactional drug it is taken to give a sense of euphoria, alertness, and to increase energy
106
Q
Neural mechanisms of amphetamines
A
- They inhibit transporter to increase synaptic levels, but also stimulates DA (dopamine) release
- They also actively release these neurotransmitters from nerve terminals
- Also prevent reuptake of Noradrenaline
- AMPH taken up by DAT, inside terminal provokes DA release. Plus DAT functions in reverse to further release DA
- Dopamine reuptake transporters are blocked by cocaine, this results in the increased dopamine in the synaptic cleft, leading to behavioural symptoms of cocaine use
107
Q
Chronic vs recreational use of amphetamines:
A
- Amphetamine psychosis (Griffith et al 1972) pp’s users had no prior history of psychosis and were given 10mg dextroamphetamine every hour for up to 5 days
- All become psychotic within 2-5 days
- Delusions mostly auditory, also included poisoning by experimenters and electric dynamo thought control
- (Inada et al 1992) 11 days of continuous iv infusion of amphetamines and results show produced tolerance
- (O’Daly 2014) Enhanced Neural Responses: Sensitization leads to increased activity in reward-related brain regions using blood oxygen level dependent (BOLD) signal during functional MRI scans
- Heightened Subjective Effects: Participants reported stronger subjective experiences of amphetamines after repeated exposure, correlating with changes in brain activity. The study involved a sensitizing dosage regime followed by acute amphetamine administration
- Implications for Psychiatric Conditions: Sensitization provides insights into the neurobiological mechanisms underlying addiction and psychiatric disorders like schizophrenia, highlighting altered dopamine signalling
108
Q
Behavioural symptoms from chronic vs reactional use of amphetamines: 7 symptoms
A
- Addiction and Dependence: Long-term use often leads to physical and psychological dependence. Users may feel unable to function without the drug and experience intense cravings
- Cognitive Impairment: Chronic use can impair cognitive functions (i.e. memory, attention, and decision-making abilities) This can affect daily activities and overall quality of life
- Mood Disorders: Amphetamine abuse is associated with mood swings, irritability, anxiety, and depression, and can become more severe over time
- Psychosis: Extended use can lead to amphetamine-induced psychosis (i.e. paranoia, hallucinations) like schizophrenia &requires medical intervention
- Aggressive Behaviour: Users may exhibit increased aggression and hostility, which can strain relationships and lead to social isolation
- Sleep Disturbances: Long-term use disrupts normal sleep patterns, leading to insomnia and other sleep-related issues
- Physical Health Decline: Chronic use can result in weight loss, malnutrition, and cardiovascular problems, further affecting mental health and behaviour
109
Q
Neurological symptoms from chronic vs reactional use for amphetamines: 5 symptoms
A
- Neurotransmitter Imbalance: Chronic use disrupts the regulation of dopamine, norepinephrine, and serotonin, leading to significant chemical imbalances and withdrawal symptoms
- Cognitive Impairment: Long-term use can impair memory, attention, and decision-making abilities, affecting daily life and mental health
- Amphetamine-Induced Psychosis: Prolonged use can result in paranoia, hallucinations, and delusions, resembling symptoms of schizophrenia
- Neurotoxicity: Extended use can cause nerve cell damage, increasing the risk of seizures and strokes
- Structural Brain Changes: Chronic use affects neural plasticity, leading to changes in brain structure and function, impacting overall brain health
110
Q
Clinical applications for amphetamines
A
- ADHD – increase focus and decrease inattention, hyperactivity and impulsivity. Low doses can reduce locomotor activity, however evidence is unclear on long term benefits
- Narcolepsy (pp who struggle with daytime sleepiness) - can stimulate wakefulness and allow then to function more adequately
- Binge eating disorder – increase dopamine and norepinephrine in the synaptic cleft and studies have shown a reduced in binge eating in rodents
111
Q
Treatment strategies for amphetamines
A
- Pharmacological – DA antagonists and vaccines
- Behavioural – avoid triggers for relapse
- Psychosocial – counselling and support
