Lecture 7 - Drugs and endogenous compounds in the brain Flashcards
What are the categories of long term effects of drugs?
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- Financial (pricy)
- Social (lose friends, or gain friends from it)
- Educational
- Emotional
- Physical
- Behavioural
- Political
What are Opiates?
They reduce pain - also know as analgesic’s
Examples: heroin, opium, morphine
What are Stimulants?
Increase alertness, intensify mood
Examples: Amphetamine, cocaine, caffeine nicotine
What are CNS Depressants?
Increase drowsiness, relax you
Examples: Barbituates, Alcohol, Benzos
What are Hallucinogens?
Alter perceptions and thoughts
Examples: LSD, Ketamine, Mushrooms
What are Cannabinoids?
Examples: Cannabis, hashish, skunk
What are the 4 drug related things that are illegal
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It is an offence to:
- unlawfully possess a controlled drug
- possess with intent to supply
- unlawfully sell/give/ share
- allow premises you occupy/ manage to be used for smoking/ drugs
Which drugs are illegal is often based upon?
- Based on harmfulness
- Social decision - e.g. may be influenced by religion, in muslim countries, alcohol is illegal
Outline the case of David Nutt
Chairman of the Advisory Committee on the Misuse of Drugs (ACMD) - fired in 2009 for publicly saying:
- Alcohol and tobacco cause more harm than LSD, ecstacy and cannabis
- came after a reconsideration of where cannabis should be classed. It kept switching from B to C
- research showed it had minimal psychosis risk, he argued it should be C, but government said B
- Debates between scientists and politicians
What are short term side effects of cannabis use?
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- Increase heart rate
- risk of lung cancer
- small risk of psychosis
- anxiety, panic attacks, paranoia: THC - the primary psychoactive ingredient
- confusion/ loss of memory or concentration
- Amotivation/ apathetic
How potent is Fentanyl?
100% more potent than morphine as an analgesic
50% more potent than heroin
Very very dangerous, lethal dose is absolutely tiny
What % of 16-24 year olds had taken an illict drug in the last year
1 in 5, 80% of 16-24 had taken an illicit dtug in the last year
When people are seekng treatment, what is it mainly sought for?
Opiates
What happens to an alcoholics brain?
Alcohlic brain has a bit of atrophy - gaps in the brain
As Blood Alcohol Content increases, what happens
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Impairment increases
- Mild impairement (0.00-0.05%) - euphoria, less anxious
- mild impairements (speech, cognitions etc), feel relaxed - Increased Impairment (0.06-0.15%) - judgement and coordination impaired
- sometimes increased Aggression
- further impairement
- risk of injury to self or others - Severe Impairement (0.16-0.30%) - sedation
- Significant impairement
- very bad driving
- judgement and decision making impaired
- unconcious, vomiting
- signs of alcohol poisoning - Life threatening (0.31-0.45%) - depressed respiration
- loss of conciousness/ coma
- could die
- suppression of vital life functions
What does alcohol do to neurotransmitters in the brain?
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- Increases Dopamine
- Decreases Serotonin
- Stimulates Optiate Neuropeptide release
- Enhances GABA receptor function (inhibit the inhibitor further)
- Inhibits Glutamate receptor (inhibit excitatory)
What are endogenous opiods?
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- Produced in pituitary glands
- Endophines, enkphalines, demorphines - natural pain killers
- Released in brain when we drink alcohol, might stimulate further drinking, releases dopamine
What impact does alcohol have on endogenous opioids and neurotransmitters? ????? ????? ????? ????? ??????????
- Drinking Alcohol releases endogenous opiods
1. These release Dopamine - increased DA in pleasure/ reward areas, e.g. nuclues accumbens
- Inhibts serotonin
- serotonin is usually a behavioural inhibitor, so when you take it away, you see increases in impulsivity and aggression - Endorphines and Enkephalins are natural neural peptides
- bind to opiate receptors, produce euphoric effects
- Euphoria stimulates further drinking
What are the 3 Endogenous opioids?
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- Endorphines (reward pathways)
- Enkephalins (reward pathways)
- Demorphines (Dysphoria - unhappiness)
What do the first 2 Endogenous opioids do in the brain
Endoprhines & Enkephalins
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- They activate the mesolimbic dopamine system (VTA -> NAc) - this is a reward pathway
- this is implicated in drug addiction due to the increased dopamine
What does the 3rd Endogenous opioids do in the brain?
Demorphines
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Decreases dopamine levels released by the NAc
- you can decrease Da by activating Dynorphines
What does Alcohol do to the Endogenous opioids
It can interfer with these 3 Endogenous opioid mechanisms
- and this can change dopamine levels
- e.g. getting reward, or dysphoria
What impact does Alcohol have on opiod binding and production
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Alcohol has direct (either acute - short term, or chronic - long term) effects on:
- Binding properties of opioid receptors
- Opioid syntehesis and secretion
- Basically just impacts how much our natural opiods can impact on the brain
What has research into alcohol self-administration in rodents and primates found?
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found:
- Low doses of morphine = increased alcohol intake
- high doses of morphine = decreased alcohol intake
- Conversely, opiod antagonists (binds to receptors but doesnt activate them) would decrease alcohol consumption
- Shows that the effects of alcohol/ willingness to drink alcohol is interacting with these opioid effects
- Alcohol depends on activity of endogenous opiod reward system. Alcohol consumptions may serve to compensate for inherent deficits in this system.
What have Opiod Agonists been used for?
Have been used to prevent relapse in alcoholics
- they bind to receptors but dont activate them
- stopping the activation of this receptor
Which receptors are involved in alcohol and opioids?
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μ-opioid (mu-opioid) receptors in the VTA and/or δ-receptors (delta receptors) in the NAC
- both are targets for endogenous endorphin
Outline Endorphines
- They are associated with pain, pleasure, exercise and reward
- Anything that puts you past a threshold will release endorphins
- Brain has similar response to pain as to pleasure
Outline runners high
Feel high after a run - not clear if it is endorphines or something else (anandamide)
- Unclear whats going on in the brain after a run
- X - can people become exercise dependent as it brings a high
What are 7 examples of Class A?
- heroin
- Cocaine
- Crack
- XTC
- LSD
- Mushrooms
- Methamphetamine (injection)
What is the penalty for Class A?
Penalty for having/ doing/ possessing = 7 years prison (max) and an unlimited fine
How does cocaine work in brain?
Binds to DA reuptake sites - impacts the amount of DA we have in the brain
What are some of the adverse effects of cocaine on the brain?
- Anxiety
- Impact on uptake of NE and 5HT
- Cerebral grey matter atrophy
- Emotional instability
- Psychosis
- Inability to feel pleasure
- Severe depression
What did the 2013/2014 opiod death in USA look like?
- Death from opiods are increasing
- but fentanyl deaths doubled in one year
- 20,000 OD in USA one year
- and these are prescription pain relief drugs!
Outline Metabolisim of heroin
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Why opiods are so harmful to the brain:
Codeine is a pain relief drug, and heroin is an illegal drug - but when they are metabolised (in liver cells), they read as Morphine ob lood tests,
- depends on your genes and enzymes, but this can happen:
Heroin + Codeine = morphine
Outline the CYP2D6 Genotype
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Our genes determine how we respond to certain drugs, the CYP2D6 Genotype is involved in metabolising codeine into morphine. There are two variants of this genotype
- Fast Variant - rapid metabolisers
- Can show a higher Morphine: codeine ratio - leading to a higher reading - Slow variant
- can lead to a lower mor:cod ratio - leading to a lower reading
Outline what the Morphine: Codeine is used for?
The morphine:codeine ratio is often used to assess whether someone has used morphine or heroin
- the cut off point is 1 - so it its above 1, they have likely used heroin recently
- debate its too low and they are reading that they have had heroin, but in fact it was just codeine
What are the functions of the Dopamine Pathways?
- Reward (motivation)- ML
- Pleasure, euphoria - ML
- Motor function (fine-tuning) - NS
- Compulsion - MC
- Perserveration- MC
What are the functions of the Serotonin Pathways
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- Functions
- Mood
- Memory processing
- Sleep
- Cognition
What do Class A drugs do to mood over time
Get the initial short term high, but then later on, due to the withdrawal of the drug you get that depressed mood
On top of mood, what else does XTC-MDMA impact?
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Cognitive functions, like memory
- XTC users make more errors on all types of memory task compared to controls
What do XTC users brains look like compared to non-users
Much more atrophy - shows class A drugs, and hallucinogens have long term imapcts
What are 6 examples of Class B drugs?
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- Amphetamine
- Methylphenidate
- Cannabis
- Codeine
- Ketamine
- Barbituates
What is the penalty for Class B drugs?
5 years in prison (max) and an unlimited fine
What is the impact of amphetamines on physical apperance?
Quite drastic effects on physical appearances
- teeth & fums: dry mouth + grinding teeth, lack of oral hygeine
- Gaunt: loss of fat in your face, because meth suppressess appetite and causes undernourishment
- Can cause achne, and poor skin health - get dry and itch skin
- Facial Scarring - get sensation of bugs under the skin
What % of meth takers have psychosis
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20% of meth takers estimated to experience psychosis
What are 3 examples of Class C drugs?
- Mild Amphetamines (diet pill, Khat)
- Anabolic steroids
- Benzodiazepines (e.g. valium)
What are the penalty for Class C drugs?
2 years max
- but usually just a warning
not a bad lawful implication, but quite an impact on your brain
Briefly outline the balance of excitatoy and inhibitory NT
- Glutamate mediates excitatory side
- allows positive Ions to enter and excite it - GABA mediates inhibitory side
- opens up GABA receptor, allowing Chlorine (anion) to come in, and inhibit the brain
they work together in a balance so we can function normally
How do Benzo’s effect the brain
They attach onto the inhibitory GABA receptors and increase their activation - meaning more inhibitory effects can occur
- increases the potency of GABA
- as you need a certain amount of GABA to open the receptor, Benzo’s act like GABA, and open it up sooner
What is the long term impact of Benzo’s on memory
The memory process:
- Acquire
- Short term memory
- Convert it to LTM
- After a long time of Benzos, you lose the ability to convert STM into LTM’s. You can acquire and hold in STM but cant convert into LTM
- Causes anterograde amnesia - cant form new memories
Outline GABA
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Associated with:
•Anxiety - Benzo’s inhibit cell and reduce rate of firing so help here
•Motor Function
•Depression - Ketamine helps with depression perhaps because it enhances GABA transmission and perhaps Glutamate - interacts with this balance - can cause long term memory issues
- In theory Benzo’s should help but they dont
How does Ketamine Help depression?
- Does it very quickly, within hours, unlike SSRI
- By enhancing GABA transmission / affecting glutamate?
- Can cause memory loss, sedation, pain relief
