Drug Dependence & Addiction Flashcards
What is the definition for addiction?
What is the DSM definition?
What are depressant examples?
Stimulants?
Psychedelics?
Inhalants?
What is the global attitude towards alcohol, tobacco & drugs?
Substance use disorder
2+ symptoms = mild, 4+ moderate, 6+ severe - in the past 12 months
ethanol, opiates e.g. heroin, barbiturates
cocaine, amphetamine * nicotine (both stimulant and depressant) * cannabis (weak depressant)
LSD, mushrooms
Glue, solvents (poppers)
Younger generations consuming less due to education, but cannabis use is increasing globally
What is a reward?
What can animals do in response to reward?
How can you define reward circuits?
Where are the most effective sites?
How does reward occur?
objects/stimuli/activities with positive value that incites animals to switch from one behaviour to another
learn to predict reward occurrence & exhibit approach behaviour towards that reward - long term effect
Rodent will press lever causing direct electrical stimulation of neurones in reward areas - find brain regions that sustain electrical self stimulation
along medial forebrain bundled
reward stimulation activates dopaminergic neurones in ventral tegmental area (VTA) which projects to the nucleus accumbens (Nac) resulting in increased dopamine release
What is the Mesocorticolimbic Dopamine Pathway?
What drugs increase dopamine levels and where does dopamine end up?
What did Wise and Bozarth conclude in 1981?
mesolimbic (dopamine from VTA to Nac) and mesocortical (VTA to PFC) pathways
Amphetamine, morphine, ethanol & nicotine - Nac in striatum
“The substrate mediating rewarding actions of opiates and psychomotor stimulants also
mediates the rewarding action of more natural rewards like food and water.”
What is withdrawal theory?
What are the 2 problems with the theory?
What is Incentive Sensitisation Theory?
What is liking?
What is wanting?
How can wanting lead to long lasting changes?
abrupt cessation of heroin and alcohol (and others) produces a profound withdrawal syndrome - such that abuse is maintained by reducing the withdrawal symptoms
- Doesn’t predict relapse in nicotine dependence (returns to abusive levels after reduction)
- People develop tolerance & withdrawal to morphine but not addicted when they leave - associated with pain
Incentive salience = behaviour that motivates a behaviour towards/away an object/stimulus
is mediated by smaller neural systems not dependent on dopamine
mediated by large neural systems including the mesolimbic dopamine pathway (and as a result a lot of dopamine release)
Makes people hypersensitive (neural sensitised) to drug-related stimuli - long-lasting changes & excessive amplification of wanting
What is Everitt & Robbins (2005) idea of habit theory?
How does the neuronal control change?
What is therefore the VTA involved in?
What is therefore the substantia nigra involved in?
What is Hyman et al. (2006) idea of addiction?
Drug is voluntary but becomes habitual & compulsive through palvonian & instrumental learning processes - such that the goal of the behaviour has been devalued through tolerance & reward
Transition in control of neurones more dorsally - such shift from PFC to striatum and ventral striatum to dentral striatum
Dopamine release & neurones towards Nac for stimulant reinforcement & conditioned reinforcement
Neurones to dorsal striatum - involved in habits
usurpation of normal systems of associative memory underlying reward related learning and behaviour
What was the 19th century idea of addiction?
1987?
1997?
What did Leshner believe that lead to the BDMA model?
Disease - Magnus Huss
Drug dependencies defined as disease by AMA
Leshner – “Addiction is a Brain Disease, and it Matters”
Drug use is initially voluntary, but move to addiction characterised by compulsive drug seeking & use - caused by changes in the brain
What are the 4 theories of addiction which BDMA is? (brain disease model of addiction)
- To begin with, drug use (voluntary) causes acute dopamine release.
- Extensive long term drug use causes neurobiological changes to happen in various
brain regions. - These brain regions control/are the reward system (mesolimbic dopamine
pathway) and the executive-control system (prefrontal areas). - Therefore, people then become hypersensitive to drug reward/drug-related stimuli
(and hyporesponsive to non-drug rewards) and have such impaired self-control,
that they are ‘diseased’ and they cannot control their drug use.
What happened when Volkow et al (1990). had 10 people addicted to cocaine & 10 controls?
What does this show?
What does cocaine do?
What is methyphendiate?
What happened when cocaine abusers had methyphendiate?
What else was shown with d2 receptors in caudate & putamen?
Compared dopamine d2 receptor binding in striatum - showed that there was a reduced density/binding in cocaine abusers
Cocaine stiatum had lower dopamine binding & hence altered reward system
Dopamine reuptake inhibitor
Dopamine reuptake inhibitor but acts slower
Less sensitive to it in striatum than controls due to altered reward system
Diminished dopamine d2 receptor in cocaine abusers
People with addiction have the following 3 changes to their brain:
Therefore how can addiction be treated?
What is PET & what is it used to measure?
- Reduced d2 receptor density in the striatum (mediates reward)
- Reduced functional sensitivity when earning natural rewards.
- Reduced inhibitory control and associated impaired prefrontal functioning.
Targeting these areas
radiotracers which label dopamine receptors, dopamine transporters, precursors of dopamine or compounds which have specificity for the enzymes which degrade dopamine
What drugs do not have suitable evidence with PET for producing high amounts of extracellular dopamine in the striatum? 4 (nutt et al 2015)
Therefore can these be used for addiction studies?
What is another difference between healthy controls & addiction?
In what people has these been found in?
Nicotine
* Ketamine
* THC
* Heroin (aka diamorphine)
no - need large amounts of extracellular dopamine release
Differences in D2/D3 receptor density
Dependent cigarette smokers, chronic opiate users & cannabis users
What happened during the vietnam war? 1972-1974
What happened after a year & what does this show?
Opium & heroin use such that when came home 20% addicted
1% addicted - context & environment is key
What are the two treatments for alcohol addiction & do they work?
What is the problem with treatments for cocaine addiction?
- Naltrexone - reduces risk alcohol addiction in placebo by 83% - non selective opioid antagonist (reduces rewarding effects)
- acamprosate - work on GABA-A receptors (inhibitory) - decreases brain glutamate
None - No significant effect of: anti-convulsants, antidepressants, antipsychotics, dopamine
agonists & no evidence of psychostimulants improved cocaine abstinence
what is Varencline (for nicotine addiction)?
bupropion?
What about therapy for nicotine dependence?
Which is the best for nicotine addiction?
partial nicotinic receptor agonist
noradrenaline & dopamine reuptake inhibitor
nicotine replacement therapy
Varenicline - at standard dose increased the chances of successful long-termsmoking cessation between two- and three-fold compared with pharmacologically unassisted quit
attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT
How can CBT aid addiction?
Motivational Interviewing?
Contingency Management?
aims to help you deal with problems in a more positive way by breaking them down into smaller parts - deal with current problems rather than focusing on issues in past to improve state mind practically & avoid high risk situations where look to drugs for abuse
directive, client-centred counselling style for eliciting behaviour change by helping clients to explore and resolve ambivalence (mixed ideas). It is most centrally defined not by technique but by its spirit as a facilitative style for interpersonal relationship
Provide financial rewards to people when they provide drug-free urine samples - effective but only during treatment (can relapse)
How can serotonergic psychedelics be used to treat addiction?
How can ketamine treat alcohol dependence?
How are treatments most effective?
What is promising?
5ht-1a receptor agonists - LSD used to treat alcohol dependence & psilocybin can treat alcohol dependence & nicotine dependence
(Johnson et al., 2015) – at 6 months, 80% of
smokers were abstinent. Substantially more than currently approved treatments, e.g. varenicline (35%). Greater “mystical experiences” are associated with greater reduction in smoking
combination with psychological
therapy, can help treat alcohol dependence, cocaine
dependence and heroin dependence - NMDA-antagonist
Classical treatments with psychosocial treatment
ketamine & psilocybin have larger & more permanent effects but unsure as to how addiction mechanism works
