Lecture 14. Substance Abuse, Dependence and Treatment Flashcards
What is substance abuse?
Refers to the harmful or hazardous use of psychoactive substances, including alcohol and illicit drugs
What is drug dependence?
The body’s physical need, or addiction, to a specific agent
What are the three main drugs people get hooked on?
Tobacco
Alcohol
Marijuana
How does drug dependence cause an enormous burden on society?
Through the repercussions on crime rate and healthcare
In 1999 what was the estimated economic cost of addiction in the US alone?
$80 billion
What was the estimated cost of illicit drug use in the UK in 2010/11?
£10.7 billion
What percentage of the cost of illicit drug use was due to health service use?
8%
What percentage of the cost of illicit drug use was due to enforcement?
10%
What percentage of the cost of illicit drug use was due to deaths linked to illicit substances?
28%
What percentage of the cost of illicit drug use was due to drug-related crime?
54%
What do drugs that are addictive have in common?
They produce euphoria by acting in the reward pathways in the brain
Their repeated use results in adaptation of circuits in the CNS. Once they are stopped there is withdrawal symptoms
They show tolerance so increased doses are required to produce the same effects
What pathways do addictive drugs act on to produce euphoria?
Reward pathways, “kidnap” brain reward circuits
Why do we need reward pathways?
To rewards us for signals that promote survival: Food consumption, drinking water, procreation, child nurturing/rearing
They reinforce behaviour for repetition
What are reward pathways also called?
Natural reinforcers
What do many addictive drugs increase?
Dopamine release by acting upon the ventral tegmental area (VTA)
What are the functions of the dopamine pathways?
Reward (motivation)
Pleasure, euphoria
Motor function (fine tuning)
Compulsion
Perseveration
What are the functions of the serotonin (5-HT) pathways?
Mood
Memory processing
Sleep
Cognition
What is salience?
Cognitive process
Confers a “desire” or “want” attribute, including a motivational component, to a rewarding stimulus
This is hijacked by drugs
What is the process of not taking a drug in a non-addicted brain?
Control and self-regulation from the prefrontal cortex (PFC)/cingulate gyrus (CG) overrides the drive to take the drug from the orbitofrontal cortex (OFC). No memories of taking drug that would be stored in the amygdala/hippocampus that would trigger salience from the nucleus accumbens (NAc)
What is the process of taking a drug in an addicted brain?
Memory of pleasurable effects from the drug from the amygdala or hippocampus triggers salience from the nucleus accumbens, triggering the drive to take the drug from the orbitofrontal cortex (OFC). The top-down control from the prefrontal cortex and the cingulate gyrus is overridden by the drug
What are the two types of dependence?
Physical and Psychological
What is physical dependence?
Results from adaptation by resetting homeostatic mechanisms in response to repeated drug use
Withdrawal syndrome: direct evidence of physical dependence
Withdrawal arises due to abrupt termination of drug use
Appearance of signs and symptoms during withdrawal are characteristic of the drug category
What is physiological dependence?
Motivational component, craving for the drug
Not always associated with physical dependence
Some drugs (cocaine) psychological dependence can persist for very long periods
What is innate tolerance?
Genetically determined sensitivity i.e. occurs after first dose
What is pharmacokinetic acquired tolerance?
Changes in metabolism and absorption reduce systemic blood concentration
What is pharmacodynamic acquired tolerance?
Adaptive changes within the system resulting in altered response to the drug i.e. receptor desensitisation
What is cross tolerance?
When two different classes of drug can interact and cause tolerance
What are examples of drugs that cause cross tolerance when taken together?
Cocaine and amphetamines
Benzodiazepines and barbiturates
What is the difference between the receptors of an addict and a normal person?
Addicts will have less receptors because more of the addicts receptors get endocytosed (take more drug but less receptors there)
What is cocaine derived from?
Leaves of the coca leaves
How is the euphoria caused by cocaine increased?
Increasing the speed the drug reaches the brain (IV/smoking/snorting)
What is the naïve cocaine binge cycle?
Euphoria ⇌ Dysphoria → Paranoia → Psychosis
What is the chronic use cocaine binge cycle?
Dysphoria → Paranoia → Psychosis (no euphoria due to tolerance and speed to dysphoria increased)
How does cocaine work?
By changing the uptake of dopamine and 5-HT, releases dopamine into nucleus accumbens (NAc) which influences motivation and goal-directed behaviour
What are the changes in the synapse caused by cocaine?
Changes in AMPAR levels
Impaired cystine-glutamate exchange
Changes in intrinsic membrane excitability of MSN
What effect does cocaine have on medium spiny neurones (MSNs)?
Increases the number of spines, huge increase in the number of synapses within the NAc
What is the criteria for effective treatment of addiction?
1) Quick and easy access to treatment.
2) Addresses all of the patient’s needs, not just their drug use (including mental health problems etc)
3) Patient must stay long enough in treatment.
4) Requirement for counselling and other behavioural therapies.
5) Medication is often an important part of treatment in combination with behavioural therapies.
6) Drug use during treatment must be monitored continuously.
7) Treatment programs should test patients for HIV/AIDS, hepatitis B and C, tuberculosis, and other infectious diseases as well as teach them about steps they can take to reduce their risk of these illnesses.
What are the pharmacological approaches to treating drug dependence?
Alleviate the withdrawal symptoms: methadone to blunt opioid withdrawal/nicotine patches/gum
Long term drug substitution: Methadone, buprenorphine, legal heroin, nicotine vaping
Blocking response to the drug: Naltrexone to block opioid effects
Aversive therapies Disulfiram to induce unpleasant response to ethanol
Reducing continued drug use (treat underlying mental health problems): Benzodiazepines to treat anxiety, anti-depressants etc.
When is disulfiram used and what does it do?
As a last resort for alcohol dependence because it breaks down alcohol through inhibiting aldehyde dehydrogenase
What are the problems with disulfiram?
Has to be taken daily
Symptoms can occur within 10 minutes and can last several hours
Extremely unpleasant
Very small amounts of alcohol can precipitate reaction ie in mouthwashes, medications etc
What are three stages of cocaine withdrawal and how long do they last?
Crash - Day 1-4 after a binge
Withdrawal - Week 1-10 after a binge
Extinction - Indefinite
What happens in the crash stage of cocaine withdrawal?
Lack of energy and motivation
Increased hunger
Irritability
Anxiety
Fatigue
Extreme depression
What happens in the withdrawal stage of cocaine withdrawal?
Trouble concentrating
Low energy
Changing moods
Dysphoria (general feeling of dissatisfaction with life)
Anxiety
Paranoia
Depression
Cravings
What happens in the extinction stage of cocaine withdrawal?
Low mood
Episodic cravings
Are there any pharmacological interventions that can be used to treat a cocaine addiction?
Currently no
What is contingency management (CM)?
Use a voucher-based system that rewards patients who abstain from cocaine and other drugs. On the basis of drug-free urine tests, the patients earn points, which can be exchanged for items that encourage healthy living, such as a gym membership, food vouchers etc.
What is cognitive-behavioural therapy (CBT)?
A talking therapy that helps with management of problems by changing the way to think and behave
CBT helps patients develop critical skills that support long-term abstinence, for example recognise the situations in which they are most likely to use cocaine, avoid these situations
What are the four opiate intoxication stages and how long do they last?
Rush - 45 seconds
Nod - 10-20 minutes
High - Several hours
Being straight - Up to 8 hours
What occurs during the rush phase of opiate intoxication?
Intense pleasure (likened to sexual orgasm)
Facial flushing
What occurs during the nod phase of opiate intoxication?
Sleepiness, to virtual unconsciousness
Calm, detached, uninterested in external stimuli
What occurs during the high phase of opiate intoxication?
General feeling of well being
(Shows tolerance)
What occurs during the straight phase of opiate intoxication?
Not experiencing a high etc but no withdrawal
What is the mechanism of opioid action?
Rush: activate opioid receptors on GABA neurons in the VTA which increase dopamine release into nucleus accumbens
What is the mechanism of opioid action in a chronic consumer?
Reduces cAMP production, adaptation occurs, thus when opioids are stopped get rebound cAMP leading to hyperactivity. Also get a fall in dopamine receptors (leads to tolerance)
When do untreated opiate withdrawal symptoms occur?
Within 8 hours
When do peak opiate withdrawal symptoms occur?
36-72 hours after
When do opiate withdrawal symptoms subside?
After 5 days
How is opiate addiction treated?
Alleviate withdrawal symptoms: methadone to blunt opioid withdrawal
Long term substitution: Methadone, buprenorphine, or legal heroin
What is methadone?
The medication with the longest history of use for opioid use disorder treatment, having been used since 1947
What are the characteristics of methadone used for maintenance and withdrawal?
Initiate at least 8 hours after last heroin dose (so don’t overdose)
Long half life means plasma concentration will rise during initial treatment (takes 3-10 days to stabilise). Thus may need to reduce dose
Withdrawal time: 4 weeks as an in-patient; 12 weeks in community
Enforced withdrawal is ineffective: if patient cannot tolerate withdrawal remain on maintenance therapy
Following withdrawal: need support for at least a further 6 months
If miss 3 days or more of regularly prescribed methadone at risk of overdose: loss of tolerance. If miss for more than 5 days test for illicit drugs
What is buprenorphine?
Preferred by some patients (i.e. if driving/skilled tasks for living) as less sedating than methadone
Can be given on alternate days and has fewer drug interactions than methadone. Lower risk of overdose than methadone
Can precipitate withdrawal in patients dependent on high doses of opiates
Currently available in two forms: alone (Subutex) and in combination with the opioid receptor antagonist naloxone (Suboxone)
Suboxone is designed to deter misuse: naloxone has no effect so long as the drug is taken orally, (poor absorption). If it is crushed, dissolved, and injected, the naloxone blocks the effect of the buprenorphine
What is naltrexone?
Naltrexone is an opioid receptor antagonist that does not produce tolerance but precipitates withdrawal
Poor adherence limits its effectiveness. As a result, there is insufficient evidence that oral naltrexone is an effective treatment
for opioid use disorder
Is given to patients to be used in case of accidental overdose
It is prescribed as an aid to prevent relapse in formerly opioid-dependent patients
What are the symptoms of nicotine withdrawal?
Headache, nausea, constipation or diarrhoea, fatigue, drowsiness and insomnia, irritability, difficulty concentrating, anxiety, depression
Symptoms wane after about 2 weeks
What are the treatments for nicotine addiction?
Nicotine replacement
Transdermal patches (replaced daily)
E-cigarettes: Mimic cigarettes. The dose of nicotine delivered is unclear and effectiveness has still not be determined. However recently been approved as withdrawal method by NHS
Varenicline: partial nicotine agonist
Bupropion: nicotine antagonist
What occurs in the process of nicotine replacement?
Reducing craving and physical withdrawal symptoms
Nicotine is poorly absorbed orally and short half life need to take oral preparations several times a day (chewing gum)
What percentage of the population are alcoholics?
4-5%
What are the pharmacological reatments for ethanol addiction?
Acamprosate calcium SR tablets : used along with counselling
Used after abstinence has been achieved
Weak NMDAR antagonist reduces craving
When used alone, acamprosate is not an effective therapy for most individuals; works best when used in combination with psychosocial support
Disulfiram (not used very much)
Alleviate withdrawal symptoms: benzodiazepines, clomethiazole, clonidine, propranolol
Opioid receptor antagonists reduce the effects of endorphins that play a role in the reward properties of alcohol
