Lecture 31 - Emerging Therapies for Drug Dependence Flashcards
Which is the biggest drug problem?
Alcohol
Define the following terms:
- Drug use
- Drug misuse
- Tolerance
- Substance dependence
- Substance addiction
-
Drug use:
- Use sanctioned by societ
-
Drug misuse
- Unsanctioned use
- Involves risk to individual
-
Tolerance
- Recquiring increased dose to elicit same effect
-
Substance dependence
- Neuroadaptatation,
- Daily physical need for the drug
-
Substance addiction
- Dependence + harm(s)
Define substance use disorder
Give some epidemiological stats on SUD
Use of a drug resulting in harm
Epidemiology:
- High prevalence, endemic
- Lifetime prevalence 15-20%
- Dependence 6-8%
- 16% nicotine dependence
- Endemic:
- Cannabis
- Methamphetamine
- Rising epidemic
- Synthetic cannabinoids
- Fly under the radar, because these compounds aren’t picked up by routine drug testing
- Most establish before the third decade of life
All drugs of abuse …
- Target the brain’s reward pathways
- Increase endogenous dopamine in the synapse in the nucleus accumbens
What is the normal role of the brain’s reward pathways
- Engender the ‘pleasure’ experienced with normal activities or experiences
- Food, music, art
Outline the reward pathway in the brain
- VTA
- Ventral tegmental area
- Located on the floor of the midbrain
- Dopaminergic projections to:
- Nucleus accumbens
- Frontal cortex
Outline the areas in the brainstem
- Midbrain
- Pons
- Medulla
Describe physical changes to neurons in neuroadaptation
- Spine growth
- Neurons sprout spines, become bushier
- Increases sensitivity to signals from VTA
- **Delta FosB **involved
- ⇒ drug sensitivity
- Receptor density
- Decreased dopamine receptor density in the brain
Outline the role of genetics in addiction
- A number of vulnerable genotypes exist
- Genetics does play a significant role in the aetiology of addiction
- Of course, the environment must be ‘right’ - ie the drug must be available
There has been much research into the genetics of drug addiction
COMT
- Genetic variation in COMT influences the harmful effects of drugs
- Homozygous individuals are 4-6 x more likely
to manifest the psychotic reaction after (even brief) exposure to cannabis
Therapeutic application
- Genotype can predict efficacy of response to treatment
- eg. Alcohol dependence treatment with Naltrexone
- Fewer relapses in individuals with Asp40, compared to Asn40
Describe the aetiology of drug dependence
Multifactorial
- Genotype + environment (psych-soc) = phenotype
- Addiction isn’t caused by a single event
- Analogous to other chronic conditions (CVD etc.)
Compare GP confidence to treat across various chronic diseases
Most confident to least confident
- Hypertension
- T2DM
- Depression
- Prescription drug abuse
- Alcoholism
- Illicit drug use
What is unusual about nicotine addiction?
- Most smokers are addicted
- Compared to other drugs, where the majority of drug users won’t become addicted (eg cannabis, methamphetamine)
- This is thought to be due to the frequent bolus dose taken per day
Describe therapy for nicotine dependence
- Rehabilitation
- Cognitive behavioural therapy (CBT)
- Relapse prevention strategies (RP)
- Nicotine replacement therapy (NRT)
- Triples quit rates
- First line therapy for nicotine dependence
- Gum, lozenge, spray, patches
- Relapse prevention pharmacotherapy
- “Anti-craving”
- Varenicline
- Bupropion (Champix)
- Immunotherapy
- Vaccine in trials
- Controversy
Describe the effects of Methoxsalen
- MOA
- Slows the metabolism of nicotine
- Nicotine remains in the blood longer
- Individuals can more easily cut down
- However, not used in Australia, as NRT is more effective
- With increasing dose:
- Decreasing desire to smoke
- Increasing blood nicotine concentration
What are the risks of cannabis use?
- Psychosis
- Liver risks
