Flashcards in Week 12 Substance Abuse Deck (102)
What can you tell me about the effects and uses of Hallucinogens?
*LSD, psilocybin mushrooms, DMT (“Ayahuasca”), mescaline (peyote), 2CB, 25i-NBOMe
*Agonists at 5HT-2a receptor
*Tolerance develops, but addiction extremely rare
*Traditional used in mystical practises; use in 1950s and 1960s for treatment of addiction and other psychotherapeutic applications; Current small studies of psychotherapeutic applications
*Overdose death rare or non-existent with older psychedelics, though some newer ones appear more physiologically dangerous (e.g. NBOMe series)
What can you tell me about dissociative Hallucinogens?
*NMDA receptor antagonists:
-Ketamine, PCP, DXM, nitrous oxide
-Some used medically as anaesthetics
-Addictive, range of physical, neural, cognitive, and psychiatric harms
*Kappa opioid agonists:
-Salvia divinorum: non-addictive, may be “anti-addictive”
What can you tell me about deliriant Hallucinogens?
*The “true” hallucinogens: Datura, belladonna alkaloids (e.g. scopolamine, atropine), diphenhydramine
*Antagonists at muscarininc cholinergic receptors
*Some alkaloids used (at very small doses) to treat motion sickness, insomnia, applications in anaesthesia
*High toxicity and unpleasant physical and mental effects limit “recreational” use:
-prolonged, often frightening delirium
What can you tell me about solvent & volatile hydrocarbon inhalants?
*Used industrially as solvents, propellants, fuels (e.g. in petrol, paint, paint thinner, aerosol sprays, industrial cleaning agents):
-Toluene: present in some types of glue, spray paint, petrol
-Butane: lighter fluid
*Mixture of depressant and deliriant effects
-“Sudden sniffing death”: sensitisation to adrenaline, leading to heart attack
What can you tell me about the long term effects of inhaling solvent & volatile hydrocarbon?
*Brain damage from repeated hypoxia
*Specific to chemical:
-Toluene: demyelination (white-matter damage): severe, long-lasting neuropsychological impairment (cognitive, movement, etc.)
-Carbon tetrachloride: potent liver toxin
-Benzene: carcinogenic, bone marrow toxin
-Recovery from neural impairments may take years, and may not be complete in most severely affected.
What is the biological model of drug dependence?
*Excitation of mesolimbic dopaminergic pathway (esp. projection from ventral tegmental area to nucleus accumbens shell) necessary (but not sufficient) for addiction.
-Signals reward value of stimuli
-Involved in learning associations between stimuli and rewards
-Energises attention towards novel stimuli, rewards and associated cues, and response to these
-Addictive drugs “high-jack” this system, increasing activity related to drugs and drug cues, reducing activation related to natural reinforcers.
-Important in early stages of establishing addiction: Once established, glutamatergic projection from prefrontal cortex to nucleus accumbens core maintains persistent craving and responsiveness to drug-related cues.
What is the Incentive-Sensitisation hypothesis of Drug Dependence proposed by Robinson & Berridge, 1993, 2000)
*Repeated stimulation of dopaminergic pathways by drugs leads to hypersensitivity to drugs and associated cues (sensitisation)
*Beyond-normal excitability to even mildly-associated cues, memories, etc.
*Long-lasting cravings, easily induced
*Independent of actual liking, tolerance, withdrawal
*Human users of opioids and cocaine show heightened neural and attentional response to drug-related imagery – some studies find association with relapse.
What is the "Final Common Pathway" for drug seeking proposed by Kalivas & Volkow (2005)?
*The amygdala experiences stress
*which leads to a cue in the ventral tegmental area & Basolateral amygdala
*triggering stress & cues in the prefrontal cortex
*triggering the 'final common pathway' which comprises:
-Nucleus accumbens Core
What is the frontocortical dysfunction caused by substance abuse?
*Hyper-activity in orbitofrontal cortex and anterior cingulate by drug-related stimuli similar to hyper-activity of these structures seen in obsessive-compulsive disorder.
*Reduced activity in these structures in cocaine and opiate-dependent samples during:
-exposure to pleasant stimuli
What is the evidence for Hedonic Allostasis in Humans?
*Anhedonia (reduced ability to feel pleasure):
-Widespread in substance-dependent samples
-May lead to drug use to “self-medicate”
-May reduce motivation to engage in activities that would compete with drug use.
-Predicts increased likelihood of relapse in tobacco smokers, increased drug use in opiate-dependent sample.
*Reduced response (subjective or neural) to pleasant imagery:
-Predicts increased likelihood of relapse in tobacco, alcohol, and opiate users
How do drugs effect the adolescent brain?
From puberty to late teens/early 20s:
*Maturation of frontal and temporal regions involved in:
*Drug use may disrupt this development, causing long-standing vulnerability to dependence
*Adolescent brain may generally be more vulnerable to adverse neuropsychological impacts of drugs
How does classical (Pavlovian) conditioning influence drug taking behaviours?
*Unconditioned stimulus (US: drug effects) becomes associated with temporally proximal conditioned stimuli (CSs: physical context, drug paraphernalia, people with whom drugs are used)
*CS alone can then elicit:
-Conditioned “A state”: drug-like physiological and psychological effects:
*Placebo response to denicotinised cigarette
* The ‘needle freak’ phenomenon
* Conditioned “B state”: conditioned tolerance, withdrawal:
* Drug-taking in a new environment may trigger overdose due to lack of cues to signal onset of drug effect.
* Addiction established in one context may not generalise to very dissimilar context: e.g. US soldiers heroin use in Vietnam in 1960s/70s
*Discomfort of withdrawal may also act as a US
How does Operant (Instrumental) conditioning influence drug taking behaviours?
*Positive reinforcement (achieve reward):
-Action (drug seeking, use) leads to drug effects
-If reinforced (pleasant effects) probability of repeating the action increases, if punished (feel ill) probability decreases
*Negative reinforcement (escape unpleasantness, physical or psychological):
-Action (drug use) in response to anxiety, withdrawal symptoms
-If reinforced (symptoms relieved), probability of repeating the response increases
*Environmental stimuli can control behaviour:
-“Pavlovian-instrumental transfer”: Classically-conditioned stimuli can energise instrumental responding, even after “extinction”.
What are the Capture Rates by Drug Type?
Proportion Used = PU
Proportion Dependent = PD
Dependence rate among users = DRAU
PU PD DRAU
Tobacco - 75/6% 24.1% 31.9%
Heroin - 1.5% 0.4% 23.1%
Cocaine - 16.2% 2.7% 16.7%
Alcohol - 91.5% 14.1% 15.4%
Cannabis - 46.3% 4.2% 9.1%
What are some of the genetic influences on the development of substance dependence?
Show greater concordance for identical twins than fraternal twins for:
*Heavy cannabis use
*Substance abuse in general
Which genes are potentially involved in the susceptibility to the development of substance dependence?
Variations in genes coding for:
*u opioid receptor: alcohol, opiates
*Dopamine D2, D3, and D4 receptors; dopamine transporter; enzymes involved in dopamine breakdown: alcohol, nicotine, opiates, stimulants
*Tryptophan hydroxylase (serotonin precursor), Serotonin receptors 1b and 2a, serotonin transporter: alcohol, opiates
*GABAA receptor subunits: alcohol
*Muscarinic acetylcholine receptor type 2: alcohol
*Cannabinoid receptor type 1: alcohol, stimulants
*Enzymes involved in alcohol metabolism: alcohol
*Enzymes involved in nicotine metabolism: nicotine
What are some of the epigenetic influences on the development of substance dependence?
*Change in function of gene, without change in gene itself (DNA and histone methylation, acetylation, phosphorylation, etc.)
*Constant process: interaction with environment, trauma, toxins, drugs. Changes last seconds to years.
*Human research on prenatal exposure to:
-Cannabis: associated with long-lasting changes in dopamine receptor expression
-Tobacco: associated with long-lasting changes in opioid transporter expression
What are some of the findings of epigenetic influences on the development of substance dependence in rats?
In adolescent rats, exposure to:
*THC: long-term changes to expression of genes coding for an opioid transmitter, increased heroin self-administration in adulthood
*Alcohol: changes in regulation of genes coding for dopamine and glutamate receptors in adulthood. Exposure to alcohol in adulthood only does not lead to same changes
*Some changes can be transferred between generations (not clear how):
-Morphine exposure in female rats in adolescence (before pregnancy) changes dopamine receptor sensitivity of offspring
How do expectancy effects influence the outcome of a drug taking experience?
Belief that a drug will have a certain effect influences likelihood of use:
*Those who believe that alcohol will reduce stress or increase social skills tend to drink more.
*Rates of cannabis use in US adolescents who perceived:
-“great risk”: 1.8%
-“no, little, or moderate risk”: 11.2%
How do personality factors influence the outcome of a drug taking experience?
*Low constraint (cautious behaviour, harm avoidance, conservative morality)
*Combination of sensation/novelty seeking and high positive affectivity
How do social & cultural factors influence the outcome of a drug taking experience?
*Acceptability: e.g. “wine-drinking countries” (e.g. France, Spain, Italy) vs. prohibitionist countries (e.g. Saudi Arabia, Iran)
-Social acceptability may differ by gender.
*Availability (prevalence, cost, etc.)
*Parental attitudes, substance use, monitoring of adolescents’ behaviour and peer networks.
*Peers’ attitudes and substance use
*Relationship breakdown associated with onset of alcohol abuse/dependence.
How do factors of environmental stress, deprivation, & enrichment influence the outcome of a drug taking experience as found by Bruce Alexander’s “Rat Park” experiments in 1970s?
*Compulsive morphine self-administration seen in socially isolated rats in barren, unstimulating cages, but little or no self-administration in rats housed in large cages with other rats, toys, etc.
-Moving rats from deprived to enriched environment after establishment self-administration reduced morphine use.
What do rodent models of facilitation by stress of learning drug self-administration tell us?
*Food restriction: opioids, alcohol
*Physical stress (tail pinch, electric shock, restraint): stimulants and opiates; increased motivation to seek opiates in those already trained.
*Social stress (aggression from dominant rats, mixed-sex housing, social isolation): opiates, stimulants, alcohol
*Witnessing another rat in distress: stimulants
*Prenatal stress (restraint stress applied to pregnant mother rat): stimulant self-administration in offspring
What do rodent models of protective effects of environmental enrichment tell us?
*Two months enrichment reduced behavioural and neural response to cocaine in mice
*Reduced contextual preference conditioning by cocaine in mice after 30 days enrichment
*Reduced contextual conditioning by heroin in mice raised from birth in enriched conditions
What are the risk & protective factors prior to birth?
-Family economic situation
-sole parent households
-Paternal genetic risk for alcoholism
-Maternal drug use in pregnancy
What are the risk & protective factors during infancy & pre-school?
-environmental tobacco smoke
-child neglect & abuse
What are the risk & protective factors age 4-11 years?
-early school failure
-Social & emotional competence
-Shy & cautious temperament
What are the risk & protective factors age 12-17 years?
-low involvement in activities with adults
-perceived & actual community drug use
-community disadvantage & disorganisation
-Availability of drugs
-positive media portrayal of drugs
-favourable parental attitude towards drugs
-impaired behavioural inhibition
-low parental conflict
-parental or adult communication
What is the treatment for substance dependence?
-Residential programs often 1-2 weeks
-Management of withdrawal symptoms
-First step, but generally high relapse rates if no further treatment
*Rehabilitation and therapeutic communities:
-Programs range from 1 month to 2 years
-Isolation from drugs and drug-using social networks (often rural locations)
-Intensive group therapy (and individual psychotherapy in some programs) to examine dynamics of addiction
-Structured activities and responsibilities
-High drop-out rate, benefits require long-term commitment