Assessable Tasks
By the end of this lecture you will be able to:
• Describe the epidemiology and differences between recreational drug use and the diagnosis of addiction
• Describe the underlying mechanisms and site of action for commonly used recreational drugs
• Identify their main wanted/unwanted effects

❌

Drugs ordered by overall harm scores and weights after normalisation (0–100) (Lancet, 2010)
1. ❌ - 72/100
2. ❌ - 55/100
3. ❌ (smoked) - 54/100
4. ❌ - 33/100
5. Cocaine - 27/100
6. Tobacco - 26/100

also cannabis - ❌/100, benzodiazepiones - ❌/100, methadone - ❌/100

DSM-5 Criteria for Substance Use Disorders:
The 11 criteria for substance use disorder are divided into four categories of behaviour related to the substance use:
1. impaired ❌
2. ❌ impairment
3. ❌ use
4. pharmacological indicators (❌).
The severity of the substance use disorder is determined by the number of criteria the person meets:
Mild - ❌ criteria
Moderate: ❌ criteria
Severe: ❌ or more criteria
Within the last 12-month period,

Probability of dependence when you have tried a drug once
❌ - 32%
❌ - 23%
❌ - 17%
❌ - 15%
Stimulants - 11%
Anxiolytics and Cannabis - 9%
❌ - 8%

Tolerance
• Can and often occurs in the absence of ❌ – reduced response after repeated administration
• Usually due to receptor/❌ desensitization and ❌-regulation
• ❌ – repeated use of a drug in a given category confers tolerance to the drug being used AND others within the same pharmacological category.
• Metabolic or ❌ - increased metabolism requires increasing doses to produce the same pharmacological effect.
• ❌ – increasing doses required to produce the same effect (learned behaviour)

Neurocircuitry of impulsive-compulsive behaviuor:
• Associated with ❌ associated with drug, noy reward of drug
• Impulsivity and compulsivity are hypothetically drives that are “❌-up,” ie controlled by suppression of higher drives.
1 - impulsivity comes from the ❌ (NAc)
2 - compulsivity comes from the ❌
3 - different areas of ❌ act “❌-down” to suppress these drives.

Addiction - shifts from ❌ drive, that comes with migration from ❌ to ❌ circuitry. With chronic drug use, compulsivity develops, as the drive changes from ❌ (impulsive) to seeking r❌ (compulsory) and anticipation of obtaining/consuming the drug.

Effects of Alcohol on reward:
Alcohol either acts directly upon µ ❌ or releases endogenous opiates such as ❌.
It causes increased ❌ release in ❌. Reinforcing effects also theoretically mediated by enhancing ❌ inhibition and reducing ❌ excitation.

Factors Associated With Alcoholism
• Environmental Factors
1. family or peer ❌ behavior
2. availability of other reinforcers (e.g. recreational resources)
3. job/educational opportunities
4. conditioned stimuli (❌ paired with drug use)
5. ❌ of alcohol
• Host Factors - Genes:
1. + and - for alcohol (reduced gene expression for alcohol dehydrogenase reduced
sensitivity to alcohol phenotype in alcoholics);
2. Antisocial or ❌ traits; risk-taking
3. Prior experience/expectations

Tx: Naltrexone on the ❌ reduces reward.
Naltrexone - µ ❌: blocks ❌ effects of alcohol, decreases cravings. ❌ used to mediate ‘withdrawal’ over a few weeks to prevent symptoms like life threatening seizures.

Cannabis - THC and cannabidiol
• ‘normal’ dose - sense of well-being, relaxation, friendliness, loss of ❌ awareness, slows ❌ processes, impairs ❌-term memory
• ‘high’ doses - can induce ❌ and rarely ❌
• “❌” in frequent/heavy users characterized by the emergence of decreased drive and ambition, thus “amotivational.”
Cannabidiol = ❌ negative modulator of ❌, potentially used to treat addiction, anxiety, psychosis and epilepsy

Cannabinoids in the mesolimbic pathway:
• ❌ interneuron feedback projections provide tonic ❌ of ❌ neurons
• ❌ receptors mediate marijuana’s reinforcing properties

Opioids in the mesolimbic pathway:
Act on ❌ which arise in the ❌ and project to the ❌. Opioids bypass the enkephalins and ❌ stimulate receptors causing ❌ release = high.

Nicotine & dopamine release:
Nicotine - full agonist at α4,β2 ❌ receptors on ❌ – cause prolonged channel ❌ until desensitization → prolonged burst of action potentials and consequently ❌

The ‘amphetamines’
• Increase ❌ conc. of DA, by"
• inducing release of newly synthesized ❌
• and inhibiting NA, 5-HT and DA ❌ and VMAT
• ❌ is an uptake inhibitor only
• Methamphetamine - similar to cocaine but ❌ lasting effects with less euphoria, associated with ❌-like psychosis
• Ecstasy - ❌, dependence rare/debatable

The amphetamines ‘undesirable effects’
- change in ❌ of the human brain
- ability to cause ❌ infarcts (❌ tissue from oxygen deprivation)

Overdose treatment is with non-selective or ❌ or ß-blockers, ❌ for seizures