PSY12 Addiction

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 [blank_start]OK[blank_end]

Drugs ordered by overall harm scores and weights after normalisation (0–100) (Lancet, 2010) 1. [blank_start]Alcohol[blank_end] - 72/100 2. [blank_start]Heroin[blank_end] - 55/100 3. [blank_start]Crack Cocaine[blank_end] (smoked) - 54/100 4. [blank_start]Meth[blank_end] - 33/100 5. Cocaine - 27/100 6. Tobacco - 26/100 also cannabis - [blank_start]20[blank_end]/100, benzodiazepiones - [blank_start]15[blank_end]/100, methadone - [blank_start]14[blank_end]/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 [blank_start]control[blank_end] 2. [blank_start]social[blank_end] impairment 3. [blank_start]risky[blank_end] use 4. pharmacological indicators ([blank_start]tolerance and withdrawal[blank_end]). The severity of the substance use disorder is determined by the number of criteria the person meets: Mild - [blank_start]2 or 3[blank_end] criteria Moderate: [blank_start]4 or 5[blank_end] criteria Severe: [blank_start]6[blank_end] or more criteria Within the last 12-month period,

Probability of dependence when you have tried a drug once [blank_start]Tobacco[blank_end] - 32% [blank_start]Heroin[blank_end] - 23% [blank_start]Cocaine[blank_end] - 17% [blank_start]Alcohol[blank_end] - 15% Stimulants - 11% Anxiolytics and Cannabis - 9% [blank_start]Analgesics[blank_end] - 8%

Speed of drug entry into brain dictates the intensity of the ‘high’.

Tolerance • Can and often occurs in the absence of [blank_start]dependence[blank_end] – reduced response after repeated administration • Usually due to receptor/[blank_start]second messenger[blank_end] desensitization and [blank_start]down[blank_end]-regulation • [blank_start]Cross-tolerance[blank_end] – 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 [blank_start]pharmacokinetic tolerance[blank_end] - increased metabolism requires increasing doses to produce the same pharmacological effect. • [blank_start]Pharmacodynamic tolerance[blank_end] – increasing doses required to produce the same effect (learned behaviour)

Neurocircuitry of impulsive-compulsive behaviuor: • Associated with [blank_start]anticipation of the reward[blank_end] associated with drug, noy reward of drug • Impulsivity and compulsivity are hypothetically drives that are “[blank_start]bottom[blank_end]-up,” ie controlled by suppression of higher drives. 1 - impulsivity comes from the [blank_start]ventral striatum[blank_end] (NAc) 2 - compulsivity comes from the [blank_start]dorsal striatum[blank_end] 3 - different areas of [blank_start]prefrontal cortex[blank_end] act “[blank_start]top[blank_end]-down” to suppress these drives.

Addiction - shifts from [blank_start]impulsive to a compulsive[blank_end] drive, that comes with migration from [blank_start]ventral[blank_end] to [blank_start]dorsal[blank_end] circuitry. With chronic drug use, compulsivity develops, as the drive changes from [blank_start]seeking pleasure[blank_end] (impulsive) to seeking r[blank_start]elief from the withdrawal symptoms[blank_end] (compulsory) and anticipation of obtaining/consuming the drug.

Choose the incorrect statement.

Which of these is not a CNS stimulant/depressant?

Effects of Alcohol on reward: Alcohol either acts directly upon µ [blank_start]receptors[blank_end] or releases endogenous opiates such as [blank_start]encephalin and endocannabinoids[blank_end]. It causes increased [blank_start]DA[blank_end] release in [blank_start]NAc[blank_end]. Reinforcing effects also theoretically mediated by enhancing [blank_start]GABA[blank_end] inhibition and reducing [blank_start]GLU[blank_end] excitation. Factors Associated With Alcoholism • Environmental Factors 1. family or peer [blank_start]group[blank_end] behavior 2. availability of other reinforcers (e.g. recreational resources) 3. job/educational opportunities 4. conditioned stimuli ([blank_start]environmental cues[blank_end] paired with drug use) 5. [blank_start]Cost/ease of availability[blank_end] 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 [blank_start]anxious[blank_end] traits; risk-taking 3. Prior experience/expectations Tx: Naltrexone on the [blank_start]VTA[blank_end] reduces reward. Naltrexone - µ [blank_start]opiate antagonist[blank_end]: blocks [blank_start]pleasurable[blank_end] effects of alcohol, decreases cravings. [blank_start]Long acting benzodiazepines[blank_end] 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 [blank_start]temporal[blank_end] awareness, slows [blank_start]thought[blank_end] processes, impairs [blank_start]short[blank_end]-term memory • ‘high’ doses - can induce [blank_start]panic, toxic delirium[blank_end] and rarely [blank_start]psychosis[blank_end] • “[blank_start]amotivational syndrome[blank_end]” in frequent/heavy users characterized by the emergence of decreased drive and ambition, thus “amotivational.” Cannabidiol = [blank_start]allosteric[blank_end] negative modulator of [blank_start]CB1 and CB2[blank_end], potentially used to treat addiction, anxiety, psychosis and epilepsy

Cannabinoids in the mesolimbic pathway: • [blank_start]GABAergic[blank_end] interneuron feedback projections provide tonic [blank_start]inhibition[blank_end] of [blank_start]VTA dopaminergic[blank_end] neurons • [blank_start]CB1[blank_end] receptors mediate marijuana’s reinforcing properties Opioids in the mesolimbic pathway: Act on [blank_start]opioid neurons[blank_end] which arise in the [blank_start]arcuate nucleus[blank_end] and project to the [blank_start]VTA and NAc[blank_end]. Opioids bypass the enkephalins and [blank_start]directly[blank_end] stimulate receptors causing [blank_start]DA[blank_end] release = high. Nicotine & dopamine release: Nicotine - full agonist at α4,β2 [blank_start]nicotinic[blank_end] receptors on [blank_start]DA neurons in the VTA[blank_end] – cause prolonged channel [blank_start]opening[blank_end] until desensitization → prolonged burst of action potentials and consequently [blank_start]prolonged DA release[blank_end]

The ‘amphetamines’ • Increase [blank_start]synaptic[blank_end] conc. of DA, by" • inducing release of newly synthesized [blank_start]stores of intraneuronal DA[blank_end] • and inhibiting NA, 5-HT and DA [blank_start]reuptake transporters[blank_end] and VMAT • [blank_start]Methylphenidate[blank_end] is an uptake inhibitor only • Methamphetamine - similar to cocaine but [blank_start]longer[blank_end] lasting effects with less euphoria, associated with [blank_start]schizophrenia[blank_end]-like psychosis • Ecstasy - [blank_start]serotonergic[blank_end], dependence rare/debatable

The amphetamines ‘undesirable effects’ - change in [blank_start]structure and function[blank_end] of the human brain - ability to cause [blank_start]cerebral and/or myocardial[blank_end] infarcts ([blank_start]dead[blank_end] tissue from oxygen deprivation) Overdose treatment is with non-selective or [blank_start]Ca2+[blank_end] or ß-blockers, [blank_start]diazepam[blank_end] for seizures