Drug Types Types –Psychoactive – alters mood or consciousness; affects neural functioning –Non-psychoactive – e.g., antibacterial Classes of psychoactive drugs –Sedative-Hypnotics E.g. Barbiturates, Anti-anxiety, alcohol Reduce anxiety (low), sedation (medium), anesthesia (high) –Behavioral Stimulants and Consultants E.g. Amphetamines, Cocaine, Caffeine, Nicotine Increase activity (increase motor activity or counter fatigue)

Drug Types Classes of psychoactive drugs –Narcotic Analgesics E.g., Opium, heroine, morphine, codeine Relieve Pain –Antipsychotic Agents E.g., Lithium, haloperidol, reserpine Used to treat schzophrenia –Psychedelics and Hallucinogens E.g., LSD, Marijuana, MDMA (Ecstasy) Alter sensory perception and cognitive processes

Drug Harm Nutt et al. (2007) – The Lancet –Two sets of experts rate drugs on dimensions of harm Physical Harm – acute, chronic, Intravenous Dependence – pleasure intensity, psychological dependence, physical dependence Social Harm – Intoxication, other social harm, health-care costs

Motivation Initial (Early) Motivation Motivation –Approach – using to increase positive/mood feelings –Avoid – using to escape negative mood/feelings »More likely to become addicted Many factors moderate likelihood of initial use –Self-medication – can be used to alleviate negative state such as anxiety or depression (e.g., high anxious people more likely to smoke & use alcohol) –Temperament – people high in novelty more likely to try –Social Aspects – peers and/or parents

Motivation Continuing Motivation (Craving) –Physical Dependency Body adapts to presence of drugs with physical changes (e.g., may change number of receptors) Drug is required for “normal” operation Tolerance –Greater doses to have same effect Withdrawal –Symptoms associated with cessation »E.g., headaches, shakes, pain, depression, anxiety, etc. –Source of motivation – people take drug to prevent negative symptoms

Motivation Continuing Motivation (Craving) –Psychological Dependency Desire for drug in absence of physical need –Can last months or years Can be triggered by cues in environment –Classical conditioning –pleasure of drug associated with context, stimulus, or event –Desire for drug can be evoked by conditioned cue

Tolerance Decreased responsiveness to same dose of drug –More likely with constant drug use Types –Metabolic Increasing enzymes to destroy drug –Cellular Cells adjust to be minimize effects –Learned Covering outward signs of intoxication Training rats to walk & avoid shock –Training - Alcohol before training, after training; or no alcohol –Test – alcohol before – rats who had trained with alcohol did better than other two conditions

Sensitization Increased responsiveness to same dose of drug –More likely with occasional drug use –Context is important Sensitization seems to occur when taken in novel environments –Very long lasting Evidence that sensitization may be due to dendrite growth

Routes of Drug Administration Chemical properties of drugs affect how they can be administered –Solubility – fat or water –Acidity – acid or base Modes –Injection (fastest) –Absorption Lungs Mucus membranes (nose) –Ingestion (slowest)

Your Interests Top Individual Drugs –Heroin (Narcotic) –Cocaine (Stimulant) –Marijuana (Psychedelic) Top Classes –Stimulant –Psychedelic –Narcotic

Stimulants (Cocaine) Psychological Effect –Euphoria (fairly reliable and intense relative to other drugs) –Appetite suppressant –Increased energy Physiological Effect –Dopamine – blocks re-uptake protein (allows DA to remain in synapse) Chronic use - DA receptor down-regulation Depression may result from decreased DA activity after withdrawal Sensitization – brain is more sensitive to things that increase DA (cocaine)

Stimulants (Cocaine) Dopamine –Central role of DA in addiction Electrical stimulation of important DA region of brain is rewarding Most drugs of abuse cause increased DA activity (increase release or block re-uptake) –Effects can be direct or indirect (via a different neural circuit that connects to DA system) Drugs that block DA or inhibit DA release are not abused

Stimulants (Cocaine) Physiological Effect –Norepinephrine Blocks re-uptake protein NE implicated in attention (stimulants increase NE in helping with ADD/ADHD) –Serotonin (5-HT) Blocks re-uptake protein –Sodium Channels Blocks sodium channels & interferes with action potentials Local anesthetic properties

Stimulants (Cocaine) Withdrawal –Craving – can last months –Depressed mood – can last months –Fatigue –Generalized malaise –Vivid and unpleasant dreams –Agitation and restless behavior –Slowing of activity –Increased appetite

Psychedelic (Marijuana - THC) Psychological Effect –Vary widely across people & situation –Mild euphoria (relative to other drugs) –Relaxation –Distortions of time and space & sometimes hallucinations –Appetite stimulation –Slight analgesic

Psychedelic (Marijuana - THC) Physical Effect –Agonist for anadamide that binds to CB1 cannabinoid receptor Cannabinoid receptors are very widely distributed in brain –Anandamide works as second messenger Less cAMP – less protein kinaese A Affects CA + & K + channels – less NTs released (many different kinds) –Dopamine influenced indirectly DA neurons don’t have CB1 receptors so THC does not cause less DA release GABA neurons normally inhibit DA –GABA neurons have CB1 receptors and become less active More DA because THC inhibits GABA which inhibits DA

Psychedelic (Marijuana - THC) Withdrawal –Insomnia & vivid dreams –Depression –Anger –Headaches –Night sweats

Narcotic (Heroin & Morphine) Heroin vs. Morphine –Same active chemical –Heroin is more fat soluble and can enter brain more easily (converted to Morphine in brain) Psychological Effect –Analgesia (pain relief) –Euphoria (greater than other opioid drugs) –Relaxation

Narcotic (Heroin & Morphine) Physical Effect –Agonist for endogenous endorphins (β- endorphin, dynorphin, leu-enkephalin, & met- enkephalin) that are used to diminish pain μ-opioid receptor that is located thought brain, spinal cord, and gut Second messenger system that influences the likelihood of action potentials (e.g., reducing pain) –Dopamine influenced indirectly μ-opioid receptor decreases GABA GABA normally inhibits DA (and many other NTs) Increase in DA (inhibit the inhibitor)

Narcotic (Heroin & Morphine) Withdrawal –Sustained use for as little as 3 days can lead to withdrawal (minor compared to longer use) –Sweating, anxiety, depression, mailaise, priapism or genital sensitivity, insomnia, vomiting, diareaha, cramps, fever Many symptoms occur because of hyperactive sympathetic nervous system –Very unpleasant but generally not fatal (s edatives can be fatal) –Methadone Same effects as heroin but is slowly absorbed in stomach Relieves withdrawal without the euphoric effect

Drugs & Reward Most drugs of abuse seem to activate “reward” circuit(s) in the brain –Dopamine is a (the) principle one –Reward circuit(s) important for normal functioning & learning Food, sex, & other necessary activities that are enjoyable (interacting with others, mastering a task, etc.) All (most) behavior is channeled through these reward circuit(s) – do not have completely difference systems for sex, hunger, etc. Recent research suggests that it is possible to separate systems – “liking” vs. “wanting” –“Liking” - system responsible for pleasure –“Wanting” – system that drives behavior