Compulsive use- We use the drug not because we like it, but we have to have it. We need it.  How do we break this?

           Social-recreational use- rough day at work, stressed use substance

1.     use of socially acceptable (beer & tobacco)

2.     use of harder substances (hard liquor & marijuana)

3.     use of illicit substances (cocaine, heroin, LSD)

            (govt cracks down on step two in hopes to prevent step 3 from ever occurring)

*Ex of gateway hypothesis: cannabinoids: found in marijuana. Animals given enough cannabinoids for brain to have an effect. Animals not given substance also. Animals given cannabinoids caught on to using cocaine faster.

DSM-IV Substance ABUSE

·      A maladaptive pattern of substance use leading to significant impairment or distress by one (or more) of the following within 12-months

*substance use stops you from filling major role

* physically hazardous

* legal related problems

*another…

·      The symptoms have never met the criteria for substance dependence for this class of substance

DSM-IV Substance DEPENDENCE

Three (or more) of the following any time during a 12-month period

1.     tolerance

2.     withdrawal: hangover

3.     substance is taken in larger amounts over a longer period of time than intended

4.     there is a desire/unsuccessful effort to cut down drug use

5.     a great deal of time is spent in activities necessary to obtain and use the substance or recover from its effects

6.     important social, occupational or recreation activities are given up or reduced

7.     the substance use is continued despite knowledge of having a persistent or recurrent physical or psychological problem caused/ exacerbated by the substance

Drug dependence and addiction

Genetic-> Sociological-> Psychological ->repeat

alcohol makes you feel sleepy, caffeine makes you more awake. Liver puts caffeine and alcohol making caffeinol. Could prevent Parkinson’s and other diseases (alcohol antagonist)

                                                                                       i.     Ups response

                                                                                      ii.     “The drugs make me feel good”

                                                                                       i.     Ups response

                                                                                      ii.     AKA escape/avoidance learning

                                                                                    iii.     Take the drug to avoid pain

                                                                                       i.     Lowers response

                                                                                      ii.     Medication given to alcoholics where they feel sick when they drink

                                                                                    iii.     Drug laws that punish if you are caught

Negative Punishment

                                                                                       i.     Lowers response

                                                                                      ii.     AKA omission training

                                                                                    iii.     Ex: Time out

 Positive Reinforcement Model

a.     Early animal research (1950s)

                                                                                       i.     Self-administration procedure

1.     Found that animals like drugs the same as people

2.     Animals will self-administer drugs

a.     Less likely to administer psychedelic drugs (marijuana, LSD, etc.) because they work on higher cognition

·      Olds & Milner (1954)

*They would implant electrodes

* they would put rat in open field with implant in. Every time the rat went to certain corner they would “stimulate the brain”

* for 25-28 of the rats they would just walk randomly around the box.

animals chose brain stimulation over food and water. Animal would press the lever to get brain stimulation as many times as necessary. 

were an animal in the wild

): squirrel  mesolimbic dopamine gets activated when the squirrel find a lot of food.

*incentive-sensitization theory of addiction (Robinson & Berridge, 1993)

                        *long-term potentiation (neural plasticity)

                        * neurons were sensitized and react more to drug. What happens when the cocaine is not available. CRAVING

                        * the more we used drug the more neurons are sensitized. More we crave

response to a certain event goes away when fixed

we think that we stayed up all night when you actually got good nights sleep

not moving around in bed. Dead asleep. Occur around an hour or an hour and half and stay in it for 15 minutes and back to slow wave.

Sedation

decreases amount of time it takes up to go to sleep. Bad night sleep though. REM sleep decreases causing bad sleep. When going to withdrawal REM sleep rebound can cause awful dreams.

+REM sleep is increased a lot the night after you take drug! Crazy dreams.

*Absorption

                        *stomach -> intestines

                        * Full vs. empty stomach

            *First- pass metabolism: longer the alcohol stays in stomach the less that gets into your system. 

Ethanol -> Alcohol Dehydrogenase-> acetaldehyde (hangover!)->Acetaldehyde Dehydrogenase (disulfiram (antabuse)) -> Acetic Acid-> Co2 + H20

negative effect. Have to take it. If you drink one beer even you will feel awful!

causes membrane to swell causing receptors embedded in membrane to change as well. Changing of neuron communication (lots of neurons non specific)

ionotropic (ex NMDA receptor)  and metabotropic (mGluR) glutamate receptors (forms spacial maps)

GABA receptors

*Two types of receptors

                        *GABA (A) (ionotropic) and

                        *GABA (B) (metabotropic)

            *synergism: we get 1+1= 4 drugs enhance each other

Allosteric activator: easier for ions to move through

·      Inhibitory

GABA neuron usually works as a break with DA (Dopamine)

            *When you drink alcohol GABA break is stopped so you get more dopamine

Behavioral effects of alcohol

*inebriation

                        *acute tolerance

            As BAL rises: stimulant & euphoria (higher dopamine levels)

            As BAL lowers: sedation & depression (lower dopamine levels)

*Anxiolytic

            *stress/anxiety (lowers levels) : you will drink more if you are stressed or have anxiety

*Sedation:  decreases amount of time it takes up to go to sleep. Bad night sleep though. REM sleep decreases causing bad sleep. When going to withdrawal REM sleep rebound can cause awful dreams.

*Disinhibition

·      Sex

o   Interest vs. performance (erectile disfunction)

*coordination (vestibular system)

            *Romberg sway test

            * “bed spins”

Barbiturates and Benzodiazepines

clinical uses

Clinical Uses

            +anxiety (GREAT FOR IT) and great for initial treatment

                        +acute and initial treatments

            +insommia

            +dissociative anesthetic: (takes us into another state.. brings us into a fog

                                                good for surgery.. don’t remember pain)

            +Muscle Relaxant

                        +Seizure disorders

                        +Alcohol withdrawal (minimize seizures withdrawal syndrome)

            +Bad for mood disorders!! Not for long time users (several years)

+Similarities to alcohol (almost identical. Behavior would be same on animals)

                        + “Downer”

                        +Disinhibition

+ “Knock-out”/ “Date rape” (Like surgery use…)

+Combinations with alcohol (don’t combine with alcohol) (synergistically .. this drug plus alcohol is equal to 4 drugs)

Kinetics

of B & B

+Oral administration

                        +available in parenteral forms (needle)

            +Variability in half-life

                        +individual differences with barbiturates

                        +benzodiazepines have active metabolites

            +Metabolized via liver enzymes

+overlap with alcohol  (if client has alcohol problem they will metabolize this drug very differently)

Dynamics

B & B

+GABA receptor (alcohol increases GABA function 1+1=4 drugs!)

                        +allosteric modulator (easy to overdose..dangerous)

                        +Barbiturates can function as GABA agonist

                                    +toxicity?

            +Glutamate receptors

                        +barbiturates (close to being dinosaur…rarely used)

                        +Neuroprotective in ischemia? (car accident … frontal lobe gets hurt from banging window… neurons get lots of calcium and get excited… neurons die … and glil cells come in. DON’T want this to happen. They prevent this by giving you a barbiturates to prevent some of the excitatory signals in the neurons. 

Problems with

B & B

bad for sleep cycle!

+sedative (stops cycling in sleep cycle)

                        +REM sleep is increased a lot the night after you take drug! Crazy dreams.

                        +Withdrawal symptoms

+Cognitive inhibitor

+Elderly and dementia (effect older people even worse! Wet blanket over head is worse than a young person)

+Tolerance (vicious cycle… keep taking more and more of drug to fix sleep and develop dependence because you need more to sleep)

                        +Kinetic and dynamic

                        +Cross-tolerance

            +Physical Dependence is possible

                        ++withdrawal symptoms (negative reinforcement)

                        +Latrogenic pattern of use

            +Use has declined

                        +Therapeutic index

                        +interactions

*opium in a poppy

            (papaver somniferum)

                        *Opium (rubbed on soldiers feet so they could walk in morning)

            *There are many natural opiate drugs (come from poppy plant. Base molecule is opium from plant. Chemist will mess with a little) cross blood brain barrier

                        *morphine

                        *codeine

                        *Laudanum

            *Heroin is a semisynthetic opiate (prodrug for morphine)

                        *diacetylmorphine: crosses blood barrier faster and better

                        *1870s- 1880s  no drug laws. Could order needle and syringe. No pain within 15-30 seconds. 

*Fentanyl  (Sublimaze/ “china white” very potent, easily gets past blood brain barrier. Don’t need a lot of drug. Administration can vary. People like to abuse use

*Merperidine (Demerol) oral administration. Adimistered with non opiate drug

*Methadone (dolophine) help people who are addicted to heroin (substitution minimizes withdrawal effects) relatively short half life.

*LAAM (i-alpha-acetylmethadol)

*Destromethorphan (Robitussin) Weak opiate

unitary hypothesis: causes membrane to swell causing receptors embedded in membrane to change as well. Changing of neuron communication (lots of neurons non specific)

*stimulant

*euphoria

*sedation

*depression

*anxiety

*insomnia

*seizure disorder

*downer (date rape)

*half life varies

*cross blood brain barrie

*oral (lipophilic)

*Liver enzymes (overlap with alcohol)

* similar to alcohol

*sedative (REM SLEEP)

*Tolerance

*physical dependence possible

*anxiety

*insomnia

*seizure disorders

* Downer (date rape)

*Sedative, but (decrease in REM & Cognitive  may develop)

(e.g., the Z drugs, buspirone (BuSpar), Rozerem).  

(2nd generation drugs)

safe for long time use

*help you sleep

*better to take it orally than parenteral

*not good a passing blood brain barrier

*great variability in half life

*increase dopamine levels

*limbic system

*brain stem (respiration vomiting, coughing)

*analgesia

*sedation

*cough sepression

* use maintained by negative reinforcement

* can be side effects

*tollerance

* positive or negative reinforcement

* typically uses larger doses than when used for medical reasons

* not very addictive