DABA final

classical neurotransmitters

Amino acids (Glutamate and GABA), Monoamines (Dopamine, Norepinephrine, and serotonin),

Nonclassical neurotransmitters

Neuropeptides (endorphins, CRF), Lipids, Gasses

Addiction

is a chronically relapsing disorder in

which the organism assumes a compulsive behaviour and in which:

• The behaviour is rewarding (pleasurable positive reinforcement)

• There is a loss of control as for the ability to limit the intake

Progression towards addiction

Like, Want, Need, Require, Loss of Control

VTA-NAc pathway

the brain reward circuitry in mood disorders, Ventral Tegmental area and Nucleus Accumbens

Different types of drugs activate different receptors in various parts of the reward

circuit.

Activation of the mesolimbic DA pathway from the VTA to the NAcc plays a central role in drug reward and reinforcement.

Addiction: constitutive elements

tolerance, dependence, toxic psychosis

tolerance

the diminishing effect of a drug resulting from repeated administration

at a given dose. It is necessary to increase the dose to achieve the same effect. It is an endogenous, defensive adaptation of the organism

dependence

the necessity to continue the consumption in order to avoid the

withdrawal syndrome, which can be emotional–motivational (e.g., craving, dysphoria and anhedonia) when dependence is psychological or physical–somatic (e.g., fatigue and delirium tremens) when dependence is physical

TOXIC PSYCHOSIS:

Psychotic disorder (hallucination1, delusion2) induced by drug use.

Can be a) dose-dependent (amphetamine, cocaine) or b) caused by witdrawal

(alcohol)

chronic metabolic tolerance

- changes in ADME (especially increased metabolism)

Ex. alcohol

chronic dynamic tolerance

- changes in affinity/number of receptors

- changes in post-transductional mechanisms (increased formation of cAMP)

Ex. heroin

the 3 Rs of animal research

replace, reduce, refine

general rules of substance abuse

1 The faster the absorption rate → the highest the concentration peak and effect that

can be reached in a particular tissue

2 The shorter the half-life of a drug → the more abruptly the effect will cease and the

more severe the withdrawal syndrome will be

3 The symptoms of an overdose are an exaggeration of the pharmacological effects of

the drug

4 The symptoms of a withdrawal syndrome are generally the opposite of the

pharmacological effects of the drug

acute intoxication classic symptoms

TRIAD: 1. COMA (non reactive, flaccid)

2. RESPIRATORY DEPRESSION (1-2 breaths per minute)

3. EXTREME MIOSIS (pinpoint pupils)

Other

5. Seizures (with morphine, meperidine, tramadol, dextropropoxyphene)

6. Acute pulmonary edema

7. Bradycardia, hypotension, shock

8. Hypothermia

9. Oliguria

Overdose therapy

Naloxone (Narcan)

- 0.4 mg i.v., if no response, then 2 mg i.v. every 2 - 3 min until

response or a total dose of 10 mg

- opioid receptor antagonist

- can precipitate a withdrawal syndrome in addicted patient

CNS depression stages

normal, anxyiolysis, sedation, hypnosis, anesthesia, coma, death

too much GABA

Calm, sedation, hypnosis, anaesthesia

too much glutamate

anxiety, restlessness, migraines, seizures

ethylometer

Measures the concentration of unaltered alcohol in breath (BrAC)

The BrAc in converted into blood alcohol concentration (BAC)

In most ethylometers the conversion factor is = 1 in BrAC:2100 in BAC

alcohol pharmokinetics

Rapidly absorbed from the stomach and small intestine, reaching peak blood alcohol concentration (BAC) in 45–60 minutes (30 mins if fasting, longer if fed).

alcohol metabolism

• Alcohol Dehydrogenase (ADH): Converts ethanol to acetaldehyde, the primary pathway.

• Aldehyde Dehydrogenase (ALDH): Converts toxic acetaldehyde to non-toxic acetate.

alcohol withdrawal

tremor, anxiety, hypertension, sweating, rapid breathing, nausea, delirium tremors hallucinations,

cannabinoids main subjective effect

More acute sensorial (perception) awareness (psychotropic effect)

→ Relaxing and well-being effects

→ Anxiety, panic attacks and fear

cannabinoids central effects

▪ Analgesia

▪ Antiemetic effect

▪ Increased appetite

▪ Muscle relaxation (antispastic)

▪ Alterations in motor coordination

▪ Poor performance in simple learning tasks

▪ Alterations of brief-term memory

▪ Catalepsis

cannabinoids peripheral effects

Reduced intraocular pressure

▪ Broncodilation

▪ Tachycardia

▪ Vasodilation

cannabinoids 5 senses

• Sight: Colors may appear more vibrant and, in some cases, visual acuity can feel increased, allowing for better identification of details.

• Sound: Music and sounds are often perceived as richer, deeper, or more nuanced, allowing individuals to focus on individual layers of music.

• Taste and Smell: Foods can taste more intense or "alive," often resulting in increased enjoyment of flavors. However, research suggests that, at least in the short term, cannabis may reduce olfactory acuity (sharpness of smell).

• Touch: Sensitivity to touch is often increased, which is a common factor in increased sexual satisfaction reported by some users.

hallucinogen drug problems

A user may have a “bad trip” with acute

anxiety or panic → suicide (also because a)

you think you can fly b) cannot appreciate

the real distance from the ground)

It appears to be related to the individual’

s

emotional state going into the trip, as well as

the external environment.

LSD addiction

What is the danger?

1) “Bad Trip”: flight (a) to escape danger, (b) because «I can

fly», (c) because «the floor is near», marked anxiety,

suicides

2) Depression, paranoid and psychotic episodes

3)“Flashbacks” or HPPD (hallucinogen persisting perception

disorders), triggered by stress, fatigue, darkness, THC,

neuroleptics, anxiety

4) Pseudohallucinations: color flashes, possible permanent

alterations of the visual system.

MDMA (ecstasy) pharmocological effects

In the range 50-100 mg (recreational doses) ecstasy produces effects that are similar to those of

amphetamines. In detail:

Euphoria and well-being: talkativeness, self-confidence, sense of peace, bliss, joy (entactogenesis)

Enhancement of communication and relational skills: emotional harmony with others

(empathogenesis), ease in communicating, rewarding interpersonal relations (“hug drug”)

Increased resistance to fatigue: allows dancing for a long time without feeling tired, but also produces tachycardia and hypertension, sweating, nausea, bruxism, dry mouth

Enhancement of sensorial perception: such as touch, proprioception, sight, taste, smell; amplifies sensations generated by music fast rhythms or psychedelic lights

pharmacological effects of nicotine

arouses brain to state of alertness, increase heart and BP, suppresses appetite, ADDICITON

Behavioral addiciton

1. Auto-destructive behavior.

2. Repeated and/or compulsive involvement in

activities that were initially hedonic.

3. Hard to quit.

4. Intense desire (craving).

5. Tolerance and withdrawal syndrome aspects.

homeostatic pathway

controls energy balance by increasing the motivation to eat following depletion of energy

stores.

• our survival depends on the ability to procure food for immediate metabolic needs and to

store excess energy in the form of fat to meet metabolic demands during fasting.

• the brain detects alterations in energy stores and triggers metabolic and behavioral responses

designed to maintain energy balance.

• energy homeostasis is controlled mainly by neuronal circuits in the hypothalamus and brain-

stem.

hedonic pathway (reward)

can override the homeostatic pathway during periods of relative energy abundance by

increasing the desire to consume foods that are highly palatable.

• eating behavior is primarily controlled by homeostatic processes but also stimulated by

hunger, cravings and hedonic sensations.

• reward and motivation aspects of eating behavior are controlled by neurons in the limbic

regions and cerebral cortex.

anorexia

Significantly low body weight, significant weight and shape concerns

People with anorexia nervosa may see themselves as overweight, even when they are

dangerously underweight.

• People with anorexia nervosa typically weigh themselves repeatedly, severely restrict

the amount of food they eat, often exercise excessively, and/or may force themselves

to vomit or use laxatives to lose weight.

• Anorexia nervosa has the highest mortality rate of any mental disorder.

• While many people with this disorder die from complications associated with

starvation, others die of suicide.

bullimia

Recurrent binge eating and compensatory behaviors

(eg, purging, laxative use); significant wieght and

s h a p e c o n c e r n s

Binge eating disorder

Recurrent binge eating; at least 3 of 5 additional

criteria related to binge eating (eg, eating large

amounts when not physically hungry, eating alone

due to embarrassment); significant distress

the female athlete triad

amenorrhea, osteoporosis & eating disorder

symptoms of overtraining

underperformance, mood disturbances (depression, anxiety, apathy), sleep disturbances or insomnia, physiological changes (no period, weigh, upper respiratory infections)

runners high

prolonged feeling of euphoria experienced by many athletes during or following extensive physical exercise

sport as “drug”

resistance training —> dopamine, cannabinoids, serotonin, endorphins —> Well-being and euphoric feeling

➢ Tolerance to pain

➢ Increase in appetite

➢ Improved reactions to fear and

aggression

➢ Reduction in nervous tension

and anxiety

Gambling

Tolerance: Needs to gamble with increasing amounts of money in order to achieve the desired

excitement.

2. Withdrawal: Is restless or irritable when attempting to cut down or stop gambling.

3. Relapse: Has repeated unsuccessful efforts to control, cut back, or stop gambling.

4. Preoccupation: Is often preoccupied with gambling (e.g., having persistent thoughts of reliving

past gambling experiences, handicapping or planning next venture, thinking of ways to get money

with which to gamble).

5. Escape: Often gambles when feeling distressed (e.g., helpless, guilty, anxious, depressed).

6. Chasing: After losing money gambling, often returns another day to get even.

7. Lying to Loved Ones: Lies to conceal the extent of involvement with gambling.

8. Risking Relationships: Has jeopardized or lost a significant relationship, job, or educational or

career opportunity because of gambling.

9. Bailouts/Relying on Others for Money: Relies on others to provide money to relieve a desperate

financial situation caused by gambling.