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294 Cards in this Set
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- Back
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What are cannabinoid drugs?
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These drugs consist of psychoactive substances that act on cannabinoid receptors in the nervous system. |
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What is cannabis? |
Plants with naturally occurring psychoactive cannabinoids |
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Name the three times of cannabis |
Cannabis sativa (mostly THC) Cannabis Indica (mostly cannabidoil) Cannabis Ruderalis (containing trichomes) |
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What are all the cannabis plants called (put together)? |
Hemp |
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What is the role of TRICHOMES that are contained in the leaves and flowers of cannabis? |
They release biologically active substances "phytocannabinoids" |
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What is the key psychoactive ingredient in phytocannabinoids? |
Δ9-THC (Tetrahydrocannabinol) |
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What are other psychoactive ingredients in phytocannabinoid? |
Δ8-THC Cannabidiol Cannabinol N-alklamide B-caryophyllene |
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What plant has the GREATEST concentration of Δ- THC relative to others? |
Cannabis Sativa plants, and the concentration of the THC increases as the plant matures |
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What plant has a greater concentration of cannabidiol than Δ9-THC? |
Cannabis indica |
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What is marijuana? |
Dried cannabis flowers, leaves, and stems compressed and rolled for smoking (weed, pot, reefer, grass) |
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What is Hashish? |
It is a condensed preparation of cannabis, containing trichome resins from the plant with high concentrations of Δ9-THC. |
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What are herbal marijuana alternatives? |
Ex. K2, Spice - Lab-synthesized cannabinoid receptor agonist - Use adds Δ9-THC to is |
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How are cannabis products and herbal marijuana alternatives classified? (what schedule) |
Schedule I controlled substances |
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What is the prescribed medical marijuana drug called? |
Dronabinol (Maronil) Class: schedule III |
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Historically, what was the medical purpose of cannabis in China? |
For female weakness and malaria |
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Cannabis and hashish were smoked in Arabia to achieve what effects? |
For mood-enhancing effects |
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What discovery lead to the use of cannabis in modern medicine? |
The discovery of sedative and anticonvulsant properties in cannabis - helped improve symptoms of rabies, tetanus and cholera |
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What was the Marijuana Tax Act of 1937? |
Patients had to pay $1/ounce of marijuana - limited medicinal use |
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How is cannabis commonly administered? |
Oral or Inhalation |
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how is cannabis prepared for oral administration? |
- baking into a dessert i.e. brownies, cookies - heated with water for tea - medicine: dronabinol (maronil) capsule |
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how is cannabis prepared for smoking/inhalation? |
- rolled in cigarette paper, lit and smoked (joint) - water pipe (hookah) - less elaborate pipe = bong |
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What does inhaling second-hand cannabis smoke lead to? |
- psychoactive levels of Δ9-THC - producing a "high" feeling |
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How is cannabis absorption distributed in the body from inhalation? |
50% of Δ9-THC releases into smoke, most of it absorbs into the bloodstream and reaches the brain |
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how is cannabis absorption distributed in the body from oral administration? |
goes thru first-mass metabolism in the liver --> only 50% of it reaches the brain
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How is Δ9-THC metabolized in the liver? |
By p450 enzymes --> produces metabolites --> exert effects in the body |
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Name the properties of Δ9-THC |
- exhibits high lipid solubility - rapid distribution to tissues, brain, helps accumulate fat - Δ9-THC gets accumulated in fats (long-term), so there is a longer elimination rate |
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what is the half-life of Δ9-TLC? |
7 days |
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Name 2 endocannabinoid active neurotransmitters |
1. Anandamide: the "bliss" molecule 2. 2-Arachidonoylglycerol (2-AG) |
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How do you produce anandamide? |
NAPE --> Anandamide via enzyme Phospholipase D |
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How do you break down anandamide? |
Anandamide goes back to neuron via anandamide transporter --> fatty acid amide hydrolase (FAAH) breaks anandamide --> inactive compounds |
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Do endocannabinoids get stored in vesicles? |
No, so they get released into the synaptic cleft right after synthesis |
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What causes behavioral and physiological effects of cannabinoids and endocannabinoids?
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They result from actions at cannabinoid receptors. |
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What is the difference between cannabinoids and THC? |
THC is a type of cannabinoid, a psychoactive constituent of the cannabis plant |
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What are the two types of cannabinoid receptors? |
CB1 and CB2 receptors - both G-protein coupled receptors, exhibiting inhibitory effects |
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where are CB1 receptors found? |
- Densely found: basal ganglia, nucleus accumbens, substantia nigra, cerebellum, hippocampus, and cerebral cortex - Hypothalamus, thalamus, brainstem, eye |
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Where are CB2 receptors found? |
outside of the brain i.e. immune system on macrophages (white blood cells), leukocytes (B cells, natural killer cells, T cells), mast cells (respond to injury) |
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Difference between THC and Cannabidiol |
THC gives a high and a buzz feeling, but cannabidiol does not. Cannabidiol is a cannabis compound that has medical benefits that counteract marijuana's adverse effects |
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Describe the affinity that cannabinoids hve for CB1 receptors |
- Δ9-THC and endocannabinoid anandamide have high affinities for the CB1 receptor
- 2-AG weakly binds CB1 receptors - Cannabinol and Cannabidiol: weak affinity for CB1 receptors |
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What neurotransmitter gets released when CB1 receptors are activated? |
Dopamine concentrations increase in the nucleus accumbens - Direct influence: CB1 receptor agonists act on CB1 R's (located on DA neurons) - Indirect influence: dopamine neuron activity --> acts on CB1 receptors on GABA/glutamate neurons |
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What are the physiological effects of cannabinoids (containing Δ9-THC) after acute administration? |
- elevation in heart rate - hypotension in heart - heart palpilations - reddening conjunctivae (mucous membrane that covers the eye) - increased appetite |
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What is the cause of munchies? |
- Cannabis increases appetite - Fat cells release leptin --> leptin is what usually tells u to stop eating - leptin reduces anandamide and 2AG concentrations in hypothalamus |
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What are the behavioral effects of cannabinoids? |
- impaired motor coordination and msucle tone - Amotivational syndrome - memory deficits - increased attention in low dose, but increased dose causes attention deficits |
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What is an amotivational syndrome? |
- Lack of motivation to engage in productive activities
- not enough evidence for this |
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Define a buzz. |
Feeling light headed after a few puffs |
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Define the feeling of being "high" |
After a few more inhalations, the high feeling is euphoric and exhilarating - increases agitation or anxiety |
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what is the stoned phase? |
- feelings of calmness and in a relaxed state - occurs after further usage - feeling like times going by so fast (accelerated passage of time) due to reduction in cerebellar blood flow |
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What happens when participants were asked to discriminate Δ9-THC vs placebo in a drug discrimination task? |
only Δ9-THC produced THC-appropriate responding but the drugs from other classes did not
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What did experienced smokers report after smoking cannabis, and having oral intake of THC? |
They experienced similar subjective effects like the "high" or stoned effects |
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What are regular cannabis users tolerant towards when using cannabis? |
memory impairment, motor coordination, and accelerated time passage
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What are some withdrawal effects when taking away cannabis for a period of time?
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agitation restlessness appetite suppression |
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Cannabis dependence |
in the fourth edition of the DSM - (DSM-IV) - meets the general criteria for substance dependence |
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What is the cannabis withdrawal syndrome? |
Characterized by the following symptoms: - irritability - anger - aggression - anxiety - difficulty sleeping - low appetite - depressed mood Physical withdrawals: stomach ache, tremor, sweating, headache, fever |
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Similarities/difference between cannabis cigarettes and tobacco cigarettes |
S: - both contain similar carcinogen content
D: - Cannabis = more chemicals that limit the risk for lung cancer Cannabis smoking --> increased TAR in lungs Cannabis smoke increases risk of respiratory disease (bronchitis, emphysema) |
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What is the purpose of medical cannabis? |
it helps with the treatment of cancer (i.e., helping patients cope with chemotherapy) - meds kill rapidly dividing cells - stops nausea and barfing in cancer patients - appetite-enhancing effects for weight gain - reduced neuropathic pain in HIV-infected patients - reduces intraocular pressure --> helps treat Glaucoma |
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What is savitex? |
A medication containing 1:1 ratio of cannabidiol: Δ9-THC |
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What are trichomes? |
they are hair-like structures that release Resin with biologically active substances called "Phytcannabinoids" |
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What are psychedelic drugs? |
Drugs that induce a reality-altering experience - Cause hallucinations, sensory distortions, delusions |
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What are three categories psychedelic drugs can be classified under? |
Hallucinogens (LSD) Mixed stimulant-psychedelics (MDMA) Dissociative Anesthetics (PCP) |
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What is the major pharmacological effect of hallucinogens? |
producing hallucinations |
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Name 4 types of hallucinogens |
1. LSD - "acid, windowpane, blotter" 2. Psilocybin- found in Psylocibe mushrooms, aka magic mushrooms or shrooms 3. mescaline- in peyote cacti --> administered by eating peyote cacti 4. dimethyltryptamine - made in body, or found in south american plants |
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What are some of the major historical events in the use of hallucinogens? |
- Hallucinogen plants were used as psychic medicines to treat maladies, communicate with "gods" and to perform magic - religious ceremonies - used by psychologists to understand unconscious thoughts of patients |
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At what amount is LSD effective? |
0.025 mg |
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How is LSD administered? |
Orally administered. Drops of LSD placed on blots of paper and then licked |
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when does LSD reach its peak absorption? |
after 60 minutes |
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What is the elimination half-life of LSD? |
3 hours - meaning that the effect lasts for 8 hours |
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How is LSD broken down in the liver? |
Cells in the liver metabolize LSD and produce 2-oxo-3-hydroxy-LSD |
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What neurotransmitter does the structure of LSD resemble? |
Serotonin |
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What is the benefit of LSD's resemblance to serotonin? |
It can act on serotonin receptors (with a high binding affinity), acting as receptor agonists |
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What two receptors does LSD activate? |
5-HT1A and 5-HT2A receptors |
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What is modal object completion?
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Perception of object boundaries inferred from incomplete representations of the object |
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What is seen on an EEG when taking hallucinogens? |
Decreased waves of N170 in the occipital lobe --> decreased activity in occipital lobe |
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How do hallucinogens alter functioning in the locus coeruleus? |
Glutamate increases signals to cerebral cortex. GABA decreases activity in locus coeruleus to refine the signals being sent to cerebral cortex |
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What happens when LSD activates 5-HT2A receptors? |
It increases glutamate release, which increases activity in prefrontal cortex --> leads to visual hallucinations |
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What are the mild physiological effects of LSD? |
change in heart rate, slight dizziness, mild nausesa
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What are the two subjective experiences for LSD? |
True hallucinations and Pseudo hallucinations |
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What is a true hallucination? |
Perception of images or sounds that are not real (can occur with LSD, rare) |
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What are pseudo hallucinations |
More common; altering your perception of something that is real/already exists (i.e. this is what LSD does) |
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What is the overall hallucinogenic experience |
Its called "trip" A good trip = desirable pseudo-hallucinations, increasing your perception and insightfulness, experiencing synesthesia (increase in sensory stimuli, but an incorrect sensory modality) A bad trip = Disturbing true hallucinations, psychotic episodes, negative emotions |
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What are factors that can affect a person's trip? |
comments from friends, physical surroundings, emotional state
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What is a flashback?
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A short and random (non-distressing) MEMORY of a previous hallucinogenic experience |
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Describe what a hallucinogenic persisting perception disorder is |
Lengthy and unpleasant memory of a previous hallucinogenic experience, often recurring |
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What are mixed stimulant-psychedelic drugs?
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substances that exhibit both psychostimulant and hallucinatory effects ex. MDMA
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how else is MDMA best known for its psychedelic and psychostimulant effects? |
Its an entactogen - "touching within" or empathogen "enhanced empathy"
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In what kind of environment is MDMA usually used? |
Raves, clubs bc they enhance club experiences |
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How is MDMA administered? |
Oral |
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When do peak blood plasma levels occur after taking MDMA? |
2 hours. |
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what is the elimination half life of MDMA |
9 hours approx, although it is inconsistent therefore its metabolism slows down and taking more doses = long lasting effects |
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What is the metabolite produced after MDMA is metabolized in the liver? |
Methylenedioxyamphetamine (MDA) (similar effects as MDMA so that means MDA produces its own effects) |
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How is MDMA metabolized in the liver? |
CYP2D6 enzymes convertsMDMA --> MDA Other enzymes: CYP1A2 (to a lesser extent) |
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What effect do SSRI's have on MDMA metabolism? |
SSRI's inhibit CYP2D6 activity, thus inhibiting MDMA metabolism --> increasing MDMA concentrations and its effects |
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How does MDMA increase serotonin levels? |
Mechanism 1: inhibiting 5HT transportation into synaptic storage in vesicles --> increase serotonin in synaptic cleft Mechanism 2: Reversal of 5-HT reuptake transporters |
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What other neurotransmitters does MDMA have an effect on?
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At high MDMA levels, it can increase dopamine thru parallel mechanisms, but its weaker than the increase in serotonin levels |
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What is the effect of chronic MDMA use on serotonin neurons? |
-produces severe damage to serotonin neurons - loss of brain serotonin, metabolite 5-HIAA, tryptophan hydroxylase, and serotonin reuptake transporter |
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What are the effects of low vs. high MDMA doses? |
Low: few physiological effects, subjective effects include heightened senses, racing thoughts, euphoria High: increased energy and feelings of closeness to people, [heightened senses, racing thoughts, euphoria], physiological effects include incr. heart rate and BP |
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Does MDMA exhibit reinforcing effects? |
Yes. Based on an animal model, subjects self-administered less MDMA compared to methamphetamine so reinforcing effects of MDMA are not as strong as amphetamine |
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What do MDMA, d-amphetamine and mCCP all have in common? |
they all produce increases friendliness and sense of improved cognition |
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What are the adverse effects of MDMA? |
High doses: activate sympathetic N.S. --> unconsciousness, brain hemorrhaging, chaotic heartbeat, severe risk of overheating and dehydration, high risk of organ failure
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What are psychological adverse effects of MDMA? |
- paranoia - true hallucinations - panic - delirium - irrational and reckless behaviour |
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What are rebound effects from MDMA use? |
This occurs after normal doses of MDMA --> occurs after 24 hrs of use - causing feelings of depression and lethargy - serotonin and dopamine levels are temporarily low --> takes several days for recovery |
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What are the cognitive effects of repeated MDMA use?
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If used repeatedly, it can impact verbal working memory
- can only remember simple words but not complex |
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What are the effects of MDMA on PTSD? |
Low doses of MDMA helps reduce PTSD symptoms (83% reduction) due to its empathogenic effects, reducing resistance to thinking about an event or facilitate emotions surrounding the effect |
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Is the rebound effect a sign of dependence?
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- it fails to meet the view on withdrawal symptoms because it occurs after using MDMA for the first time, and withdrawal symptoms rarely occur
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What are dissociative anesthetics?
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Sedative, pain-relieving drugs, produce feelings of disconnection from body, have depressant and stimulant effects
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What are the three types of dissociative anesthetics? |
1. PCP (angel dust- most abused)
2. Ketamine (Special K, or K) 3. Dizocilpine (MK801- used in research) |
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How were dissociative anesthetics used for psychiatric research? |
PCP or ketamine produced a temporary schizophrenic-like state - this helped understand schizophrenia |
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How is PCP administered? |
Intravenous injection, inhalation, insufflation
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How long until psychoactive effects are achieved from smoking PCP? |
1-5 mins, peak effects are reached within 5-30 mins |
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How long until drug effects are achieved from insufflation of PCP? |
30 sec to 1 min Elimination half life = 18-51 hrs |
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How does PCP increase serotonin and dopamine neurotransmission? |
1. Inhibiting serotonin and dopamine reuptake transporters
2. A good agonist for serotonin receptors or partial agonist for DA receptors |
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At high concentrations of PCP, how does it act on receptors?
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Nicotinic cholinergic receptors (located at neuromuscular junctions and ganglia in PNS): non-competitive antagonist
Antagonist at muscarinic receptors in CNS and ANS. |
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What is the effect of PCP on glutamate NMDA receptors?
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Acts as an antagonist, interfering wit long-term potentiation |
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What is long-term potentiation?
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Increased/strengthened synaptic plasticity in the brain allowing for learning and memory |
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What receptors does glutamate bind to at synapse? |
AMPA and NMDA. - first can only activate AMPA, since NMDA activation is blocked by Mg2+ ion |
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how does PCP prevent long-term potentiation? |
Activation of AMPA causes Mg2+ to leave, and Na+ and Ca2+ ions can pass thru NMDA receptors, causes depolarization, facilitates neuronal activity BUT THEN PCP acts like a Mg2+ and binds onto NMDA Receptor --> prevents long-term potentiation - decreases synaptic strength |
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when does Long term potentiation occur? |
When the membrane depolarizes sufficiently to repel the Mg2+ ion from the channel |
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What are the depressant effects of PCP? |
low dose PCP = drunken like state causes numbness in fingers, toes moderate doses - impairs memory |
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Psychedelics impairs memory. True or false? |
True. Study: ketamine-treated patients recalled fewer words compared to placebo-treated patients when asked to recite a message played from a recorder 10-80 mins earlier |
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What are some unique psychedelic effects? |
out-of-body experiences, feeling disconnected
@ high doses - psychostimulant effects (arousal, rush) and sympathetic nervous system activation |
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When are adverse effects likely to occur? |
at large doses of PCP |
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What are adverse effects of PCP? |
cataleptic-like effects on movement Schizophrenia-like state (hypothesis: schizophrenia symptoms occur from low glutamate transmission) |
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Dependenc and tolerance occur often in PCP use. True or false? |
False. They rarely occur since users administer the drug once or less a week. If they do occur, it is only during more FREQUENT use - and dependence is manifested by cravings, lethargy, or depression |
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What are examples of other psychedelics? |
1. Dextromethorphan 2. Salvinorin A 3. Scopolamine or Atropine |
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Describe the use of dextromethorphans. |
- opioid cough suppressant found in meds - consuming large amounts of cough syrup --> achieve Robo-tripping (high) effect - high dose = drug acts as a glutamate NMDA receptor antagonist (like PCP) - Effects: visual perception changes, transcendent feeling, mystical experiences |
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Where does Salvinorin A come from? |
It is a psychoactive ingredient in the plant: Salvia divinorum (magic mint, diviner's sage)
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How is salvinorin A administered?
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chewing, smoking salvia leaves- |
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Salvinorin A exhibits no activity on 5-HT2a receptors. True or false?
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True. |
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What is the role of Salvinorin A? |
- plays a role in perception
- produces an increase in DA levels in nucleus accumbens - feelings of becoming an object, revisiting places from the past, depersonalization, uncontrollable laugh, perceiving several places at once all this at only 0.2 to 1.0 mg! |
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What do scopolamines and atropines do? |
- They are muscarinic receptor antagonists
- produce true visual hallucinations, delusional thinking, disorientation about time or place |
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what is synesthesia?
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An abnormality in integrating sensory info into one single multisensory scene |
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How do activation of serotonin receptors affect synesthesia?
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1. activation of 5-HT2A receptors leads to synesthesia (i.e. H-HT2A receptor agonists)
2. antidepressants (SSRI'S) activate 5-HT1A receptors, which reduce activation of 5-HT2A receptors, which inhibit synesthesia 3. drugs acting like norepinephrine reuptake inhibitors --> Elevate NE levels --> increase a2- adrenoceptors --> reduce 5-HT2A receptor activation --> inhibit synesthesia 4. melatonin inhibits serotonin levels --> reduces inhibition of 5-HT2A receptors (since 5-HT1A is not activated) --> causes synesthesia |
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What is a mental disorder? |
An impairment in normal behavioural, cognitive, or emotional function.
- individual must experience significant distress from this disorder |
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How many people qualify for a mental disorder diagnosis? |
450 million people |
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Major depressive disorder |
Symptoms: - dysphoria, anhedonia, body weight fluctuations, sleep (excessive or insomnia), fatigue, hopelessness, cognitive impairment, suicide ideation - if atleast 5 are prevalent in a range of two weeks, then they have major depressive disorder |
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Dsythmic Disorder |
a milder form of clinical disorder - have atleast 2 symptoms nearly every day for 2 years. |
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Major depression with psychotic features
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Hallucinations and delusions relate to depressed mood and negative thoughts |
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What is the prevalence of major depressive disorder during a lifetime? |
16% |
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Are women or men 2x as likely to be diagnosed with major depressive disorder? |
Women |
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Women are also twice as likely to commit suicide. True or false? |
False. Men are twice as likely to commit suicide. |
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What is vascular depression? |
Reduced blood flow to the brain due to depression |
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What structures are involved in structural abnormalities in depression? |
Amygdala, prefrontal cortex, hippocampus, and nucleus accumbens |
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What is the effect of depression on the AMYGDALA? |
The amygdala is overactive. It is important for fear and aggression. |
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What is the effect of depression on the HIPPOCAMPUS? |
A decrease in volume in the hippocampus |
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What is the effect of depression on the DORSOLATERAL PFC? |
There is under activity. |
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What is the effect of depression on the NUCLEUS ACCUMBENS? |
It is underactive. The nucleus accumbens is important for reward and goal-directed behaviour, and other basal ganglia structures facilitate movement |
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What was the first antidepressant drug that was discovered by accident? |
Iproniazid - it reversed sedation |
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What are the categories of antidepressant drugs? |
- Monoamine oxidase inhibitors
- Tricyclic antidepressant drugs - SSRI's - SNRI's - Atypical antidepressant drugs |
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What is the monoamine hypothesis? |
Monoamine deficiency causes depressive mood |
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What are examples of a monoamine neurotransmitter?
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serotonin, dopamine, norepinephrine, tyramine |
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What is the major role of a MAO inhibitor? |
They prevent MAO from breaking down MAO neurotransmitters. |
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What are two types of MAO's? |
MAO[a] and MAO[b] |
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Where can you find MAO[a]? |
Mostly in the brain, peripheral nervous system and intestinal tract |
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Where can you find MAO[b]? |
Mostly in the brain, not so much in the peripheral nervous system |
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Irreversible MAO inhibitors |
The drug does not release from MAO. Neurons synthesize more MAO to make up for the lost ones. - increases serotonin and NE levels (promotes the cheese reaction) |
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Reversible MAO inhibitors |
hatDrug temporarily binds MAO. Other compounds like tyramine displace the drug from MAO. (this is preferable because it prevents the cheese reaction from occurring) |
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What is the cheese rxn? |
An adverse effect. Activated sympathetic nervous system function leading to increased heart rate, hypertension, sweating and inhibited digestion. -occurs when MAO inhibitors increase levels of NE and tyramine (both activate sympathetic nervous system functions) |
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What is the function of a selective MAO[b] inhibitor? |
Drugs inhibit MAO[b] enzyme --> weak binding to MAO[a] enzymes --> increase DA, NE, and serotonin |
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what is the function of a reversible inhibitor of MAO[a] (RIMA)? |
They selectively inhibit MAO[a] but allow for displacement from MAO[a] by Tyramine |
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What do tricyclic antidepressants do? |
- block reuptake of NE and serotonin - antagonists for other receptors - provide high levels of serotonin and NE without causing the cheese rxn |
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What was the first drug developed in this category? |
Imipramine
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What is the difference between tricyclic antidepressants and MAO inhibitors? |
They both achieve an elevation of serotonin and NE in synapses BUT Tricyclic antidepressants don't inhibit MAO, but rather prevents the reuptake of serotonin and NE into the neurons that released them. |
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What is the effect of tricyclic antidepressants on muscarinic receptors? |
They exert antagonistic actions on muscarinic R's.
- prevents parasympathetic ACh from binding to the receptors |
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What are the adverse effects of tricyclic antidepressants?
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dry mouth, dry eyes, constipation, urinary retention, and other effects related to the nervous system - cognitive and memory difficulties (bc it blocks muscarinic R's) - dangerous cardiovascular effects (bc blocks a1 adrenoceptors) - weight gain --> type II diabetes |
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What are SSRI's?
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They block serotonin transporters, increasing serotonin levels- |
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Why was Zimelidine withdrawn from the market?
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It damaged myelin sheathing around central and peripheral nervous system axons |
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What drug is prevalently prescribed, as an MAO inhibitor and tricyclic antidepressant drug? |
Fluoxetine (Prozac) |
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What is serotonin syndrome? |
A drug reaction with another serotonin compound. Causes agitation, restlessness, cognitive impairment and hallucinations
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How can you avoid serotonin syndrome? |
By taking low doses of SSRI |
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What kind of drug was developed as a new class of antidepressants due to the negative side effects from SSRI's? |
SNRI's - serotonin-norepinephrine reuptake inhibitors |
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What is the serotonin discontinuation syndrome? |
Its caused by an abrupt withdrawal of antidepressant drug resulting in: sensory/sleeping impairments, disequilibrium, flu-like symptoms and gastrointestinal effects |
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What sexual side effects are caused by elevated levels of serotonin?
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Erectile dysfunction, inability to achieve an orgasm, loss of sexual drive |
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What is the role of SNRI's? |
- enhance serotonin and NE levels, by blocking their transporters
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Why were SNRI's made? |
There was a need for a new class of antidepressant drugs resulting from: a) side effect profile of SSRIs b) failure of many patients' response to SSRI drugs |
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The effects of SNRI's were consistent and there was a slightly greater improvement in it. True or false? |
True. |
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What are atypical antidepressant drugs? |
They reduce depression by increasing levels of NE and DA (not serotonin) |
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What is an example of an atypical antidepressant drug? |
Bupropion - a reuptake inhibitor for norepinephrine and dopamine, lacks serotonin elevation |
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All antidepressants have a very short response time and have full effect in hours. True or false? |
False. THEY ALL HAVE A LENGTHY RESPONSE TIME. - Significant effects occur after 2 weeks, and full effects after 4 weeks of treatment |
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What is treatment resistance depression? |
Depression diagnosed after successive failed attempts to reduce their depressive symptoms. Clinicians would increase SSRI dose or use a diff antidepressant drug.
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Describe the approach of a Pharmacological Dissection of Mental Disorders
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it infers neuronal abnormalities in a mental disorder from the pharmacological actions of treatments |
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What may be the possible reason for delayed treatment response in antidepressant drugs? |
Changes in dopamine neurotransmission- |
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What happens when rats administer ketamine?
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In lab rats, it increased dopamine and glutamate concentrations in the prefrontal cortex |
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What can help shorten response time to antidepressants? |
Chronic administration of antidepressant drugs causing neuronal proliferation in the hippocampus |
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What is a bipolar disorder? |
Abnormal changes between depressive and manic mood states |
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What happens during a manic episode? |
Individuals engage in excessive spending, reckless behaviors, drastic decision making, drug abuse, hypersexuality |
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What is a Type I bipolar disorder? |
Depression + episodes of SEVERE mania (hypermania) |
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What is a Type II bipolar disorder? |
Depression + less-severe mania (hypomania) |
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What are some mood changes associated with Mania in Bipolar Disorder? |
Long periods of feeling high, overly happy, outgoing
- extremely irritable mood, agitation, feeling jumpy or wired |
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What are the behavioral changes with Mania in Bipolar disorder? |
talking fast, jumping from one idea to another, racing thoughts, really distracted, increased goal-directed activities, restless, sleeping little, unrealistic belief in one's abilities, impulsive behavior, spending sprees, impulsive sex, impulsive business investments
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Areas of reduced activity in the ____ and _____ of the _______ hemisphere have a tendency to produce manic episodes.
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frontal, temporal, right |
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Areas of the left hemisphere have a tendency to produce ____ episodes. |
depressive |
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functional MRI in bipolar disorder reveals areas of excessive activity in cortical white matter areas. What are they called? |
Unidentified bright objects (UBOs) |
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What can be considered a mood stabilizer? |
Lithium - an effective treatment for bipolar disorder, provides greater efficacy for mania than depression
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What are the adverse effects of lithium treatment? |
Lithium concentrations have to be controlled. AT high concentrations (1.5 to 2.0 mEg/l) --> gastrointestinal effects like nausea, vomiting, diarrhea - thirst, increased urination, tremor 2.0-2.5 mEg/L --> produces renal failure and muscle rigidity |
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At what concentrations does lithium have therapeutic effects?
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0.6 to 0.8 mEg/l (this dose must be maintained after 2 weeks of using it) |
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What enzyme promotes apoptosis and regulates inflammation?
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Glycogen synthase kinase (GSK-3) |
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What is the effect of lithium on bipolar disorder (neuroprotective effects) |
Can cause neurodegeneration --> lead to cortical abnormalities |
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What are anticonvulsant drugs? |
Positive modulators for GABA[a] receptors |
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What is the mechanism of anticonvulsant drugs? |
They inhibit Na1 functioning, inhibit GSK3 activity (similr to lithium) --> high frequency action potentials - treats bipolar disorder - reduces manic symptoms |
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What happens if GSK3 enzyme activity is inhibited? |
Wit decreases behavioral activity, decreased immobility time in swim tests (antidepressant effects(, increase hyperactivity (mania) |
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What is an atypical antipsychotic drug?
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it treats BD - safer than lithium - after 3 weeks of treatment: 50% of participants were responsibe to the olamzapine |
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What is an anxiety disorder? |
It can be classified as the following according to DSM IV: 1. panic disorders 2. specific phobias 3. social phobias 4. OCD 5. PTSD 6. generalized anxiety disorder |
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What is agoraphobia? |
The fear of being in a situation that you can not escape (will feel embarrassed) |
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What are panic attacks? |
Strong physiological fear responses associated with intense apprehension, fearfulness, or terror |
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What are specific phobias? |
Phobia towards a specific object or situation |
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Panic attacks are often mistaken for a _____ _____. |
heart attack |
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What is a social phobia? |
It is also known as social anxiety; the fear of being in or performing in social situations |
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What is OCD (obsessive compulsive disorder?) |
when anxiety arises over obsession and compulsive behavior
- attempting to reduce the obsession by catering to it |
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What is DSM's definition of OCD? |
Persistent ideas, thoughts, impulses, or images experienced as intrusive and inappropriate, cause marked anxiety or distress |
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What is post-traumatic stress disorder?
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State of physiological arousal, exaggerated response to stimuli, often occurs due to a traumatic event - flashbacks of the event |
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What is a generalized anxiety disorder? |
Defined as excessive worrying about events, individuals, activities - genetic risk: 30-40% of anxiety disorder diagnoses |
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How does increased anxiety affect the amygdala?
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It causes a state of fear and anxiety, thus increases amygdala activity - amygdala dysfunction occurs in every type of anxiety disorder except OCD |
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what causes OCD? |
abnormal functioning in thalamus, cingulate cortex, prefrontal cortex, orbitofrontal cortex, basal ganglia and nucleus accumbens
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What are the two pathways that the amygdala receives information from? |
1. thalamo-amygdala pathway
2. thalamo-cortical-amygdala pathway |
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What is significant about the thalamo-amygdala pathway? How is it different from the latter pathway? |
The thalamo-amygdala pathway is a short route, that sends crude/unprocessed sensory info DIRECTLY to the amygdala example: hearing a loud noise, but not knowing what it is/where its coming from. |
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What makes the thalamo-cortical-amygdala pathway different from the thalamo-amygdala pathway?
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It is a long route. Information about what the stimulus is gets processed through the cerebral cortex. |
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What is the role of the hippocampus during information processing to the amygdala?
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The hippocampus acts to send information on the CONTEXT of the stimulus to the amygdala |
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What is the role of the prefrontal cortex when it sends information to the amygdala? |
Its role is to decide how to react to the stimulus
- can reduce amygdala activity --> inhibited reaction to fearful stimulus - also impt for extinction of fear conditioning (i.e, unlearning that a stimuli is fearful) |
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After receiving fear-related stimuli, where does the amygdala send output signals to? |
PFC (note that the amygdala can even receive signals from here), hypothalamus, locus coeruleus |
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what are the roles of the hypothalamus and locus coerulus when receiving fear-related info from the amygdala? |
- facilitate physiological reactions to fear (activated sympathetic nervous system) |
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Describe the pathway of receiving a fear-related signal from the amygdala
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signals from amygdala and hypothalamus --> goes to locus coeruleus --> causes release of ACh from presynaptic ganglion cells (symp nerv system) --> release epinephrine and norepinephrine via adrenal glands --> increase respiration, heart rate, BP, sweating |
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Individuals with panic disorder appear less sensitive to CO2-induced panic than individuals with other anxiety disorders. True or false? |
False. They are MORE sensitive to CO2-induced panic. |
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What is the general adaptation syndrome? |
Stress occuring in the following steps: 1) Alarm stage, 2) Resistance, 3) Exhaustion
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What happens during the alarm stage of the general adaptation syndrome? |
- increased physiological arousal - hypothalamus activates the sympathetic nervous system |
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What happens during the resistance stage of the general adaptation syndrome? |
- maintaining physiological arousal in response to prolonged stress - hypothalamus releases ACTH from pituitary glands Adrenal glands release cortisol - increased metabolic activity, immune system activity |
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What is the hypothalmic-pituitary-adrenal axis (HPA)? |
It is the combined distinct roles in stress response (combined structures involved in stress response) |
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What happens during the exhaustion stage of the general adaptation syndrome? |
the body cant maintain the high levels of physiological arousal, so it impairs the immune system function and reduces metabolic activity |
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What are the two phases that refer to changes in hormone or neurochemical levels? |
Tonic phase and phasic phase |
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What is the tonic phase? |
It is a baseline state - in PTSD, there can be altered levels of cortisol before a traumatic event, or altered cortisol levels during a normal day after being diagnosed w/ PTSD |
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What is the phasic phase?
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It occurs during a stressful event - For PTSD, it can be the actual traumatic event that led to PTSD, or the presence of stimuli that triggers reminders of the traumatic event |
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What are two anxiolytic drugs mentioned in this course? |
Barbiturates and benzodiazepenes. |
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What are anxiolytic drugs? |
Drugs that treat anxiety |
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What are the categories of barbiturates by time course? |
Long-acting barbiturates and ultra-short acting barbiturates |
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What are long-acting barbiturates?
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They take about 1 hr to take effect, effects last for 10-20 hours - poor lipid solubility - low metabolism (takes longer for degradation) |
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What are ultrashort-acting barbiturates? |
produce effects within 10-20 seconds
- last approx 30 mins - high lipid solubility - high metabolism |
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What is hexobarbital? |
The first barbiturate capable of producing general anesthesia |
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Why are barbiturates served as drugs of abuse? |
Short-acting barbiturates were commonly abused in the 1960s - barbiturates = "downers" - have positive reinforcing effects - rewarding effects - reduced anxiety, but also produced feelings of well-being and lowered inhibition |
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How do barbiturates cause respiratory depression? |
It causes inhibitory effects at the medulla - causes respiratory depression |
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How do people accidently overdose on barbiturates? |
They have memory-impairing effects, so people forget if they took it earlier --> leads to overdose - increases during long-term usage --> shrinking therapeutic index |
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What is a barbiturate abstinence syndrome? |
It is characterized by anxiety, muscle weakness, and abdominal pain - when u stop taking barbs - severe case: developing seizure at higher doses |
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Barbiturates facilitate GABA neurotransmission. True or false? |
True. This is how they produce pharmacological effects. |
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What is the mechanism of barbiturates on GABA receptors? |
1. barb binds to the barb site on GABA[a] receptors (acts as a positive modulator to enhance inhibitory effects of GABA)
2. GABA[a] receptors located at amygdala, thalamus, cerebral cortex, and medulla |
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How do barbiturates cause anxiolytic effects?
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inhibition of amygdala activity |
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How do barbiturates cause sedative effects?
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Suppressing cortical functioning and structures important for cortical arousal |
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What are benzodiazepines? |
Anxiolytic drugs, made after barbiturates |
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What physiological dependence factors is benzodiazepene characterized by? |
anxiety, mania, suicidality, convulsions (occur after withdrawal of chronically-used benzodiazepines) |
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Even when physical dependence develops in chronic use of benzodiazepenes, psychological dependence also develops. True or false?
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False. Psychological dependence does not develop. |
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What are the 4 points that prove Benzodiazepines have low abuse potential? |
1. physical dependence develops, but not psychological dependence. 2. patients dont develop tolerance to benzodiazepines 3. most patients use benziodiazepines appropriately 4. patients use it for brief periods, rather than long-term/frequently |
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What kind of receptor is a GABA[a] receptor? |
An ionotropic receptor - 5 subunits (2a, 2b, and 1 y/delta/epsilon) - each subunit = multiple subtypes a subunit = 6 subtypes b subunit = 4 subtypes y subunit = 6 subtypes |
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Benzodiazepines have high affinity for benzodiazepine sites contained within an ___ subunit. |
alpha-1 |
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Which BZ sites does benzodiazepine have a lower affinity for? |
a2, a3, and a5 |
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What are BZ I and BZ II sites? |
BZ I: high affinity sites- contained in a1 subunit BZ II: low affinity sites, contained in a2, a3, and a5 subunits |
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where are BZ I sites highly expressed? |
Cerebellum, substantia nigra, and thalamus (this is why it disrupts balance, reduces seizures, produces hypnotic effects by inhibiting cortical arousal) |
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where are BZ II sites highly expressed? |
amygdala and hypothalamus - impt for anxiet and stress |
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What are endozepines? |
Endogeneous benzodiazepines - benzodiazepine receptors facilitate GABA binding |
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What are diazepam-binding-inhibitors?
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They reduce the binding of benzodiazepine to the BZ site. |
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What are anticonvulsant drugs used for? |
treating seizures, facilitating neurotransmission of GABA - treat anxiety |
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Antidepressant drugs can not treat anxiety. True or false?
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False. They can. |
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which antidepressant drugs help reduce and prevent anxiety? |
SSRIs and SNRI's - enhance elevations of serotonin in the brain - first line treatment for anxiety - approx 1/3 of patients dont respond to this - also help panic disorder, social phobia, GAD, and PTSD |
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What is Buspirone? |
A partial agonist for serotonin 5HT1A receptor
- produces anxiolytic effects -effective for general anxiety disorder |
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How exactly do antidepressants reduce anxiety? |
5-HT1a receptors are autoreceptors that inhibit serotonin release from the neuron - found on dendrites and somas - called "somatodendritic autoreceptors" - activation of the receptors --> inhibition --> prevent serotonin release - chronic activation of these receptors --> they become desensitized and release lots of serotonin |
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How do postsynaptic norepinephrine receptors located in the LOCUS COERULEUS reduce anxiety?
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- antidepressants increase norepinephrine levels - B1- adrenoceptors get desensitized - weak activation of the amygdala --> reduces anxiety |
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what is the alois alzhemier?
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Dementia in elderly patients, corresponding to degeneration of the cerebral cortex, hippocampus, and other parts of the brain |
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What is dementia praebox? |
Dementia in young adults - later changed to "schizophrenia" |
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Neurological Disorders |
neurological disorders stemming from a BIOLOGICAL cause |
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Psychiatric disorder |
No clear biological cause |
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What is schizophrenia? |
- a life long mental illness - disturbed thought processes - poor emotional responsivesness - positive and negative symptoms - deficits in working memory, reference memory |
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What are the positive symptoms of schizo? |
increase in abnormal behavior
- hallucinations - delusions |
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Negative symptoms
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reduction in normal behaviors - reduced emotional responsiveness - reduced social withdrawal - reduced movement - lack of motivation |
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what are the 5 types of schizophrenia? |
1. paranoid (+ symptoms) 2. catatonic (neg. symptoms) 3. disorganized (silly, immature emotional expressions) 4. undifferentiated (doesn't fit to any other category) 5. residual (the rest; less prominent symptoms) |
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What are treatment-resistant patients?
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no or minimal improvements after 2 trials with an atypical or typical antipsychotic drug |
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What is a sensory-gating deficit? |
- shown in many schizophrenic patients
- diminished capacity to filter out unimportant stimuli --> causes delusions (ex. in textbook = they are more sensitive to low frequency sounds and had a bigger reaction to it compared to normal people) |
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What is the purpose of the MATRICS program? |
seeks to identify cognitive featurs of schizophrenia -helps determine the best treatment strategies to reduce impairments |
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When is the first diagnosis for schizophrenia found in a person? |
During their late teens, early 20s - usually when ppl are born during winter months |
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What is the genetic basis of schizophrenia? |
2-3% risk --> if uncle or cousin 13% - if one parent 50% if both parents or identical twin has schizo |
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What is the prodromal phase of schizophrenia?
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Symptoms that are schizophrenia-like, occurs less frequently w less severity than the actual symptoms found in schizophrenia - mostly attention impairments - environmental factors can later make this become actual schizophrenia (due to responding to stress and life events) |
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What is the gene studied for the risk of schizophrenia? |
Disruption in the Schizophrenia 1 (DISC1) gene - affects cell migration --> leads to abnormalities in cellular networks |
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What are some structural differences found in schizophrenia that vary across diff patients (Found in neuroimaging studies)?
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- reduced volume size of: - left hemisphere (lateral + third ventricle + temporal lobe) - frontal lobe (prefrontal cortex, thalamus in left hemisphere) - hippocampus (both hemispheres) - disorganization of axons in cortical white matter - fewer stimuli going from thalamus to PFC |
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What is the neurodevelopment hypothesis for schizophrenia? |
Abnormal nervous system development leads to irregular neuronal signaling in the brain--> leads to schizophrenia characteristics - ex. genetics: altered neuronal growth & development --> impacts synaptogenesis and myelination --> can cause prodromal phase of schiz. |
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What does the term "schizophrenia"actually mean? |
"splitting of psychic functions" |
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What are some historical treatments for schizophrenia? (hint: they were horrible...) |
- frontal lobotomy (hemorrhaging of the brain)
- shock therapy - putting them into an ice bath - inducing flu - Chlorpromazine drug to manic patients --> induced calmness in patients |
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What is the dopamine hypothesis? |
It suggests that POSITIVE symptoms of schizophrenia come from EXCESSIVE dopamine release in the limbic system
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What is the glutamate hypothesis? |
Low levels of glutamate in the cerebral cortex and high levels of dopamine in the limbic system lead to symptoms of schizophrenia -diminished glutamate levels lead to low levels of DA in prefrontal cortex, but high DA levels in limbic system (a positive feedback loop) |
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what is a "typical" antipsychotic drug? |
reduces positive symptoms via mesolimbic D2 receptor antagonism and counteracting the high levels of DA - produces extrapyramidal side effects (EPS) |
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What are extrapyramidal side effects? |
Tremor, muscle rigidity, and involuntary movements |
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Describe the 3 types of extrapyramidal side effects. |
1. Tardive Dyskinesia: motor disorder, involuntary muscle movements in jaw, facial muscles, tongue (excessive lip smacking, licking) 2. Neuroleptic malignant syndrome (NMS): flu-like symptoms i.e. sweating, fever, changes in BP, heart rate, autonomic nervous system irregularities 3. Hyperprolactinemia: high levels of prolactin --> reduce lactation --> loss of libido, disrupted menstrual cycles, erectile dysfunction, hypogonadism |
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What are atypical antipsychotic drugs? |
They reduce positive and negative symptoms of schizo.
- Influence D2 and 5HT receptors - LOWER RISK of extrapyr side effects - good for patients that are usually treatment-resistant |
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Despite the positive effects of atypical antipsych. drugs, what are its adverse effects?
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- at high doses, can produce extrapyr side effects - NLS and hyperprolactinemia can occur (but low risk) - increased body weight --> type II diabetes - cardiovascular effect (QT interval prolongation) --> prolonged heartbeat --> cardiac arrest - produce agranulocytosis - reduced white blood cell count in immune system *must get regular blood tests to see WBC count* |
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What are the TWO primary hypotheses for the actions of atypical antipsychotic drugs? |
1. Atypical antipsychotic drug effects come from preferential antagonism of serotonin receptors (5HT-2A) 2. they do not block D2 receptors, as long as TYPICAL antipsychotic drugs do so |
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What happens when you combine the administration of an a2 adrenoceptor antagonist + a dopamine D2 receptor antagonist? |
Leads to atypical antipsychotic drug-like effects - prefrontal cortical dopamine release --> improves cognitic functioning and neg. symptoms - conditioned avoidance responding - catalepsy assessments |
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What happens when muscarinic receptor antagonists bind to the receptor? |
dry mouthcause dry eyes and
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What causes sedation? |
Clozapine: A histamin H1 receptor antagonist |
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How do antipsychotic drugs cause weight gain?
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Due to them binding to 5-HT2C receptors.
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What is considered to be a third generation antipsychotic drug? |
These are meds that don't match up with the other categories of antipsych drugs ex. Aripiprazole (abilify) - weak partial agonist for D2 R's, antagonistic effects on serotonin R's, safe for diabetes risk |
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How are antipsychotic drugs administered? |
Orally - in pill form.
- intramuscular injections -dissolvable pill -nasal spray |
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What is the active metabolite produced by antipsychotic drugs? |
Risperidone called "paliperidone" (an antipsych drug) |
