psychoactive stimulants

3 CNS stimulant types (from least to most psychological effects)

respiratory stimulants + convulsants

psychomotor stimulants

psychotomimetic stimulants

List 2 respiratory stimulants/convulsants

bicuculline

picrotoxin

bicuculline moa

competitive antagonist of GABA A receptors (block Cl- flux lead to decreased hyperpolarization and increased neuronal firing)

picrotoxin moa

non competitive antagonist (has its own binding site) of GABA A receptors(block Cl- flux lead to decreased hyperpolarization and increased neuronal firing)

effects of resp stim/convulsants occur primarily in which center

vasomotor center

what are resp stimulants/convulsants used for

Tx of resp failure

styrchnine moa

blocks glycerine receptors in the spinal cord

increases reflex excitability and causes violent muscle spasms

powerful convulsant

ephedrine moa

alpha and beta adrenergic agonist

many sympathomimetic effects (ex: bronchodilation)

increase the release of NE and leads to psychostimulant effects

mild-mod effects of psychomotor stimulants

mood amplification, heightened energy, sleep disturbance/insomnia, motor excitement, restlessness, talkativeness, inflated self esteem, increased sexual drive, anger, verbal aggression, mild to mod anorexia, sympathomimetic actions (Increase BP and HR)

severe effects of psychomotor stimulants

irritability, hostility, anxiety, fear, withdrawal, extreme energy/exhaustion, total insomnia, compulsive motor stereotypes, rambling, incoherent speech, disjointed, flight of ideas, decreased sexual interest, possible extreme violence, total anorexia, delusions of grandeur

cocaine is derived from

erythroxylon coca

cocaine use

local anesthetic

cocaine moa as a local anesthetic

Block Na channels stopping AP in neurons = block pain

users of cocaine usually desire more in how long

10-30min

cocaine metabolism/excretion

metabolized in liver, excreted in urine

how does cocaine cause intense/immediate euphoria

rapidly absorbed intravenously, by smoke or nasal inhalation

half life of cocaine

50 min

cocaine causes blockade of….

reuptake of NE, DA, 5HT

low dose cocaine prefentially affects…

NE reuptake

moderate dose cocaine preferentially affects..

NE and DA reuptake

high dose cocaine affects….

NE, DA, 5HT reuptake

chronic use of cocaine effects

enhancement of NE, DA, 5HT

examples of psychostimulants

amphetamine, methylphenidate, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA)

amphetamines absorption

readily absorbed from GI tract + nasal mucosa

freely penetrate BBB

excretion of amphetamines

excreted unchanged in the urine

half life of amphetamines

5-20hr

explain how fast tolerance to different effects occurs with amphetamines

tolerance develops rapidly to sympathomimetic effects and anorexic effects

tolerance develops more slowly to euphoric effects and locomotor effects

physical withdrawal syndrome not as profound as other drug classes

amphetamine MOA

1. amphetamines block reuptake of NE/DA (and 5HT at high doses)

2.cause additional release of NE by unknown mechanism of NT that are already packaged up

3.minor mechanism- inhibit breakdown by MAO, any NT that makes it back into neuron just gets repackaged right away

amphetamines used for ADHD

methylphenidate, dexmethylphenidate, lisdexamfetamine

ADHD is related to abnormal __________

DA Pathways

amphetamines used for narcolepsy

dextroamphetamine, methylphenidate, amphetamine/dextroamphetamine mix

amphetamines used for obesity

dextroamphetamine

long term negative effects of methamphetamine use

degradation of neuronal tissue.

areas of greatest loss are limbic system (emotion, reward), hippocampus (memory)

nicotine is derived from

nicotiana tabacum

2 main parts of reward pathway

nucleus accumbens, ventral tegmental area

examples of methylxanthines

caffeiene, theophylline, theobromine

what do methylxanthines not cause that other psychostimulants cause

do not cause euphoria or behavioral patterns typical of other psychostimulants

does tolerance occur to methylxanthines

yes- rapidly, therefore a slight physical withdrawal withdrawal syndrome can occur (h/a, fatigue, nausea)

caffeine is derived from

coffea arabica

caffeine moa

caffeine blocks A2 adenosine receptor- which blocks GABA release in prefrontal cortex= results in stimulation

caffeine blocks A1 receptor which increases cAMP and results in psychomotor stimulation

caffeine also blocks phosphodiesterase (PDE usually breaks down cAMP) therefore increase cAMP and cause stimulation

3 steps in the addiction process

1. drug use gives immediate positive effects

2. effects lessen w/ repeated use

3. attempts to stop result in negative effects

what happens to set point signal with drug use

euphoria from drug increases set point and have to take more to match it

2 lever drug discrimination

one lever is for water, one lever is a drug that is being screened to be marketed

train rats to discriminate brain btwn water and drug

if they choose water over PCP (drug being tested) prob a sign that theres no hallucinogens/addictive properties present

stimulants effects on pathway of reward

inhibit DAT = increase dopamine projects to nucleus accumbuns which causes you to feel good

proposed reason as to why cannabinoids are less addictive than other stimulants

receptors on GABA and Glutamate neurons are both inhibited therefore they cancel eachother out

sensory effects of psychedelics

changes in sense or perception or time

hallucinations, including seeing, hearing, touching or smelling things in a distorted way or perceiving things that do not exist

intensified feelings and sensory experiences (brighter colors, sharper sounds)

mixed senses (seeing sounds or hearing colors)

impulsiveness and rapid emotional shifts that can range from fear to euphoria, with transitions so rapid that the user may seem to experience several emotions simultaneously

physical effects of psychadelics

increased energy and HR

nausea

dizziness and sleepiness

increased BP, HR, body temp

loss of appetite, dry mouth, and sweating

numbness, weakness and tremors

list some psychomimetics

mescaline

psilocybin

dimethyltryptamine

mescaline is from what

peyote buttons

psilocybin is from what

mushrooms

what does ayahuasca do

inhibits MAOI (which can break down dimethyltriptamine) therefore you can take dimethyltriptamine orally and absorb it

dimethyltriptamine gets broken down normally when taken oral

example of a plant that has dimethyltriptamine

psychotria viridis

what do LSD and other hallucinogens resemble

serotonin

what receptors do LSD and other hallucinagens work thru

type 2 serotonin receptors primarily

what part of the brain do LSD/hallucinogens tap into while awake

rostral and caudal raphe nuclei

what are raphe nuclei involved in

RAS- involved with sleep/awake states

dream in stage 3,4, REM

Ibogaine is derived from

tabernathe iboga

name an effect that ibogaine causes

oneirophrenia- dream like state

what is ibogaine used for

treating addiction

which parts of the brain does psilocybin affect in Tx resistent depression

1. amygdla in limbic system

2. prefrontal cortex (judgement)

what types of conditions have psilocybin been studied in

treatment resistant depression, anxiety, bipolar, alcohol use disorder

what types of conditions have MDMA been studied in

PTSD/Tx resistent depression

ketamine effects on NMDA receptor

blocks it