Drug Dependence Test 3

When was stimulant misuse most prevalent?

most stimulants’ use surged in 1980-1990s and tailed off considerably since

What is the general order of peak use of stimulants?

amphetamines, then cocaine, then methamphetamine, then back to prescription amphetamines

What does it mean for a stimulant to be an indirect sympathomimetic?

indirectly activate the sympathetic nervous system (the “flight or fight” system)

What amphetamines are indirect sympathomimetics

d-amphetamine, methamphetamine, phenmetrazine, methylphenidate, d and l amphetamine

What are differences between cocaine and methamphetamine

cocaine has a shorter half life, methamphetamine is more potent and they are equally effective

how are stimulants attributing to overdose risk?

second most likely source of overdose risk behind all sorts of opioids. heavy recent overlap between stimulant overdose and co-abuse with opioids, or possibly opioid-tainted stimulants. most new overdose risk associated with methamphetamine risk

What fight or flight mechanisms do stimulants activate?

alertness/energy and movement, heart rate, blood pressure, less sleep, body temperature increase

List methylphenidate, methamphetamine, cocaine, cathinone, amphetamine, and caffeine from highest to lowest efficacy and potency

Methamphetamine = Amphetamine > Cocaine > methylphenidate > cathinone > caffeine

Which routes of administration produce highest plasma concentration

IV/smoked is fast on/off, nasal is fast-ish on and more stable, oral slow on and slow off

What is the pharmacology of stimulants?

reuptake blockers and mixed releasers, cocaine is a specific dopamine reuptake blocker, most other amphetamine and cathinone class both block reuptake and cause neurotransmitter release. SSRI and SNRI drugs and selective reuptake blocker. primary targets are dopamine, serotonin, and norepinephrine. cocaine targets all roughly equally, most others less serotonin. chronic use causes desensitization and loss of DAT, SERT, D1, receptors (mediate positive effects), and most sensitively D2 receptors (mediate aversive effects)

what are stimulant behavioral effects?

euphoria (increased talkativeness and confidence, supreme sense of well-being, improves performance, alleviates fatigue, decreases appetite (anorexic), increases violence, increases sexual motivation)

What is stereotyped behavior associated with stimulants?

integrated behavioral sequences that acquire a stereotyped (simplified) character being performed at an increasing rate in a repetitive manner. A decreased amount of response categories but the rate of behavior increases.

what is punding

a stereotyped stimulant behavior. goal directed but meaningless activity.

what is catatonia

a stereotyped stimulant behavior. immobility caused by rigidity

what is stimulant paranoia

psychosis, unable to recognize reality. cognitive stereotyped behavior

what are physical effects of stimulant use

activates the autonomic nervous system. increased heart rate, increased blood pressure, increased body temperature (hyperthermia), dilated bronchial tubes

what are physical syndromes from stimulant use

physical pathology- akathisia (urge to be in motion), akinesia(lack of movement), tremors, dyskinetic movements (abnormal, involuntary movements), skin picking(stereotyped behavior), tooth loss (meth mouth)

what are symptoms for the crash stage in stimulant acute withdrawal

depression, lethargy and sleepiness, increased irritability and anxiety, suicidal tendencies

what is the psychostimulant addiction cycle

euphoria → dysphoria → paranoia → psychosis

what are the stimulant overdose risks?

hemorrhagic stroke, seizure, infarction/arrhythmia , heart failure, ischemic injury

what are the stimulant chronic use consequences

sexual dysfunction, septum deterioration, heart infections, ulcers, renal failure

what is the treatment for stimulant addiction?

cocaine anonymous , contingency contracting, cognitive behavioral therapy, psychotherapy

what are the medical uses for cocaine?

topical anesthetic, vasoconstrictor , local anesthetic

what are medical uses for amphetamines?

narcolepsy, ADHD, weight control

what is the diagnostic criteria for ADHD?

inattention, hyperactivity, impulsivity

what is the most used psychoactive substance?

caffeine

what are the three methylxanthines

caffeine, theophylline, theobromine

what are behavioral effects of caffeine

latency to fall asleep, mild euphoria, sustain performance in times of fatigue

what are medical uses of caffeine

dietary supplement, analgesia, migraines (vasoconstriction in brain), asthma (bronchial dilation)

what are the effects of caffeine at 50-200 mg?

sleepy first 5 min, stimulant properties

what are the effects of caffeine at 300-1000mg

stimulant, exaggeration of side effects

what are the effects of caffeine at 1000+ mg

caffeinism, GI disturbances, cardiac arrhythmia, symptoms of generalized anxiety disorder

what are health concerns of daily high doses of caffeine

incidence of heart attacks, risk of coronary artery disease, low birth weight of babies, ulcers, calcium bone density, acute toxicity

what is the tolerance of caffeine

takes 3-5 days to gain/lose tolerance , no cross tolerance to other stimulants

what are withdrawal symptoms of caffeine

dysphoria, fatigue, irritability, nervousness, nausea, muscle pain, difficulty concentrating, headache

what are hallucinogens

substance that produces perceptual and cognitive distortions. classical ones do so without producing toxic delirium

what a psychedelic

“mind manifesting” produce profound changes in consciousness and perception

what does entheogenic mean

create god within"

what schedule are hallucinogens

Schedule I

what are the 5 tryptamines?

serotonin, psilocybin, bufotenine, LSD, DMT

what are the 6 substituted phenethylamines?

dopamine, norepinephrine, mescaline, methamphetamine, MDA/MDMDA

what is the serotonin pathway in the brain

partial/full agonist at 5HT2A(5-hydroxytryptamine) subtype of serotonin receptors

how do 5HT2A receptors produce effects on the body

GPCRs linked to complex behaviors and neuropsychiatric disorders. centrally(cognition, memory, schizophrenia, depression) and peripherally(vasoconstriction , bronchoconstriction)

what are acute sympathomimetic effects of hallucinogens

elevated heart rate and blood pressure, elevated temperature, pupillary dilation, psychomotor stimulation, euphoria

what are acute subjective and psychological effects of hallucinogens

labile moods, altered thought processes, altered perception, perception of insight, impaired judgement

why are hallucinogens unique experiences

no two trips are alike, individual neurochemistry set-mindset and setting-enviroment play a role on your experience.

what is the tolerance of hallucinogens

classical hallucinogens produce rapid tolerance. impacts abuse/use patterns. cross tolerance prevents switching

what is the dependence rate of hallucinogens

can be produced in animal models but is not seen in humans

what are adverse events produced by hallucinogens

impaired judgement, bad trips, psychosis, flashbacks (HPPD), vascular effects, neurotoxicity, depression

What hallucinogens are commonly adulterated/contaminated as street drugs?

anticholinergic hallucinogens (atropine, scopolamine) are sometimes contaminated. can cause delirium, amnesia, and anticholinergic poisoning. treated with physostigmine. potent synthetic hallucinogens can also be contaminated

what are common uses of hallucinogens

religious purposes, creativity/art, psychotherapy, biochemical warfare, headaches, abuse

what are psychotherapy uses of hallucinogens

end of life anxiety/depression, OCD, PTSD, treatment resistant depression, substance abuse

why is psilocybin a breakthrough therapy

is used for treatment resistant depression. increases: neuroplasticity, dendritic spines formation and growth, axon branching synapse, fromation

what is LSD mechanism of action

5HT1A agonist - presynaptic autoreceptor
Decreases activity of serotonergic neurons

what is LSD used to treat?

used to treat generalized anxiety disorder

what is microdosing

chronic and intermittent low doses that can have beneficial effects on mood, anxiety, cognition, social interaction, creativity, concentration, and spiritual awareness. an effect noted was an increase in anxiety levels. A limited number of preclinical studies suggest antidepressant effects and improvement of fear associated behavior (model of PTSD) IN SUBSETS of subjects
but also showed negative physiological side effects

what are LSD pharmacokinetics

taken orally, very potent, lipophilic, very high therapeutic index

what are LSD physiological effects

slight increase in heart rate and blood pressure, pupils dilate, increased body temp

what are subjective effects of LSD across time

somatic phase(sympathomimetic euphoria, restlessness), sensory phase (begins with simple distortion and becomes increasingly complex), and psychic phase(timelessness, ego disintegration, profound insight)

what are the effects of psilocybin/psilocin

similar hallucinogenic effects to LSD but more visually and emotionally intense, greater incidence of side effects. unpleasant taste, potency varies with growing conditions, species, breakthrough drug for depression

what is DMT

made from synthetic and natural sources, “buisnessman’s LSD”

what are substituted phenethylamines

cross between hallucinogens and stimulants that have stronger rewarding effects. at a low dose they are stimulant like and at a moderate dose they are hallucinogenic

what is mescaline

derived from peyote cactus, used by Native Americans past and present, orally active, duration of action up to 10 hours, effects similar to LSD and other hallucinogens

what is bromo dragonfly

a synthetic phenethylamine, very potent and long lasting. vasconstriction due to alpha1 agonist activity leads to toxicity

what are NBOMe compounds

5HT2a full agonist. toxicities noted are agitation, tachycardia, hypertension, seizures, death

what is MDMA (XTC, Ecstasy, Molly)

a stimulant at low doses and a hallucinogen at high doses(better defined as entactogen/empathogen)

what is the mechanism of action for MDMA

potent releaser of 5HT, DA & NE. uptake via monoamine transporter → disrupt vesicular storage → increase cytoplasmic transmitter levels → reuptake transporter reversal. also causes indirect indirect oxytocin release.

what are acute toxicity effects of MDMA

hypertension, cardiac effects, hyperthermia, renal failure , seizure

what are chronic toxicity effects of MDMA

5HT neuronal damage/death, paranoid psychosis, HPPD

what are toxic drug interactions of MDMA

serotonin syndrome, competition for metabolism

What are general effects and properties of dissociative agents

amphetamine like effects, classical CNS depressant effects with hallucinogenic properties

what are the stimulant like effects of dissociative agents

pressor effects, increased motor activity, stereotyped behavior, enhancement of amphetamine effects, schizophrenogenic

what are the CNS depressant effects of dissociative agents

motor impairment, anticonvulsant, additive effect with other depressants, anti-anxiety effects in animals, convulsant effects during withdrawal

what are characteristics of dissociative anesthesia

Sympathomimetic anesthetic: respiration normal or increased, blood pressure increased, reflex activity or exaggerated, nystagmus, insensitivity to pain, amnesia, poor muscle relaxation, emergence delirium

what is a Sympathomimetic anesthetic

type of anesthesia produced is very dissimilar from inhalation and barbiturate anesthesia

what is the mechanism of action for dissociative agents

antagonist of (NMDA) receptors. important excitatory neurotransmitter system-glutamate as neurotransmitter . ligand-gated ion channels. normal activation of NMDA receptors are important for learning and memory, CNS development and neuronal adaptation. PCP and ketamine bind at a channel site preventing ion movement into the cell

what are potential beneficial effects of dissociative agents mechanism of action

NMDA receptor over activation has been associated with neuronal toxicity following stroke or brain injury as well as a number of chronic neurodegenerative disorders

what are inhalants

a heterogenous grouping compounds which are defined only by their route of administration

what are the use-based categories of inhalants

volatile solvents, aerosols, volatile anesthetics, nitrites, nitrous oxide, halocarbon gasses

what are physical signs of inhalant abuse

chemical odor on breath, spots or sores in or around the mouth, rhinorrhea(runny nose), red eyes, perioral dermatitis

what are common signs of inhalant abuse

chemical odor on breath, paint stains, hidden empty solvent, lack of coordination, disoriented appearance, slurred speech, inattentiveness

what are acute behavioral effects of inhalants

depressant/alcohol like intoxication, omnipotent feelings, loss of consciousness

what is the absorption and elimination route of inhalants

a large portion absorbed into the bloodstream is eliminated by the lungs unchanged rather than by metabolism by liver enzymes.

how are inhalants distributed in the body

distribution may be selective. the blood brain barrier and placental barrier easily corssed

what are the three classifications of inhalants

chemical structure, product type, and neurochemical actions

what are solvent containing inhalants

gasoline, paint thinners, permanent markers, spray paint, glues

what are some volatile solvents used for inhalants

aromatic hydrocarbons(toluene, xylene), chlorinated hydrocarbons, alkanes(pentane, hexane), ketones(acetone)

what are halocarbon gases used for

used as refrigerants, in computer dusters and in topical freezing sprays

what is ether abuse

abuse of diethyl ether by inhalation. “hoffmann’s drops” substitute for alcohol during temperance movement

what is the clinical use of nitrous oxide

must be administered in combination with oxygen, as an analgesic but a poor anesthetic, used as an analgesic and anxiolytic in dentistry

what is nitrous oxide mechanism of action

vitamin b12 is turned into methionine by methionine synthase. nitrous oxide disrupts action of this methionine synthase enzyme. methinone is necessary for maintenance of spinal cord so without it can lead to neuropathy

what are neurological symptoms of chronic nitrous oxide abuse

numbness and weakness in limbs, loss of dexterity, sensory loss, loss of balance, cognitive and emotional changes

what are akyl nitrates effect on the body

the effects are peripherally mediated. acts as a vasodilator, source of nitric oxide which causes smooth muscle relaxation

what are acute effects of nitrites

muscle relaxant effects, enhance sexual performance and pleasure, may be used to treat angina or an antidote to cyanide poisoning

what is the neurochemical classification of inhalants

most inhalants are CNS depressants. inhalants do not appear to act upon the same receptor sites as ethanol, barbiturates, and benzodiazepines

what neurotransmitter receptors does inhalants act on

GABA, NMDA, 5-HT

what is the meyer-overton correlation

inhalants are disordering the lipid bilayer, pushing different components in the bilayer and causing CNS changes

how do inhalants influence GABA neurotransmitters

GABA is an inhibitory amino acid neurotransmitter. inhalants make GABA work better, responsible for maintaining inhibition in the CNS.

how do inhalants influence NMDA neurotransmitters

NMDA is a sub-type of glutamate receptor. glutamate is an excitatory amino acid neurotransmitter. Calcium goes through NMDA receptors. When an NMDA receptor opens, Ca goes in. makes the neuron less negative and more likely to fire. inhalants mimic actions of ketamine and will block the action of Ca and the NMDA receptor. inhalants inhibit transmission at NMDA receptors.

what are long term consequences of inhalant abuse

inhalants may damage the brain (demyelination) , cerebral cortex(personality changes, memory impairment), cerebellum (loss of coordination, slurred speech), ophthalmic nerve(eyesight), brain will shrink, cause huge ventricles