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Psychoactive Agents. Stimulants Psychodelics. Psychoactive stimulants. Stimulants: activate the central nervous system to produce arousal, increased alertness, elevated mood Typically affect dopamine, norepinephrine and serotonin Several drugs in this category Cocaine

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psychoactive agents

Psychoactive Agents

Stimulants

Psychodelics

psychoactive stimulants
Psychoactive stimulants
  • Stimulants:
    • activate the central nervous system to produce
      • arousal,
      • increased alertness,
      • elevated mood
  • Typically affect dopamine, norepinephrine and serotonin
  • Several drugs in this category
    • Cocaine
    • Amphetamine
    • Methamphetamine
    • Ritalin, Adderal, and most ADHD medications
    • Ephedrine
psychoactive stimulants3
Psychoactive stimulants
  • Cocaine,
    • extracted from the South American coca plant,
    • produces
      • Euphoria
      • decreases appetite,
      • increases alertness
      • relieves fatigue.
  • Cocaine blocks the reuptake of dopamine and serotonin at synapses,
    • Potentiating effect of these neurotransmitters
    • Makes neurotransmitter remain longer in synapse.
  • Presumably, cocaine produces euphoria and excitement because dopamine removes the inhibition the cortex usually exerts on lower structures.
psychoactive drugs
Psychoactive Drugs
  • Amphetamines
    • group of synthetic drugs
    • Again produce euphoria
    • increase confidence
    • In low doses: increases concentration.
  • increase the release of norepinephrine and dopamine
  • Common examples:
    • Amphetamine (Adderal®); Dextroamphetamine (Dexedrine®, Dextrostat®)
    • Methamphetamine (Desoxyn®)
  • Highly related:Ritalin:
    • Ritalina, Rilatine, Attenta, Methylin, Penid, Rubifen); and the sustained release tablets Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR. Focalin
amphetamine action
Amphetamine Action
  • DA neurons release DA into the synapse: From there 1 of 3 things can happen:
    • DA can then attach to the post-synaptic membrane
    • DA can be degraded by enzymes
    • DA can be taken back up by the pre-synaptic membrane.
  • Amphetamine appears to affect all three mechanisms:
    • Promotes release of DA into the synapse
    • Inhibits the DA degredative enzyme, monoamine oxidase (MAO),
    • Blocks the uptake proteins in the pre-synaptic membrane
  • The result : Amphetamine effectively promotes a flood of DA into the brain reward center:
    • Nucleus Accumbens or Nac
    • This area is highly involved in both learning and reward.
amphetamine action7
Amphetamine Action
  • Amphetamine and related compounds elicit a variety of dose-dependent deleterious effects.
  • low doses of AMPH may
    • improve attention
    • improve vigilance
  • At high doses:
    • over-stimulation of the motor and cognitive systems
    • behavioral stereotypy, repetitive thoughts and even hallucinations.
  • In rodents, a high AMPH dose elicits behavioral stereotypy:
    • continuous digging
    • Searching
    • Licking
    • Gnawing
    • Circling
  • In humans, high doses of AMPH may elicit:
    • psychotic state,
    • High rates of locomotion and repetitive behavior
    • high potential for self-injury or injury to others
psychoactive drugs nicotine
Psychoactive Drugs: Nicotine
  • Nicotine:
    • primary psychoactive and addictive agent in tobacco
    • Also in chewing tobacco, nicotine gum, etc.
  • It stimulates nicotinic acetylcholine receptors.
    • In the periphery,
      • it activates muscles
      • may cause twitching.
    • In CNS:
      • produces increased alertness
      • Also faster response to stimulation.
  • Given peripheral effects, why might individuals on antipsychotics or those with Parkinson’s like to smoke?
psychoactive drugs caffeine
Psychoactive Drugs: Caffeine
  • Caffeine:
    • active ingredient in coffee, many soda pops; teas; energy drinks, etc.
    • produces arousal, increased alertness, and decreased sleepiness.
    • Cardiovascular response: direct stimulation of the heart
      • mitigated to some extent by concurrent vagal stimulation.
      • CNS + PNS effects sometimes result in ventricular irritability
    • Also get direct vasodilation with concurrent vasoconstriction from stimulation of the medulla
      • Result: either increases or decreases in blood pressure.
    • Smooth muscle is relaxed by caffeine, while skeletal muscle is stimulated.
  • Action: blocks receptors for the neuromodulator adenosine
  • This increases the release of dopamine and acetylcholine.
    • Because adenosine has sedative and depressive effects, blocking its receptors contributes to arousal
    • Acts like amphetamine in releasing DA.
psychodelic drugs
PsychodelicDrugs
  • Psychedelic drugs:
    • compounds that cause perceptual distortions in the user.
    • May be referred to as hallucinogenic
  • Not really inducing hallucinations, but distortions in perception:
    • Light and color details are intensified,
    • objects may change shape,
    • sounds may evoke visual experiences,
    • light may produce auditory sensations.
    • Synesthesia: stimulation of one sensory or cognitive pathway leading to automatic, involuntary experiences in a second sensory or cognitive pathway
psychoactive drugs13
Psychoactive Drugs
  • lysergic acid diethylamide (LSD)
    • best-known psychedelic
    • is structurally similar to serotonin
    • stimulates serotonin receptors
    • Appears to disrupt the brain stem’s ability to screen out irrelevant stimuli.
  • psilocybin and psilocin
    • Another serotonin-like psychedelics
    • both derived from the mushroom,Psilocybemexicana
  • Mescaline
    • the active ingredient in peyote (the crown or button on the top of the peyote cactus),
    • psychedelic properties result from stimulation of serotonin receptors.
psychoactive drugs ecstasy
Psychoactive Drugs: Ecstasy
  • Ecstasy
    • street name for a drug developed as a weigh-loss compound
    • methlenedioxymethamphetamine (MDMA).
  • At low doses:
    • psychomotor stimulant
    • Increases energy, sociability, and sexual arousal.
  • At higher doses:
    • produces hallucinatory effects like LSD.
    • Also can overstimulate muscles resulting in “locked” or frozen muscles
  • MDMA stimulates
    • the release of dopamine which accounts for muscle and arousal effects
    • the release of serotonin, which probably accounts for the hallucinatory effects.
slide15

These brain sections have been stained with a chemical that makes neurons containing serotonin turn white. Photos in the top row are from a normal monkey; those below are from a monkey given MDMA a year earlier.

psychoactive drugs pcp
Psychoactive Drugs: PCP
  • Phencyclidine (PCP):
    • Developed as an anesthetic typically used by veterinarians
    • was abandoned for human use because it produces schizophrenia-like disorientation and hallucinations.
  • PCP increases activity in the dopamine pathways
    • This stimulates motivation system
    • Also, drug’s motivating properties apparently are partly due to its inhibition of a subtype of glutamate receptors.
marijuana
marijuana
  • Marijuana
    • is the dried and crushed leaves and flowers of the Indian hemp plant, Cannabis sativa.
    • The major psychoactive ingredient is delta-9-tetrahydrocannabinol (THC)
    • .
  • THC actions:
    • THC binds with cannabinoid receptors, which ordinarily respond to endogenous cannabinoids.
    • Two known cannabinoids receptors:
      • anadamide
      • 2-arachidonyl glycerol, or 2-AG.
      • These receptors are found on axon terminals;
  • Unusual action:
    • cannabinoids are released by postsynaptic neurons
    • act as retrograde messengers, regulating the presynaptic neuron’s release of neurotransmitter.
addiction
Addiction
  • Reward refers to the positive effect an object or condition – such as a drug, food, sexual contact, and warmth – has on the user.
  • Drug researchers have traditionally identified the mesolimbicortical dopamine system as the location of the major drug reward system.
    • It takes its name from the fact that it begins in the midbrain (mesencephalon) and projects to the limbic system and prefrontal cortex.
    • The most important structures in the system are the nucleus accumbens, the medial forebrain bundle, and the ventral tegmental area.