Part II Drugs

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Lecture 8
Part II - Drugs
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alcohol, opiates, nicotine, cocaine marijuana
Because plants have the same Neurotransmitters as
humans - drugs of abuse are derived from plants
or grains DRUGS OF ABUSE
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3,4-methylenedioxy-N-methamphetamine (MDMA)
Ecstasy

• Stimulant, amphetamine derivative
• Synthetic chemical - oil of the sassafras tree
• Patented (Merck) 1914
• 1976 Dr. Alexander Shulgin (pharmacologist)
  used as a
• psychotherapeutic tool difficult inter
  personal issue
• appetite suppressant (1986-DEA)

• Behavioral outcome
• emotional openness open up
• euphoria, stimulation
• reduction of critical and cynical thought

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• POSITIVE
• extreme mood lift
• increased willingness to communicate
• increase in energy (stimulation)
• feelings of comfort, belonging, and closeness to
  others
• feelings of love and empathy
• forgiveness
• increased awareness appreciation of music
• increased awareness of senses. (eating,
  drinking, smell)
• profound life-changing spiritual experiences
• fear dissolution
• sensations bright and intense
• urge to hug and kiss people

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• NEUTRAL
• appetite loss
• visual distortion
• rapid, involuntary eye jiggling (nystagmus)
• moderately increased heart rate and blood
  pressure (increases with dose)
• restlessness, nervousness, shivering
• change in body temperature regulation
• strong desire to do or want more when coming down
  

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• NEGATIVE (increase with higher doses and
  frequent use)
• trisma (jaw clenching), tongue and check chewing
  bruxia (teeth grinding)
• mild to extreme difficulty concentrating ST
  memory
• muscle tension
• erectile dysfunction and difficulty reaching
  orgasm
• hyperthermia, dehydration or hyponatremia
• nausea and vomiting
• headaches, dizziness, loss of balance, and
  vertigo
• post-trip Crash - unpleasantly harsh comedown
  from the peak effect
• hangover the next day, lasting days to weeks
• mild depression and fatigue for up to a week
• small risk of death Approx. 2 per 100,000 have
  extreme negative reactions
• resulting in death. (rare)
• Possible neurotoxicity (controversial)

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MOOD Pleasure 5HT DA temp state
of peace and love with
oneself the world
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Serotonergic Projections
Projections to the telencephalon diencephalon
Sleep, mood
Arousal, mood
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MDNA blocks reuptake of 5HT
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CON 2wks 7yrs
5-HT immunoreactive axons in monkeys
Note the reduction in axon density
2 weeks after MDMA exposure and the persistent
regional deficits in axon density 7 years after
MDMA exposure
Frontal Parietal Visual
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Survery of ecstasy users (2001) 9.2 - 12th
graders 6.2 - 10th graders 3.5 - 8th
graders College students 2.4 15
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• Lysergic acid diethylamide (LSD)
• first synthesized from a fungus that grows on
  rye
• and other grains
• 1938 - Albert Hofmann (Sandoz) produced LSD for
  
• the first time ? New drug to stimulate
  circulation
• and respiration flop
• 1943 - Hofmann accidentally ingested (or somehow
  
• absorbed) a bit of LSD and experienced some of
  
• the psychedelic effects of this chemical
  dizziness,
• visual distortions and restlessness

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A few days later he prepared 0.25 mg (0.05-0.10
mg) of LSD in water and drank it. He again
experienced the mood and thought altering effects
of LSD
Hallucinogens or Psychedelics These drugs can
cause auditory, visual or somatosensory
hallucinations, paranoia or dream-like states
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• Behavioral Effects
• Feelings of "strangeness"
• Vivid colors
• Hallucinations
• Confusion, panic, psychosis, anxiety
• Emotional reactions like fear, happiness or
  sadness
• Distortion of the senses and of time and space
• "Flashback - even after months or even a year
• Increases in heart rate and blood pressure
• Chills
• Muscle weakness

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How LSD works??? not completely known Chemical
structure similar to 5HT Agonist/Antagonist
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Serotonergic Projections
Projections to the telencephalon diencephalon
Sleep, mood
Arousal RN inhibitory ascending Signalsprotec
ts the brain from sensory OverloadLSD causes
DISINHIBITION ..decreases the firing of 5HT
neurons
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Mushrooms (..that contain hallucinogens)
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Effects on the Nervous System Psilocin Serotonin
ergic agonist ? blocks reuptake of 5HT Binds to
5HT receptors
Muscimol and ibotenic (Amanita muscari) GABA ?
Muscimol GABA agonist
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• Phencyclidine (PCP) (stimulant, depressant,
  analgesic, hallucinogen, dissociative)
• developed in 1950s as IV anesthetic
• used in veterinary medicine
• stopped after some people experienced psychotic
  rx
• dissociative anesthetic out of body experience
• not visual hallucinations but causes changes in
  body image
• In addition to these distortions of reality, PCP
  can cause frightening side effects such as
  feelings of terror and confusion.

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People do crazy things on PCP!
In a study of 1000 episodes of PCP intoxication,
unpredictable outbursts leading to shootings,
stabbings, grotesque murders self-inflicted
injuries occurred in 35 of the cases 32 of the
users displayed bizarre behaviors ?wandering
about nude in public ?lying down in the middle
of a busy street ?driving 10 mph on the freeway
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Effects of PCP on the Brain (multiple
NT) inhibits the reuptake of dopamine,
norepinephrine and serotonin inhibits
glutamate by blocking receptors NMDA
(N-methyl-D-aspartate) Some types of opioid
receptors in the brain are also affected by PCP
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Many natural substances affect the functioning of
synapses plants Many animals release chemicals
that affect functioning of synapses -
snakes spiders
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Natural Cholinergic Agonist and Antagonists
ACh
Addiction-DA
salivation , sweating, tears
swelling, Muscles rigid, abdomen back
mydriatic, HR spasmolytic, memory
Dbl. Vision swallowing, Res. suffocation
Paralysis, Respir. fail
Paralysis
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