SOCW 4340 Introduction to Alcohol/Drug Addiction

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SOCW 4340Introduction to Alcohol/Drug Addiction

• CHAPTER 6 All Arounders

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Hallucinogens/Psychedelics

• Alterations in cortical functions
• Cognition
• Perception
• Mood

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Hallucinogens/Psychedelics

• Tetrahydrocannabinol (THC)
• From Cannabis sativa
• Active ingredients
• ?9-tetrahydrocannabinol (major component)
• Cannabinol
• Cannabidiol
• Marijuana.Bhang lower grade leaves/stems 2-5
  THC
• Hashish/charas resin of female flowers 10-20
  THC
• Ganja/sinsemilla tops of female plants 5-8 THC

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Hallucinogens/Psychedelics

• THC
• Primary effects
• Disruption of attention
• Impaired short-term memory
• Altered sensory awareness
• Analgesia
• Altered motor/posture control
• Immunosuppressive?
• Structurally unrelated to other drugs
• Binds to specific cannabinoid receptors

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Hallucinogens/Psychedelics

• THC
• History
• Millennia used as mild intoxicant
• Few native cultures use medicinally
• Introduced to West in mid-19th century
• 1920s-40s Reefer Madness
• 1990s medical marijuana laws
• Future
• Have current laws been effective?
• Should THC be available for medical use?
• In what form?
• Recreational THC?
• What would be the effect of legal THC?
• What to do?????

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Hallucinogens/Psychedelics

• THC
• Cannabinoid Receptor
• Inhibits adenylate cyclase
• Receptors found on presynaptic terminals
• Inhibit Ca ions
• Facilitate K channels
• Stimulation of these receptors inhibits release
  of neurotransmitters
• Huge number of receptors 10-20x opioid
  receptors may be most common receptor in brain

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Hallucinogens/Psychedelics

• THC Receptor
• Natural ligand (agonist) anandamide
• Partial agonist similar to THC
• Chemically dissimilar, but 3-D structure very
  similar
• Inhibits glutamate release
• Cannabinoid1
• Hippocampus - memory
• Cerebral cortex - psychoactivity
• Cerebellum movement/posture
• Basal ganglia movement/posture
• Cannabinoid2
• Peripheral Lymphoid system immunosuppression?

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Hallucinogens/Psychedelics

• THC
• Pharamcokinetics
• Average dose 0.4-10 mg - smoked
• Time to peak 10 min
• Blood level 80-150 ng/mL
• Detectable 12hr
• Rapid onset high lasts 12hr
• Oral dose
• Absorption abut 30-60 min
• Peak 2-3 hr post
• 1st pass metabolism?
• Distributed quickly
• Highly lipophilic
• Crosses b/b and b/p barriers
• Metabolites 11-hydroxy-?9-THC,
  11-nor-?9-THC-carboxylic acid

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Hallucinogens/Psychedelics

• THC
• Elimination
• Primarily as COOH in urine
• t1/2 30hr
• Excretion time depends on previous history with
  drug

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Hallucinogens/Psychedelics

• THC
• Pharmacological Effects animals - Humans?
• Memory disruption ?
• Analgesic ?
• Decreased body temp ?
• Calming agent ?
• Decreases aggression ?
• Impairs behavioral tasks ?
• Hallucinations ?
• Temporal distortions ?
• Depress ovarian function?
• Decrease sperm production?
• Induce over eating ?
• Euphoria ?

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Hallucinogens/Psychedelics

• THC
• Cardiovascular system
• Increase heart rate, BP
• Corneal vessels dilate
• Pulmonary system
• Toxins in smoke very dangerous
• Similar to tobacco toxins, likely same
  carcinogenic effects

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Hallucinogens/Psychedelics

• THC
• Reproductive system
• Reduces testosterone and sperm levels
• FSH/LH decreased - females
• May disrupt menstrual cycle
• Pregnancy?
• Little data on fetal/infant development issues

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Hallucinogens/Psychedelics

• THC
• Side effects
• Sedation
• Impaired motor skills
• Impaired cognition
• Impaired memory
• Impaired driving
• Impairment may last hours beyond feeling

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Hallucinogens/Psychedelics

• THC
• Tolerance/dependence
• Desensitization of receptors
• Preoccupation, compulsive use, relapse
• Withdrawal
• Restlessness
• Irritability
• Agitation
• Anxiety
• Depression
• Reduced appetite
• Insomnia/sleep disorders
• Nausea/cramping
• Starts within 48hr, lasts 2-6 days

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Hallucinogens/Psychedelics

• THC
• Therapeutic uses
• Appetite stimulant for AIDS patients
• Anti-nausea chemotherapy
• Not as effective as prescribed antiemetics
• Potential
• MS
• Glaucoma
• Brain protection trauma, stroke, ischemia
• LOTS of research needed

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Hallucinogens/Psychedelics

• Other drugs
• Most psychedelics mimic
• Acetylcholine anticholinergic
• Norepinephrine/dopamine catecholamine-like
• Serotonin-like

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Hallucinogens/Psychedelics

• Scopolamine
• From
• Atropa belladonna - nightshade
• Datura stanonium jimson weed
• Mandragora officinarum mandrake
• Above plants may also include atropine

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Hallucinogens/Psychedelics

• Scopolamine
• Pharmacological effects
• Anticholinergic
• Dry mouth
• Reduced sweating
• Dry skin
• Increased body temperature
• Dilated pupils
• Blurred vision
• Tachycardia
• Hypertension

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Hallucinogens/Psychedelics

• Scopolamine
• CNS effects
• Delirium
• Intoxication
• Drowsiness
• Euphoria
• Amnesia profound
• Fatigue
• Mental confusion
• Dreamless sleep
• Loss of attention
• Clouds consciousness
• Restlessness/excitement
• Hallucinations
• Disorientation

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Hallucinogens/Psychedelics

• Scopolamine
• Higher/toxic doses
• Delusions
• Mental confusion
• Stupor
• Coma
• Respiratory depression
• hot as a hare, blind as a bat, dry as a bone,
  red as a beet, and mad as a hen.

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Hallucinogens/Psychedelics

• Catecholamine-like
• Phenylethylamines amphetamine family
• Stimulants Catecholamine action
• Psychedelics serotonin action
• 5-HT2 serotonin receptor
• Emotional responses
• Sensory-perception/color distortion
• Dreamlike feeling
• Depersonalization
• Somatic effects (tingling, tremor, etc.)

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Hallucinogens/Psychedelics

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Hallucinogens/Psychedelics

• Mescaline
• Peyote cactus Laphaphora williansii
• Used in SW Native American religious rites
• Generally taken orally
• Rapid, complete absorption
• 1-2 hr to significant brain levels
• 3.5-4 hr to peak effect, particularly visual
• Other effects anxiety, stimulation, increased
  reflexes, tremors
• Seldom abused?

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Hallucinogens/Psychedelics

• Synthetic Amphetamines
• DOM, MDA, DMA,MDE, TMA, MDMA
• Close relatives to methamphetamine and mescaline
  with similar effects

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Hallucinogens/Psychedelics

• MDMA prototypical synthetic
• Metabolizes to MDA (more hallucinogenic)
• Neurotoxin
• Damage to serotonin transport
• Attention impaired
• Increased impulsivity
• Typical amphetamine-like side effects
• Severe toxicity - can cause fatalities

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Hallucinogens/Psychedelics

• Myristin/Elemicin
• Nutmeg/Mace
• Unreality
• Confusion
• Disorientation
• Euphoria
• Visual hallucinations
• Acute psychotic reactions
• Unpleasant side-effects nausea/vomiting/tremors
• Usually only use once

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Hallucinogens/Psychedelics

• Serotonin-like
• LSD
• Psilocbin
• Psilocin
• Dimethyltryptamine
• Bufotemine

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Hallucinogens/Psychedelics

• Serotonin-like
• Very similar structure to serotonin
• Suspected serotonin agonist
• Possible dopamine agonist
• Possible interruption of filtering or sorting
  of sensory input
• Serotonin itself does not display similar effects

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Hallucinogens/Psychedelics

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Hallucinogens/Psychedelics

• Lysergic acid diethyl amide LSD
• Synthesized 1938
• Very low dose required for effect - 25 ug
• Very strong visual/perceptional hallucinations

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Hallucinogens/Psychedelics

• LSD
• Pharmacokinetics
• Taken orally
• Rapidly absorbed
• Peak levels in about 3 hr
• Readily diffuses to brain and across placenta
• Duration 6-8 hr
• Difficult to detect in drug tests due to very low
  concentration and instability

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Hallucinogens/Psychedelics

• LSD
• Physiological effects
• Slight body temp increase
• Dilation of pupils
• Slightly increased heart rate/BP
• Low level of toxicity

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Hallucinogens/Psychedelics

• LSD
• Psychological effects
• Altered
• Perception
• Thinking
• Emotion
• Arousal
• Self image
• Time
• Sensory input (intensified)

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Hallucinogens/Psychedelics

• LSD
• Psychological effects
• 3-phases of LSD experience
• Somatic phase CNS stimulation
• Sensory phase sensory distortions,
  pseudohallucinations
• Psychic phase maximum drug effect bad trip
• Tolerance/Dependence
• Rapid tolerance physiological and psychological
• Little to no dependence

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Hallucinogens/Psychedelics

• LSD
• Adverse reactions/Toxicity
• Chronic or intermittent psychotic states
• Major effective disorder (depression)
• Exacerbation of preexisting condition
• Disruption of personality (burnout)
• Flashbacks

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Hallucinogens/Psychedelics

• DMT
• Similar effects as LSD
• Very short duration 30 min
• Bufotemine
• Also similar
• 2hr t1/2
• Related to autism/depression??

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Hallucinogens/Psychedelics

• Psilocybin/Psilocin
• From many mushroom species
• LSD-like effects
• Active drug is psilocin
• Can produce psychosis
• Ololiuqui
• Morning Glory seeds
• Active drug - Relative of LSD
• Severe unpleasant side effects
• Harmine
• Similar action to LSD and DMT
• Also severe side effects

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Hallucinogens/Psychedelics

• Phencyclidine/Ketamine
• Developed as anesthetics
• PCP no longer used due to severe psychiatric
  reactions, but more commonly abused
• Agitation
• Excitement
• Delirium
• Disorientation
• Hallucinations
• Similar to schizophrenia

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Hallucinogens/Psychedelics

• PCP/Ketamine
• Pharmocokinetics
• Smoked - peak reached in 15 min - 40 of dose
  absorbed
• Oral peak reached in 2 hr
• Elimination t1/2 about 18hr

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Hallucinogens/Psychedelics

• PCP/Ketamine
• Mechanism of action
• Antagonist to NMDA/Glutamate
• Psychotomimetic
• Analgesic
• Amnesia
• Schizophrenic
• Psychological effects
• Dissociation of individual from self and
  environment
• Intense analgesia and amnesia blank stare
• Low (recreational0 dose agitation, euphoria,
  disinhibition, excitement, gross drunkenness
• Coma, stupor
• BP elevated
• Exaggerated/violent reaction to outside stimuli

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Hallucinogens/Psychedelics

• PCP/Ketamine
• Side effects/Toxicity
• Severe anxiety, aggression, panic, paranoia, rage
• Violent reactions to sensory input
• Self inflicted injuries - Lack of response to
  pain
• Respiratory depression, Seizure, Pulmonary edema
• Tolerance/Dependence/Abuse
• Compulsive abuse stimulates reward areas
• Therapy for PCP intoxication
• Minimize sensory input isolate
• Activated charcoal
• Physical restraint
• Sedation benzodiazepine and/or antipsychotic
• Supportive therapy