CHAPTER 6 All Arounders. Hallucinogens/Psychedelics Alterations in cortical functions Cognition...
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Transcript of CHAPTER 6 All Arounders. Hallucinogens/Psychedelics Alterations in cortical functions Cognition...
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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
THCPrimary 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/PsychedelicsTHC
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
THCCannabinoid 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 ReceptorNatural 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/PsychedelicsTHC
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
THCElimination
Primarily as COOH in urine t1/2 ~30hr Excretion time depends on previous history with
drug
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Hallucinogens/PsychedelicsTHC
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
THCCardiovascular 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
THCReproductive 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
THCSide effects
Sedation Impaired motor skills Impaired cognition Impaired memory Impaired driving Impairment may last hours beyond feeling
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Hallucinogens/PsychedelicsTHC
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
THCTherapeutic 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 drugsMost psychedelics mimic
Acetylcholine – anticholinergic Norepinephrine/dopamine – catecholamine-like Serotonin-like
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Hallucinogens/Psychedelics
ScopolamineFrom
Atropa belladonna - nightshade Datura stanonium – jimson weed Mandragora officinarum – mandrake Above plants may also include atropine
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Hallucinogens/Psychedelics
ScopolaminePharmacological effects
Anticholinergic Dry mouth Reduced sweating Dry skin Increased body temperature Dilated pupils Blurred vision Tachycardia Hypertension
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Hallucinogens/PsychedelicsScopolamine
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
ScopolamineHigher/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-likePhenylethylamines – amphetamine familyStimulants – Catecholamine actionPsychedelics – serotonin action5-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
MescalinePeyote cactus – Laphaphora williansiiUsed 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 AmphetaminesDOM, MDA, DMA,MDE, TMA, MDMAClose relatives to methamphetamine and
mescaline with similar effects
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Hallucinogens/Psychedelics
MDMA – prototypical syntheticMetabolizes to MDA (more hallucinogenic)NeurotoxinDamage to serotonin transportAttention impairedIncreased impulsivityTypical amphetamine-like side effectsSevere toxicity - can cause fatalities
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Hallucinogens/Psychedelics
Myristin/ElemicinNutmeg/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-likeLSDPsilocbinPsilocinDimethyltryptamineBufotemine
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Hallucinogens/Psychedelics
Serotonin-likeVery similar structure to serotoninSuspected serotonin agonistPossible dopamine agonistPossible interruption of “filtering” or sorting of
sensory inputSerotonin itself does not display similar effects
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Hallucinogens/Psychedelics
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Hallucinogens/Psychedelics
Lysergic acid diethyl amide – LSDSynthesized 1938Very low dose required for effect - 25 ugVery strong visual/perceptional hallucinations
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Hallucinogens/Psychedelics
LSDPharmacokinetics
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
LSDPhysiological effects
Slight body temp increase Dilation of pupils Slightly increased heart rate/BP Low level of toxicity
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Hallucinogens/Psychedelics
LSDPsychological 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 experience1. Somatic phase – CNS stimulation2. Sensory phase – sensory distortions,
pseudohallucinations3. Psychic phase – maximum drug effect – bad trip
Tolerance/Dependence Rapid tolerance – physiological and psychological Little to no dependence
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Hallucinogens/Psychedelics
LSDAdverse 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
DMTSimilar effects as LSDVery short duration – 30 min
BufotemineAlso similar2hr t1/2Related to autism/depression??
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Hallucinogens/PsychedelicsPsilocybin/Psilocin
From many mushroom speciesLSD-like effectsActive drug is psilocinCan produce psychosis
OloliuquiMorning Glory seedsActive drug - Relative of LSDSevere unpleasant side effects
HarmineSimilar action to LSD and DMTAlso severe side effects
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Hallucinogens/Psychedelics
Phencyclidine/KetamineDeveloped as anestheticsPCP 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/KetaminePharmocokinetics
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/PsychedelicsPCP/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/PsychedelicsPCP/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