confuse-ant ® drugs part 1 kim edward light, ph.d. professor, college of pharmacy university of...
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Confuse-Ant® Drugs Part 1
Kim Edward Light, Ph.D.
Professor, College of Pharmacy
University of Arkansas for Medical Sciences
Objectives – Part 1
Define the meaning of Confuse-ant® drugs Describe the different families of drugs that
confuse thinking, feeling, and behavior Discuss marijuana, THC, and the
endocannabinoid system. Identify and discuss the amphetamine-like
hallucinogenic agents
Confuse-ant® Drug Actions
Confused or disorganized sensorium Altered perception and interpretation of sensory
information “Psychotomimetic” Euphoric
Synesthesia
Synesthesia – “crossing-over” of sensory information
Sight Sound Smell Taste Touch
Visual Cortex
Auditory Cortex
Hear Colors
See Sounds
INPUT
Confuse-Ant® Drugs
Tetrahydrocannabinol Amphetamine-like
Mescaline, Amphetamine analogs, MDMA
(ecstasy) Serotonin-like
LSD, Psilocybin, Bufotenine, “tryptamines”
Dissociative Anesthetics Phencyclidine, Ketamine
Miscellaneous Gamma hydroxybutyrate (GHB) Nitrites, Nitrous oxide Solvents
® University of Arkansas
Endocannabinoid System Brain reward systems Motor control Food intake, body weight Sensory processing and interpretation Reproduction - control of prolactin & LH secretion,
implantation of embryo Immune function Cardiovascular - heart rate, blood pressure
Endocannabinoid SitesCerebral cortex – cognition, processing, interpretation of sensations
Cerebellum - fine motor coordination
Hippocampus – learning, memory, emotional control
Basal ganglia – movement control
Reward Pathway – reward
Endogenous THC
Made from membrane fatty acids, especially arachidonic acid
Related to the prostaglandins
Anandamide
2-Arachidonoyl glycerol
Noladin ether
Endocannabinoid Neuromodulation
Formation of Anandamide (A) is
triggered by the electrical aspects of neurotransmission
Interaction with G-protein coupled
receptors
G-protein
Anandamide is degraded by other
enzymes – turning of the signal.
Marijuana Cannabis sativa plant Hemp fiber for rope,
paper, etc. Source of THC Cultivation technology Hashish
THC Pharmacology
Vasodilation – low BP and red eyes Tachycardia – fast heart rate Relaxation and increased sociability In some,
dysphoria (panic, paranoia) altered perceptions enhanced emotional responding occasionally hallucinations
Increased risk of accidents
Marijuana Impairments
Acute Short-term memory Attention, judgment, cognitive function Coordination and balance
Persistent Memory Learning skills
College aged students - 65 "heavy" vs. 64 "light” users Heavy use = smoked ~29 of the past 30 days; Light use = smoked ~1 of past 30 days.
Heavy marijuana users: made more errors, had more difficulty sustaining attention, displayed difficulty in shifting attention to meet the
demands of changes in the environment, had trouble registering, processing, and using
information. The findings suggest that the greater impairment
among heavy users is likely due to an alteration of brain activity produced by marijuana.
Heavy Marijuana Use
Marijuana Use
Marijuana use by people below college age lower achievement, more acceptance of abnormal behavior, more antisocial behavior and aggression, greater rebelliousness, poorer relationships with parents, more associations with drug-using friends.
Marijuana & Development
Toddlers whose parents use marijuana more anger more thumb sucking more temper tantrums
Marijuana Withdrawal
Increased aggressive responses Increased sleep difficulties Increased irritability Increased craving
THC Antagonists
SR141716 also called Rimonabant (Acomplia®)
Blocks actions of THC Prevents cue-induced cocaine relapse Decreases DA release in N.Ac. of reward
pathway.
Medical Marijuana
Dronabinol Marinol® Pharmaceutical THC Oral use to prevent nausea Oral use to stimulate appetite
Amphetamine-Like
Phenylethylamine-type hallucinogens Mescaline Analogs - MDMA (ecstasy), MDA, DOM, PMA
Psychedelics Psychotomimetic Psychotogenic
Peyote - Mescaline
Religious practices of natives the southwest US and northern Mexico for almost 3,000 years
Effects last about 12 hours Rich visual hallucinations Also produced synthetically
Mescaline
Ability to dramatically alter perception
German chemist Arthur Heffter. American psychologist Heinrich Kluver Weston La Barre 1930’s anthropologist Aldous Huxley “The Doors Of Perception” in
1954 Native American Church, 1918
Mescaline Use
Pharmacology Ingested orally Hallucinations: 300 - 600 mg Lethality at doses 5-10x effective Death from convulsions and respiratory arrest Onset 3-4 hours Duration for about 2+ hours
Mescaline - Actions
Increase heart rate & temperature Behavioral arousal/ trembling, Nausea,
dizziness vomiting Heavy perspiration / chills Dilation of pupils (mydriasis), Dry mouth Anxiety, Mild ataxia (coordination and reflex
disruptions) Hyperreflexia with Muscle weakness Depressed heart rate, Increase blood pressure
Decreased respiratory rhythm
Mescaline - Impairments
Enhanced emotional responses Sensory-perceptual distortion: space & time Altered perception of colors, sounds, shapes, etc. Complex hallucinations: animals, people Dreamlike feelings with depersonalization
Ecstasy
Methylenedioxymethamphetamine (MDMA) Slang/Street Names: Ecstasy, XTC, X, Adam, Clarity,
Lover's Speed Stimulant-psychedelic Duration 3-6 hours Long-term effects may be severe One of the “Club Drugs” due to its wide presence and use
at “Raves” or similar all-night dance parties
Ecstasy - Actions CNS stimulation similar to
methamphetamine Increase in body temperature (malignant
hyperthermia) Dehydration and hypertension Bruxism – teeth grinding Heart attacks, strokes, and seizures Heart or kidney failure and muscle breakdown
Areas of the Brain Affect by Ecstasy
Thinking, memory and interpretation of sensory information Emotional state and responding.
Ecstasy - Neurotoxicity?
Recent study 60 volunteers age 18-35. 31 had used MDMA at least 5x 29 never usedBrain scans at least 3 weeks
after any MDMAReductions in concentration of
grey matter (cell bodies) in MDMA users
Ecstasy - Response Test?
The discrepancy between the meaning of the word and the color of the word can cause a momentary confusion that slows response time, and subjects frequently mistakenly read the word instead of naming the ink color.
Heavy MDMA users took longer to read the lists and made more errors than the moderate users.
Stroop Interference TestAs quickly as possible recite the ink
color of the following words.
Amphetamine Analogs
Related to mescaline Enhance psychedelic effects MDMA / Ecstasy is most popular Others still present in select circles
Amphetamine Analogs Examples MDA, PMA, DOM, and many others Major or minor contaminants of ecstasy Often sold as ecstasy Some (i.e. PMA) show much greater
toxicity than ecstasy Unexpected death
Amphetamine Analogs
PMA, paramethoxyamphetamine or 4-Methoxyamphetamine
amphetamine methamphetamine mescaline
DOM, 3,4-dimethoxy-4-methylamphetamine
MDMA, 3, 4-methylenedioxyamphetamine
2CB, 4-Bromo-2,5-dimethoxyphenethylamine