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 & Opioid Systems

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 – Use

Dramatic increase in ecstasy since 1995 Concordant increase in ER incidents

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

Summary

Meaning of Confuse-ant® drugs The different families of drugs that confuse thinking,

feeling, and behavior Marijuana, THC, and the endocannabinoid system. Amphetamine analogs that are less known but

relatively prevalent