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ASAM
Review Course in Addiction Medicine
Dissociatives, Hallucinogens, Steroids & Inhalants
Shannon C. Miller, M.D., FASAM, FAPA, CMRO
Staff Psychiatrist
Addiction Services
Cincinnati VAMC
Associate Professor of Clinical Psychiatry
Co-Director, Addiction Psychiatry Fellowship
Assoc. Dir. for Education in the Addiction Sciences
University of Cincinnati
Lieutenant Colonel, USAFR
Research Physician
USAF Research Lab
Consultant, Addiction Services
Lindner Center of HOPE Hospital
Lindner
Center of Hope
ASAM’s 2008 Review Course
in Addiction Medicine
ACCME required disclosure ofACCME required disclosure of
relevant commercial relationships:relevant commercial relationships:
Dr. Miller has nothing to disclose.Dr. Miller has nothing to disclose.
Outline
Clubbing
Cleaning up “hallucinogens”
Dissociatives: PCP-like structure
(Arylcyclohexylamines, opioid derivative)
– Phencyclidine, Ketamine, Dextromethorphan
Hallucinogens:
• Serotonin-like structure (Indolealkylamines)
– LSD, LSA
– Psilocybin, Psilocin, DMT-like …
• Amphetamine-like structure (Phenylalkylamines)
– Mescaline, Nexus, DOM, DOB, DOI
Steroids
Inhalants
Anatomy of a Rave
• Promoters - ideological theme
• Venues - secret, 0400-daybreak
(event now becomes “underground”)
“Outlaw” = smaller raves (<50 dancers), portable
generator, turntable, $1-2 admission
Medium -Large = legal sites, off-duty cops for
security, searching for
drugs/cameras/markers/H2O bottles, $20-40
admission, better amenities/DJ’s
Large = thousands dancers, “chill-out” rooms,
carnival-like amenities
Anatomy of a RaveAnatomy of a Rave
The Ravers
• Young (15 – 25)
• White, middle class
• NYC: 70% white, 20% Hispanic, 10% black
• Admission = $10 - $50
• Drugs = $10 - $40/night
• Average raver “shelf life” = 2 years
Dissociatives,
Hallucinogens
Anatomy of a Rave
Clothing
• Function > Style
• Androgynous (M vs F, attractive vs not)
• Theme = Infancy/baby clothes vs aliens
• Headbands, b-ball caps, sneakers, baggy
pants, backpacks (candies, etc)
• Glitter, hair barrettes, infant toys
• Safe haven for “nerds”, “geeks” – attracted
by computer-driven music and internet
promotions
Anatomy of a Rave.
Drugs? True ravers dislike stigmatized drugs (cocaine,
heroin, etc.).
• Alcohol uncommonly served, thus no age limit for
admission and avoid ATF regulation. However, b/c
open after others close  reports of many patrons
showing up drunk
• Club Drugs less stigmatized … either because in pill
form or medically made
• Most common drug found is THC
• Promoters disallow bringing your own water (GHB)
Anatomy of a RaveAnatomy of a Rave
Staples sold on premises
Water bottles
“Power Drinks”
• Marathon dancing
• Fruit juice, sugars
• Caffeine, guaranaCaffeine, guarana
• Amino acidsAmino acids
• B & C vitaminsB & C vitamins
“Smart drinks”
• GinsengGinseng
• TryptophanTryptophan
“Go-go” drinks
• “Viagra for women”
• Ginseng, Yohimbine,
guarana
Herbal ecstasy
• Ma huang, ephedra
• Metabolift, Metabolife
356
• Ephedra:ephedrine
= 10:1
Anatomy of a RaveAnatomy of a Rave -- StaplesStaples
Drug paraphenalia
• Face masks
• Dust exposure
• Vicks menthol rub
Preloading (reduce
toxicity):
• Prozac
• 5-HT
• L-Tyrosine
• Vitamin C
Glow stix
Pacifiers
Candy
“Sextasy”
• Take Viagra with MDMA
Chill-out rooms
“Hallucinogens” a poorly defined term
• LSD, psilocins, DMT, Mescaline … PCP, THC,
amphetamines
• Diagnosis of exclusion
• Additional criteria
Hallucinogens   Dissociatives
• Developed as surgical anesthetics
• Distortion of reality
– External
– Internal (senses)
• “Dissociative anesthetics”
• Disrupt Glutamate-NMDA
– Pain perception
– Responses to environment
– Memory & Learning
Dissociatives
• PCP
(PhenylCyclohexylPiperidine)
• Ketamine
• DM (Dextromethorphan)
Dissociatives: Pharmacodynamics
• Glutamate turns on
PFC NDMA receptors,
which normally help
ensure the thalamus
can “filter” out sensory
“noise”
• PCP blocks NMDA
receptors, resulting in
sensory overflow -- >
noise/psychosis (ie:
PCP intox’n, SCZ)
Tsai G, Gastfriend DR, Coyle JT. The glutaminergic basis of human
alcoholism. Am J Psychiatry 1995 Mar;152(3):334.
Dissociatives: Pharmacodynamics
• NMDA blockade may result in:
– Midbrain and PFC D release (?addiction)
– Activation of 5-HT systems, targeting 5-HT1A
receptor
• PCP proposed to have effects on:
– Acetylcholine
– DRI
– SRI
– Norepinephrine
Dissociatives: DSM
PCP Intoxication
A) Recent use
B) maladaptive changes, soon after use:
belligerence, assaultiveness, impulsivity,
unpredictability, agitation, poor judgment,
impaired social/occupational fxning)
C) >= 2:
Nystagmus (vertical/horizontal),
HTN/tachycardia, numbness/decreased
pain response, ataxia, dysarthria, rigidity,
seizures/coma, hyperacusis
D) Not due to GMC
Helpful …
• Detachment, floating, distortion
• Inner/outer world
(time, space, body image)
• Hallucinations
• Increased HR, BP, T
PANIC
PCP – CSA Schedule I
• 1950’s, Parke, Davis & Co
• 1963-5 Sernyl: emergence delirium, agitation
• Brief 1960’s surge (delayed onset, agitation)
• 70’s = powder  snort, smoke  potent & popular
 vet Sernylan diversion  pulled 1978
• LA-based Street Gangs own market share
• Tablets($5-15), vials($1-3), dipped cig’s ($20)
• Added to leafy material (tobacco, THC, parsley)
 smoked (most common)
Annual Numbers of New Users of
Ecstasy, LSD, and PCP: 1965-2002
Ecstasy
LSD
PCP
Thousands of New Users
0
200
400
600
800
1,000
1,200
1,400
1,600
1,800
2,000
1965 1970 1975 1980 1985 1990 1995 2000
PCP: Illicit manufacture
• Piperzine, cyclohexane, potassium cyanide
• PC (1-piperidinocyclohexancarbonitrile)
– Intermediate product
– Breaks down within physiologic saline to cyanide
(CN)  some deaths
PCP: Intoxication
• Invulnerable, strength  ~1/3:
agitation, violence towards others
• Nystagmus (vertical, rotatory, horizontal)
• Rarely see dilated pupils (unlike stimulants,
hallucinogen intoxication, opioid withdrawal)
• Hyper-reflexia, HTN (unlike sed-hyp’s)
• CPK, SGOT/AST may be elevated
NMDA
antagonism,
monoamine RI,
Na+
& K+
channel
blockade
Stage I Stage II Stage III
Dose 2-5mg 5-25mg >25mg
[Serum] 25-90ng/mL 90-300 >300
CNS ↓conc,
dysarthria
Stupor-mild
coma
Deep coma
Cardiac ↑ ↑ ↑ ↑ ↑ ↑, failure
Temp 98-101 101-103 103-8, +/-
malignant
hyperthermia
Neuro Rigidity,
↑ DTR’s
… & seizures,
twitching
… & no deep
pain response,
no DTR’s,
decerebrate
posturing
PCP: Intoxication
Management
• Low-stimulation environment
• Avoid “talking them down” (unlike with hall’s)
• Rhabdomyolysis
– Musc. Rigidity, agitation, +/- physical restraints
– Progression to ARF in as many as 2% in ER (DSM IV)
– Serial CPK’s may be helpful
• Acidification of urine (ammonium chloride,
ascorbic acid) -- ?
• Benzo’s +/- antipsychotics PRN (avoid
anticholinergics)
Dissociatives (PCP)
Withdrawal*
– Animal models show severe withdrawal:
vocalizations, bruxism, oculomotor
hyperactivity, diarrhea, piloerection,
somnolence, tremor, seizures
– Long half life in humans; accum. in fat/brain
– It may be that a significant part of what DSM
IV attributes to intoxication delirium is actually
withdrawal,
– *
but PCP Withdrawal is NOT a DSM IV
diagnosis
PCP: Street Names
• Rocket fuel
• Love boat
• Ozone
• Hog
• Embalming Fluid
• Superweed
• Angel
• Angel Dust
• Dummy Dust
• Zombie
• Supergrass
• PeaCePill
Ketamine: CSA Schedule II
Injectable dissociative anesthetic (1963)
Manufactured for veterinary and pediatric surgery
anesthesia (theft)
– minimal cardiac, respiratory effects
– less agitation, psychoses
NMDA receptor blockade
Less potent, shorter-acting …
Drug facilitated sexual assault (odor, color, taste,
amnesia, testing)
90% of legal K sold = vets (street value 6X this)
Ketamine
• Gained popularity for abuse in the 1980’s by
New Age spiritualists
• Large doses cause effects ~ PCP
• K-Hole (helpless detachment), K-slide
• Liquid, topical gel, powder snorted; smoked
with THC or tobacco products; injected
• Lower doses: poor attn, learning, memory
• At higher doses: HTN, amnesia, delirium,
poor motor control, depression, respiratory
decompensation, minimal risk OD (LD50 is
30X anesthetic dose)
Street Names:
• Kit Kat
• Cat Valiums
• K
• Special K
• Super K
• Vitamin K
• Ket nip
• Horse trank
Ketamine
PCP and Ketamine
Long term adverse effects from chronic use:
• Depression/dysphoria
• Memory and cognition
• Apathy
• Irritability
• Flashbacks
Âź of pts originally treated for PCP psychosis are
diagnosed < 1 yr later with SCZ (without drug
use)
Dextromethorphan
• At indicated doses, DM inhibits medullary
cough centers to approximately the same
extent as opiate alkaloids such as codeine,
but without other opioid effects such as
analgesia, CNS depression, and respiratory
suppression
• As approved: efficacious, safe for OTC use
Dextromethorphan
Maximum/Extra Strength Cough Suppressant: 15
mg Dextromethorphan Hydrobromide per
teaspoon [5mL]  8 oz bottle = ~711mg DXM
Abuse: 300 to 1,800 mg (20-120X recc’d dose)
Cases of 24 oz/d (40oz/d peak, = 237x recc
dose)
Some ongoing for 10–15 yrs (HCP)
Dextromethorphan
• Stigma
• Money
• Access
• Risks
• Testing
Dextromethorphan
Likely used more than any
dissociative, or hallucinogen, today
Wide appeal
• Teens
• Middle-aged workers
• Later life (from 1960’s)
Dextromethorphan
Powder and the Internet
.
Coricidin ® HBP Cough & Cold – largest/30mg
Gel caps
Mixed with heroin, MDMA, or cannabis (“candy
blunts”)
Intranasal
“Robofire” – 2002 Dec
• DM dissolved in lighter fluid crack-like
rocksmoked (?better hallucinations)
• DM drank, then lighter fluid inhaled
Dextromethorphan
• DM Readily absorbed from gut
• Peak serum levels @ ~2-3 hrs for immediate
release, 6 hrs for sustained release
preparations
• Dextrorphan (DOR) peak levels @ ~1.6-7 hrs
• Euphoria and hallucinosis occur within 15-30
min of ingestion, peak effects in about 2.5
hrs. “Plateaus” = 3-6 hrs
• Weaker sigma opioid agonist,
stronger NMDA antagonist than DM
• Relatively inactive at mu, kappa and
delta receptor sites – thus essentially
devoid of more conventional opiate properties,
although respiratory depression has been reported
with massive ingestion
Dextromethorphan
• Sigma-1 opioid receptor site is
involved in the regulation of
glutamatergic NMDA receptor
functioning, dopaminergic tone, and
serotonin release
• (DM binding at sigma-2 opioid
receptor sites may alternatively
cause impaired motor movements
that may be observed during DM
intoxication)
Dextromethorphan
Serotonergic action
1.increasing the synthesis and
release of 5HT
2.re-uptake pump inhibition
Dextromethorphan
Characteristics of the dextromethorphan (DM) intoxication syndrome
Psychiatric Neurological General
• Auditory hallucinations Slurred speech Nausea
• Visual hallucinations Ataxia Vomiting
• Tactile hallucinations Mydriasis Diaphoresis
• Hyper-excitability Blurry vision Hypertension
• Pressure of thought Bi-directional nystagmus Respiratory depression*
• Lethargy Hypertonia Coma*
• Nervousness Choreoathetoid movement Fatality*
• Euphoria Dystonic movements
• Confusion/disorientation Dyskinesia
• Altered time perception Restlessness
• Paranoia Tremor
• Feeling of “floating” Hyper-reflexia
• Heightened perceptual Seizures*
awareness * Rarely
Dextromethorphan
Over-the-counter sources of DM +
• Antihistamines (chlorpheniramine, *))
• Decongestants (pseudophedrine) - cardiac
• Pain (acetaminophen) – liver
• Bromides - Br poisoning
• Serotonin Syndromes
Truly addictive?
Abuse
Dependence
Rodent & primate animal models
• Biochemical reinforcement (DOR) ~ to PCP
• Stimulus discrimination (DOR)
• Stimulus generalization with PCP
• DM strongly self-administered
Dextromethorphan
Street Names:
• C-C-C
• Dex
• DM
• DMX
• DXM
• Red devils
• Robo
• Skittles
• Slang robe
• Syrup
• Triple C’s
• Vitamin D
Dextromethorphan
Treatment - Pharmacotherapy
• Naltrexone
Hallucinogens
• Psychotomimetics (producer of psychoses)
• Psychedelics (mind manifesting)
• Intoxicants
• Inebriants
Hallucinogens
• Serotonin-like structure (Indolealkylamines)
– Lysergamides: LSD (Lysergic Acid Diethylamide), LSA
(Lysergic Acid Amide)
– Substituted tryptamines: Psilocybin, Psilocin, DMT, 5-
MeO-DMT, DET, DPT, AET, AMT, 5-MeO-AMT
• Amphetamine-like structure (Phenylalkylamines)
– Phenethylamines: Mescaline, Nexus
– Phenylisopropylamines: A-M-Mescaline, MDA (MDMA),
DOB, DOM, DOI
– Structurally similar to phenylalkylamine hallucinogens,
but functionally NOT primarily hallucinogenic; have
stimulant and/or other properties.
Hallucinogens:
Pharmacodynamics
Illusionogen = better term
• Illusions = alteration or enhancement of an existing
sensory perception (visual, time, sound). Intact reality
testing in most (?). Effect varies greatly with set
(expectations) and setting (environment)
5HT2A agonists (both Indolealkyl- and Phenethyl-amines)
• Any 2 of the 3 correlate significantly:
– Higher 5HT2 receptor affinity
– Animal drug discrimination-derived potencies
– Human hallucinogenic potency
• 5HT2 antagonists (ketanserin, pirenperone, etc)
reduce hallucinogen effects
Also bind at 5HT2B and 5HT2C receptors
Hallucinogens: Intoxication
B) Maladaptive changes developing during/shortly after
use: anxiety, depression, ideas of reference, fear of
losing one’s mind, paranoia, poor judgment, etc.)
{euphoria most common, though}
C) Perceptual changes occurring in a state of full
wakefulness and alertness, during/shortly after use:
intensification of perceptions, depersonalization,
derealization, illusions, hallucinations, synesthesias)
D) >=2 developing during/shortly after use: pupillary
dilation, tachycardia, sweating, palpitations, blurring
of vision, tremors, incoordination {stimulant effects}
E) Not due to GMC {also, see hyper-reflexia}
Hallucinogens: Intoxication
• Effect depends upon set and setting
• Geometric shapes
• Worse w/eyes closed
• Afterimages
• Hyperacuity (not auditory hallucinations)
• Touch hypersensitivity
• Time standing still
Hallucinogens: Diff Dx
• Clear sensorium (delirium)
• Intact remote and recent memory
• Fairly oriented (delirium)
• Hyperalert (drowzy in THC)
• Intact reality testing – usually (otherwise,
consider dx of a primary Psychotic D/O
NOS, SCZ, or A intox)  thus, “talking
down” might prove beneficial
• Visual >>> auditory (SCZ, mood, etc)
• EEG = arousal (delirium = slowing)
• SPECT = hyperfrontal (hypo- in SCZ)
Hallucinogens
Withdrawal
None (per DSM)
Serotonin-like structure
(Indolealkylamines)
LSD
• Most potent hallucinogen (micrograms)
• Hallucinogen (Illusionogen) - 5HT2A
partial agonist
• Difficult to make (ingredients = CSA III)
• California groups owned market share,
protect it
• Potency ? Much less than 1960’s
LSD
• Albert Hofmann
(Sandoz chemist)
1938
• Lysergic acid
compounds
derived from a rye
fungus, ergot
• “Accident,” 1943
LSD
• Water soluble; clear, white, odorless crystals
• Sold in plastic, opaque canisters (film) –
oxidation/degrades  discolors (distributors
use colored paper for the blotter art)
• Pressed into pills = “microdots” ... thin gelatin
squares = “window panes”
• Breath mints, sugar cubes (dropping acid),
blotter paper (most common)
• Street dose = 70-300mcg, effects reported
from as little as 20mcg
LSD
• Marketed as Delysid in 1947:
– Rx’d for schizophrenia, alcoholism,
criminal behavior, sexual perversion
– Medical students, help understand SCZ
• Schedule I, CSA:
1. High abuse potential
2. No legitimate medical indication
3. Lack of accepted safety under medical
supervision
LSD
• Readily absorbed from gut
• Diffuses to all tissues; brain, placenta, fetus
• Onset 30-60 min (oral)
• Peak = 2-4 hours
• Resolves 8-12 hrs
LSD: Street names
Often based on carrier:
• Acid
• Bart Simpsons
• Liquid
• Liquid A
• Lucy in the sky with
diamonds
• Microdots
• Dots
• Mind detergent
• Blue unicorn
• Orange cubes, micro-
• Tabs
• Barrels
• Paper acid
• Sandoz
• Sugar, sugar cubes
• Sunshine
• Twenty five (-th)
• Windowpanes
LSD
• Hallucinogen Persisting Perception
Disorder (Flashbacks)
– Unrelated to dose, # exposures
– Usually none after 1-2 years (cases of after
5 years)
– beltway bumper
– High lifetime prevalence of mood d/o’s vs
non-LSD using substance users
• Rapid (psychological) tolerance; crosses
with psilocybins, mescaline –> lower f of
use
LSA (LySergic acid Amide)
• Morning Glory Seeds  grind up
• 5-10% the potency of LSD
• 20-30 mcg LSD ~ 100-300 morning glory
seeds (insecticide exposure)
Psilocybins, Psilocins
• Use dates back to 1000 - 500 BC
• Aztecs
• 1957 Sandoz assisted researchers in
extracting it
• Synthesis technique developed
• May 13, 1957 LIFE issue: described
Mazatech velada, 7 varieties of mush’s
• “Magic Mushrooms” in the 1960’s
(Psilocybe mexicana)
Psilocybins, Psilocins
• Central America, Mexico
• Both psychoactive (psilocin more) --
ratio varies among mushrooms
• Psilocin less stable,oxidized upon
drying
• Dried mushrooms = 0.2% - 0.4%
psilocybin, only trace psilocin
• 4-8 mg of mixed psilocin/cybins =
hallucinations (~2gm of mushrooms)
Psilocybins, Psilocins
• Intoxication duration = 2 hours
• Synesthesias
• Detachment from reality, Enmeshment with
surroundings
• Inability to discern fantasy from reality -->
panic attacks, psychoses
• More “natural” high than w/LSD
• Rapid tolerance … cross tolerance w/LSD
DMT
Naturally occurring
– Plants: Phalaris aruninacea = DMT + 5-MeO-DMT
(MeO- increases lipid solubility, 10X potent)
• “Businessman’s Trip” – rapid onset, short duration (<60min) –
snorted/ IV/smoked (oral – inactivated)
• MAOI enables oral use (lengthens catabolism)
– Toads: Bufo alvarius (Sonoran Desert Toad)
• Glandular venom = 6-16% 5-MeO-DMT
• Skin contains 5-MeO-DMT (50-160mg/g skin)
• 3-5mg = psychoactive effect
• 1959: predominant alkaloid in the hallucinogenic snuffs of
several tribes in South America
DMT user’s account …
Within thirty seconds, there will be an onset of almost
overwhelming psychedelic effects. You will be
completely absorbed in a complex chemical event
characterized by an overload of thoughts and perception,
brief collapse of the EGO, and loss of the space-time
continuum. Relax, breathe regularly, and flow with the
experience. After two to three minutes, the initial
intensity fades to a pleasant LSD-like sensation in which
visual illusions, hallucinations, and perceptual distortions
are common. You may sense a distortion in your
perceived body image or notice the world shrinking or
expanding. You may notice that colors seem brighter and
more beautiful than usual. And, most likely, you will
experience a euphoric mood interspersed with bursts of
unmotivated laughter.
DET, DPT, AET
• Substituted tryptamines
• Similar in effect to DMT
• Less potent
• Schedule I of CSA
Amphetamine-like structure
(Phenethylamines)
Mescaline
• Principal psychoactive agent found naturally in
the peyote cactus
• 3,4,5-trimethoxy-phenethylamine
• 1st
hallucinogen isolated (Arthur Heffter 1896)
• Peyote cactus: central Mexico – south Texas
• 300BC – religious rites
• Comanche, Kiowa, Navajo, Sioux
• Supreme Court protects religious use within
Native American Church (no synthetics)
• Canada
Mescaline
• Peyote cactus
• Crown (top) contains buttons
• Buttons are cut off, dried
• 1-6% of dried button = mescaline
• 6-10 buttons =
intoxication (100–350mg required)
• Chewed or soaked in water
Mescaline: Intoxication
• 30 min delay
• 2 phases:
First hour
– Minor perceptual changes
– Adrenergic stimulation (increased resp. rate; face
& neck muscular tension)
– Nausea (can be severe) -- other alkaloids
Next several hours (as much as 5-10)
– Visual illusions, hallucinations
– synesthesias
Importance of set, setting
• Religious rituals, guides
Mescaline
– A&E documentary (father gives drug to
son); religious leader
Beta-carbolines
– Harmaline +/- DMT, 5-MeO-DMT
– Sting’s memoir (exploring personal life
meaning)
– ayahuasca (South American ritual
beverage)
– Mestre
Nexus
• “2-CB”
• “CB’s”
• Similar in structure to mescaline
• Analog of DOB
DOM, DOB, DOI
• DOM (“STP”)= “model”/reference
hallucinogen in drug discrimination studies
• dimethoxymethylamphetamine
Hallucinogens –
sub-grouped by effect, not by structure
S
H P
• H (nonintersecting) = Hallucinogens “proper” (model = DOM)
• S = Central stimulants (model = +amphetamine)
• P = Other effects (empathy) (model = PMMA)
MDA, MDMA (ecstasy)
deferred to stimulants lecture
S
H P
• Central region = racemic MDA
• H/P = -MDA S/P = +MDA, MDMA
• P = PMMA (“white death”), MBDB (“eden, methyl J”), 4-
MTA (“flatliners”)
SteroidsSteroids
• Synthetic derivatives of the male
hormone testosterone
• Rx uses: delayed puberty, impotence,
wasting due to HIV, etc.
• 2 effects:
1. Anabolic (maximize): skeletal muscle growth
(via retaining N, directly stimulate protein
production, increase availability of ATP to
muscles, increased Hct)
2. Androgenic (minimize): male sexual char’s
Steroids
• 1930’s: testosterone synthesized
• 1940’s-50’s: use in sports
• 1950’s: brought to US by Dr John Zeigler,
nat’l weightlifting team doc; f/Eastern Bloc
countries after 1952 Olympics success
• 1968: drug testing at Olympics
• 1975: banned by IOC
• 1990: CSA Schedule III
Steroids
• Purpose of abuse: muscle, appearance
– Triad: athletes, aesthetes, fighting elite
• Doses: abused @ up to 100X recc’d dose
• Routes:
– Oral: Anadrol (oxymetholone), Oxandrin (oxandrolone),
Dianabol (methandrostenolone), Winstrol (stanozolol), etc.
– IM: Deca-Durabolin (nandrolone decanoate), Durabolin
(nandrolone phenpropionate), Depo-Testosterone
(testosteronecypionate), Equipoise (boldenone
undecylenate), etc
• “reward” = delayed
• Many case reports of “dependence”
Steroids: Terminology
• Stacking: taking 2 or more (a)
steroids/stimulants/pain killers and/or (b)
routes {po, IM}. “The whole is greater than
the sum of the parts.”
• Pyramiding: taper-up the doses over 6-12
weeks, then taper-down over next 6-12
weeks just before the event
• Plateauing: when a drug becomes ineffective
at a certain level
• Cycling: different drugs/times
Steroids: Epidemiology
Ages 13-25, 90% male
Prevalence studies
• Power lifters @ nat’l competition = 55%
• High school athletes = 4.9-6.6%, 2/3 began < age 16
• College athletes = 17%, male football = 30%
• More likely to use alcohol, drugs, tobacco
• 30% inject, 1/3 share the needle
Steroids: Complications
• General: liver cysts/tumors (17α-alkylated
androgens), jaundice, fluid retention, HTN,
tremor, acne, (HIV, Hep B+C, endocarditis),
myocardial necrosis, lower HDL + higher LDL
• Males: shrinking testes (as they reduce
endogenous T prod’n), low sperm count,
balding, gynecomastia (excess T  E) (poss.
irreversible)
• Females: facial + body hair, altered menses,
enlarged clitoris, deep voice, balding, less fat
• Adolescents: premature epiphyseal plate
closure, accelerated pubertal changes
Steroids: Psychiatric
• Aggression, mania, psychoses, depression;
post-withdrawal depression & drug-craving
• Larger doses  more pronounced psych sx’s
• Maj. mood d/o prev. = 23% (>300 – 1000
mg/week needed for mania), psychotic sx’s =
12%
• Personality types: histrionic, antisocial, +/-
narcissistic
Inhalants
A) Volatile solvents (vaporize @ room temp):
Adhesives: airplane glue, rubber cement, polyvinylchloride cement
Aerosols: spray paint, metallic spray paint, hair spray, deodorant, air
freshener, vegetable oil spray, analgesic spray, asthma spray
Solvents and Gases: nail polish remover, paint remover, paint
thinner, typing correction fluid, fuel gas, cigarette lighter
fluid/butane, gasoline, freon
Cleaning agents: dry cleaning fluid, spot remover, degreaser
Propellant gases: nitrous oxide (whipped cream), propane
B) Nitrites: cyclohexyl-, amyl-, butyl-, isobutyl- nitrite
(butyl, propyl, and certain other nitrites banned in 1991)
C) Anesthetics: (gaseous, liquid, local injection)
Inhalants
• 1/6 adolescents tries inhalants, most 1-5x
• Males, non-Hispanic white youths
• Inhalant Dependence is uncommon
(0.3% prevalence, 1 in 27 lifetime
users)
• Not passing fad, 10% use > 6 years
• Strong assoc. with ASPD, PSA, later IVDA (5-9X)
• Developing countries
Inhalants
• Highly lipophyllic HC chains, cross into brain
Pharmacodynamics
• Unknown, ~ to dissociatives (NMDA) and
alcohol/sedatives (GABA)
• Drowsiness settles in for several hours
• Toluene increases extracellular D in PFC
• Toluene, nitrous oxide, & chloroform have
reinforcing properties in self-administration
studies
.
Inhalants: Terminology
• Sniffing
• Huffing: cloth (or mask) (soaked with substance) applied to
face and breathed in
• Bagging: enclosing the substance in a bag and breathing it in
• Poppers, snappers: ampules of amyl nitrite Rx’d for angina
(broken and inhaled). 1960 FDA allowed OTC use. Increase in
abuse (gay men: smooth muscle relaxation, vasodilation 
sexual enhancement). FDA restored Rx requirement. Also:
butyl/isobutyl nitrite/cyclohexyl (nowadays find them sold as
video head cleaner or room deodorizer in adult sex shops)
• Whippet: balloons/bags filled w/ N2O (laughing gas)
• Torch, fire-breathing: exhaling + igniting volatile gases
(propane, butane)
• Texas shoe shine: toluene-containing spray paint
• Odor of paint, solvents (clothes, breath)
• Residues, burns, related traumas
• ‘Glue sniffer’s rash” around nose & mouth, conjunctival
irritation
• Cough, sinus discharge, dyspnea, rales, rhonchi
• Neuro: weakness, peripheral neuropathy,
cerebral/cerebellar/brain stem atrophy, white matter
lesions, MS-like syndrome, dementia, delirium
• Hepatitis, cirrhosis
• Metabolic acidosis with distal renal tubular acidosis, CRF
• Bone marrow suppression
• Neuropsychological testing problems in chronic inhalant
users
Inhalants: PE, lab
Inhalants
Intoxication
A) Recent use/exposure
B) Maladaptive changes developing during or
shortly after use: belligerence,
assaultiveness, apathy, impaired judgment,
etc.
C) >=2 developing within 2 hours of use:
dizziness, nystagmus, incoordination, slurred
speech, unsteady gait, lethargy, depressed
reflexes, psychomotor retardation, tremor,
gen. muscle weakness, blurred
vision/diplopia, stupor/coma, euphoria
D) Not due to GMC
Inhalants
Withdrawal
None, per DSM.
However, a mild syndrome beginning 1-2 day after
last use and extending for 2-5 days has been
described. Symptoms may include sleep
problems, tremor, irritability, diaphoresis, nausea,
fleeting illusions.
Abuse, dependence, and tolerance are
confirmed
Inhalants:
“Sudden sniffing death”
Falling unconscious on source/rag; “hands-free” use during sex
Acute arrhythmia ***
Heart failure (from butane or chlorofluorocarbons
associated hyper-excitability to NE)
Hypoxia **
Suffocation (as substance replaces oxygen)
Methyl chloride  carbon monoxide
Poppers (ampules of amyl/butyl/isobutyl nitrite ) –
reduce oxygen carrying capacity
CNS, respiratory depression
Electrolyte abnormalities *
Inhalants: Fetal effects
• Cross placenta  renal tubular acidosis
• Data primarily from occupational exposures
– Cleft malformations, gastroschisis, esophageal stenosis
– Omphalocele
– Ventricular septal defects
– CNS defects
– Spontaneous abortions
• Inhalant using women create higher exposure levels
– Limb abnormalities
– Growth retardation
– Craniofacial defects
– Developmental delays, language
• Toluene in animals
– Neuronal migration, proliferation affected
SummarySummaryDissociatives:
Phencyclidine, Ketamine, Dextromethorphan
Hallucinogens:
Serotonin-like structure
– LSD, LSA
– Psilocybin, Psilocin, DMT-like …
Amphetamine-like structure
– Mescaline, Nexus, DOM, DOB, DOI
Steroids
Inhalants
Lindner
Center of Hope

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Drug addiction-2

  • 1. ASAM Review Course in Addiction Medicine Dissociatives, Hallucinogens, Steroids & Inhalants Shannon C. Miller, M.D., FASAM, FAPA, CMRO Staff Psychiatrist Addiction Services Cincinnati VAMC Associate Professor of Clinical Psychiatry Co-Director, Addiction Psychiatry Fellowship Assoc. Dir. for Education in the Addiction Sciences University of Cincinnati Lieutenant Colonel, USAFR Research Physician USAF Research Lab Consultant, Addiction Services Lindner Center of HOPE Hospital Lindner Center of Hope
  • 2. ASAM’s 2008 Review Course in Addiction Medicine ACCME required disclosure ofACCME required disclosure of relevant commercial relationships:relevant commercial relationships: Dr. Miller has nothing to disclose.Dr. Miller has nothing to disclose.
  • 3. Outline Clubbing Cleaning up “hallucinogens” Dissociatives: PCP-like structure (Arylcyclohexylamines, opioid derivative) – Phencyclidine, Ketamine, Dextromethorphan Hallucinogens: • Serotonin-like structure (Indolealkylamines) – LSD, LSA – Psilocybin, Psilocin, DMT-like … • Amphetamine-like structure (Phenylalkylamines) – Mescaline, Nexus, DOM, DOB, DOI Steroids Inhalants
  • 4. Anatomy of a Rave • Promoters - ideological theme • Venues - secret, 0400-daybreak (event now becomes “underground”) “Outlaw” = smaller raves (<50 dancers), portable generator, turntable, $1-2 admission Medium -Large = legal sites, off-duty cops for security, searching for drugs/cameras/markers/H2O bottles, $20-40 admission, better amenities/DJ’s Large = thousands dancers, “chill-out” rooms, carnival-like amenities
  • 5. Anatomy of a RaveAnatomy of a Rave The Ravers • Young (15 – 25) • White, middle class • NYC: 70% white, 20% Hispanic, 10% black • Admission = $10 - $50 • Drugs = $10 - $40/night • Average raver “shelf life” = 2 years Dissociatives, Hallucinogens
  • 6. Anatomy of a Rave Clothing • Function > Style • Androgynous (M vs F, attractive vs not) • Theme = Infancy/baby clothes vs aliens • Headbands, b-ball caps, sneakers, baggy pants, backpacks (candies, etc) • Glitter, hair barrettes, infant toys • Safe haven for “nerds”, “geeks” – attracted by computer-driven music and internet promotions
  • 7. Anatomy of a Rave. Drugs? True ravers dislike stigmatized drugs (cocaine, heroin, etc.). • Alcohol uncommonly served, thus no age limit for admission and avoid ATF regulation. However, b/c open after others close  reports of many patrons showing up drunk • Club Drugs less stigmatized … either because in pill form or medically made • Most common drug found is THC • Promoters disallow bringing your own water (GHB)
  • 8. Anatomy of a RaveAnatomy of a Rave Staples sold on premises Water bottles “Power Drinks” • Marathon dancing • Fruit juice, sugars • Caffeine, guaranaCaffeine, guarana • Amino acidsAmino acids • B & C vitaminsB & C vitamins “Smart drinks” • GinsengGinseng • TryptophanTryptophan “Go-go” drinks • “Viagra for women” • Ginseng, Yohimbine, guarana Herbal ecstasy • Ma huang, ephedra • Metabolift, Metabolife 356 • Ephedra:ephedrine = 10:1
  • 9. Anatomy of a RaveAnatomy of a Rave -- StaplesStaples Drug paraphenalia • Face masks • Dust exposure • Vicks menthol rub Preloading (reduce toxicity): • Prozac • 5-HT • L-Tyrosine • Vitamin C Glow stix Pacifiers Candy “Sextasy” • Take Viagra with MDMA Chill-out rooms
  • 10. “Hallucinogens” a poorly defined term • LSD, psilocins, DMT, Mescaline … PCP, THC, amphetamines • Diagnosis of exclusion • Additional criteria
  • 11. Hallucinogens   Dissociatives • Developed as surgical anesthetics • Distortion of reality – External – Internal (senses) • “Dissociative anesthetics” • Disrupt Glutamate-NMDA – Pain perception – Responses to environment – Memory & Learning
  • 13. Dissociatives: Pharmacodynamics • Glutamate turns on PFC NDMA receptors, which normally help ensure the thalamus can “filter” out sensory “noise” • PCP blocks NMDA receptors, resulting in sensory overflow -- > noise/psychosis (ie: PCP intox’n, SCZ) Tsai G, Gastfriend DR, Coyle JT. The glutaminergic basis of human alcoholism. Am J Psychiatry 1995 Mar;152(3):334.
  • 14. Dissociatives: Pharmacodynamics • NMDA blockade may result in: – Midbrain and PFC D release (?addiction) – Activation of 5-HT systems, targeting 5-HT1A receptor • PCP proposed to have effects on: – Acetylcholine – DRI – SRI – Norepinephrine
  • 15. Dissociatives: DSM PCP Intoxication A) Recent use B) maladaptive changes, soon after use: belligerence, assaultiveness, impulsivity, unpredictability, agitation, poor judgment, impaired social/occupational fxning) C) >= 2: Nystagmus (vertical/horizontal), HTN/tachycardia, numbness/decreased pain response, ataxia, dysarthria, rigidity, seizures/coma, hyperacusis D) Not due to GMC
  • 16. Helpful … • Detachment, floating, distortion • Inner/outer world (time, space, body image) • Hallucinations • Increased HR, BP, T PANIC
  • 17. PCP – CSA Schedule I • 1950’s, Parke, Davis & Co • 1963-5 Sernyl: emergence delirium, agitation • Brief 1960’s surge (delayed onset, agitation) • 70’s = powder  snort, smoke  potent & popular  vet Sernylan diversion  pulled 1978 • LA-based Street Gangs own market share • Tablets($5-15), vials($1-3), dipped cig’s ($20) • Added to leafy material (tobacco, THC, parsley)  smoked (most common)
  • 18. Annual Numbers of New Users of Ecstasy, LSD, and PCP: 1965-2002 Ecstasy LSD PCP Thousands of New Users 0 200 400 600 800 1,000 1,200 1,400 1,600 1,800 2,000 1965 1970 1975 1980 1985 1990 1995 2000
  • 19. PCP: Illicit manufacture • Piperzine, cyclohexane, potassium cyanide • PC (1-piperidinocyclohexancarbonitrile) – Intermediate product – Breaks down within physiologic saline to cyanide (CN)  some deaths
  • 20. PCP: Intoxication • Invulnerable, strength  ~1/3: agitation, violence towards others • Nystagmus (vertical, rotatory, horizontal) • Rarely see dilated pupils (unlike stimulants, hallucinogen intoxication, opioid withdrawal) • Hyper-reflexia, HTN (unlike sed-hyp’s) • CPK, SGOT/AST may be elevated
  • 21. NMDA antagonism, monoamine RI, Na+ & K+ channel blockade Stage I Stage II Stage III Dose 2-5mg 5-25mg >25mg [Serum] 25-90ng/mL 90-300 >300 CNS ↓conc, dysarthria Stupor-mild coma Deep coma Cardiac ↑ ↑ ↑ ↑ ↑ ↑, failure Temp 98-101 101-103 103-8, +/- malignant hyperthermia Neuro Rigidity, ↑ DTR’s … & seizures, twitching … & no deep pain response, no DTR’s, decerebrate posturing
  • 22. PCP: Intoxication Management • Low-stimulation environment • Avoid “talking them down” (unlike with hall’s) • Rhabdomyolysis – Musc. Rigidity, agitation, +/- physical restraints – Progression to ARF in as many as 2% in ER (DSM IV) – Serial CPK’s may be helpful • Acidification of urine (ammonium chloride, ascorbic acid) -- ? • Benzo’s +/- antipsychotics PRN (avoid anticholinergics)
  • 23. Dissociatives (PCP) Withdrawal* – Animal models show severe withdrawal: vocalizations, bruxism, oculomotor hyperactivity, diarrhea, piloerection, somnolence, tremor, seizures – Long half life in humans; accum. in fat/brain – It may be that a significant part of what DSM IV attributes to intoxication delirium is actually withdrawal, – * but PCP Withdrawal is NOT a DSM IV diagnosis
  • 24. PCP: Street Names • Rocket fuel • Love boat • Ozone • Hog • Embalming Fluid • Superweed • Angel • Angel Dust • Dummy Dust • Zombie • Supergrass • PeaCePill
  • 25. Ketamine: CSA Schedule II Injectable dissociative anesthetic (1963) Manufactured for veterinary and pediatric surgery anesthesia (theft) – minimal cardiac, respiratory effects – less agitation, psychoses NMDA receptor blockade Less potent, shorter-acting … Drug facilitated sexual assault (odor, color, taste, amnesia, testing) 90% of legal K sold = vets (street value 6X this)
  • 26. Ketamine • Gained popularity for abuse in the 1980’s by New Age spiritualists • Large doses cause effects ~ PCP • K-Hole (helpless detachment), K-slide • Liquid, topical gel, powder snorted; smoked with THC or tobacco products; injected • Lower doses: poor attn, learning, memory • At higher doses: HTN, amnesia, delirium, poor motor control, depression, respiratory decompensation, minimal risk OD (LD50 is 30X anesthetic dose)
  • 27. Street Names: • Kit Kat • Cat Valiums • K • Special K • Super K • Vitamin K • Ket nip • Horse trank Ketamine
  • 28. PCP and Ketamine Long term adverse effects from chronic use: • Depression/dysphoria • Memory and cognition • Apathy • Irritability • Flashbacks Âź of pts originally treated for PCP psychosis are diagnosed < 1 yr later with SCZ (without drug use)
  • 29. Dextromethorphan • At indicated doses, DM inhibits medullary cough centers to approximately the same extent as opiate alkaloids such as codeine, but without other opioid effects such as analgesia, CNS depression, and respiratory suppression • As approved: efficacious, safe for OTC use
  • 30. Dextromethorphan Maximum/Extra Strength Cough Suppressant: 15 mg Dextromethorphan Hydrobromide per teaspoon [5mL]  8 oz bottle = ~711mg DXM Abuse: 300 to 1,800 mg (20-120X recc’d dose) Cases of 24 oz/d (40oz/d peak, = 237x recc dose) Some ongoing for 10–15 yrs (HCP)
  • 31. Dextromethorphan • Stigma • Money • Access • Risks • Testing
  • 32. Dextromethorphan Likely used more than any dissociative, or hallucinogen, today Wide appeal • Teens • Middle-aged workers • Later life (from 1960’s)
  • 33. Dextromethorphan Powder and the Internet . Coricidin ÂŽ HBP Cough & Cold – largest/30mg Gel caps Mixed with heroin, MDMA, or cannabis (“candy blunts”) Intranasal “Robofire” – 2002 Dec • DM dissolved in lighter fluid crack-like rocksmoked (?better hallucinations) • DM drank, then lighter fluid inhaled
  • 34. Dextromethorphan • DM Readily absorbed from gut • Peak serum levels @ ~2-3 hrs for immediate release, 6 hrs for sustained release preparations • Dextrorphan (DOR) peak levels @ ~1.6-7 hrs • Euphoria and hallucinosis occur within 15-30 min of ingestion, peak effects in about 2.5 hrs. “Plateaus” = 3-6 hrs
  • 35. • Weaker sigma opioid agonist, stronger NMDA antagonist than DM • Relatively inactive at mu, kappa and delta receptor sites – thus essentially devoid of more conventional opiate properties, although respiratory depression has been reported with massive ingestion
  • 36. Dextromethorphan • Sigma-1 opioid receptor site is involved in the regulation of glutamatergic NMDA receptor functioning, dopaminergic tone, and serotonin release • (DM binding at sigma-2 opioid receptor sites may alternatively cause impaired motor movements that may be observed during DM intoxication)
  • 37. Dextromethorphan Serotonergic action 1.increasing the synthesis and release of 5HT 2.re-uptake pump inhibition
  • 38. Dextromethorphan Characteristics of the dextromethorphan (DM) intoxication syndrome Psychiatric Neurological General • Auditory hallucinations Slurred speech Nausea • Visual hallucinations Ataxia Vomiting • Tactile hallucinations Mydriasis Diaphoresis • Hyper-excitability Blurry vision Hypertension • Pressure of thought Bi-directional nystagmus Respiratory depression* • Lethargy Hypertonia Coma* • Nervousness Choreoathetoid movement Fatality* • Euphoria Dystonic movements • Confusion/disorientation Dyskinesia • Altered time perception Restlessness • Paranoia Tremor • Feeling of “floating” Hyper-reflexia • Heightened perceptual Seizures* awareness * Rarely
  • 39. Dextromethorphan Over-the-counter sources of DM + • Antihistamines (chlorpheniramine, *)) • Decongestants (pseudophedrine) - cardiac • Pain (acetaminophen) – liver • Bromides - Br poisoning • Serotonin Syndromes
  • 40. Truly addictive? Abuse Dependence Rodent & primate animal models • Biochemical reinforcement (DOR) ~ to PCP • Stimulus discrimination (DOR) • Stimulus generalization with PCP • DM strongly self-administered
  • 41. Dextromethorphan Street Names: • C-C-C • Dex • DM • DMX • DXM • Red devils • Robo • Skittles • Slang robe • Syrup • Triple C’s • Vitamin D
  • 43. Hallucinogens • Psychotomimetics (producer of psychoses) • Psychedelics (mind manifesting) • Intoxicants • Inebriants
  • 44. Hallucinogens • Serotonin-like structure (Indolealkylamines) – Lysergamides: LSD (Lysergic Acid Diethylamide), LSA (Lysergic Acid Amide) – Substituted tryptamines: Psilocybin, Psilocin, DMT, 5- MeO-DMT, DET, DPT, AET, AMT, 5-MeO-AMT • Amphetamine-like structure (Phenylalkylamines) – Phenethylamines: Mescaline, Nexus – Phenylisopropylamines: A-M-Mescaline, MDA (MDMA), DOB, DOM, DOI – Structurally similar to phenylalkylamine hallucinogens, but functionally NOT primarily hallucinogenic; have stimulant and/or other properties.
  • 45. Hallucinogens: Pharmacodynamics Illusionogen = better term • Illusions = alteration or enhancement of an existing sensory perception (visual, time, sound). Intact reality testing in most (?). Effect varies greatly with set (expectations) and setting (environment) 5HT2A agonists (both Indolealkyl- and Phenethyl-amines) • Any 2 of the 3 correlate significantly: – Higher 5HT2 receptor affinity – Animal drug discrimination-derived potencies – Human hallucinogenic potency • 5HT2 antagonists (ketanserin, pirenperone, etc) reduce hallucinogen effects Also bind at 5HT2B and 5HT2C receptors
  • 46. Hallucinogens: Intoxication B) Maladaptive changes developing during/shortly after use: anxiety, depression, ideas of reference, fear of losing one’s mind, paranoia, poor judgment, etc.) {euphoria most common, though} C) Perceptual changes occurring in a state of full wakefulness and alertness, during/shortly after use: intensification of perceptions, depersonalization, derealization, illusions, hallucinations, synesthesias) D) >=2 developing during/shortly after use: pupillary dilation, tachycardia, sweating, palpitations, blurring of vision, tremors, incoordination {stimulant effects} E) Not due to GMC {also, see hyper-reflexia}
  • 47. Hallucinogens: Intoxication • Effect depends upon set and setting • Geometric shapes • Worse w/eyes closed • Afterimages • Hyperacuity (not auditory hallucinations) • Touch hypersensitivity • Time standing still
  • 48. Hallucinogens: Diff Dx • Clear sensorium (delirium) • Intact remote and recent memory • Fairly oriented (delirium) • Hyperalert (drowzy in THC) • Intact reality testing – usually (otherwise, consider dx of a primary Psychotic D/O NOS, SCZ, or A intox)  thus, “talking down” might prove beneficial • Visual >>> auditory (SCZ, mood, etc) • EEG = arousal (delirium = slowing) • SPECT = hyperfrontal (hypo- in SCZ)
  • 51. LSD • Most potent hallucinogen (micrograms) • Hallucinogen (Illusionogen) - 5HT2A partial agonist • Difficult to make (ingredients = CSA III) • California groups owned market share, protect it • Potency ? Much less than 1960’s
  • 52. LSD • Albert Hofmann (Sandoz chemist) 1938 • Lysergic acid compounds derived from a rye fungus, ergot • “Accident,” 1943
  • 53. LSD • Water soluble; clear, white, odorless crystals • Sold in plastic, opaque canisters (film) – oxidation/degrades  discolors (distributors use colored paper for the blotter art) • Pressed into pills = “microdots” ... thin gelatin squares = “window panes” • Breath mints, sugar cubes (dropping acid), blotter paper (most common) • Street dose = 70-300mcg, effects reported from as little as 20mcg
  • 54. LSD • Marketed as Delysid in 1947: – Rx’d for schizophrenia, alcoholism, criminal behavior, sexual perversion – Medical students, help understand SCZ • Schedule I, CSA: 1. High abuse potential 2. No legitimate medical indication 3. Lack of accepted safety under medical supervision
  • 55. LSD • Readily absorbed from gut • Diffuses to all tissues; brain, placenta, fetus • Onset 30-60 min (oral) • Peak = 2-4 hours • Resolves 8-12 hrs
  • 56. LSD: Street names Often based on carrier: • Acid • Bart Simpsons • Liquid • Liquid A • Lucy in the sky with diamonds • Microdots • Dots • Mind detergent • Blue unicorn • Orange cubes, micro- • Tabs • Barrels • Paper acid • Sandoz • Sugar, sugar cubes • Sunshine • Twenty five (-th) • Windowpanes
  • 57. LSD • Hallucinogen Persisting Perception Disorder (Flashbacks) – Unrelated to dose, # exposures – Usually none after 1-2 years (cases of after 5 years) – beltway bumper – High lifetime prevalence of mood d/o’s vs non-LSD using substance users • Rapid (psychological) tolerance; crosses with psilocybins, mescaline –> lower f of use
  • 58. LSA (LySergic acid Amide) • Morning Glory Seeds  grind up • 5-10% the potency of LSD • 20-30 mcg LSD ~ 100-300 morning glory seeds (insecticide exposure)
  • 59. Psilocybins, Psilocins • Use dates back to 1000 - 500 BC • Aztecs • 1957 Sandoz assisted researchers in extracting it • Synthesis technique developed • May 13, 1957 LIFE issue: described Mazatech velada, 7 varieties of mush’s • “Magic Mushrooms” in the 1960’s (Psilocybe mexicana)
  • 60. Psilocybins, Psilocins • Central America, Mexico • Both psychoactive (psilocin more) -- ratio varies among mushrooms • Psilocin less stable,oxidized upon drying • Dried mushrooms = 0.2% - 0.4% psilocybin, only trace psilocin • 4-8 mg of mixed psilocin/cybins = hallucinations (~2gm of mushrooms)
  • 61. Psilocybins, Psilocins • Intoxication duration = 2 hours • Synesthesias • Detachment from reality, Enmeshment with surroundings • Inability to discern fantasy from reality --> panic attacks, psychoses • More “natural” high than w/LSD • Rapid tolerance … cross tolerance w/LSD
  • 62. DMT Naturally occurring – Plants: Phalaris aruninacea = DMT + 5-MeO-DMT (MeO- increases lipid solubility, 10X potent) • “Businessman’s Trip” – rapid onset, short duration (<60min) – snorted/ IV/smoked (oral – inactivated) • MAOI enables oral use (lengthens catabolism) – Toads: Bufo alvarius (Sonoran Desert Toad) • Glandular venom = 6-16% 5-MeO-DMT • Skin contains 5-MeO-DMT (50-160mg/g skin) • 3-5mg = psychoactive effect • 1959: predominant alkaloid in the hallucinogenic snuffs of several tribes in South America
  • 63.
  • 64.
  • 65. DMT user’s account … Within thirty seconds, there will be an onset of almost overwhelming psychedelic effects. You will be completely absorbed in a complex chemical event characterized by an overload of thoughts and perception, brief collapse of the EGO, and loss of the space-time continuum. Relax, breathe regularly, and flow with the experience. After two to three minutes, the initial intensity fades to a pleasant LSD-like sensation in which visual illusions, hallucinations, and perceptual distortions are common. You may sense a distortion in your perceived body image or notice the world shrinking or expanding. You may notice that colors seem brighter and more beautiful than usual. And, most likely, you will experience a euphoric mood interspersed with bursts of unmotivated laughter.
  • 66. DET, DPT, AET • Substituted tryptamines • Similar in effect to DMT • Less potent • Schedule I of CSA
  • 68. Mescaline • Principal psychoactive agent found naturally in the peyote cactus • 3,4,5-trimethoxy-phenethylamine • 1st hallucinogen isolated (Arthur Heffter 1896) • Peyote cactus: central Mexico – south Texas • 300BC – religious rites • Comanche, Kiowa, Navajo, Sioux • Supreme Court protects religious use within Native American Church (no synthetics) • Canada
  • 69. Mescaline • Peyote cactus • Crown (top) contains buttons • Buttons are cut off, dried • 1-6% of dried button = mescaline • 6-10 buttons = intoxication (100–350mg required) • Chewed or soaked in water
  • 70. Mescaline: Intoxication • 30 min delay • 2 phases: First hour – Minor perceptual changes – Adrenergic stimulation (increased resp. rate; face & neck muscular tension) – Nausea (can be severe) -- other alkaloids Next several hours (as much as 5-10) – Visual illusions, hallucinations – synesthesias
  • 71. Importance of set, setting • Religious rituals, guides Mescaline – A&E documentary (father gives drug to son); religious leader Beta-carbolines – Harmaline +/- DMT, 5-MeO-DMT – Sting’s memoir (exploring personal life meaning) – ayahuasca (South American ritual beverage) – Mestre
  • 72. Nexus • “2-CB” • “CB’s” • Similar in structure to mescaline • Analog of DOB
  • 73. DOM, DOB, DOI • DOM (“STP”)= “model”/reference hallucinogen in drug discrimination studies • dimethoxymethylamphetamine
  • 74. Hallucinogens – sub-grouped by effect, not by structure S H P • H (nonintersecting) = Hallucinogens “proper” (model = DOM) • S = Central stimulants (model = +amphetamine) • P = Other effects (empathy) (model = PMMA)
  • 75. MDA, MDMA (ecstasy) deferred to stimulants lecture S H P • Central region = racemic MDA • H/P = -MDA S/P = +MDA, MDMA • P = PMMA (“white death”), MBDB (“eden, methyl J”), 4- MTA (“flatliners”)
  • 76. SteroidsSteroids • Synthetic derivatives of the male hormone testosterone • Rx uses: delayed puberty, impotence, wasting due to HIV, etc. • 2 effects: 1. Anabolic (maximize): skeletal muscle growth (via retaining N, directly stimulate protein production, increase availability of ATP to muscles, increased Hct) 2. Androgenic (minimize): male sexual char’s
  • 77. Steroids • 1930’s: testosterone synthesized • 1940’s-50’s: use in sports • 1950’s: brought to US by Dr John Zeigler, nat’l weightlifting team doc; f/Eastern Bloc countries after 1952 Olympics success • 1968: drug testing at Olympics • 1975: banned by IOC • 1990: CSA Schedule III
  • 78. Steroids • Purpose of abuse: muscle, appearance – Triad: athletes, aesthetes, fighting elite • Doses: abused @ up to 100X recc’d dose • Routes: – Oral: Anadrol (oxymetholone), Oxandrin (oxandrolone), Dianabol (methandrostenolone), Winstrol (stanozolol), etc. – IM: Deca-Durabolin (nandrolone decanoate), Durabolin (nandrolone phenpropionate), Depo-Testosterone (testosteronecypionate), Equipoise (boldenone undecylenate), etc • “reward” = delayed • Many case reports of “dependence”
  • 79. Steroids: Terminology • Stacking: taking 2 or more (a) steroids/stimulants/pain killers and/or (b) routes {po, IM}. “The whole is greater than the sum of the parts.” • Pyramiding: taper-up the doses over 6-12 weeks, then taper-down over next 6-12 weeks just before the event • Plateauing: when a drug becomes ineffective at a certain level • Cycling: different drugs/times
  • 80. Steroids: Epidemiology Ages 13-25, 90% male Prevalence studies • Power lifters @ nat’l competition = 55% • High school athletes = 4.9-6.6%, 2/3 began < age 16 • College athletes = 17%, male football = 30% • More likely to use alcohol, drugs, tobacco • 30% inject, 1/3 share the needle
  • 81. Steroids: Complications • General: liver cysts/tumors (17Îą-alkylated androgens), jaundice, fluid retention, HTN, tremor, acne, (HIV, Hep B+C, endocarditis), myocardial necrosis, lower HDL + higher LDL • Males: shrinking testes (as they reduce endogenous T prod’n), low sperm count, balding, gynecomastia (excess T  E) (poss. irreversible) • Females: facial + body hair, altered menses, enlarged clitoris, deep voice, balding, less fat • Adolescents: premature epiphyseal plate closure, accelerated pubertal changes
  • 82. Steroids: Psychiatric • Aggression, mania, psychoses, depression; post-withdrawal depression & drug-craving • Larger doses  more pronounced psych sx’s • Maj. mood d/o prev. = 23% (>300 – 1000 mg/week needed for mania), psychotic sx’s = 12% • Personality types: histrionic, antisocial, +/- narcissistic
  • 83. Inhalants A) Volatile solvents (vaporize @ room temp): Adhesives: airplane glue, rubber cement, polyvinylchloride cement Aerosols: spray paint, metallic spray paint, hair spray, deodorant, air freshener, vegetable oil spray, analgesic spray, asthma spray Solvents and Gases: nail polish remover, paint remover, paint thinner, typing correction fluid, fuel gas, cigarette lighter fluid/butane, gasoline, freon Cleaning agents: dry cleaning fluid, spot remover, degreaser Propellant gases: nitrous oxide (whipped cream), propane B) Nitrites: cyclohexyl-, amyl-, butyl-, isobutyl- nitrite (butyl, propyl, and certain other nitrites banned in 1991) C) Anesthetics: (gaseous, liquid, local injection)
  • 84. Inhalants • 1/6 adolescents tries inhalants, most 1-5x • Males, non-Hispanic white youths • Inhalant Dependence is uncommon (0.3% prevalence, 1 in 27 lifetime users) • Not passing fad, 10% use > 6 years • Strong assoc. with ASPD, PSA, later IVDA (5-9X) • Developing countries
  • 85. Inhalants • Highly lipophyllic HC chains, cross into brain Pharmacodynamics • Unknown, ~ to dissociatives (NMDA) and alcohol/sedatives (GABA) • Drowsiness settles in for several hours • Toluene increases extracellular D in PFC • Toluene, nitrous oxide, & chloroform have reinforcing properties in self-administration studies .
  • 86. Inhalants: Terminology • Sniffing • Huffing: cloth (or mask) (soaked with substance) applied to face and breathed in • Bagging: enclosing the substance in a bag and breathing it in • Poppers, snappers: ampules of amyl nitrite Rx’d for angina (broken and inhaled). 1960 FDA allowed OTC use. Increase in abuse (gay men: smooth muscle relaxation, vasodilation  sexual enhancement). FDA restored Rx requirement. Also: butyl/isobutyl nitrite/cyclohexyl (nowadays find them sold as video head cleaner or room deodorizer in adult sex shops) • Whippet: balloons/bags filled w/ N2O (laughing gas) • Torch, fire-breathing: exhaling + igniting volatile gases (propane, butane) • Texas shoe shine: toluene-containing spray paint
  • 87. • Odor of paint, solvents (clothes, breath) • Residues, burns, related traumas • ‘Glue sniffer’s rash” around nose & mouth, conjunctival irritation • Cough, sinus discharge, dyspnea, rales, rhonchi • Neuro: weakness, peripheral neuropathy, cerebral/cerebellar/brain stem atrophy, white matter lesions, MS-like syndrome, dementia, delirium • Hepatitis, cirrhosis • Metabolic acidosis with distal renal tubular acidosis, CRF • Bone marrow suppression • Neuropsychological testing problems in chronic inhalant users Inhalants: PE, lab
  • 88. Inhalants Intoxication A) Recent use/exposure B) Maladaptive changes developing during or shortly after use: belligerence, assaultiveness, apathy, impaired judgment, etc. C) >=2 developing within 2 hours of use: dizziness, nystagmus, incoordination, slurred speech, unsteady gait, lethargy, depressed reflexes, psychomotor retardation, tremor, gen. muscle weakness, blurred vision/diplopia, stupor/coma, euphoria D) Not due to GMC
  • 89. Inhalants Withdrawal None, per DSM. However, a mild syndrome beginning 1-2 day after last use and extending for 2-5 days has been described. Symptoms may include sleep problems, tremor, irritability, diaphoresis, nausea, fleeting illusions. Abuse, dependence, and tolerance are confirmed
  • 90. Inhalants: “Sudden sniffing death” Falling unconscious on source/rag; “hands-free” use during sex Acute arrhythmia *** Heart failure (from butane or chlorofluorocarbons associated hyper-excitability to NE) Hypoxia ** Suffocation (as substance replaces oxygen) Methyl chloride  carbon monoxide Poppers (ampules of amyl/butyl/isobutyl nitrite ) – reduce oxygen carrying capacity CNS, respiratory depression Electrolyte abnormalities *
  • 91. Inhalants: Fetal effects • Cross placenta  renal tubular acidosis • Data primarily from occupational exposures – Cleft malformations, gastroschisis, esophageal stenosis – Omphalocele – Ventricular septal defects – CNS defects – Spontaneous abortions • Inhalant using women create higher exposure levels – Limb abnormalities – Growth retardation – Craniofacial defects – Developmental delays, language • Toluene in animals – Neuronal migration, proliferation affected
  • 92. SummarySummaryDissociatives: Phencyclidine, Ketamine, Dextromethorphan Hallucinogens: Serotonin-like structure – LSD, LSA – Psilocybin, Psilocin, DMT-like … Amphetamine-like structure – Mescaline, Nexus, DOM, DOB, DOI Steroids Inhalants Lindner Center of Hope