Download Hallucinogens - People Server at UNCW

Methylated AmphetaminesMDA and MDMA
• Methylenedioxymethamphetamine (MDMA, Ecstasy,
XTC)-MDA is a metabolite of MDMA and may be
responsible for much of the MDMA effect.
• Synthesized in 1912
• Structurally related to amphetamines
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–
–
–
Sympathomimetic
Weak in altering perceptual functions
But strong effects on emotions - empathogen
Used in combo with psychotherapy
Of interest: http://www.biopsychiatry.com/interview/index.html
Ecstasy (MDMA): Physiological Effects
• Sympathomimetic
• Bruxism & Trismus—teeth grinding & jaw
clenching (pacifiers)
• Dehydration/Overhydration
• Hyperthermia
• Tachycardia
Ecstasy (MDMA): Psychological Effects
• Increased alertness, arousal, insomnia-stimulant effects
• Euphoria, increased emotional warmth
• Increased empathy and insight?
• Hallucinogenic effects are largely absent
Percent Using
Percent
School Seniors
Seniors reporting
Percent
HighHigh
School
reporting
use during their Senior year
MDMAMDMA
use
during their Senior year
(Johnston, O'Malley,Bachman
(Johnston,
O'Malley,Bachman
& Schulenberg,
2005)
& Schulenberg, 2005)
8
6
4
2
98
96
96
98
00
Year
02
00
04
06
History
• Patented by Merck in 1914
• Advocated by some as adjunct to
psychotherapy (1970s-80s)
• A “Designer Drug”…Picked up the name
“ecstasy” & became significant street drug
(1980s)
• Schedule I drug (1986- The Analogue drug Act)
• Prototype “club drug” (1990s)
MDMA: Prototype Club Drug
Pharmacodynamics
Monoamine neurotransmission
– increase synaptic DA and 5-HT
– blocks 5-HT transporter
– enters neuron and causes release of 5-HT
Ecstasy and brain Damage?:
Preclinical research
• Serotonin depletion, damage to serotonergic
neurons reported in several species including rats
and primates (see Morton, 2005 for a review)
• Effects were present in primate brain 7 years after
MDMA exposure Hatzidimitrious et al., 1999)
MDMA & MDA neurotoxicity
5-HT immunoreactive fibers in rat parietal cortex
MDMA
Normal
MDA
9.9
Are doses used in preclinical research too
high?
• neurotoxic doses in non-humans (5-20 mg/kg
twice or more/day for several days) are
generally higher than would be typical of
human use.
• However, people often take several tablets at
a time or throughout a night’s binge and a
tablet may contain up to 300 mg: 4-5 mg/kg in
an average person.
X Toxicity
• Malignant hyperthermia and dehydration
• Idiopathic toxic response (not common but
nasty)
– Renal failure
– Rhabdomyolysis – disintegration of muscle tissue
• seizures, arrhythmias, heart failure, stroke,
• Most MDMA-related fatalities have been
attributed to symptoms of heat stroke and
hyperthermia
Residual (long-term) adverse
effects?
• Topp et al. (1999) Australia study
• Physical side effects
– Loss of energy (65%), Muscular aches (60%)
– Hot/cold flashes (48%), Numbness (47%)
– Profuse sweating (43%), Tremors (42%)
• Psychological side effects
–
–
–
–
–
Depression (56%), rritability (63%),
Sleep difficulty (56%), Confusion (47%)
Anxiety (45%), Paranoia (40%)
Memory deficits?
( note issue of sample problems/poly-drug use etc..)
What is PMA?
• Paramethoxy-amphetamine
• "Death" "Mitsubishi Double Stack"
"Killer" "Red Mitsubishi"
• Substitute for MDMA
• Cheaper to make
• Slower, longer effects
• More hallucinogenic
• Incidence of toxic side effects much higher than
MDMA (narrow safety margin)
Myristin and Elemicin
•
•
•
•
Found in nutmeg and mace
Structurally similar to mescaline
Significant nausea and vomiting
The sickness usually limits use
Glutamatergic
Psychedelics
AKA-Dissociative Anesthetics:
-Phencyclidine (PCP, Angel dust, Lovely)
-Ketamine (Special K)
Phencyclidine
 PCP
 Glutamate (NMDA) receptor antagonist
Blocks the function of glutamate
 Used as an analgesic and anesthetic
 Can be administered by any route
 Oddly enough, animals self-administer
(euphoria)
PCP- physiological effects
• numbness, loss of motor coordination, slurred
speech, blurred vision, Nystagmus






Higher doses lead to:
hyper excitability or stupor
coma
seizures
death
A perfect example of a Schedule I drug
• High rate of psychotic episodes some long-term
Subjective Effects of PCP/Ketamine
• Sensations of light coming through the body and/or
colorful visions
• Complete loss of time sense
• Bizarre distortions of body shape or size
• Altered perception of body consistency
• Sensations of floating or hovering in space
• Feelings of leaving one’s body
• Visions of spiritual or supernatural beings
• Emotions ranging from euphoria to hositlity
 true psychosis
 Hallucinations, paranoia, agitation, dissociation
Dalgarno & Shewan (1996)
Ketamine
• Special K
• Very similar to PCP, not as
powerful
• Liquid, but can be
powdered for snorting or
smoking
• Another perfect example of
a Schedule I drug
Dextromethorphan
•
•
•
•
•
Active ingredient in most OTC cough medicine
NMDA receptor blockade at high doses
Mostly teenage males abuse it
Like PCP and K at 20-30 X OTC dose
Coricidin –Bad news
Cholinergic
Hallucinogens
Anticholinergic hallucinogens
• Atropine-Deadly nightshade, Datura, Jimson
weed, and Mandrake, Atropa belladonna
• Scopolamine-from Datura, Jimson weed,
Mandrake and Henbane
Cholinergic
Hallucinogens
Acetylcholine receptor (muscarinic) antagonists
Dissociatives that induces delirium , hallucinations, and amnesia
Classic anti-cholinergic symptoms
Hot as hell
Dry as a bone
Mad as a hatter
Blind as a bat
Red as a beet
Used in the treatment of motion sickness & to dilate
pupils during eye-exams.
Datura
Jimson weed
Anticholinergic effects
• Dry mouth, blurred vision, loss of motor
control
• Dream-like trance state
• Little or no memory of experience
Muscarine/Muscimol
 Found in mushrooms
(Amanita Muscaria)
 Muscimol is a GABAA
agonist
 Trance-like, dreamy state
with dreamlike illusions
 Like Ambien
 Muscarine is an
Acetylcholine agonist
(muscarinic receptors)
 Not psychotropic
 Peripheral effects: sweating,
limb twitching, seizure
activity
Salvia Divinorum
• Plant used by the Mazatec people of Southern
Mexico: Diviner’s sage—leaves chewed or smoked
• Active substance = salvinorum A (affects Kappa
receptors)--most potent natural hallucinogen (100
microgram ED50)
Salvia Divinorum
Brief (30-60 min) intense trip: visual hallucinations,
dissociative state, some bad trips, recent highly publicized
suicide
Marketed legally in US (in most states) as herbal dietary
supplement—currently under DEA review