Transcript Amphetamines, Ketamine and LSD

Amphetamines, Ketamine and
LSD
Jonathan Wood
Consultant in Substance Misuse
Outline
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Prevalence
Amphetamine (stimulant)
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Prevalence, Use etc
Amphetamine Psychosis
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Ketamine (dissociative anaesthetic)
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LSD (Hallucinogen)
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Hallucinogenic mushrooms
Prevalence
Amphetamines
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Group of compounds:
Amphetamine (α-Methyl-2-phenylethylamineMethamphetamine)
Methamphetamine (N-Methylamphetamine, (1R,2S)-)
Fenfluramine (3-Trifluoromethyl-N-ethylamphetamine)
Bupropion (β-Keto-3-chloro-N-tert-butylamphetamine)
Mephedrone (β-Keto-4-methyl-N-methylamphetamine)
Amphetamine
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Synthesised in Germany in 1887
Used rarely in nasal decongestants in early 1930s
Tested medically in 1930s on hospital workers –
achieved feelings of wellbeing, exhilaration and relief
from fatigue
Used extensively in WWII to combat fatigue and
increase alertness
OTC medication throughout 1950s but POM and then
banned in 1964
For sale for £15 per gram. Second most commonly
injected drug
Psychostimulants
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The ‘up’
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euphoria
alertness
energy
sociability
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increased libido
concentration
self-esteem
self-confidence
…And the down
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Low mood
Fatigue
Irritability
- anxiety/agitation
- increased appetite
- excessive sleeping
Other side effects
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Irritability
Aggression
Obsessive behaviours
Paranoia
Psychosis
Mode of acton
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Dopamine
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Causes presynaptic dopamine vesicles to
release dopamine into cytosol
Causes reversal of the DAT transporters so it
tansports Dopamine into the cleft
Serotonin
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Reversal of SERT transporter
Particularly in mesocorticolimbic pathways
increasing glutamatergic neurons
Physical sequelae
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Cardiovascular
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CNS
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HT, ↑Pulse, MI, cardiomyopathy, Aortic dissection,
Ischemic strokes, intracereberal haemorrhagges,
seizure, abnormal movements
Ischemic colitis
Rhabdomyolysis
hepatotoxicity
Methamphetamine
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common nicknames: "ice", "crystal meth",
"crank", "glass", "speed" (United States),
"shabu" (Philippines) and "tik" (South
Africa) and "ya ba" (Thailand)
Routes of administration: oral, snorting,
smoking, injection
Often cut with a cutting material therefore
infections/rashes common.
Pharmacology
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½ life 9-15hrs excreted by kidney
Lipid soluble – fast entry to brain
Resistance to MAO degradation
Causes reversal of Dopamine, NA uptake
enzymes.
Tolerance occurs partially due to transmitter
depletion
Neurotoxic to dopamine & serotonin neurons
Effects
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Desired: Euphoria, alertness,
concentration, self confidence, energy.
Unwanted: aggression, agitation,
irritability, paranoia, psychosis.
Physical: anorexia, tachycardia,
hypertension, constipation, palpitations,
stroke, MI, convulsions
Production
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Combination of red phosphorus,
(psuedo)ephedrine and iodine
Extremely dangerous – phosphine gas
produced
Continues to be used
for treatment of narcolepsy
Long term effects
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‘Meth Mouth’ – dry mouth, poor hygene,
grinding teeth.
Injecting related problems
Unsafe sex
Withdrawal: excessive sleeping, increased
appetite and depression, often
accompanied by anxiety and drug-craving.
Amphetamine/Methamphetamine
Treatment
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Poor evidence for effective treatments
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Substitution therapies equivocal or of poor
quality
Occasional use of modafinil, baclofen &
mirtazapine
Amphetamine Psychosis
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Characteristics
Assessment
Investigations
Treatment
Characteristics of amphetamine
psychosis
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Study of 309 regular amphetamine users
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13% of participants screened positive for psychosis,
23% had experienced a clinically significant
symptoms of suspiciousness, unusual thought content
or hallucinations in the past year.
Swift onset
Delusions & hallucinations which may mimic
schizophrenia or bipolar
Abates within days with restoration of sleep and
cessation of amphetamines
Treatment Guides
Cochrane conclusions:
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Authors' conclusions
Only one RCT of treatment for amphetamine
psychosis has been published.
Antipsychotic medications effectively reduce
symptoms of amphetamine psychosis
Olanzapine, demonstrates significantly better
tolerability than the more affordable and
commonly used medication, haloperidol.
Assessment
1. Vital signs, blood sugar level, oximetry
2. Orientation
3. Insight
4. Delusional thinking
5. Types and nature of any hallucinations
6. History of psychiatric illness
7. Medical history
8. Current medications
9. Drug use history, specifically:
• number and types of different drug types used (both licit and illicit)
• changes in recent use patterns, particularly escalation
• time and amount of most recent use of each drug
• route of administration
• presence of injection sites or ‘track marks’
10. Recent sleep patterns
Investigations
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Organic screening
Drug tests
Treatment
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Assessment
Tests
Stepped care approach
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Lorazepam 2-4mg, repeat after an hour
(Consider midazolam i.m.)
Try Olanzapine i.m.
Use physical restraints only as a last resort if the
steps above have failed. Appropriate close supervision
is necessary. Sudden unexpected deaths are more
common when physical, rather than chemical restraint
is used.
Ketamine
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Developed in 1962 by Pfizer
Used as general anaesthetic or in pain
management
NMDA (Glutamate) receptor antagonist
Action particularly in the prefrontal cortex
and hippocampus
At higher levels binds opioid receptors,
partial D2 agonist & inhibits dopamine
reuptake
Illicit use
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Sold in powder or liquid
Can be sniffed, injected or swallowed
Significant first pass metabolism so larger
amounts required if swallowing
Currently Class C drug
Dependence rare, tolerance develops
reasonably quickly, no abstinence
syndrome
Effects
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Dissociative amnesia ‘k-hole’
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Feelings of detachment from the world
(depersonalization/derealization)
Spiritual experiences
Feeling connected to others
Visual hallucinations,, other perceptual abnormalities
changes in time
Lasts about 2 hours
Health Consequences
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Bladder problems – BMJ 2008 case series of 9
patients
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Changes in cognition
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severe urinary frequency, urgency, macroscopic
haematuria, and suprapubic pain
ulcerative cystitis and a severely denuded urothelium
Heavy users worse verbal, short-term memory and
visual memory
Occasional users no difference from controls
No evidence for long term effects
Overdose
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Commonly from i.v. use
LSD
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Synthesised by Hoffman in 1938
Used in 1950s to ‘enhance psychotherapy’
Used extensively recreationally in 1960s
Used by US government whilst
investigating mind altering substances
Effects a wide range of neuroreceptors
mainly mediated throught 5HT2A rexeptor
antagonism
Illicit use
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Sold currently in tablets, liquid or on paper
Effective dosages are 100-500 micrograms
Unlikely to overdose
Low dependence potential
Effects
Onset in 1hr lasts 6-14 hrs
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Sensory modalities intensified
Visual Hallucinations with insight
Distortions of sensory inputs or
synaestheia
Changes in experience of time
Spiritual experiences
Physical effects
Pupil dilation, reduced appetite
wakefulness
Rare significant other effects
 Hyperreflexia
 Tachycardia
 Increased WBC
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Long term effects
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Flashbacks
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Perceptual – minor visual to frank
hallucinations
Somatic – altered body sensation or pain
Emotional – mood instability
loneliness/depression
No clear evidience and schizophrenia
Mushrooms
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Psilocybin mushrooms containing psilocybin and
psilocin
Some evidence of use dating back to prehistoric
times.
Can be cooked, eaten raw, brewed in tea
Thought not to be addictive whatsoever
Tolerance gained and lost quickly
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Most common Psylocybe
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semilanceata
Mushrooms effects
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Psilocin acts as a 5HT2A, 5HT2C and 5HT1A
agonist no effect on dopamine
Desired detachment, euphoria,
synaesthesia, illusions ,hallucinations
Undesired nausea, vomiting, tachycardia,
accidents, anxiety/panic, acute confusion,
psychosis
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In 2006, Johns Hopkins University studied the spiritual effects of
psilocybin mushrooms. The study involved 36 college-educated
adults who had never tried psilocybin nor had a history of drug use,
religious or spiritual interests; the average age of the participants
was 46 years. The participants were closely observed for eight-hour
intervals in a laboratory while under the influence of psilocybin
mushrooms.
One-third of the participants reported that the experience was the
single most spiritually significant moment of their lives and more
than two-thirds reported it was among the top five most spiritually
significant experiences. Two months after the study, 79 percent of
the participants reported increased well-being or satisfaction;
friends, relatives, and associates confirmed this.
Despite highly controlled conditions to minimize adverse effects,
22% of subjects (8 of 36) had notable experiences of fear, some
with paranoia. However, the authors reported that all these
instances were "readily managed with reassurance".
Management
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Not routinely tested for
Management supportive
Legal Status:
The Drugs Act 2005 changed the law so that
now both fresh and prepared (e.g. dried or
stewed) magic mushrooms that contain
psilocin or psilocybin are classified as Class A
drugs. Possession can get you up to seven
years in jail and/or an unlimited fine.