Transcript Slide 1 - The University of Sydney

Cannabis
© 2009 University of Sydney
Module learning outcomes
To be able to:
• Describe the mechanism of action, pharmacology
• Describe its desired and undesired effects
• Describe the therapeutic uses of cannabis
• Describe the prevalence of cannabis use
• Assess cannabis use clinically, predisposing
factors, and associated harms
• Understand the management of cannabis use
disorders
Case study: Mark
• Mark is a 34 year old who comes for help with
his cannabis use. He is smoking 10 cones a
day. He has tried to cut down on several
occasions but finds he can’t bear his edginess
and poor sleep when he stops.
• Is there such a thing as cannabis withdrawal?
• Would you say Mark is addicted to cannabis?
• What harm is Mark’s cannabis use likely to
cause?
• Are there treatments available for cannabis
dependence?
Historical perspective
• Cannabis cultivated in China 6000 yrs ago
• American Indians widely used cannabis
1000 yrs ago
• Multipurpose and hardy crop yielding
–
–
–
–
Cooking oil
Edible seeds
Animal fodder
Hemp fibre
• Psychoactive drug
Courtwright, Forces of Habit, 2001
Pharmacology and
mechanism of action
What are cannabinoids?
• Group of >60 dibenzopyran chemicals found in
leaves and flowering tops of female cannabis
plant (Cannabis sativa and Cannabis indica)
• Some common cannabinoids are:
In the plant:
In your body
(endogenous):
Synthetic:
Δ9 – THC
2-arichidonyl
glycerol (2 – AG)
CP 55,940
Δ8 – THC
anandamide
HU – 210
cannabidiol and
cannabinol
Structure of THC and
synthetic analogs
Lipophilic side chain
Most potent
analog: 100s
times more
potent than THC
Mode of cannabis action
• Two specific cannabinoid receptors
– CB1 - brain and peripheral tissues
– CB2 - immune system
• Linked to G-proteins with diverse
downstream signalling pathways
• Euphoria results from stimulation of
mesolimbic dopaminergic neurons, like
other drugs of abuse
Neurotransmitter
Receptor
Influences nt release
Neurotransmitter
Receptor
Post-synaptic
release of
endog.
cannabinoid
Central mediation of some of
the effects of cannabinoids
Cannabinoid receptor
antagonists
• SR 141716
(Rimonabant),
LY320135 and
AM281
• All have marked
selectivity for
CB1 receptors
over CB2.
Myths: for & against
• Harmless, and safer than the licit drugs
• You can’t get addicted to cannabis
• It’s a gateway drug (leads to ‘hard
drugs’)
• Rising potency in recent years, leading
to more harms
• ‘it causes schizophrenia’
Commonly used terms
• Cannabis is the preferred general term.
• Other terms: marijuana, ganga, mull, grass,
hash, pot, weed, dope
• Types of cannabis, in increasing strength
– Leaf << Head << Oil/resin
• Diverse methods of smoking
– joint = cigarette of cannabis, typically 0.5g
– cone: smoked via a water pipe (bong), typically
0.25g
– bucket bongs
– vaporisers (increased ammonia levels via this
method)
Is high potency a problem?
• For naive users:
– higher risk of dysphoric & psychotic
symptoms
• higher rates of discontinuation?
– higher rates of accidental injury?
• For regular users:
– lower respiratory risk, if users titrate dose
– higher risk of dependence?
• especially among adolescents
– more cognitive impairment?
THC content: 1990 - 2008
United States
Non-normalized average THC % vs year of
confiscation
12
10
THC %
8
6
4
2
0
90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08
Year
National Institute on Drug Abuse, Potency Monitoring Project
Quarterly Report, No. 100, 2008.
Effects of Cannabis
Why do people use
cannabis?
• To experience euphoria or perceptual
distortions
• Because others do so
• To relieve mental symptoms
– negative symptoms of schizophrenia
– anxiety
• To relieve physical symptoms
– eg nausea, anorexia, cancer & HIV
Typical effects of cannabis
• Mental effects
– Euphoria, relaxation and wellbeing
– Increased appetite (‘munchies’)
– Talkativeness, disinhibition
• Physical effects
– Vasodilator (systemic and portal)
– Bronchodilation (short-term effect only)
• Highly variable
– Many people dislike it and discontinue use
– Influenced by surroundings
Prevalence of Cannabis Use
Patterns of cannabis use in
Australia
2007 National Drug Strategy Household Survey
Lifetime illict drug use
cannabis
33.5
inhalants
3.1
meth/amphetamine
6.3
hallucinogens
6.7
ecstasy
8.9
heroin
1.6
cocaine
5.9
0
5
10
15
20
25
30
35
40
Percent
AIHW, 2008
Changes in drug use over
time (ever used)
2007 National Drug Strategy Household Survey
50.0
1991
1993
1995
1998
2001
2004
2007
37.5
%
25.0
12.5
.0
Cannabis
Heroin
Amphetamines
Cocaine
Ecstasy
AIHW, 2008
Changes in recent drug use
over time
2007 National Drug Strategy Household Survey
50.0
1991
1993
1995
1998
2001
2004
2007
37.5
%
25.0
12.5
.0
Cannabis
Heroin
Amphetamines
Cocaine
Ecstasy
AIHW, 2008
Cannabis use across age
groups
2007 National Drug Strategy Household Survey
Ever used
%
Recent use
2007 National Drug Strategy Household Survey
60
50
Percent
40
30
20
10
0
14-19
20-29
30-39
40-49
50-59
60+
Age
AIHW, 2008
Changing patterns of
cannabis use
• Weekly or more frequent use
accounts for 96% of use
• Earlier initiation of use:
– increased risk of dependence
• More use among vulnerable
groups
• remote indigenous people
• persons with schizophrenia
• conduct disordered
adolescents
Natural history of cannabis
use in Australia
• Initiation in mid teens
• Most use intermittently
– Surveys capture relatively low daily use
• Discontinue in mid to late 20s
– Impact of ‘marriage, mortgages & children’
• Persistent use relatively rare
– Predicted by early initiation
– Heavier use
Drug use with increasing age
Chen, K. & Kandel, D.B.
1995, Am J Pub Health,
85(1):41-47. © American
Journal of Public Health.
Reprinted with permission.
To obtain the full article,
reprints of the article, or
subscribe to the American
Journal of Public Health, visit
www.ajph.org
Concept of gateway drug use
• Sequence of drug involvement
– alcohol & tobacco precede cannabis, leading
in turn to heroin & other drugs
– harms derive from ‘hard drugs’
• BUT < 5% of those who’ve tried cannabis
go on to use ‘harder’ drugs
• Progression predicted by:
– earlier initiation & heavier use
– other psychosocial issues
Why the association with
other drugs?
• Selective recruitment to use
– at risk & troubled youth more likely to use
• Peer networks
– regular users affiliate with peers who use
– peer culture supportive of drug use & crime
• Drug markets
– provide opportunities to use other illicit drugs
• Genetic vulnerability to drug
dependence?
Harms of cannabis use
Acute adverse effects
• Anxiety, dysphoria, panic, paranoia
– especially among naive users
• Cognitive and psychomotor impairment
while intoxicated
• Psychotic symptoms (probably rare)
– high doses of THC
– vulnerability
Accidental injury
• Impaired performance on complex tasks
• Reduced risk-taking (in contrast to alcohol)
– awareness of impairment
• Simulated driving impaired
• Epidemiological evidence
– dose related risk of MVA1
– measurement of impairment not reliable
– confounding with alcohol
1Ramaekers,
et al, 2004, DAD, 72: 109 -119
Adverse effects of chronic use
• Chronic intoxication
• Dependence
• Effects on adolescent development and school
performance
• Motivation, learning, memory
• Respiratory disease
• Effects of maternal & paternal? use
• Schizophrenia & psychosis
Cannabis and
adolescent development
• Concerns
– Effect on educational performance, especially
in heavier users
– Progression to “harder” drugs?
• Issues
– Heavy use uncommon
– Causal attribution
• Other drug use
• User characteristics
Respiratory effects
Position statement of RACP
• Cannabis is primarily smoked
• Cannabis smoke similar to tobacco smoke
• Most also smoke tobacco and the
differential effects are difficult to study
• There is every reason to believe that the
long-term harms are similar to those of
tobacco
Taylor & Hall, 2003, Intern Med J. 33(7):310-3
Evidence
• Cannabis-smoking causes chronic
bronchitis in 20-30% (cough, sputum)
• Histopathological changes in bronchi:
acute and chronic bronchitis and
dysplasia
• Impaired immunological responses
– pulmonary alveolar macrophages
• Increased health service use
• Decreased respiratory function not proven
Public health impact of
respiratory risks
• In comparison with tobacco
– Small in public health terms
– Large in terms of personal risk
• A consequence of smoking as a
route
– Encourage non-smoking use?
• Most smoke tobacco also
– amplification of respiratory risks
Cannabis and psychosis
• ‘Cannabis psychosis’
– Toxic psychosis i.e. as a direct result of the
cannabis intoxication
– Functional psychosis i.e. persists once
cannabis no longer present
• Cannabis as a risk factor for schizophrenia
– Precipitation
– Exacerbation
• High prevalence of cannabis use
– Especially at period of risk for psychosis
– Complicates causal attribution
‘Cannabis Psychoses’
• i.e. as a direct result solely of heavy
cannabis use
• Conflicting opinions
– clinical observations
– limited case-control evidence
• Probably exist but severe toxic pschosis
rare
– either require large doses of THC or
vulnerability
• Mild dose-dependent paranoia common
• Can’t do a randomised controlled trial !
Cannabis Psychosis:
NSMHWB
Unadjusted OR: 2.86 95% CI: 1.37, 5.99
Adjusted OR: 2.39 95% CI: 1.21, 4.72
Those with cannabis dep. 2.4 times more likely to report psychosis symptoms.
Hall & Degenhardt, 2000, ANZJP
Cannabis and Schizophrenia
Consistent evidence that:
• Cannabis use can precipitate schizophrenia
– Four longitudinal studies in 3 countries
– Consistent RR ~ 2 and AR ~ 13%
• Cannabis can exacerbate schizophrenia
–
–
–
–
Clinical evidence
Retrospective studies
Prospective studies
Interventions studies
• But were these people susceptible and likely to
develop this illness in time anyway?
Role of endocannabinoid
system in schizophrenia
• Schizophrenics have heightened
levels of anandamide in their CSF
than controls
• Schizophrenics (that have never taken
cannabis) have increased CB1
receptors in their forebrain compared
to matched controls.
Evidence for Precipitation
•
•
•
•
Swedish conscript study
N = 50,000
N times used cannabis by age 18
Diagnosis of schizophrenia next 15
years
Andreasson et al, 1987, Lancet, 330
Evidence for Precipitation
10.0
7.5
RR
5.0
2.5
.0
No use
1-10 times
11-50 times
50+ times
Risk of diagnosis of schizophrenia 2.4 times higher in those who
tried cannabis before 18 years
Dose Response which decreased but persisted after adjustment
for psych history
Evidence against self medication
Andreasson et al, 1987, Lancet, 330
Further Evidence for
Precipitation
• Two New Zealand birth cohort studies:
• Dunedin1 N = 759
• Christchurch2 N=900
• Both studies found that cannabis use
• Predicted psychotic symptoms RR ~ 2
• Stronger prediction for early onset
cannabis use
1Arsenault
et al, 2002, BMJ, 325
2Fergusson et al, 2003, Psych Med, 33
Public health model for prevention
of problem cannabis use
• Development of credible health education
– Young are sceptical about ‘scare tactics’
– Parallels with the effects of alcohol & tobacco:
• respiratory risks, MVA, dependence,
psychosis
• Prevention of problem use in young people is
a broader issue than drug education:
– e.g. sense of belonging and purpose, sense of
self-worth, and independent decision making all
influence drug use and require many
community changes
Suggested Message
• Communicate the risk while honestly
acknowledging the uncertainties that
remain
– people with psychosis or a first degree
relative with psychosis avoid using cannabis
– one in seven people who use cannabis
report unpleasant, psychotic-like symptoms;
avoid use
– discouraging young people from using
cannabis daily or near daily
Disorders of cannabis use
Assessment and Treatment
Assessment of cannabis use
• Quantity and frequency of use
– Route (Cones v Joints) and their number
– Estimated amount (grams)
– $ spent per day or week
• Also gives estimate of economic impact of
use
• Presence of dependence
• Predisposing factors, e.g. psychiatric
illness, other substance misuse
• Complications : physical, psychological
and social
Clinical features of
dependence
• Withdrawal syndrome: common in users seeking help
• Compulsive use: common in problem users
– Impaired control
– Strong desire to use
• Tolerance
• Large amounts of day spent using (salience)
• ?? Continued use despite clear evidence of harm:
– less common than for alcohol
• May continue use despite self reported paranoia, or
past exacerbation of schizophrenia; despite social
conflict arising from use, wheeze; all known to be
associated with use
Prevalence of dependence
• 2-4% of the general population
– ECA study (USA in 1980s)
– Australia: National Survey of Mental
Health and Well Being
• 9% of lifetime users (NCS study)
• 33-50% of daily users become
dependent
Withdrawal
• Symptoms worse in first week
• Symptoms (rarely life-threatening):
– irritability, anger
– restlessness, anxiety
– sleep difficulties, including strange dreams
– craving, weight/appetite change, depressed
mood, physical discomfort
• To some extent still controversial
• No validated rating scale
Adverse consequences of
dependence
– Withdrawal
– Physical complications: e.g.
respiratory symptoms
– Impaired memory
– Poor work performance
– Criminal involvement
– Social disapproval
Demand for treatment
• Fewer than 10% seek any treatment
• Why so few?
– high rates of remission?
– fewer short term consequences?
– existing treatment services
unattractive?
Treatment options
•
•
•
•
•
Self-help
Mutual support
Brief interventions
Psychotherapy
Pharmacotherapy for withdrawal?
– Diazepam (e.g. 5 mg tds x 3-5 days) for
troublesome withdrawal? Limited evidence for
a role
– Short course of Lithium - ongoing RCT at
USyd
– Cannabis antagonist ineffective; trials
abandoned
Goals of psychotherapy
• Reviewing benefits of cutting
down/stopping
• Reviewing harms of continued use
• Identifying likely risk times for using
• Discussing means of avoiding risk
situations
• Setting realistic goals
Medical uses of cannabinoids
• Antiemetic agent
– Better than placebo but not as good as most
modern anti-emetics
– Side effect of feeling stoned!
– All data derived from medicinal preparations not
available in Australia (but most patients use
smoked cannabis)
• Appetite stimulant
– particularly in advanced HIV patients
• Analgesic and antispasmodic
• Dependencies (obesity, tobacco, alcohol)
using antagonists (limited by depression)
Should cannabis use be
decriminalised?
Putative harms caused by
cannabis prohibition
• A large scale cannabis black-market
–
–
–
–
controlled by criminals
unregulated and no quality control
untaxed
corruption of public officials
• ‘Arms race’ in policing technology
– helicopters and satellite surveillance
– indoor hydroponic cultivation
• ?Loss of individual liberty to use
cannabis, esp. for medicinal uses
Other harms of prohibition
• Discriminatory law enforcement
– only 1-2% of past year users are prosecuted
– more often lower SES, unemployed indigenous
males
– most cannabis use goes undetected but majority
of drug offences are for cannabis use
• Brings law into disrepute among the young
• Effects on convicted users
– stigma of criminal record
– no impact on cannabis use
– disproportionate penalty for self-harm
• Poor use of scarce police and criminal
justice resources
Options for reducing
cannabis-related harms
• Intensified enforcement of prohibition
– US and Swedish models
• Legalisation of cannabis use
– de facto e.g. the Netherlands
– or de jure
• ‘Decriminalisation’:
– prohibition with civil penalties
– diversion into treatment or education
Arguments in favour
• Current laws ineffective
– Fails to prevent widespread use
– Criminalises 50% of our youth!
– Discriminatory enforcement (young indigenous
males are 10x more likely to be convicted of
use)
• A cautious step - easily reversed
• Reduces
– harms to users
– discriminatory enforcement
• Better use of scarce resources
• Minimal impact on use
Arguments against
•
•
•
•
•
Only desired by a minority in Australia (25%)
Really an irreversible step
Likely to increase heavy & regular use
Contrary to international treaties
Little or no effect on black-market (legal product
taxed)
• Inconsistent:
– use not a crime but cultivation and sale would still
be a crime
• Symbolism
– implies cannabis use is safe & acceptable
Proposed changes in
penalties for personal use
• Removal of jail penalties for 1st offenders
• Cautioning and diversion as an alternative
– may increase number of users dealt with
– a more proportionate response to self-harm
• Reduce push for more radical reform
– more reversible policy and
– consistent with international agreements
• Penalties for use when driving
– to address most probable adverse effect on
non-users
Key points
• Occasional use of cannabis is widespread,
socially accepted and causes little harm
• The legal status of cannabis use is likely to
remain controversial
• Disorders of cannabis use are increasingly
recognised and contribute to loss of
productivity, respiratory and mental illness
• Management options are currently limited to
counselling
• Elucidation of the pharmacology of the
endocannabinoid system offers new targets for
drug therapy for many illnesses
Self-test case: Paul
• Paul presents with insomnia and
feeling ‘on edge’. He gave up
smoking cannabis late last week
after a fight with his partner over his
pot smoking. He had been smoking
7 bongs per day.
Self-test case: questions
1.
How long is his withdrawal syndrome
likely to last?
2.
What complications of his past
cannabis use might you check for?
3. How might you reduce his risk of
relapse?
Self-test case: answers
1. Around one week
2. Respiratory complications (airways
disease, wheeze); psychiatric
complications (e.g. exacerbation of
schizophrenia if ever present)
3. Brief intervention: reinforcing
benefits of cutting down, identifying
at risk periods
Contributors
University of Sydney
•
•
•
Dr Jonathon Arnold
Associate Professor Kate Conigrave
Professor Paul Haber
University of Queensland
•
Professor Wayne Hall
University of New South Wales
•
•
Dr Anthony Arcuri, National Cannabis Prevention and Information Centre
Professor Jan Copeland, National Cannabis Prevention and Information
Centre
•
Professor Maree Teesson, National Drug Alcohol Research Centre
All images used with permission, where applicable
Further learning
Latt, et al (eds.), Addiction Medicine, Oxford University Press,
2009. (Chapter 7, Cannabis)
•
Hulse et. al. (eds.), Management of Alcohol and Drug Problems,
Oxford University Press, 2002 and companion workbook.
•
Hall WD. Drug Alc Review 28: 100-116, 2009.
•
NCPIC website (www.ncpic.org.au)
•
Free national information and helpline (1800 304050)
•
www.nida.nih.gov and nsw.health.gov.au
•
Courtwright, DT, Forces of Habit: Drugs and the making of the
modern world , Harvard Press, 2001
•
Booth, M. (2004). Cannabis: A history. Bantam Books, London.