psychiatric comorbidity and cannabis use · dr. francina fonseca institut de neuropsiquiatria i...
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Psychiatric comorbidity and
cannabis use
Dr. Francina FonsecaInstitut de Neuropsiquiatria i Addiccions
Parc de Salut Mar
25709/2014
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UNODC, 2014
Cannabis use
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EMCDDA, 2013
Cannabis use
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Plan Nacional sobre Drogas, 2013
Cannabis use
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• Smoked:
– Cigarettes, cigars, pipes, water pipes,
blunts/joints
• Ingested orally
– Cakes, infusions…
Cannabis administration
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• Cannabis Sativa
• Active component: delta-9-THC
• Derivates:
• Marijuana: dried flowering tops and leaves (0.5-12% THC)
• Hashish: resin of marijuana flowers (2-20% THC)
• Hash oil (15-50% THC)
Cannabis products
Hall & Degenhardt., 2009
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• Cannabidiol (CBD)
– Not impairs cognition
– Anxiolytic and antipsychotic effects
Cannabis products
Martín-Santos et al., 2012
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Volkow et al., 2014
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• The smoked cannabis is the most efficacy
way to achieve the desired effects
• The THC delivered ranges from 20-70%
• Brain availability: 5-24%
Cannabis pharmacology
Hall & Degenhardt, 2009
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Synthetic cannabinoids
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• Known as Spice:
– K2, Moon Rocks, Yucatan Fire
– JWH-018 � JWH-073
• More potent than natural THC
• Elevate the mood, aid relaxation and alter
perceptions
• Psychological disorders
Synthetic cannabinoids
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Cannabis adverse effects
Volkow et al., 2014
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Cannabis adverse effects
Volkow et al., 2014
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• Is cannabis…
– An addictive drug?
– A gateway drug to the use of harder drugs?
– A risk factor for impaired brain development?
– A risk factor for affective, anxiety disorders and suicide?
– A risk factor for psychosis?
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• The 9% of those who experiment with
cannabis will become addicted
• The risk increases if:
– Adolescent use: 1 out of 6
– Daily use: 25-50%
Risk of addiction
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• Cannabis withdrawal syndrome:
– Irritability
– Sleeping difficulties
– Dysphoria
– Craving
– Anxiety
Risk of addiction
Gorelick et al., 2012
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• Regular cannabis users were most likely to
later use other illicit drugs
• The earlier the age of onset of cannabis
use, the more likely to use other drugs
Gateway drug
Hall & Degenhardt, 2007
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Gateway drug
Chadwick et al., 2013
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• Can cannabis prime the brain by decreasing
the reactivity of the mesolimbic dopamine
neurons?
• Or,
• People with high risk to drug use, will start
first with marijuana because of its
accessibility?
Gateway drug
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• Endogenous cannabinoid system involved in
brain development
• Decrease in IQ in regular use of cannabis during
adolescence
– Verbal learning
– Memory
– Attention
Brain development
Meier et al., 2012
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Brain development
Meier et al., 2012
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• Impairments in memory function depending
on the type of cannabis:
– THC > CBD
• Some impairments are recovered after
abstinence, but some could persist
Memory
Schoeler & Bhattacharyya, 2013
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Cannabis, depression and suicide
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• Likelihood of depression in heavy cannabis
users:
– OR: 1.62 (95% CI: 1.21-2.16)
Cannabis, depression and suicide
Lev-Ran et al., 2013
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• Risk factor for suicide
– It is not possible to prove causality
• Familial co-aggregation
• Related to the endocannabinoid system:
CNR1
– Modulates mood
Cannabis, depression and suicide
Serafini et al., 2012
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Cannabis and anxiety
Kedzior & Laeber, 2014
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- Anxiety and cannabis use:
- OR=1.24 (95% CI: 1.06-1.45)
- Anxiety and cannabis use disorders:
- OR=1.68 (95% CI: 1.23-2.31)
- Anxiety + depression and cannabis use:
- OR=1.68 (95% CI: 1.17-2.40)
Cannabis and anxiety
Kedzior & Laeber, 2014
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- Anxiety and cannabis use:
- OR=1.24 (95% CI: 1.06-1.45)
- Anxiety and cannabis use disorders:
- OR=1.68 (95% CI: 1.23-2.31)
- Anxiety + depression and cannabis use:
- OR=1.68 (95% CI: 1.17-2.40)
Cannabis and anxiety
Kedzior & Laeber, 2014
But the association disappears after
controlling for other confounding
factors
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• Worsen the course of psychotic disorders
(including schizophrenia)
• Induce immediate-onset psychomimetic
symptoms (during intoxication)
• Acute episodes of psychosis:
– Manifest immediately following exposure
– Last beyond the intoxication
– Require clinical intervention
Cannabis and psychosis
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Cannabis and psychosis
D’Souza et al., 2004
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• Worsen the course of psychotic disorders
(including schizophrenia)
• Induce immediate-onset psychomimetic
symptoms (during intoxication)
• Acute episodes of psychosis:
– Manifest immediately following exposure
– Last beyond the intoxication
– Require clinical intervention
Cannabis and psychosis
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• Mediators:
– Age of exposure
– Degree of schizotypy
– Familial risk
– Childhood trauma
– Genetic factors
Cannabis and psychosis
Meier et al., 2012
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• Age of exposure:
– The earlier the age of exposure to cannabis,
the greater the risk of psychosis outcome
– Age of onset of psychosis in cannabis users
was 2.7 years earlier than in non-users
Cannabis and psychosis
Radhakrishnana et al., 2014
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Cannabis and psychosis
Leeson et al., 2011
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• Age of exposure:
– Window of vulnerability hypothesis
• Cannabis affects the brain during a critical period
of development
– Earlier age of onset � increased cannabis
exposure
– Subjects prone to psychoses would self-
medicate with cannabis to relieve symptoms
Cannabis and psychosis
Radhakrishnana et al., 2014
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• Schizotypy:
– High scoring schizotype subjects that use cannabis
are more likely to experience psychotic-dysphoric
phenomena and intoxicating effects during and
after use
Cannabis and psychosis
Stirling et al., 2008
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• Family history:
– A familial predisposition to persistent
psychotic disorders precipitated by cannabis
use
– 2.5 fold increased risk of cannabis induced
psychosis in offspring of schizophrenic
mothers
Cannabis and psychosis
Radharkrishnan et al., 2014
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Cannabis and psychosis
Arendt et al., 2008
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• Childhood abuse:
– Association of psychosis among children with a
history of abuse who used cannabis prior to
age 16 (OR: 11.96; 95% CI 2.10-68.22)
– Not replicated in all studies
Cannabis and psychosis
Radharkrishnan et al., 2014
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• Genetic factors:
– COMT
– AKT1
– DAT1
– NRG1
– BDNF
– CNR1
Cannabis and psychosis
Pelayo-Terán et al., 2012; Radharkrishnan et al., 2014
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• COMT:
– Higher psychosis risk in Val/Val and Val/Met
individuals
– Carriers of Val are more sensitive to THC, conditional
on prior psychosis liability
– Earlier age of onset of psychosis
– Longer duration of untreated psychosis
– Interaction with cannabis, childhood abuse and Val
allele, and increased risk for psychosis
Cannabis and psychosis
Pelayo-terán et al., 2012; Caspi et al., 2005
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Cannabis and psychosis
Caspi et al., 2005
40% enzyme activity
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• AKT1:
– Involved in cell proliferation, apoptosis and
transcription
– Increased risk of psychosis in the C/C carriers,
when having used cannabis (rs2494732)
– Impairment of the Continuous Performance Test
reaction time and accuracy
Cannabis and psychosis
Van Winkel et al., 2011
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Cannabis and psychosis
Van Winkel et al., 2011
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• DAT1:
– VNTR: 9 repeat allele � lower enzymatic
activity, higher dopamine levels
– Associated with schizophrenia independent of
cannabis use
– The nine-repeat allele showed increased
sensitivity to THC induced psychotomimetic
effects
Cannabis and psychosis
Bhattacharyya et al., 2012
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Cannabis and psychosis
Bhattacharyya et al., 2012
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• NRG1:
– Candidate gene for schizophrenia �
neurodevelopmental processes
– Mutant mice more sensitive to the behavioral
effects of THC after stress interaction
Cannabis and psychosis
Spencer et al., 2013
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• BDNF:
– Neurtrophin, encourages growth and
differentiation of neurons
– Met66 allele:
• Associated with the age of onset of psychosis
• In females, cannabis was associated with earlier
age of onset of psychosis
Cannabis and psychosis
Decoster et al., 2011
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• CNR1:
– Negative association with risk of psychosis
– Schizophrenic G allele carriers were more
sensitive to the effect of cannabis
Cannabis and psychosis
Zammit et al., 2007; Ho et al., 2011
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Cannabis and psychosis
Parakh & Basu, 2013
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• Cannabis is associated with adverse effects
with variable degree of confidence:
– Addiction to cannabis � High
– Progression to other drugs � Medium
– Diminished lifetime achievement � High
– Anxiety / Depression � Medium
– Psychosis � Medium/High
Conclusions
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• The effects are clearly worse if the age of
onset is earlier and the use is regular
Conclusions
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Brain development
Caspi et al., 2006