XI Congresso della Società Italiana di Psicopatologia Psichiatria ...

23 FEBBRAIO 2005 - ORE 14.15-15.45
SALA ELLISSE
S31 - Uso di cannabinoidi e psicosi:
un’epidemia silenziosa
COMT Val 158 Met moderation of cannabisinduced
effects on psychosis and cognition
C. Henquet, J. van Os
Department of Psychiatry and Neuropsychology, Maastricht
University
Introduction: epidemiological reseach has suggested that a
functional polymorphism in the Catechol-O-Methyltransferase
(COMT Val 158 Met) gene moderates the psychosis inducing
effects of cannabis. To replicate this finding using an
experimental design and to extent it to the complex world of
daily life, experimental exposure procedures and momentary
assessment methodology were applied to test for geneenvironment
interactions within the cannabis-psychsis relationship.
Methods: a double blind, placebo-controlled cross-over design
was used in which genotyped individuals at low and
high risk of schizophrenia were exposed to ∆-9-THC
(THC). Moment-to-moment experiences associated with
cannabis in the flow of daily life were furthermore assessed
in an experience sampling study. COMT Val 158 Met moderation
of cannabis-induced effects on psychosis and cognition
was then investigated using multilevel random regression
analyses.
Results: carriers of the Val allele were most sensitive to
THC-induced effects on psychosis, however this was conditional
on prior evidence of psychometric psychosis liability.
THC impacted negatively on cognitive measures. Carriers
of the Val allele were also more sensitive to THC-induced
memory and attention impairments compared to carriers of
the Met allele. In the flow of daily life, cannabis appeared to
be associated with hallucinatory experiences conditional on
COMT Val158Met genotype.
Conclusion: these findings provide confirmatory evidence
that COMT Val 158 Met genotype moderates the effects of
cannabis on the occurrence of positive psychotic symptoms.
Cannabis may be causally associated with psychosis,
but it is increasingly apparent that any causal contribution
is conditional on a number of moderators reflecting underlying
gene-environment and possibly gene-gene interactions.
Cannabis use and psychotic disorders:
an update
F. Nicoletti, F. Matrisciano
Department of Human Physiology and Pharmacology, University
of Rome “La Sapienza”
The cannabis plant has been cultivated for centuries both
for the production of hemp fiber and for its presumed med-
MODERATORI
G. Bersani, F. Nicoletti
81
SIMPOSI TEMATICI
icinal and psychoactive properties. The smoke from burning
cannabis contains many chemicals, including 61 different
cannabinoids that have been identified. One of
these, ∆-9-tetrahydrocannabinol (∆-9-THC), produces
most of the characteristic pharmacological effects of
smoked marijuna.
The pharmacological effects of THC vary with the dose,
rout of administration, experience of the user, vulnerability
of psychoactive effects and setting of use. Intoxication
with marijuana produces changes in mood, perception and
motivation.
The effects vary with dose and produce impairment of
cognitive functions, perception, reaction time, learning
and memory. Marijuana also produces complex behavioural
changes, such as giddiness and increased hunger. Unpleasant
reactions such as panic or hallucinations and even
acute psychosis may occur.
While there is no convincing evidence that marijuana can
produce a lasting schizophrenia-like syndrome, there are
precipitate a recurrence in people with a history of schizophrenia.
A cannabinoid receptor has been identified in the
brain and cloned. An arachidonic acid derivative has been
proposed as an endogenous ligand and named anandamide.
While the physiological function of these receptors
or their putative endogenous ligand has not been fully
elucidated, they are widely dispersed with high densities in
the cerebral cortex, hippocampus, striatum and cerebellum.
Recent investigations of patients with schizophrenia
found increased density of cannabinoid receptors in the
dorso-lateral prefrontal cortex and the anterior cingulate
cortex. Several genetic studies have reported an association
between genes encoding the cannabinoid receptor and
schizophrenia.
Thus, an alternative explanation of the association between
cannabis use and schizophrenia might be that
pathology of the cannabinoid system in schizophrenia patients
is associated with both increased rates of cannabis
use and increased risk for schizophrenia, without cannabis
being a causal factor for schizophrenia. Several authors
show that young consumers and previous consumers have
higher scores in schizotypy, borderline and psychoticism
scales. They also show deficits in attentional inhibition
and decreased reaction time. The causal relationship of
this association is not yet clear but cannabis consuption
modulates dopamine concentrations, may induce reversible
acute psychosis and it may induce the manifestation
of schizophrenic psychosis in vulnerable patients
(“dopaminergic stress”).
References
1 O’Brien et al., 1997.
2 Hall et al., 2004.
3 Drewe et al., 2004.