are in Library / Conferences
and Mental Health conference
Institute of psychiatry
2nd / Friday 3rd December 2004
conference presentations addressed a wide range of topics including the new findings
on the neurobiology of cannabis, its effects on mental health, its interaction
with severe mental illness and clinical interventions to reduce cannabis consumption.
debate at the end proposing that legalised cannabis would reduce the risk of mental
health was lost.
1 - Thursday 2nd December.
remarks - Sue Arnold - UK
is a journalist who contributes weekly columns to the Observer on radio, the Guardian
on audio books and the Independent on anything at all. She won the British press
award for magazine writer of the year 1984 an has written several books - her
last, A Burmese Legacy about her families history. Sue Arnold was registered blind
in 1990 with a congenital condition Retinus Pigmenttoso. She has six children
and lives in Chelsea.
Sue cannot read print or Braille, she spoke without notes, her theme being her
own personal twofold view of the pros and cons of cannabis use.. Pro because after
smoking a joint of skunk eight years ago, her vision was significantly improved
- she wrote several articles about it. Con because three years ago her 21 year
old university student son had a psychotic episode triggered by smoking too much
cannabis and has been diagnosed as paranoid schizophrenia and has been sectioned
under the mental health act.
new in our knowledge of cannabis
Neuroprotective role of the endocannabislinoid system
injury triggers the accumulation of harmful mediators, that lead to secondary
damage. Protective mechanisms that attenuate the secondary damage are also set
in motion. The endocannabinoids, anadomide and 2-arachidonoylglycerol (2-AG),
should now be included in the list of neuroprotective endogenous chemicals.
have observed that the levels of 2-AG sharply increase after closed head injury
(CHI). In order to test whether this phenonmenonon has a physiological significance
we administered synthetic 2-AG after CHI in mice and found significant reduction
in brain edema, better clinical recovery, reduced infarct volume and reduced hippercampel
cell death compared to controls. 2-Acyl glycerol's, such as 2-palmitoyl glycerol
and 2-linoleoyl glycerol, which are present in brain but do not bind to the cannibinoid
receptors, enhance the activity of 2-AG as a neuro protective agent. This effect
is probably due to their partial blocking 2-AG uptake, as well as their inhibition
of 2-AG enzmatic hydrolysis. The neuroprotective effect of 2-AG was attenuated
by the CB1 receptor antagonist SR141716A indicating that the mechanism involves
the BC1 cannabbinoid receptor.
mechanism of neuroprotection imparted by cannabinoids is far from clear, but we
have already found that it involves reduction of TNF-levels, anti-oxidative action,
blocking of NF B formation and strengthening of blood brain barrier.
endocannabinoid system consists of endogenous limpids, mostly derived from arachidonic
acid, able to selectively activate canniboid receptors. The endocannabinoids are
synthesized and released upon neuronal stimulation, undergo reuptake by selective
mechanism and are hydrolyzed intracellularly by fatty acid amide hydrolase.
and endogenous cannabinoids selectively bind and activate at least two different
cannabinoid receptors that have been identified and cloned: The CB1 and CB2 cannabinoid
receptor. Recent data suggests the presence of a third, uncloned cannabiniod receptor,
the CBx receptor. The endocannabinoid system has been involved in a large variety
of physiological functions, including the central control of nociception. motor
behavior, learning, memory, reward, food intake, neuroprotection and several vegetative
and peripheral responses..
size of the problem - how common is cannabis use?
use of cannabis by adolescents and young adults has risen steadily for over the
the past three decades in most developed countries, with the result that many
adolescents in these countries will have used cannabis at least once by the age
of 21. In Australia one in five young adults use cannabis at least weekly. The
rising prevalence of cannabis use has cause parental and community concern. Initially,
a major concern was the use of cannabis would increase the likelyhood that young
people would use other more harmful illicit drugs such as heroin and cocaine.
A more recent concern has been that regular cannabis use in adolescence may increase
the likelyhood of delinquency, poor educational performance, depression and psychosis.
I summarise evidence on trends in cannabis use in developed countries over the
past 20 or so years, including trends in lifetime and regular use, the typical
course of cannabis use in adolescence and young adulthood, changes in the age
of initiation and the more frequent use of more potent cannabis products. I end
with a brief discussion of the challenges in communicating with young people about
the mental health risks of cannabis use in the midst of policy debates about the
legal status of cannabis in many developed countries.
cannabis affects on the brain
Atakan/Philip McGuire, UK
has well established effects on cognitive and emotional processing but the neural
basis of these is unclear. We used functional neuroimaging to investigate this,
focussing on tasks that engaged memory, attention and emotional processing.
results were presented to the conference.
theories, crime and cannabis
cannabis a gateway drug and what are the links between cannabis and crime.
concern that cannabis might be a gateway to a much more extended repertoire of
drug use has existed for the past half century or thereabouts. The use of one
illegal drug is associated with the likelihood of using other illegal drugs is
beyond question but it is whether there is a causal association is a more difficult
and contentious issue. This talk explored the pro and cons of the different approaches
to this question.
addition, the links between cannabis and crime were explored. There is a striking
dearth of literature on this topic, indicating that cannabis and crime doesn't
generate a lot of concern. However, the vast majority of convictions for drugs
offenses are related to cannabis but overall there is little acquisitive crime
associated with cannabis use. Indeed, despite discussions and explorations of
the issue of cannabis and dependence there appears to be very little reported
negative social behaviors such as acquisitive crime associated with cannabis acquisition.
there is an area of concerns around cannabis and violence and the links between
psychotic disorders increased risk of violence and use of cannabis.
population expression of psychosis be related to population rate of canabis use?
Van Os, Netherlands
the population rate of a psychiatric phenotype such as use of a substance such
as cannabis represents a formidable challenge. The expression of psychosis at
the clinical and subclinical level is relatively common (prevalence rate of 5
- 15%) and so is the rate of use of cannabis. Therefore by chance alone psychosis
and cannabis use will overlap to a certain degree, even more so because both are
a phenomena that are strongly associated with younger age, In addition, cannabis
use is frequently accompanied by use of other drugs that may precipitate psychosis,
such as methamphetamine and cocaine, causing the effect of cannabis to be potentially
confounded. The association between cannabis and psychosis may also be the result
of reverse causality, as individuals who are vulnerable for psychosis or in the
early throws of a psychotic state may use cannabis to "self medicate"
feelings of dysphoria or paranoia. On the other hand, cannabis may also exert
a true causal influence on the population rate of psychosis,. As the use of cannabis
in some societies has risen dramatically without (probably) a similar increase
in the incidence of psychotic disorders, the most likely causal scenario for cannabis
is one of biological synergism, whereby cannabis co-participates in a causal pathway
together with preexisting liability for psychosis. The different models and explanations
for the co-occurance of cannabis and psychosis were systematically examined using
data population based studies.
cannabis worsten the longitudinal course of schizpphrenia?
prospective studies of patients with schizophrenia and related disorders, cannabis
use appeared to be an independent risk factor for more psychotic relapses and
aggravation of psychotic and disorganization symptoms. When a distinction with
respect to the intensity of use was made, it appeared that particularly heavy
cannabis users suffered more relapses and more florid psychotic and disorganization
symptoms. In those studies that controlled for alcohol and other (psychoactive)
substance use (Linszen et al, 1994, Van Os et al 2002) these were not found to
be confounding factors. Furthermore, antipsychotic medication dosage and adherence
could not explain away the findings.
additional findings indicate a possible causal relationship between cannabis exposure
and psychotic relapse, First, most of the cannabis using patients reported an
immediate exacerbation of psychotic symptoms after resuming cannabis use. Second,
in all but one patient, cannabis use preceded the onset of the first psychotic
episode by at least a year.
support is given for the self-medication hypothesis of schizophrenia and cannabis
use as schizophrenia patients successfully reduced their negative symptoms (Perata
and Cuesta 1992), effective symptoms (Dixon et al 1991) or anxiety and depression
with mild cannabis use (Linszen et al 1994).
of cannabis on the foetal brain
L Hurd, Sweden
is the most common illicit drug used by pregnant women. We studied the expression
of genes coupled to the cannabiniod system in the brains of human fetus exposed
to cannabis during development. Our findings revealed significant gene (eg dopamine
receptor and opiod neuropeptide) and region (eg amygdala and striatum) specific
alterations associated with maternal cannabis use. Experimental animal models
have also been used to explore the long impact of prenatal cannabis exposure alters
mesolimbic and striatal neural systems that apparently lasts into adulthood with
significant effects on behavior.
to psychosis and responce to cannabis
studies exploring the association between THC and psychosis in non clinical populations
samples show that THC users present with higher psychosis proneness scores than
nonusers. A limited number of perspective studies have explored the link between
THC use and psychosis proneness, In a sample of students selected on their level
of THC use and of psychosis proneness, we have prospectively explored over one
week the relationship between THC use and occurrence of psychotic experience in
daily life. Compared to subjects with low psychosis vulnerability subjects with
high psychosis vulnerability were more likely to report abnormal perceptions and
thought influence when they used THC. Conversely, the positive effects of THC
on social relationships were exclusively reported by subjects with low vulnerability.
These findings suggests that cannabis use is a risk factor for the acute occurrence
of psychotic experiences in daily life and that the effects of cannabis are modified
by the subjects level of vulnerability to psychosis.
effects - cannabis and psychosis
a longitudinal study of a representative birth cohort followed through to adulthood,
we tested why cannabis use is associated with the emergence of psychosis in a
minority of users but not in others. A functional polymorphism in the catechol-O-methyltransferease
(COMT) gene moderated the influence of adolescent cannabis use on developing psychosis.
Carriers of the COMT valine allele were most likely to exhibit psychotic symptoms
and to develop schizophreniaform disorder if they used cannabis. Cannabis use
had no such adverse effects on individuals with two copies of the methionine allele.
The findings provide evidence of a gene x environment interaction and suggest
that a role of some susceptibility genes is to influence vulnerability to environmental
2 - Friday 3rd December
remarks - Richard Doll, UK
to smoking tobacco has been common for centuries, but the discovery of its harmful
effects has been slow. They were few until the modern cigarette was introduced,
the smoke from which is easy to inhale. Nicotine, responsible for addiction, is
not known to cause any of the harmful effects, These are attributable to chemicals
formed by the combustion of vegetable matter, some only at high temperatures.
Some 40 diseases are increased in proportion to the amount smoked and a power
of the duration of smoking. On stopping smoking the risks stabilise or fall.
efects of cananbis
potential of cannabis
has been used as a medicine for several thousand years. Symptomatic relief is
evident with smoked cannabis, but this is unacceptable as a modern medicine. Pant-derived
and synthetic cannabis based medicines (CBM) provide a safer and more reliable
alternative. Major advances in understanding their mechanisms of action and psychological
role of the endogenous cannabinoid system have rekindled interest in exploring
therapeutic potential in a range of intractable diseases. Recent UK clinical research
suggests that CBM maybe effective against refractory neurogenetic symptoms such
as muscle spasticity, neuropathic pain and impaired bladder control. CBM appear
to be safe and generally well tolerated by patients. The evidence was reviewed
and future directions for clinical research discussed.
as an antipsychotic
endogenous cannabinoid system has recently been shown of particular importance
in the pathophysiology of acute schizophrenia. It interacts with various neurotransmitter
systems in the central nervous system including the dopaminergic, glutamintergic
and GABAergic system.
the psychedelic properties of natural cannabis compound delta-9-TCH are widely
known, there is some experimental and clinical evidence that other herbal cannabinaoid
compounds may have anti psychotic properties. Based on these confounders we designed
a double blind, controlled clinical trial of the effects of purified cannabidiol,
a major compound of herbal cannabis, in acute schizophrenia and schizophreniaform
psychosis compared to the antipsychotic amisulpride. The anti psychotic properties
of both drugs were the primiliminary target of the study. Furthermore, side effects
and anxiolytic properties of both treatment strategies were investigated. A detailed
study design and first results were presented and discussed with a particular
focus on the underlying pharmacological mechanisms.
anti-anxiety of cannabidiol
constitutes up to 40% of cannabis sativa and has quite different psychological
effects to the plants best known constituent D-9-THC. In particular in animal
studies CBD has similar effects to anxioltic properties drugs in conditioned emotional
paradigms, the Vogal conflict test and the elevated plus maze test. In humans,
oral administration of CBD in healthy volunteers attenuates the anxionigenic effect
of D-9-THC. CBD may thus possess inherent anxiolytic properties unrelated to THC-type
activity. This is consistent with its anxiolytic effect on anxiety elicited by
simulated public speaking. In addition a SPECT neuro imaging study has confirmed
that CBD has anxiotic properties and that these effects are medicated by an action
on limbic and paralimbic brain areas.
and cognition: Relevance to psychotic disorders
impairments are among the most debilitating symptoms of mental illness. Cannabis
intoxication impairs cognitive processes and there is increasing evidence for
longer-lasting impairment with long term or heavy cannabis use. The prevalence
of cannabis use among people with psychotic disorders, the potential for cannabis
to trigger psychotic symptoms and episodes, and the neurobiological interactions
between the endogenous cannabinoid systems and the pathology associated with psychosis,
indicate a need to further investigate the nature and mechanisms of cognitive
impairments associated with cannabis use. This presentation summarised what is
known about the long term effects of cannabis, described some of the most recent
research and its relevance to psychotic disorders.
strategies for cannabis use
youth treatment programme: Outcomes and implications
kaminer's main interest has focused on clinical research of assessment and treatment
of high-Risk behavior particularly associated with substance abuse and gambling
behavior in youth with comorbid psychiatric disorders. He has authored/co-authored
more than 100 publications including: Articles, book chapters, rating scales (including
the teen index and the teen treatment services review) and treatment manuals.
He also authored the book "Adolescent substance abuse: A comprehensive guide
to theory and practice- plenum medical.
treatment for psychosuis and cannabismisuse
high rates of problematic substance use in psychosis, the evidence base to direct
treatment remains limited. In Manchester we have been developing an individual
treatment intervention that combines motivational interviewing and cognitive behavior
therapy. Since in psychosis, cannabis is most often used alongside other harmful
substances, the intervention may be directed at a range of substances. The treatment
aims to take account of the dual and interactive nature of substance use and psychosis
problems and the motivational stage of the patient. The results of the studies
were reviewed and an outline if the treatment model currently being evaluated