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and Mental Health conference Thursday 2nd / Friday 3rd December 2004 The 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. The debate at the end proposing that legalised cannabis would reduce the risk of mental health was lost. __________________________________________________ Day 1 - Thursday 2nd December. Opening remarks - Sue Arnold - UK Sue 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. Since 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. __________________________________________________ Session 1 What's new in our knowledge of cannabis __________________________________________________ The Neuroprotective role of the endocannabislinoid system Rafael Mechoulam, Israel Brain 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. We 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. The 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. __________________________________________________ The Cannabinoid system Rafael Maldonado, Spain. The 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. Exogenous 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.. __________________________________________________ The size of the problem - how common is cannabis use? Wayne Hall, Australia The 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. __________________________________________________ Neuromimaging cannabis affects on the brain Zerrin Atakan/Philip McGuire, UK Cannabis 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. Preliminary results were presented to the conference. __________________________________________________ Gateway theories, crime and cannabis Mike Farrell, UK Is cannabis a gateway drug and what are the links between cannabis and crime. The 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. In 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. However, there is an area of concerns around cannabis and violence and the links between psychotic disorders increased risk of violence and use of cannabis. __________________________________________________ Session 2 Cannabis and psychosis __________________________________________________ Can population expression of psychosis be related to population rate of canabis use? Jim Van Os, Netherlands Linking 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. __________________________________________________ Does cannabis worsten the longitudinal course of schizpphrenia? Don Linszen, Netherlands In 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. Two 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. Some 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). __________________________________________________ Effects of cannabis on the foetal brain Yasmin L Hurd, Sweden Cannabis 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. __________________________________________________ Vulnerability to psychosis and responce to cannabis Helene Veroux, France All 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. __________________________________________________ Genetic effects - cannabis and psychosis Mary Bannon, Ireland In 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 pathogens __________________________________________________ Day 2 - Friday 3rd December Opening remarks - Richard Doll, UK Addiction 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. __________________________________________________ Session 3 Other efects of cananbis __________________________________________________ Thereputic potential of cannabis Philip Robson, UK 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. __________________________________________________ Cannabidiol as an antipsychotic Markus Leweke, Germany The 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. While 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. __________________________________________________ The anti-anxiety of cannabidiol Jose Cripps, Brazil CBD 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. __________________________________________________ Cannabis and cognition: Relevance to psychotic disorders Nadia Solowij, Australia Cognitive 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. __________________________________________________ Session 4 Treatment strategies for cannabis use __________________________________________________ Cannabis youth treatment programme: Outcomes and implications Yifrah Kaminer, USA Dr 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. __________________________________________________ Psychological treatment for psychosuis and cannabismisuse Christine Barrowclough, UK Despite 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 was presented.
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