Drug Alcohol Rev. 2010 May;29(3):318-30.

1. Drug Alcohol Rev. 2010 May;29(3):318-30. Does cannabis use increase the risk of death? Systematic review of epidemiological evidence on adverse effects of cannabis use. Calabria B, Degenhardt L, Hall W, Lynskey M. National Drug and Alcohol Research Centre, University of New South Wales, Randwick, Australia. b.calabria@unsw.edu.au

2. Abstract KEY FINDINGS:. Case-control studies suggest that some adverse health outcomes may be elevated among heavy cannabis users, namely, fatal motor vehicle accidents, and possibly respiratory and brain cancers. The evidence is as yet unclear as to whether regular cannabis use increases the risk of suicide. CONCLUSIONS: There is a need for long-term cohort studies that follow cannabis using individuals into old age, when the likelihood of any detrimental effects of cannabis use are more likely to emerge among those who persist in using cannabis into middle age and older.

3. Rev Med Suisse. 2007 Oct 3;3(127):2248. [new insights on the neurotoxicity of ecstasy and cannabis] [Article in French] Nau JY.

4. Farmacol Biochem Behav. 2009 Mar;92(1):105-10. Epub 2008 Nov 13. N-acetylaspartate (NAA) correlates inversely with cannabis use in a frontal language processing region of neocortex in MDMA (Ecstasy) polydrug users: a 3 T magnetic resonance spectroscopy study. Cowan RL, Joers JM, Dietrich MS. Psychiatric Neuroimaging Program, Nashville, TN 37212, USA. Ronald.l.cowan@vanderbilt.edu

5. Abstract Impaired verbal memory is common in MDMA (Ecstasy) polydrug users. The contributions of Ecstasy or polydrug exposure to reduced verbal memory are unclear, as is the neural basis for this cognitive deficit. Ecstasy users have reduced gray matter in brain regions mediating verbal memory (BA 18, 21 and 45). N-acetylaspartate (NAA) as a neuronal marker and myoinositol (mI) as a glial marker are inconsistently affected in Ecstasy users. In contrast, there were no statistically significant associations for lifetime use of Ecstasy, alcohol, or cocaine with NAA. These findings suggest that cannabis use may contribute to altered neuronal integrity in Ecstasy polydrug users in a brain region associated with verbal memory processing.

6. Brain haemorrhage and cerebral vasospasm associated with chronic use of cannabis and buprenorphine. Renard D, Gaillard N. Department of Neurology, CHU Montpellier, Hôpital Gui de Chauliac, Montpellier, France. dimitrirenard@hotmail.com

7. Am J Psychiatry. 2008 Apr;165(4):490-6. Epub 2008 Feb 15. Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Rais M, Cahn W, Van Haren N, Schnack H, Caspers E, Hulshoff Pol H, Kahn R. Department of Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3584CX Utrecht, the Netherlands. mrais@umcutrecht.nl Comment in: Am J Psychiatry. 2008 Apr;165(4):416-9. Am J Psychiatry. 2008 Oct;165(10):1357-8; author reply 1358.

8. Abstract OBJECTIVE: Cerebral gray matter volume reductions have been found to progress over time in schizophrenia, with larger decreases related to poorer outcome, which has also been associated with cannabis use in schizophrenia patients. Progressive gray matter changes in patients who use cannabis may be more extensive than in those who do not. CONCLUSIONS: First-episode schizophrenia patients who use cannabis show a more pronounced brain volume reduction over a 5-year follow-up than patients with schizophrenia who do not use cannabis. These results may help explain some of the detrimental effects of cannabis use in schizophrenia

9. JBR-BTR. 2007 May-Jun;90(3):218-9. Cannabis-induced brain ischemia. Termote B, Verswijvel G, Gelin G, Palmers Y. Department of Radiology, Ziekenhuis Oost-Limburg, Genk, Belgium

10. Cancer Epidemiol Biomarkers Prev. 2010 May;19(5):1174-84. Extent of alcohol consumption among adult survivors of childhood cancer: the British ChildhoodCancer Survivor Study. Frobisher C, Lancashire ER, Reulen RC, Winter DL, Stevens MC, Hawkins MM; British Childhood Cancer Survivor Study. Collaborators (11)Easton D, Hawkins M, Jenkinson H, Jenney M, Lancashire E, Pritchard-Jones K, Stevens M, Stiller C, Sugden E, Toogood A, Wallace H. Centre for Childhood Cancer Survivor Studies, School of Health and Population Sciences, Public Health Building, University of Birmingham, Birmingham B15 2TT, United Kingdom. c.frobisher@bham.ac.uk

11. RESULTS: Of 10,389 survivors who responded, 77.2% were alcohol drinkers, 23.8% consumed over weekly recommendations, and 3.9% consumed potentially harmful amounts. Survivors were less likely than the general population to be a current drinker CONCLUSION: Overall adverse drinking behaviors were less frequent in survivors than expected from the general population, but subgroups with adverse drinking behaviors were identified, and it is these subgroups who are most in need of intervention

12. Alcohol. 1995 Mar-Apr;12(2):97-104. Alcohol-related cancer risk: a toxicokinetic hypothesis. Anderson LM, Chhabra SK, Nerurkar PV, Souliotis VL, Kyrtopoulos SA. Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, MD 21702, USA.

13. Experiments conducted with rodents and primates support this hypothesis, demonstrating increased exposure of posthepatic organs to nitrosamines when given in combination with ethanol, followed by enhancement of DNA adduct formation and, at least in rodents, of tumor development. In addition, ethanol may induce enzymes responsible for carcinogen activation, including hepatic cytochrome P450 2E1 in rodents and humans, and in lung, kidney, and brain in rodents. Studies have also shown that these effects can extend to the next generation via maternal and in utero fetal exposure. What impact such ethanol-induced modulations have on tumorigenesis during childhood and later stages of life needs to be investigated further.

14. Alcohol Clin Exp Res. 2001 Jun;25(6 Suppl):7S-10S. Polymorphism of tumor necrosis factor-beta and alcohol dehydrogenase genes and alcoholic brain atrophy in Japanese patients. Yamauchi M, Takamatsu M, Maezawa Y, Takagi M, Araki T, Satoh S, Toda And G, Saito S. Division of Gastroenterology and Hepatology, Jikei University School of Medicine, Tokyo, Japan. yamauchi@fantasy.plala.or.jp

30. armacol Biochem Behav. 2009 Mar;92(1):105-10. Epub 2008 Nov 13. N-acetylaspartate (NAA) correlates inversely with cannabis use in a frontal language processing region of neocortex in MDMA (Ecstasy) polydrug users: a 3 T magnetic resonance spectroscopy study. Cowan RL, Joers JM, Dietrich MS. Psychiatric Neuroimaging Program, Nashville, TN 37212, USA. Ronald.l.cowan@vanderbilt.edu

31. Abstract Cannabis consumption has varying effects over the whole life span, especially on achievements in the areas of schooling, professional life and performance in a social environment. Data from studies on remission from neurocognitive deficits following chronic cannabis consumption are ambiguous. The outcome range included everything from complete remission over considerable lasting deficits up to even chronic psychotic disorders. The data seem to be consistent however, when a differentiation between early begin of consumption (before the age of 16) and late begin of consumption is taken into account. Mainly those cannabis users with an early begin of consumption are prone to developing lasting neurocognitive deficits and even a decrease in grey substance volume, as well as an increase in the risk of psychosis.

32. The correlation of this outcome with cannabis consumption during a phase of brain development that includes the consolidation of higher cognitive functions, awareness of social cues, planning of concepts and motivation as well as tools of functional control, is highly convincing. The endocannabinoid system reaches the point of highest receptor density during this age of 16/17 years, and many of the above-mentioned developmental processes are modulated by this system. A chronic damage to this system (e.g., down-regulation or desensitisation of CB1 receptors by exogenous cannabinoids) therefore holds the potential for permanent neurophysiological as well as neurocognitive deficits, and also for the development of psychotic disorders

33. Arch Gen Psychiatry. 2008 Jun;65(6):694-701. Regional brain abnormalities associated with long-term heavy cannabis use. Yücel M, Solowij N, Respondek C, Whittle S, Fornito A, Pantelis C, Lubman DI. MAPS, ORYGEN Research Centre, 35 Poplar Rd, Melbourne, Victoria, Australia. murat@unimelb.edu.au

34. Abstract CONTEXT: Cannabis is the most widely used illicit drug in the developed world. Despite this, there is a paucity of research examining its long-term effect on the human brain. OBJECTIVE: To determine whether long-term heavy cannabis use is associated with gross anatomical abnormalities in 2 cannabinoid receptor-rich regions of the brain, the hippocampus and the amygdala. DESIGN: Cross-sectional design using high-resolution (3-T) structural magnetic resonance imaging.

35. SETTING: Participants were recruited from the general community and underwent imaging at a hospital research facility. PARTICIPANTS: Fifteen carefully selected long-term (>10 years) and heavy (>5 joints daily) cannabis-using men (mean age, 39.8 years; mean duration of regular use, 19.7 years) with no history of polydrug abuse or neurologic/mental disorder and 16 matched nonusing control subjects (mean age, 36.4 years). MAIN OUTCOME MEASURES: Volumetric measures of the hippocampus and the amygdala combined with measures of cannabis use. Subthreshold psychotic symptoms and verbal learning ability were also measured.

36. RESULTS: Cannabis users had bilaterally reduced hippocampal and amygdala volumes (P = .001), with a relatively (and significantly [P = .02]) greater magnitude of reduction in the former (12.0% vs 7.1%). Left hemisphere hippocampal volume was inversely associated with cumulative exposure to cannabis during the previous 10 years (P = .01) and subthreshold positive psychotic symptoms (P < .001). Positive symptom scores were also associated with cumulative exposure to cannabis (P = .048). Although cannabis users performed significantly worse than controls on verbal learning (P < .001), this did not correlate with regional brain volumes in either group.

37. CONCLUSIONS: These results provide new evidence of exposure-related structural abnormalities in the hippocampus and amygdala in long-term heavy cannabis users and corroborate similar findings in the animal literature. These findings indicate that heavy daily cannabis use across protracted periods exerts harmful effects on brain tissue and mental health.