The safety of cannabinoids for the treatment of multiple sclerosis

References

• IVERSEN L: Cannabis and the brain. Brain (2003) 126:1252–1270.
   PubMed Web of Science ®Google Scholar
• •Good recent review of cannabinoid pharmacology.
   Google Scholar
• PIOMELLI D, GIUFFRIDA A,CALIGNANO A et al: The endocannabinoid system as a target for therapeutic drugs. Trends Pharmacol Sci. (2000) 21:218–224.
   PubMed Web of Science ®Google Scholar
• LUTZ B: On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem. Pharmacol (2004) 68:1691–1698.
   PubMed Web of Science ®Google Scholar
• ••Excellent review of the recent and earlyevidence relating to the anticonvulsant effects of cannabinoids.
   Google Scholar
• MARSICANO G, GOODNEOUGH S,MONORY K et al: CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science (2003) 302:65–67.
   PubMedGoogle Scholar
• ••Seminal paper reporting the potentialneuroprotective role of endocannabinoids in the brain.
   Google Scholar
• RICE AS: Cannabinoids and pain. Curr. Opin. Investig. Drugs (2001) 2:399–414.
   PubMedGoogle Scholar
• PERT WEE RG: Cannabinoid receptors and pain. Frog. Neurobiol (2001) 63.569–611
   Google Scholar
• KREITZER AC, REGEHR WG: Retrograde signalling by endocannabinoids. Curr. Opin. Neurobiol (2002) 12:324–330.
   PubMed Web of Science ®Google Scholar
• ALGER BE: Retrograde signalling in the regulation of synaptic transmission: focus on endocannabinoids. Frog. Neurobiol (2002) 68:247–286.
   Google Scholar
• ACHIRON A et al.: Dexanabinol (HU-211) effect on experimental autoimmune encephalomyelitis: implications for the treatment of acute relapses of multiple sclerosis.Neuroimmunol (2000) 102:26–31.
   PubMed Web of Science ®Google Scholar
• BAKER D, PRYCE G, CROXFORD JL et al.: Endocannabinoids control spasticity in a multiple sclerosis model. FASEB (2001) 15.300–302.
   PubMed Web of Science ®Google Scholar
• BAKER D et al.: Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature (2000) 404:84–87.
   PubMed Web of Science ®Google Scholar
• BERRENDERO F, SANCHEZ A, CABRANES A et al: Changes in cannabinoid (CB1) receptors in striatal and cortical regions of rats withexperimental allergic encephalomyelitis,an animal model of multiple sclerosis. Synapse (2001) 41:195–202.
   PubMed Web of Science ®Google Scholar
• BRITISH MEDICAL ASSOCIATION: Therapeutic Uses Of Cannabis. Harwood Academic Publishers, Netherlands (1997).
   Google Scholar
• CONSROE P, MUSTY R, REIN J et al: The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur. NeuroL (1997) 38.44–48.
   PubMed Web of Science ®Google Scholar
• HALL WD, DEGENHARDT LJ, CURROW D: Allowing the medical use of cannabis. Med. J. Aust. (2001) 175.39–40.
   PubMed Web of Science ®Google Scholar
• SMITH PF: Cannabinoids for the treatment of multiple sclerosis:No smoke without fire? Expert Review of Neurotheipeutics (2003) 3:327–357.
   PubMedGoogle Scholar
• SMITH PF: Medicinal cannabis extracts for the treatment of multiple sclerosis. Curr. Opin. Investig. Drugs (2004) 5:727–730.
   PubMedGoogle Scholar
• KILLESTEIN J, HOOGERVORST ELJ, REIF M et al.: Safety, tolerability and efficacy of orally administered cannabinoids in MS. Neurol (2002) 58:1404–1407.
   PubMed Web of Science ®Google Scholar
• ••One of the first systematic clinical trialsof the effects of cannabinoids in multiple sclerosis.
   Google Scholar
• DYER 0: Cannabis trial launched inpatients with MS. BE Med. J. (2001) 322:192.
   Web of Science ®Google Scholar
• ZAJICEK J, FOX P, SANDERS H et al: Cannabinoids for the treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre, randomised placebo-controlled trial. Lancet (2003) 362:1517–1526.
   PubMed Web of Science ®Google Scholar
• ••Paper describing the first results of theCAMS trial of cannabinoids for the treatment of multiple sclerosis.
   Google Scholar
• ZAJICEK J, FOX P, SANDERS H et al: The cannabinoids in MS study - final results from 12 months follow-up. Mult. Scler. (2004) 10\(Suppl. 2):5115.
   Google Scholar
• ••12 month follow-up of the originalCAMS study.
   Google Scholar
• WADE DT, ROBS ON P, HOUSE H et al.: A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Chit. Rehabil (2003) 17:21–29.
   Web of Science ®Google Scholar
• FOX P, BAIN PG, GLICKMAN S et al: The effects of cannabis on tremor in patients with multiple sclerosis. NeuroL (2004) 62:1105–1109
   PubMed Web of Science ®Google Scholar
• GW PHARMACEUTICALS LTD: IDdb report for GW-1000. IDdb Reports. (2004) 1–4.
   Google Scholar
• SMITH PF: Evaluation of Sativex (GW-1000). IDdb3 Current Drugs Database. http://www.iddb3.com (2004) pp. 1–19.
   Google Scholar
• SMITH PF: Sativex (GW-1000). Curr. Opin. Investig. Drugs (2004) 5:748–754.
   PubMedGoogle Scholar
• WADE DT, MAKELA P, ROBSON P et al.: Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler. (2004) 10:434–441.
   PubMed Web of Science ®Google Scholar
• ••Recent report of the effects of Sativex, anarrow ratio delta-9-THC:CBD extract, on the symptoms of multiple sclerosis.
   Google Scholar
• KILLESTEIN J, POLMAN C: The therapeutic value of cannabinoids in MS: real or imaginary? Mult. Scler. (2004) 10:339–340.
   PubMed Web of Science ®Google Scholar
• •Interesting commentary on the most recent clinical trials of cannabinoids.
   Google Scholar
• VANEY C, HEINZEL-GUTENBRUNNER M, JOBIN P et al.: Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult. Scler. (2004) 10:417–424.
   PubMed Web of Science ®Google Scholar
• ••Recent report of the effects of oralcannabinoids on the symptoms of multiple sclerosis.
   Google Scholar
• SHAKESPEARE DT, BOGGILD M, YOOUNG C: Anti-spasticity agents for multiple sclerosis. Cochrane Database Systematic Reviews. (2000) 4:CD001332.
   Google Scholar
• BRADY CM, DASGUPTA R, DALTON C et al.: An open-label pilot study of cannabis based extracts for bladder dysfunction in advanced multiple sclerosis. Mult. Scler. (2004) 10:425–433.
   PubMed Web of Science ®Google Scholar
• ••Recent report of the effects ofcannabinoids on the urogenic symptoms of multiple sclerosis.
   Google Scholar
• MECHOULAM R, HANUS L: Cannabidiol: An overview of some chemical and pharmacological aspects. Part I: Chemical aspects. Chem. Phys. Lipids (2002) 121:35–43.
   Google Scholar
• OFFERTALER L, MO FM, BATKAI S et al.: Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol. Pharmacol (2003) 63:699–705.
   PubMed Web of Science ®Google Scholar
• PETITET F, JEANTAUD B, REIBAUD M et al: Complex pharmacology of naturalcannabinoids: evidence for partial agonist activity of delta-9-tetrahydrocannabinol and antagonist activity of cannabidiol on rat brain cannabinoid receptors. Life Sci. (1998) 63:PL1-PL6.
   Google Scholar
• MECHOULAM R, DI MARZO V: Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br .j Pharmaccol. (2001) 134.845–852.
   PubMed Web of Science ®Google Scholar
• MECHOULAM R, PARKER LA, GALLILY R: Cannabidiol: An overview of some pharmacological aspects. j Clip. Pharmacol (2002) 42\(Suppl. 11):11S–19S.
   Google Scholar
• PERT WEE RG, ROSS RA, CRAIB SJ et al.: 0-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. Eur.j Pharmacol (2002) 456.99–106.
   PubMed Web of Science ®Google Scholar
• MALFAIT AM, GALLILY R, SUMARIWALLA PF et al.: The non-psychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Nati Acad. Sci. USA (2000) 97.9561–9566.
   PubMed Web of Science ®Google Scholar
• PARKER LA, KWIATKOWSKI M, BURTON P et al: Effect of cannabinoids on lithium-induced vomiting in the Suncus MIlliIIIIS (house musk shrew). Psychopharmacol (2003) 171:156–161.
   Web of Science ®Google Scholar
• BORHEIM LM, GRILLO MP: Characterization of cytochrome P450 3A inactivation by cannabidiol: possible involvement of cannabidiol-hydroxyquinone as a P450 inactivator. Chem. Res. Toxicol (1998) 11:1209–1216.
   PubMed Web of Science ®Google Scholar
• CAMPBELL FA, TRAMER MR, CAROLL D et al: Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BE Med. j (2001) 323:13–16.
   PubMed Web of Science ®Google Scholar
• ••Interesting review of the clinical trial dataon the use of cannabinoids as analgesics.
   Google Scholar
• TRAMER MR, CAROLL D,CAMPBELL FA et al: Cannabinoids for control of chemotherapy-induced nausea and vomiting: quantitative systematic review. Br. Med .j (2001) 323:16–21.
   PubMed Web of Science ®Google Scholar
• ••Interesting review of the clinical trialdata on the use of cannabinoids for the treatment of nausea and vomiting.
   Google Scholar
• NAEF M, CURATOLO M, PETERSEN-FELIX S et al: The analgesic effect or oral delta-9-tetrahydrocannabinol (THC), morphineand a THC and morphine combinationin healthy subjects under experimental pain conditions. Path (2003) 105:79–88.
   Google Scholar
• NOTCUTT W, PRICE M, MILLER R et al.: Initial experiences with medicinal extracts of cannabis for chronic pain: results from 34 N of 1' studies. Anaesthesia (2004) 59:440–452.
   PubMed Web of Science ®Google Scholar
• KARST M, SALIM K, BURTSEIN S et al.: Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain. A randomized controlled study. jAMA (2003) 290:1757–1762.
   Google Scholar
• ••Important recent trial of the effects of anew synthetic cannabinoid on neuropathic pain.
   Google Scholar
• BERMAN JS, SYMONDS C, BIRCH R: Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlledtrial. Path (2004) 112:299–306.
   Google Scholar
• ••One of the most recent trials to bepublished, supporting the analgesic effects of CBMEs.
   Google Scholar
• SVENDSEN KB, JENSEN TS,BACH FW: Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double-blind placebo controlled crossover trial. Br. Med. j (2004) 329:253–261.
   PubMed Web of Science ®Google Scholar
• ••Recent clinical trial of the effectsof oral dronabinol on chronic pain.
   Google Scholar
• SMITH RA, FATHI Z: Recent advances in the research and development of CB1 antagonists. IDrugs. (2005) 8:53–66.
   PubMed Web of Science ®Google Scholar
• GRIEBEL G, STEMMELIN J, SCATTON B: Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents. Biol. Psychiat. (2005) 57:261–267.
   PubMed Web of Science ®Google Scholar
• TASHKIN DP: Airway effects of marijuana, cocaine and other inhaled illicit agents. Curr. Opin. Pulm. Med. (2001) 7.43–61.
   PubMedGoogle Scholar
• TASHKIN DP: Respiratory risks from marijuana smoking. In F. Grotenhermen and E. Russo (Eds), Cannabis and Cannabirmids. Pharmacology Toxicology and Therapeutic Potential. The Haworth Press, Inc. New York, (2002) pp.325–335.
   Google Scholar
• •Good recent review of the respiratory effects of smoking cannabis.
   Google Scholar
• TASHKIN DP, BALDWIN GC, SARAFIAN T et al.: Respiratory and immunologic consequences of marijuana smoking. J. Clin. Pharmacol (2002) 42\(Suppl. 11):71S–81S.
   Google Scholar
• ROTH MD, ARORA A, BARSKY SH et al: Airway inflammation in young marijuana and tobacco smokers. Am. j Respir. Grit. Care Med.(1998) 157.928–937.
   PubMed Web of Science ®Google Scholar
• FLIGIEL SEG, ROTH MD,KELLERUP EC et al.: Trachiobronchial histopathology in habitual smokers of cocaine, marijuana and/or tobacco. Chest (1997) 112.319–326.
   Google Scholar
• SHERMAN MP, AEBERHARD EE, WONG VZ et al: Effects of smoking marijuana, tobacco or cocaine alone or in combination on DNA damage in human alveolar macrophages. Life Sci. (1995) 56:2201–2207.
   PubMed Web of Science ®Google Scholar
• BALDWIN GC, TASHKIN DP, BUCKLEY DM et al: Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am. j Respir. Grit. Care Med. (1997) 156:1606–1613.
   PubMed Web of Science ®Google Scholar
• TAYLOR DR, POULTON R, MOFFITT TE et al.: The respiratory effects of cannabis dependence in young adults. Addiction (2000) 95:1669–1677.
   PubMed Web of Science ®Google Scholar
• ZIMMER L, MORGAN JP: Marijuana Myths Marijuana Facts. The Lindesmith Center, New York and San Francisco (1997).
   Google Scholar
• TASHKIN DP, SIMMONS M, SHERRILL D et al: Heavy habitual marijuana smoking does not cause an accelerated decline in FEVI with age: A longitudinal study. Am. j Respir. Grit. Care Med. (1997) 155:141–148.
   PubMed Web of Science ®Google Scholar
• VAN HOOZEN BE, CROSS CE: Marijuana. Respiratory tract effects. Clia Revs Allergy and Immunol (1997) 15:243–269.
   PubMed Web of Science ®Google Scholar
• BENSON M, BENTLEY AM: Lung disease induced by drug addiction. Thorax (1995) 50:1125–11237.
   PubMed Web of Science ®Google Scholar
• ROTH MD, MARQUES-MAGALLANES JA, YUAN M et al: Induction and regulation of the carcinogen-metabolizing enzyme CYP1A1 by marijuana smoke and delta-(9)-tetrahydrocannabinol. Am. Respir. Cell Mol. Biol. (2001) 24:339–344.
   PubMed Web of Science ®Google Scholar
• SARAFIAN TA, MAGALLANES JA, SHAU H et al.: Oxidative stress produced by marijuana smoke. An adverse effects enhanced by cannabinoids. Am. j Respir. Cell Mol. Biol. (1999) 20:1286-1293.64. FLIGIEL SEG, BEALS TF, VENKAT H et al: Pulmonary pathology in marijuanasmokers. In: Chesher, GB, Consroe, P. and Musty, R. (Eds.), Marijuana: An International Research Report. National Campaign Against Drug Abuse, Monograph No. 7, Canberra,Australian Government Publishing service, (1988) pp. 43–48.
   Google Scholar
• BARSKY, SH, ROTH, MD,KLEERUP EC et al: Histopathological and molecular alterations in bronchial epithelium in habitual smokers of marijuana, cocaine and/or tobacco.Nat. Cancer Inst. (1998) 90:1198-1205.
   Google Scholar
• GUZMAN M, SANCHEZ C, GALVE-ROPERH I: Control of the cell survival/death decision by cannabinoids. ./. Mol. Med. (2001) 78:613–625.
   PubMed Web of Science ®Google Scholar
• AMMENHEUSER MM,BERENSON AB, BABIAK AE et al: Frequencies of hprt mutant lymphocytes in marijuana-smoking mothers and their newborns. Mutat. Res. (1998) 403:55–64.
   PubMed Web of Science ®Google Scholar
• ZHU LX, SHARMA S, STOLINA M et al.: Delta-fl-tetrahydrocannabinol inhibits antitumour immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J. Immunol (2000) 165:373–380.
   PubMed Web of Science ®Google Scholar
• HASHIBE M, FORD DE, ZHANG ZF: Marijuana smoking and head and neck cancer. J. Clin. Pharmacol (2002) 42\(Suppl. 11):103S–107S.
   Google Scholar
• SIDNEY S, BECK JE, TEKAWA IS et al.: Marijuana use and cancer incidence. Am. J. Pub. Health (1997) 8:585–590.
   Google Scholar
• ZHANG Z-F, MORGENSTERN H, SPITZ MR et al.: Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prey. (1999) 8:1071–1078.
   PubMed Web of Science ®Google Scholar
• HALL W: The respiratory risks of cannabis smoking. Addiction (1998) 93:1461-1463.
   Google Scholar
• GUY GW, FLINT ME: A singlecentre, placebo-controlled, four period, crossover, tolerability study assessing pharmacodynamic effects, pharmacokinetic characteristics and cognitive profiles of a single dose of three formulations of cannabis based medicine extracts (CBMEs) (GWPD9901). J. Connell:ft Therap. (2003) 3/4:35–77.
   Google Scholar
• ••Important Phase I trial of Sativex.
   Google Scholar
• GUY GW, ROBSON PJ: A Phase I, openlabel, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract (CBME) administered on 3 different areas of the buccal mucosaand to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers. ./. Cannabis Therap. (2003) 3/4:79-120.Important Phase I trial of Sativex.
   Google Scholar
• GUY GW, FLINT ME: A Phase I, double-blind, three-way crossover study to assess the pharmacokinetic profile of cannabis based medicine extract (CBME) administered sublingually in variant cannabinoid ratios in normal healthy male volunteers. J. Cannabis Therap. (2003) 3/4:121–152.
   Google Scholar
• ••More Phase I trial data on Sativex.
   Google Scholar
• RUSSO E: Cannabis and cannabis based medicine extracts: Additional results. J. Cannabis Therap. (2003) 3/4:153–161.
   Google Scholar
• ••More clinical trial data on Sativex.
   Google Scholar
• POPE HG, GRUBER AJ, HUDSON JI et al.: Neuropsychological performance in long-term cannabis users. Arch. Gen. Psychiat. (2001) 58:909–915.
   PubMed Web of Science ®Google Scholar
• •Important paper on the long-term cognitive effects of cannabis use.
   Google Scholar
• POPE HG, GRUBER AJ, YURGELUN-TODD D: Residual neuropsychological effects of cannabis. Curr. Psych. Rep. (2001) 3:507–512.
   PubMedGoogle Scholar
• •Important paper on the long-term cognitive effects of cannabis use.
   Google Scholar
• FRIED P, WATKINSON B, JAMES D et al.: Current and former marijuana use: preliminary findings of a longitudinal study of effects on IQ in young adults. CMAI (2002) 166:887–891.
   PubMed Web of Science ®Google Scholar
• ••Paper describing the effects of cannabisuse on IQ.
   Google Scholar
• WRIGHT A, TERRY P: Modulation of the effects of alcohol on driving-related psychomotor skills by chronic exposure to cannabis. Psychopharmacol (2002) 160:213–219.
   PubMed Web of Science ®Google Scholar
• HAMPSON RE, SIMERAL JD, KELLY EJet al.: Tolerance to the memory disruptive effects of cannabinoids involves adaptation by hippocampal neurons. Hippocampus (2003) 13:543–556.
   Google Scholar
• KELLEHER LM, STOUGH C, SERJEJEW AA et al: The effects of cannabis on information-processing speed. Addict. Behav. (2004) 29:1213-1219.
   Google Scholar
• MULLER-VAHL K, PREVEDEL H, THELOE K et al.: Treatment of Tourette syndrome with delta-9-THC: No influence on neuropsychological performance. Neuropsychopharmacol (2003) 28:384-388.Important evidence for lack of adverse cognitive effects with therapeutic use of A9-THC.
   Google Scholar
• MULHERAN M, MIDDLETON P, HENRY JA: The acute effects of tetrahydrocannabinol on auditory threshold and frequency resolution in human subjects. Hum. Exp. Toxicol (2002) 21:289–292.
   PubMed Web of Science ®Google Scholar
• KEMPEL P, LAMPE K, PARNEFJORD R et al.: Auditory-evoked potentials and selective attention: different ways of information processing in cannabis users and controls. Neuropsychobiol (2003) 48:95–101.
   PubMed Web of Science ®Google Scholar
• HUESTEGGE L, RADACH R,KUNERT HJ et al.: Visual search in long-term cannabis users with early age of onset. Prog. Brain Res. (2002) 140:377–394.
   Google Scholar
• •Evidence that cannabis use results in deficits in visual search patterns.
   Google Scholar
• SEMPLE DM, RAMSDEN F, MCINTOSH AM: Reduced binocular depth invesrion in regular cannabis users. Pharmacol Biochem. Behav. (2003) 75:789–793.
   PubMed Web of Science ®Google Scholar
• POPE HG, GRUBER AJ, HUDSON JI et al.: Early-onset cannabis use and cognitive deficits: what is the nature of the association? Drug Alcohol Depend. (2003) 69:303–310.
   Google Scholar
• WILSON W, MATHEW R, TURKINGTON T et al.: Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study. j Addict Dis. (2000) 19:1-22.
   Google Scholar
• •Evidence that early cannabis use causes morphological changes in the brain.
   Google Scholar
• DEAS D, GERDING L, HAZY J:Marijuana and panic disorder. I Am. Acad. Child Adolesc. Psychiat. (2000) 39:1467-1469.
   Google Scholar
• •Evidence that marjinua ause can cause panic attacks in some people.
   Google Scholar
• WILLIAMSON EM, EVANS FJ: Cannabinoids in clinical practice. Drugs (2000) 60:1303-1314.
   Google Scholar
• REY JM, MARTIN A, KRABMAN P: Is the party over? Cannabis and juvenile psychiatric disorder: the past 10 years. I Am. Acad. Child Adolesc. Psychiat. (2004) 43:1194–205.
   PubMed Web of Science ®Google Scholar
• ••Paper evaluating the link between earlycannabis use and psychiatric disorder.
   Google Scholar
• REY JM, SAWYER MG, RAPHAEL B et al.: Mental health of teenagers who usecannabis. Results of an Australian survey. Br. J. Psychiat. (2002) 180:216–221.
   Google Scholar
• FERGUSSON DM, HORWOOD LJ, SWAIN-CAMPBELL N: Cannabis use and psychosocial adjustment in adolescence and young adulthood. Addiction (2002) 97:1123–1135.
   PubMed Web of Science ®Google Scholar
• KALANT H: Adverse effects of cannabis on health: an update of the literature since 1996. Frog. Neuropsychopharmacol Biol. Psychiat. (2004) 28:849–863.
   PubMed Web of Science ®Google Scholar
• MACLEOD J, OAKES R, COPELLO A et al.: Psychological and social sequelae of cannabis and other illicit drug use by young people: a systematic review of longitudinal, general population studies. Lancet (2004) 363:1579–1588.
   PubMed Web of Science ®Google Scholar
• ••Recent review of the data linkingcannabis use to psychiatric disorders.
   Google Scholar
• BOVASSO GB: Cannabis abuse as a risk factor for depressive symptoms. Am. J. Psychiat. (2001) 158:2033–2037.
   PubMed Web of Science ®Google Scholar
• ••Evidence that cannabis useIncreases the incidence of depression.
   Google Scholar
• DEGENHARDT L, HALL W, LYNSKEY M: Alcohol, cannabis and tobacco use among Australians: a comparison of their associations with other drug use and use disorders, affective and anxiety disorders, and psychosis. Addiction (2001) 96:1603–1614.
   PubMed Web of Science ®Google Scholar
• EISEN SA, CHANTARUJIKAPONG S, XIAN H et al.: Does marijuana use have residual adverse effects on self-reported health measures, socio-demographics and quality of life? A monozygotic co-twin control study in men.Addiction (2002) 97:1137–1144.
   PubMed Web of Science ®Google Scholar
• NUNEZ LA, GURPEGUI M: Cannabis-induced psychosis: a cross-sectional comparison with acute schizophrenia. Acta Psychiat. Scand. (2002) 105:173–178.
   PubMed Web of Science ®Google Scholar
• JOHNS A: Psychiatric effects of cannabis. Br. J. Psychiat. (2001) 178:116–122.
   PubMed Web of Science ®Google Scholar
• VAN OS J, BAK M, HANSSEN M et al: Cannabis use and psychosis: a longitudinal population-based study. Am. J. Epidemiol. (2002) 156:319–327.
   PubMed Web of Science ®Google Scholar
• SMIT F, BOLTER L, CUIJPERS P: Cannabis use and the risk of later schizophrenia: a review. Addiction (2004) 99:425–430.
   PubMed Web of Science ®Google Scholar
• HALL W, DEGENHARDT L: Cannabis use and psychosis: a review of clinical and epidemiological evidence. Aust. NZI. Psychiat. (2000) 34:26–34.
   PubMed Web of Science ®Google Scholar
• ARSENEAULT L, CANNON M, WITTON J et al.: Causal association between cannabis and psychosis: examination of the evidence. Br. Psychiat. (2004) 184:110–117.
   PubMed Web of Science ®Google Scholar
• ••Recent review of the possible linkbetween cannabis use and psychosis.
   Google Scholar
• FERGUSSON DM, HORWOOD LJ, SWAIN-CAMPBELL NR: Cannabis dependence and psychotic symptoms in young people. Psycho] Med. (2003) 33:15–21.
   PubMed Web of Science ®Google Scholar
• JOCKERS-SCHERUBL MC, MATTHIES U, DANKER-HOPFE H et al.: Chronic cannabis abuse raises nerve growth factor serum concentrations in drug-naïve schizophrenic patients.Psychopharmacol (2003) 17:439–445.
   Web of Science ®Google Scholar
• PENCER A, ADDINGTON J: Substance use and cognition in early psychosis. I Psychiat. Neurosci. (2003) 28:48–54.
   PubMed Web of Science ®Google Scholar
• FRIED PA, WATKSINSON B: Differential effects on facets of attention in adolescents prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol.(2001) 23:421–430.
   PubMed Web of Science ®Google Scholar
• FRIED PA, SMITH AM: A literature review of the consequences of prenatal marihuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicol. Teratol (2001) 23:1–11.
   Google Scholar
• ••Useful review of the evidence that prenatalexposure to cannabis can cause deficits in cognitive function.
   Google Scholar
• FRIED PA, WATKINSON B, GRAY R: Differential effects on cognitive functioning in 13- to 16 year-olds prenatally exposed to cigarettes and marihuana. Neurotoxicol Teratol (2003) 25:427–436.
   PubMed Web of Science ®Google Scholar
• ••Interesting paper describing the effects ofprenatal cannabis exposure on cognitive function.
   Google Scholar
• GOLDSCHMIDT L,RICHARDSON GA, CORNELIUS MD et al.: Prenatal marijuana and alcohol exposure and academic achievement at age 10. Neurotoxicol. Teratol (2004) 26:521–532.
   Google Scholar
• ••Recent evidence that prenatal cannabisexposure can impact on achievement at school.
   Google Scholar
• GOLDSCHMIDT L, DAY NL, RICHARDSON GA: Effects of prenatal marijuana exposure on child behavior problems at age 10. Neurotoxicol 7eratol. (2000) 22:325–336.
   PubMed Web of Science ®Google Scholar
• SMITH AM, FRIED PA, HOGAN MJ et al: Effects of prenatal marijuana on response inhibition: an fMRI study of young adults. Neurotoxicol Teratol (2004) 26:533–542.
   PubMed Web of Science ®Google Scholar
• WANG X, DOW-EDWARDS D, KELLER E et al.: Preferential limbic expresion of the cannabinoid receptor mRNA in the human fetal brain. NeuroscL (2003) 118:681–694.
   PubMed Web of Science ®Google Scholar
• GOMEZ M, HERNANDEZ M, JOHANSSON B et al: Prenatal cannabinoid and gene expression for neural adhesion molecule Li in the fetal rat brain. Dev. Brain Res. (2003) 147:201–207.
   PubMedGoogle Scholar
• PARK B, MCPARTLAND JM, GLASS M: Cannabis, cannabinoids and reproduction.Prostaglandins Leukot. Essent. Fatty Acids(2004) 70:189–197.
   PubMed Web of Science ®Google Scholar
• •Interesting review of the potential consequences of prenatal cannabis exposure.
   Google Scholar
• NEWSHAM-WEST D,DARLINGTON CL, SMITH PF: Potent effects of a selective cannabinoid receptor agonist on some medial vestibular nucleus neurons. Eur. Pharmacol. (1998) 348:R1–R2.
   PubMed Web of Science ®Google Scholar
• ASHTON JC, ZHENG Y, LIU P et al: Immunohistochemical characterization and localization of cannabinoid CB1 receptor protein in the rat vestibular nucleus complex and effects of unilateral vestibular deafferentation. Brain Res. (2004) 1021:266–273.
   Google Scholar
• •Recent evidence suggesting that the potential effects of cannabis on the vestibular system have been underestimated.
   Google Scholar
• O'LEARY DS, BLOCK RI, TURNER BM et al.: Marijuana alters the human cerebellar clock. NeuroReport (2003) 14:1145–1151.
   PubMed Web of Science ®Google Scholar
• BACHS L, MORLAND H: Acute cardiovascular fatalities following cannabis use. Forensic Sci. Int. (2001) 124:200–203.
   PubMed Web of Science ®Google Scholar
• SIDNEY S: Cardiovascular consequences of marijuana use. J. Clin. Pharmacol (2002) 42\(Suppl. 11):645–705.
   Google Scholar
• BATKAI S, PACHER P, OSEI-HYIAMAN D et al: Endocannabinoids acting at cannabinoid-1 receptors regulate cardiovascular function in hypertension. Circulation (2004) 110: 1996-2002.
   Google Scholar
• MCKALLIP RJ, LOMBARD C, FISHER M et al: Delta-9-tetrahydrocannabinol-induced apoptosisin the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J. Pharmacol Exp. Therap. (2002) 302:451–465.
   PubMed Web of Science ®Google Scholar
• •Evidence that A9-THC can adversely affect the immune system.
   Google Scholar
• EL-GOHARY M, EID MA: Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students. Hum. Exp. Toxicol (2004) 23:149–156.
   PubMed Web of Science ®Google Scholar
• ABRAMS DI, HILTON JF, LEISER RJ et al.: Short-term effects of cannabinoids in patients with HIV-1 infection. Ann. Intern. Med. (2003) 139:258–266.
   PubMed Web of Science ®Google Scholar
• ••Important evidence for lack of adverseeffects on the immune system with therapeutic use of cannabinoids.
   Google Scholar
• HANEY M, WARD AS, COMER SD et al.: Abstinence symptoms following oral THC administration in humans. Psychopharmacol (1999) 141.385–494.
   PubMed Web of Science ®Google Scholar
• •One of the first systematic studies to demonstrate that cannabis dependence develops in humans.
   Google Scholar
• HANEY M, WARD AS, COMER SD et al.: Abstinence symptoms following smoked marijuana in humans. Psychopharmacol (1999) 141:395–404.
   PubMed Web of Science ®Google Scholar
• •One of the first systematic studies to demonstrate that cannabis dependence develops in humans.
   Google Scholar
• BUDNEY AJ, HUGHES JR, MOORE BA et al.: Marijuana abstinence effects in marijuana smokers maintained in their home environment. Arch. Gen. Psychiat. (2001) 58:917–924.
   PubMed Web of Science ®Google Scholar
• SMITH NT: A review of the published literature into cannabis withdrawal symptoms in human users. Addiction (2002) 97:621–632.
   PubMed Web of Science ®Google Scholar
• TANDA G, MUNZAR P,GOLDBERG SR: Self-administration behavior is maintained by the psychoactive ingredient of marijuana in squirrel monkeys. Nat. NeuraccL (2000) 3:1073–1074.
   PubMed Web of Science ®Google Scholar
• TANDA G, PONTIERI FE, DICHIARA G: Cannabinoid andheroin activation of mesolimbic dopamine transmission by a common p-1 opioid receptor mechanism. Science (1997) 276:2048–2050.
   PubMed Web of Science ®Google Scholar
• TANDA G, GOLDBERG SR: Cannabinoids: reward, dependence and underlying neurochemical mechanisms - a review of recent preclinical data. Psychopharmacol (2003) 169:115-134.Good recent review of the evidence relating to cannabis dependence.
   Google Scholar
• WALLACE MJ, BALIR RE,FALENSKI KW et al: The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J. Pharmacol Exp. Therap. (2003) 307:129–137.
   PubMed Web of Science ®Google Scholar
• ••Interesting paper on the effects ofcannabinoids on seizure activityIn the pilocarpine model of epilepsy.
   Google Scholar
• HOFFMAN AF, LUPICA CR: Mechanisms of cannabinoid inhibition of GABA(A) synaptic transmission in the hippocampus. j Neurosci. (2000) 20:2470–2479.
   PubMed Web of Science ®Google Scholar
• ••Important paper on the effects ofcannabinoids on GABAergic function in the hippocampus and evidence that cannabinoids can have pro-convulsant effects.
   Google Scholar
• NAKATSUKA T, CHEN H-X,ROPER SN et al: Cannabinoid receptor-I activation suppresses inhibitory synaptic activity in human dentate gyrus. NeuropharmacoL (2003) 45:116–121.
   PubMed Web of Science ®Google Scholar
• ••Recent demonstration of the potentialpro-convulsant effects of cannabinoids In the hippocampus.
   Google Scholar
• LAMBERT DM, VANDEVOORDE S, DIEPENDALE G et al.: Anticonvulsant activity of N-palmitoylethanolamide, a putative endocannabinoid, in mice. Epilepsia (2001) 42:321–327.
   PubMed Web of Science ®Google Scholar
• SHEERIN AH, ZHANG X, SAUCIER DM et al:Selective anti-epileptic effects of N-palmitoylethanolamide, a putative endocannabinoid. Epilepsia (2004) 45:1184-1188.Recent evidence suggesting that N-palmitoylethanolamide may also have anticonvulsant effects
   Google Scholar
• CLEMENT AB, HAWKINS EG, LICHTMAN AH et al.: Increased seizure susceptibility and proconvulsant activity of anandamide in mice lacking fatty acid amide hydrolase. I Neurosci. (2003) 23:3916–3923.
   Google Scholar
• ••Recent evidence that anandamide mayhave pro-convulsant effects under some circumstances.
   Google Scholar
• WHALLEY BJ, WILKINSON JD, WILLIAMSON EM et al.: A novel component of cannabis extract potentiates excitatory synaptic transmission in rat olfactory cortex in vitro. NeuraccL Letts. (2004) 365.68–63.
   Google Scholar
• ••Interesting paper reporting that cannabisextracts may have effects beyond those predicted by their known constituents.
   Google Scholar
• BEAL JE, OLSON R, LEFKOWITZ L et al.: Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome associated anorexia./. Path Symptom Management. (1997) 14:7–14.
   PubMed Web of Science ®Google Scholar
• WILKINSON JD, WHALLEY BJ, BAKER D et al.: Medicinal cannabis: Is delta-9-tetrahydrocannabinol necessary for all its effects?' Pharm. Pharmacol (2003) 55: 1687-1694.
   Google Scholar
• •Analysis and comparison of the effects of the different constituents of cannabis extracts.
   Google Scholar
• www.gwpharm.cominews pres 05 nov 02.html.GW Pharmaceuticals website report (2002).
   Google Scholar