Advertisement

Cannabinoids pp 719-756 | Cite as

Human Studies of Cannabinoids and Medicinal Cannabis

  • P. Robson
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 168)

Abstract

Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with some suggestions as to future directions for human research.

Keywords

Cannabinoids Medicinal cannabis Human research Therapeutic potential 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abel EL (1980) Outlawing marihuana. In: Marihuana: the First twelve thousand years. Plenum Press, New York, pp 237–247Google Scholar
  2. Abrahamov A, Abrahamov A, Mechoulam R (1995) An efficient new cannabinoids antiemetic in pediatric oncology. Life Sci 56:2097–2102PubMedCrossRefGoogle Scholar
  3. Abrams DI, Hilton JF, Leiser RJ, et al (2003) Short-term effects of cannabinoids in patients with HIV-1 infection. A randomized, placebo-controlled clinical trial. Ann Intern Med 139:258–266PubMedGoogle Scholar
  4. Advisory Council on the Misuse of Drugs (2002) The classification of cannabis under the Misuse of Drugs Act 1971. Home Office, LondonGoogle Scholar
  5. Arseneault L, Cannon M, Witton J, et al (2004) Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry 184:110–117PubMedCrossRefGoogle Scholar
  6. Ashworth B (1964) Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 192:540–542PubMedGoogle Scholar
  7. Astley SJ, Little RE (1990) Maternal Maijuana use during lactation and infant development at one year. Neurotoxicol Teratol 12:161–168PubMedCrossRefGoogle Scholar
  8. Baker D, Pryce G, Croxford JL, et al (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404:84–87PubMedCrossRefGoogle Scholar
  9. Baker D, Pryce G, Croxford JL, et al (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302PubMedGoogle Scholar
  10. Beal JE, Olson R, Laubenstein L, et al (1995) Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 10:89–97PubMedCrossRefGoogle Scholar
  11. Beal JE, Olson R, Lefkowitz L, et al (1997) Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated nausea. J Pain Symptom Manage 14:7–14PubMedCrossRefGoogle Scholar
  12. Benowitz NL, Jones RT (1981) Cardiovascular and metabolic considerations in prolonged cannabinoid administration in man. J Clin Pharmacol 21:214–223SGoogle Scholar
  13. Brady C, DasGupta R, Wiseman O, et al (2003) Sublingual cannabis based medicinal extracts for bladder dysfunction in advanced multiple sclerosis. Int Cannabinoid Res Soc 13th Annu Symp Cannabinoids, Abstr 56Google Scholar
  14. Bredt BM, Higuera-Alhino D, Shade SB, et al (2002) Short-term effects of cannabinoids on immune phenotype and function in HIV-1-infected patients. J Clin Pharmacol 42:82S–89SPubMedGoogle Scholar
  15. Brenneissen R, Egli A, Elsohly MA, Henn V, Spiess Y (1996) The effect of orally and rectally administered delta-9-THC on spasticity: a pilot study with two patients. Int J Clin Pharmacol Ther 34:446–452Google Scholar
  16. Bridges D, Ahmad K, Rice, AS (2001) The synthetic cannabinoid WIN55,212-2 attenuates hyperalgesia and allodynia in a rat model of neuropathic pain. Br J Pharmacol 133:586–594PubMedCrossRefGoogle Scholar
  17. Brotchie JM (2000) The neural mechanisms underlying levodopa-induced dyskinesia. Ann Neurol 47:105–114SGoogle Scholar
  18. Budney AJ, Moore BA, Vandrey RG, et al (2003) The time course and significance of cannabis withdrawal. J Abnorm Psychol 112:393–402PubMedCrossRefGoogle Scholar
  19. Buggy DJ, Toogood L, Maric S, et al (2003) Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain 106:169–172PubMedCrossRefGoogle Scholar
  20. Campbell FA, Tramer MR, Carroll D, et al (2001) Are cannabinoids an effective and safe option in the management of pain? A qualitative systematic review. Br Med J 323:13–16Google Scholar
  21. Carmichael J (1992) The principles of cancer chemotherapy. In: Grahame-Smith DG, Aronson JK (eds) Oxford textbook of clinical pharmacology, 2nd edn. Oxford University Press, Oxford, 505–515Google Scholar
  22. Chan HSL, Correia JA, MacLeod SM (1987) Nabilone versus prochlorperazine for control of cancer chemotherapy-induced emesis in children: a double-blind crossover trial. Pediatrics 79:946–952PubMedGoogle Scholar
  23. Chang AE, Shiling DJ, Stillman RC, et al (1979) Delta-9-THC as an antiemetic in cancer patients receiving high-dose methotrexate. Ann Intern Med 91:819–830PubMedGoogle Scholar
  24. Chaperon F, Thiebot MH (1999) Behavioural effects of cannabinoid agents in animals. Crit Rev Neurobiol 13:243–281PubMedGoogle Scholar
  25. Cichewicz DL, McCarthy EA (2003) Antinociceptive synergy between delta-9-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther 304:1010–1015PubMedGoogle Scholar
  26. Cichewicz DL, Welch SP (2003) Modulation of oral morphine antinociceptive tolerance and naloxone-precipitated withdrawal signs by oral delta 9-tetrahydrocannabinol. J Pharmacol Exp Ther 305:812–817PubMedCrossRefGoogle Scholar
  27. Cichewicz DL, Rubo A, Welch SP (2003) Recovery of morphine-and codeine-induced antinociception by delta-9-tetrahydrocannabinol. Int Cannabinoid Res Soc 13th Annu Symp Cannabinoids, Abstr 40Google Scholar
  28. Clifford DB (1983) THC for tremor in multiple sclerosis. Ann Neurol 13:669–671PubMedCrossRefGoogle Scholar
  29. Consroe P, Snider SR (1986) Therapeutic potential of cannabinoids in neurological disorders. In: Mechoulam E (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, 21–49Google Scholar
  30. Consroe P, Sandyk R, Snider SR (1986) Open label evaluation of cannabidiol in dystonic movement disorders. Int J NeuroSci 30:277–282CPubMedCrossRefGoogle Scholar
  31. Consroe P, Laguna J, Allender J, et al (1991) Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 40:701–708CPubMedGoogle Scholar
  32. Consroe P, Musty R, Rein J, Tillery W, Pertwee RG (1997) The Perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol 38:44–48PubMedGoogle Scholar
  33. Consroe PF, Wood GC, Buchsbaum H (1975) Anticonvulsant nature of marihuana smoking. J Am Med Assoc 234:306–307CrossRefGoogle Scholar
  34. Cunha JM, Carlini EA, Pereira AE, et al (1980) Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21:175–185PubMedGoogle Scholar
  35. Dahl V, Raeder JC (2000) Non-opioid postoperative analgesia. Acta Anaesthesiol Scand 44:1191–1203PubMedCrossRefGoogle Scholar
  36. Dalzell AM, Bartlett H, Lilleyman JS (1986) Nabilone: an alternative antiemetic for cancer chemotherapy. Arch Dis Child 61:502–505PubMedGoogle Scholar
  37. Degenhardt L, Hall W (2002) Cannabis and psychosis. Curr Psychiatry Rep 4:191–196PubMedGoogle Scholar
  38. Dunn M, Davis R (1974) The perceived effects of marijuana on spinal cord injured males. Paraplegia 12:175PubMedGoogle Scholar
  39. Einhorn LH, Nagy C, Furnas B, et al (1981) Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol 21:64S–69SPubMedGoogle Scholar
  40. Fabre LF, McLendon D (1981) The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin Pharmacol 21:377S–382SPubMedGoogle Scholar
  41. Foltin RW, Fischman MW, Byrne MF (1986) Behavioural analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 25:577–582PubMedCrossRefGoogle Scholar
  42. Formukong EA, Evans AT, Evans FJ (1989) The medicinal use of cannabis and its constituents. Phyto Ther Res 3:219–231Google Scholar
  43. Fox A, Kesingland A, Gentry, et al (2001) The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain 92:91–100PubMedCrossRefGoogle Scholar
  44. Fox SH, Kellett M, Moore AP, et al (2002) Randomised, double-blind, placebo-controlled trial to assess the potential of cannabinoid receptor stimulation in the treatment of dystonia. Mov Disord 17:145–149PubMedGoogle Scholar
  45. Georgotas A, Zeidenberg P (1979) Observations on the effects of heavy marijuana smoking on group interaction and individual behaviour. Compr Psychiatry 20:427–432PubMedCrossRefGoogle Scholar
  46. Gonzalez R, Carey C, Grant I (2002) Nonacute (residual) effects of cannabis use: a qualitative analysis and systematic review. J Clin Pharmacol 42:48–57SGoogle Scholar
  47. Grant I, Gonzalez R, Carey CL, et al (2003) Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study. J Int Neuropsychol Soc 9:679–689PubMedCrossRefGoogle Scholar
  48. Greenberg HS, Werness SA, Pugh JE, et al (1994) Short-term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clin Pharmacol Ther 55:324–328PubMedCrossRefGoogle Scholar
  49. Greenwald MK, Stitzer ML (2000) Antinociceptive, subjective and behavioural effects of smoked marijuana in humans. Drug Alcohol Depend 59:261–275PubMedGoogle Scholar
  50. Grinspoon L, Bakalar JB (1993) The history of cannabis. In: Marihuana: the forbidden medicine. Yale University Press, New Haven, pp 1–23Google Scholar
  51. Grinspoon L, Bakalar JB (1998) The use of cannabis as a mood stabilizer in bipolar disorder: anecdotal evidence and the need for clinical research. J Psychoactive Drugs 30:171–177PubMedGoogle Scholar
  52. Guz A (1996) Respiratory sensations: some clinical perspectives. In: Eds Abrams L, Guz A (eds) Lung biology in health and disease, vol 90. Marcel Dekker, New York, 389–395Google Scholar
  53. Guzmán M (2003) Cannabinoids: potential anticancer agents. Nat Rev Cancer 3:745–755PubMedGoogle Scholar
  54. Hadorn D (2004) A review of cannabis and driving skills. In: Guy G, Whittle B, Robson P (eds) The medicinal use of cannabis and cannabinoids. Pharmaceutical Press, London, 329–365Google Scholar
  55. Hagenbach U, Gafoor N, Brenneisen R, et al (2001) Clinical investigation of delta-9-tetrahydrocannabinol (THC) as an alternative therapy for overactive bladders in spinal cord injury patients. Congress on Cannabis and Cannabinoids, Cologne, Germany. International Association for Cannabis as Medicin, p 10Google Scholar
  56. Hall W, Solowij N, Lemon J (1994) The health and social consequences of cannabis use. Monograph series No. 25. Australian Government Publishing Service, CanberraGoogle Scholar
  57. Hampson A, Grimaldi M, Axelrod J, et al (1998) Cannabidiol and delta-9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 95:8268–8273PubMedCrossRefGoogle Scholar
  58. Hanigan WC, Destree R, Truong XT (1985) The effect of delta-9-THC on human spasticity. Clin Pharmacol Ther 35:198Google Scholar
  59. Hemming M, Yellowlees PM (1993) Effective treatment of Tourette’s syndrome with marijuana. J Clin Pharmacol 7:389–391Google Scholar
  60. Hepler RS, Frank IM (1971) Marihuana smoking and intraocular pressure. JAMA 217:1392PubMedCrossRefGoogle Scholar
  61. Hepler RS, Frank IM, Petrus R (1976) Ocular effects of marihuana smoking. In: Braude MC, Szara S (eds) The pharmacology of marihuana. Raven Press, New York, pp 815–824Google Scholar
  62. Herkenham M, Lynn AB, Little MD, et al (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–1936PubMedGoogle Scholar
  63. Hinderer SR, Gupta S (1996) Functional outcome measures to assess interventions for spasticity. Arch Phys Med Rehabil 77:1083–1089PubMedCrossRefGoogle Scholar
  64. Hodges C (1992) Very alternative medicine. Spectator, 1 August 1992, p 18Google Scholar
  65. Hohmann AG, Farthing JN, Zvonok AM, Makriyannis A (2004) Selective activation of cannabinoid CB2 receptors suppresses hyperalgesia evoked by intradermal capsaicin. J Pharmacol Exp Ther 308:446–453PubMedGoogle Scholar
  66. Holdcroft A, Smith M, Jacklin A, et al (1997) Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia 5:483–486Google Scholar
  67. Hollister LE (1971) Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 12:44–49PubMedGoogle Scholar
  68. House of Lords Select Committee on Science and Technology (1998) Ninth Report. LondonGoogle Scholar
  69. Ilaria RL, Thornby JI, Fann WE (1981) Nabilone, a cannabinoid derivative, in the treatment of anxiety neurosis. Curr Ther Res Clin Exp 29:943–949Google Scholar
  70. Institute of Medicine (1999) The medical value of marijuana and related substances. In: Joy JE, Watson SJ, Benson JA (eds) Marijuana and medicine: assessing the science base. National Academic Press, Washington, 137–191Google Scholar
  71. Iversen L (2001) Few well controlled trials of cannabis exist for systematic review. Br Med J 323:1250Google Scholar
  72. Jain AK, Ryan JR, McMahon FG, Smith G (1981) Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J Clin Pharmacol 21:320S–326SPubMedGoogle Scholar
  73. Jarvinen T, Pate D, Laine K (2002) Cannabinoids in the treatment of glaucoma. Pharmacol Ther 95:203–220PubMedGoogle Scholar
  74. Jatoi A, Windshitl HE, Loprinzi CL, et al (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia. J Clin Oncol 20:567–573PubMedCrossRefGoogle Scholar
  75. Javid FA, Wright C, Naylor RJ, et al (2002) An inhibitory role for cannabinoids in the control of motion sickness in Suncus murinus. In: Symposium on the Cannabinoids; Asilomar Conference Center, Pacific Grove, CA. International Cannabinoid Research Society, 13 July 2002: abstr 141Google Scholar
  76. Johns A (2001) Psychiatric effects of cannabis. Br J Psychiatry 178:116–122PubMedCrossRefGoogle Scholar
  77. Jones RT (2002) Cardiovascular system effects of marijuana. J Clin Pharmacol 42:58–63SGoogle Scholar
  78. Jones RT, Benowitz NL, Herning RL (1981) Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol 21:143S–152SPubMedGoogle Scholar
  79. Jones SE, Durant JR, Greco FA, et al (1982) A multi-institutional phase III study of nabilone vs placebo in chemotherapy-induced nausea and vomiting. Cancer Treat Rev 9:45–48SPubMedGoogle Scholar
  80. Karler R, Turkanis SA (1981) The cannabinoids as potential antiepileptics. J Clin Pharmacol 21:437S–448SPubMedGoogle Scholar
  81. Karniol IG, Carlini EA (1973) Pharmacological interaction between cannabidiol and delta-9-THC. Psychopharmacologia 33:53–70PubMedCrossRefGoogle Scholar
  82. Karst M, Salim K, Burstein S, et al (2003) Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomised controlled trial. JAMA 290:1757–1762PubMedCrossRefGoogle Scholar
  83. Kaslow RA, Blackwelder WC, Ostrow DG, et al (1989) No evidence for a role of alcohol or other psychoactive drugs in accelerating immunodeficiency in HIV-1-positive individuals. JAMA 261:3424–3429PubMedCrossRefGoogle Scholar
  84. Keeler MH, Reifler CB (1967) Grand mal convulsions subsequent to marihuana smoking. Dis Nerv Syst 18:474–475Google Scholar
  85. Killestein J, Hoogervorst EL, Reif M, et al (2002) Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology 58:1404–1407PubMedGoogle Scholar
  86. Kirkham TC (2003) Endogenous cannabinoids: a new target in the treatment of obesity. Am J Physiol Regul Integr Comp Physiol 284:R343–R344PubMedGoogle Scholar
  87. Kirkham TC, Williams CM (2001) Endogenous cannabinoids and appetite. Nutr Res Rev 14:65–86CrossRefPubMedGoogle Scholar
  88. Knoller N, Levi L, Shoshan I, et al (2002) Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomised, placebo-controlled, phase II clinical trial. Crit Care Med 30:548–554PubMedGoogle Scholar
  89. Levitt M (1986) Cannabinoids as antiemetics in cancer chemotherapy. In: Mechoulam R (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, 71–83Google Scholar
  90. Leweke FM, Giuffrida A, Wurster U, et al (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10:1665–1669PubMedGoogle Scholar
  91. Malec J, Harvey RF, Cayner JJ (1982) Cannabis effect on spasticity in spinal cord injury. Arch Phys Med Rehabil 63:116–118PubMedGoogle Scholar
  92. Malfait AM, Gallily R, Sumariwalla PF, et al (2000) The non-psychoactive cannabis-constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci USA 97:9561–9566PubMedCrossRefGoogle Scholar
  93. Marsicano G, Wotjak CT, Azad SC, et al (2002) Endogenous cannabinoid system controls extinction aversive memories. Nature 418:530–534PubMedCrossRefGoogle Scholar
  94. Martyn CN, Illis LS, Thom J (1995) Nabilone in the treatment of multiple sclerosis. Lancet 345:579PubMedCrossRefGoogle Scholar
  95. Mathews PM, De Stefano N, Narayanan S, et al (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol 18:327–336CrossRefGoogle Scholar
  96. Maurer M, Henn V, Dittrich A, Hoffman A (1990) Delta-9-THC shows antispastic and analgesic effects in a single case double blind trial. Eur Arch Psychiatry Clin Neurosci 240:1–4PubMedCrossRefGoogle Scholar
  97. McKerral S, Berman J, Lee J, et al (2003) Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial. Int Cannabinoid Res Soc 13th Annu Symp Cannabinoids, Abstr 45Google Scholar
  98. McPartland J, Russo E (2001) Cannabis and cannabis extracts: greater than the sum of their parts? J Cannabis Ther 1:103–132Google Scholar
  99. Mead A (2004) International control of cannabis: changing attitudes. In: Guy G, Whittle B, Robson P (eds) The medicinal use of cannabis and cannabinoids. Pharmaceutical Press, LondonGoogle Scholar
  100. Mechoulam R (1986) The pharmacohistory of cannabis sativa. In: Mechoulam R (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, pp 1–19Google Scholar
  101. Meinck HM, Schonle PW, Conrad B (1989) Effect of cannabinoids on spasticity and ataxia in multiple scleroris. J Neurol 236:120–122PubMedCrossRefGoogle Scholar
  102. Merritt JC, Crawford WJ, Alexander PC, et al (1980) Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology 87:222–228PubMedGoogle Scholar
  103. Merritt JC, Olsen JL, Armstrong PC, et al (1981) Topical delta-9-THC in hypertensive glaucomas. J Pharm Pharmacol 33:40–41PubMedGoogle Scholar
  104. Metz L, Page S (2003) Oral cannabinoids for spasticity in multiple sclerosis: will attitude continue to limit use? (editorial). Lancet 362:1513PubMedCrossRefGoogle Scholar
  105. Mittleman MA, Lewis RA, Maclure M, et al (2001) Triggering myocardial infarction by marijuana. Circulation 103:2805–2809PubMedGoogle Scholar
  106. Muller-Vahl K, Schneider U, Kolbe H, et al (1999) Treatment of Tourette’s syndrome with delta-9-tetrahydrocannabinol. Am J Psychiatry 156:495PubMedGoogle Scholar
  107. Muller-Vahl KR, Schneider U, Prevedel H, et al (2003) Delta-9-tetrahydrocannabinol (THC) is effective in the treatment of Tourette syndrome: a 6-week randomised trial. J Clin Psychiatry 64:459–465PubMedCrossRefGoogle Scholar
  108. National Institute of Health (1997) Report from a workshop on the medical utility of marijuana, 19–20 February 1997: p 6. http://www.parklandtrading.com/users/thc4ms/pdf/0211.pdfGoogle Scholar
  109. Nelson K, Walsh D, Deeter P, et al (1994) A phase-II study of delta-9-THC for appetite-stimulation in cancer-associated anorexia. J Palliat Care 10:14–18PubMedGoogle Scholar
  110. Nicholson AN, Turner C, Stone BM, Robson P (2004) Effect of delta-9-THC and cannabidiol on nocturnal sleep and early morning behaviour in young adults. J Clin PsychoPharmacol (in press)Google Scholar
  111. Niederle N, Schutte J, Schmidt CG (1986) Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy. Klin Wochenschr 64:362–365PubMedGoogle Scholar
  112. Niiranen A, Mattson K (1985) A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 8:336–340PubMedGoogle Scholar
  113. Notcutt W, Price M, Chapman G (1997) Clinical experience with nabilone for chronic pain. Pharm Sci 3:551–555Google Scholar
  114. Notcutt W, Price M, Sansom C, et al (2002) Medicinal cannabis extract in chronic pain: overall results of 29 “n of 1” studies (CBME-1) In: Symposium on the Cannabinoids; Asilomar Conference Center, Pacific Grove, CA: International Cannabinoid Research Society; 13 July 2002: abstr 55Google Scholar
  115. Noyes R, Brunk SF, Baram DA, Canter A (1975a) Analgesic effects of delta-9-THC. J Clin Pharmacol 15:139–143PubMedGoogle Scholar
  116. Noyes R, Brunk SF, Avery DH, Canter A (1975b) The analgesic properties of delta-9-THC and codeine. Clin Pharmacol Ther 18:84–89PubMedGoogle Scholar
  117. O’shaughnessy WB (1843) On the cannabis indica or Indian hemp. Pharmacol J 2:594Google Scholar
  118. Orr LE, McKernan JF (1981) Antiemetic effect of delta-9-THC in chemotherapy-associated nausea and emesis as compared to placebo and compazine. JClin Pharmacol 21:76S–80SGoogle Scholar
  119. Panegyres PK (1992) The drug therapy of neurological disorders. In: Grahame-Smith DG, Aronson JK (eds) Oxford textbook of clinical pharmacology, 2nd edn. Oxford University Press, 441–442Google Scholar
  120. Parker LA, Mechoulam R, Schlievert C (2002) Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 13:567–570PubMedGoogle Scholar
  121. Patel S, Shua-Haim JR, Pass M (2003) Safety and efficacy of dronabinol in the treatment of agitation in patients with Alzheimer’s disease with anorexia: a retrospective chart review. International Psychogeriatric Association, Eleventh International CongressGoogle Scholar
  122. Penta JS, Poster DS, Bruno S, et al (1981) Clinical trials with anti-emetic agents in cancer patients receiving chemotherapy. J Clin Pharmacol 21:11S–22SPubMedGoogle Scholar
  123. Perez-Reyes M, Wagner D, Wall ME, et al (1976) Intravenous administration of cannabinoids and intraocular pressure. In: Braude MC, Szara S (eds) The pharmacology of marihuana. Raven Press, New York, pp 829–832Google Scholar
  124. Pertwee RG (2001) Cannabinoids and the gastrointestinal tract. Gut 48:859–867PubMedCrossRefGoogle Scholar
  125. Pertwee RG (2004) The pharmacology and therapeutic potential of cannabidiol. In: Di Marzo V (ed) Cannabinoids. Kluwer Academic/Plenum Publishers (http://www.eurekah.com/)Google Scholar
  126. Petro DJ (1980) Marihuana as a therapeutic agent for muscle spasm or spasticity. Psychosomatics 21:81–85CPubMedGoogle Scholar
  127. Petro DJ, Ellenberger C (1981) Treatment of human spasticity with delta-9-THC. J Clin Pharmacol 21:413S–416SPubMedGoogle Scholar
  128. Plasse TF, Gorter RW, Krasnow SH, et al (1991) Recent clinical experience with dronabinol. Pharmacol Biochem Behav 40:695–700PubMedCrossRefGoogle Scholar
  129. Pomeroy M, Fennelly JJ, Towers M (1986) Prospective randomised double-blind trial of nabilone versus domperidone in the treatment of cytotoxic-induced emesis. Cancer ChemoTher Pharmacol 17:285–288PubMedCrossRefGoogle Scholar
  130. Pope HG, Gruber AJ, Hudson JI, et al (2002) Cognitive measures in long-term cannabis users. J Clin Pharmacol 42:41–47SGoogle Scholar
  131. Portenoy RK (1990) Chronic opioid therapy in non-malignant pain. J Pain Symptom Manage 5(Suppl 1):46–62Google Scholar
  132. Porter J, Jick H (1980) Addiction rare in patients treated with narcotics (letter). N Engl J Med 302:123PubMedGoogle Scholar
  133. Prunte C, Orgul S, Flammer J (1998) Abnormalities of microcirculation in glaucoma: facts and hints. Curr Opin Ophthalmol 9:50–55PubMedGoogle Scholar
  134. Pryce G, Ahmed Z, Hankey DJR, et al (2003) Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126:2191–2202PubMedCrossRefGoogle Scholar
  135. Ravinet Trillou C, Arnone M, Delgorge C, et al (2002) Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. AmJ Physiol Regul Integr Comp Physiol 284:R345–R353Google Scholar
  136. Regelson W, Butler JR, Schulz J, et al (1976) Delta-9-THC as an effective antidepressant and appetite-stimulating agent in advanced cancer patients. In: Braude MC, Szara S (eds) The pharmacology of marijuana. Raven Press, New York, pp 763–776Google Scholar
  137. Regier DA, Farmer ME, Swift W, et al (1990) Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) study. J Am Med Assoc 264:2511–2518CrossRefGoogle Scholar
  138. Reynolds JR (1890) Therapeutic uses and toxic effects of cannabis indica. Lancet 1:637–638Google Scholar
  139. Robson P, Bruce M (1997) A comparison of’ visible’ and’ invisible’ users of amphetamine, cocaine and heroin: two distinct populations? Addiction 92:1729–1736PubMedCrossRefGoogle Scholar
  140. Robson P, Guy GW (2004) Clinical studies of cannabis based medicines. In: Guy G, Whittle B, Robson P (eds) The medicinal use of cannabis and cannabinoids. Pharmaceutical Press, LondonGoogle Scholar
  141. Robson PJ (1999) Drug policy— time for change? In: Forbidden drugs. Oxford University Press, Oxford, pp 239–259Google Scholar
  142. Russo E (2001) Hemp for headache: an in-depth historical and scientific review of cannabis in migraine treatment. J Cannabis Ther 1:21–92Google Scholar
  143. Russo E, Merzouki A, Mesa JM, Frey K (2003) Cannabis improves night vision: a pilot study of visual threshold and dark adaptometry in kif smokers in the Rif region of Northern Morocco. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 61Google Scholar
  144. Sandyk R, Awerbuch G (1988) Marijuana and Tourette’s syndrome. J Clin PsychoPharmacol 8:444–445PubMedGoogle Scholar
  145. Sharief MK, Notcutt WG, Mutiboko I, et al (2004) Sativex in the treatment of patients with chronic refractory pain due to MS or other defects of neurological function. Association of British Neurologists Spring Scientific Meeting, 14-16 April 2004, LondonGoogle Scholar
  146. Sidney S (2001) Marijuana use in HIV-positive and AIDS patients: results of an anonymous mail survey. J Cannabis Ther 1:35–43Google Scholar
  147. Sidney S, Beck JE, Tekawa IS, et al (1997) Marijuana use and mortality. Am J Public Health 87:585–590PubMedGoogle Scholar
  148. Sieradzan KA, Fox SH, Hill M, et al (2001) Cannabinoids reduce levodopa-induced dyskinesia in Parkinson2019;s disease: a pilot study. Neurology 57:2108–2111PubMedGoogle Scholar
  149. Solowij N (1998) Acute effects of cannabis on cognitive functioning In: Cannabis and cognitive functioning. Cambridge University Press, Cambridge, pp 29–38Google Scholar
  150. Solowij N, Stephens RS, Roffman RA, et al (2002) Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA 287:1123–1131PubMedCrossRefGoogle Scholar
  151. Sugiura T, Kodaka T, Nakane S (1998) Detection of anendogenous cannabimimetic molecule, 2-arachidonoylglycerol, and cannabinoid CB1 receptor mRNA in human vascular cells: Is 2-arachidonoylglycerol a possible vasomodulator? Biochem Biophys Res Commun 243:838–843PubMedCrossRefGoogle Scholar
  152. Svendsen KB, Jensen TS, Bach FW (2003) Dronabinol (delta-9-THC) alleviates pain in multiple sclerosis. Congress of the European Federation of IASP Chapters (EFIC), 2-6 September 2003, PragueGoogle Scholar
  153. Tashkin DP, Shapiro BJ, Frank IM (1974) Acute effects of smoked marihuana and oral delta-9-THC on specific airway conductance in asthmatic subjects. Am Rev Respir Dis 109:420–428PubMedGoogle Scholar
  154. Tashkin DP, Reiss S, Shapiro BJ, et al (1977) Bronchial effects of aerosolised delta-9-THC in healthy and asthmatic subjects. Am Rev Respir Dis 115:57–65PubMedGoogle Scholar
  155. Taylor PC (2001) Anti-TNF therapy for rheumatoid arthritis and other inflammatory diseases. Mol Biotechnol 19:153–168PubMedCrossRefGoogle Scholar
  156. Thomas H (1993) Psychiatric symptoms in cannabis users. Br J Psychiatry 163:141–149PubMedGoogle Scholar
  157. Thompson AJ, Baker D (2002) Cannabinoids in MS: potentially useful but not just yet? Editorial. Neurology 58:1323–1324PubMedGoogle Scholar
  158. UK Parliament Select Committee on Home Affairs (Third Report) (2002) The government’s drug policy: is itworking: different controls for different drugs; cannabis paragraph 108. HC318:1; ISBN 0-10-500334-9 http://www.publications.parliament.uk/pa/cm200102/cmselect/cmhaff/318/31807.htm a25. Cited 12 Oct 2004Google Scholar
  159. Ungerleider T, Andrysiak T, Fairbanks L, et al (1982) Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine. Cancer 50:636–645PubMedGoogle Scholar
  160. Vaney C, Jobin P, Tschopp F, Heinzel M, Schnelle M (2002) Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis. In: Symposium on the Cannabinoids; Asilomar Conference Center, Pacific Grove, CA: International Cannabinoid Research Society; 13 July 2002, p 57Google Scholar
  161. Venderova K, Ruzicka E, Vorisek V, Visnovsky P (2003) Cannabis and Parkinson’s disease: subjective improvement of symptoms and levodopa-induced dyskinesias. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 145Google Scholar
  162. Volicer L, Stelly M, Morris J, McLaughlin J, Volicer BJ (1997) Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 12:913–919PubMedGoogle Scholar
  163. Wade DT, Robson PJ, House H, et al (2003) A preliminary controlled study to determine whether whole-plant cannabis extracts can improve intractable neurogenic symptoms. Clin Rehabil 17:18–26Google Scholar
  164. Wade DT, Makela P, Robson P, et al (2004) Docannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomised, placebo-controlled study in 160 patients. Mult Scler 10:434–442PubMedCrossRefGoogle Scholar
  165. Wallace MJ, Blair RE, Falenski KW, et al (2003) The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 307:129–137PubMedCrossRefGoogle Scholar
  166. Ware MA, Adams H, Guy G (2003) The medicinal use of cannabis in the United Kingdom. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 139Google Scholar
  167. Whittle BA, Guy GW, Robson P (2001) Prospects for new cannabis-based prescription medicines. J Cannabis Ther 1:183–205Google Scholar
  168. Williams CM, Kirkham TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 143:315–317PubMedCrossRefGoogle Scholar
  169. Williams SJ, Hartley JPR, Graham JDP (1976) Bronchodilator effect of delta-9-THC administered by aerosol to asthmatic patients. Thorax 31:720–723PubMedCrossRefGoogle Scholar
  170. Wisbeck GA, Schuckit MA, Kalmijn JA (1996) An evaluation of the history of a marijuana withdrawal syndrome in a large population. Addiction 91:1469–1478Google Scholar
  171. Wright K, Rooney N, Tate J, et al (2003) Functional cannabinoid receptor expression in human colonic epithelium. International Cannabinoid Research Society 13th Annual Symposium on the Cannabinoids, abstr 25Google Scholar
  172. Young CA, Rog DJ (2003) Randomised controlled trial of cannabis based medicinal extracts (CBME) in central neuropathic pain due to multiple sclerosis. Congress of the European Federation of IASP Chapters (EFIC), 2-6 September 2003, PragueGoogle Scholar
  173. Young RR (1994) Spasticity: a review. Neurology 44:S12–S20PubMedGoogle Scholar
  174. Zajicek J, Fox P, Sanders H, et al (2003) Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 362:1517–1526PubMedCrossRefGoogle Scholar
  175. Zuardi AW, Guimaraes FS (1997) Cannabidiol as an anxiolytic and antipsychotic. In: Mathre ML (ed) Cannabis in medical practice: a legal, historical and pharmacological overview of the therapeutic use of marijuana. McFarland, Jefferson, pp 133–141Google Scholar
  176. Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG (1982) Action of cannabidiol on the anxiety and other effects produced by delta-9-THC in normal subjects. Psychopharmacology (Berl) 76:245–250PubMedCrossRefGoogle Scholar
  177. Zuardi AW, Rogdrigues JA, Cunha JM (1991) Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl) 104:260–264PubMedCrossRefGoogle Scholar
  178. Zuardi AW, Cosme RA, Graeff FG, Guimaraes FS (1993) Effects of ipsapirone and cannabidiol on human experimental anxiety. J PsychoPharmacol 7:82–88Google Scholar
  179. Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R (1995) Antipsychotic effect of cannabidiol. J Clin Psychiatry 56:485–486PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • P. Robson
    • 1
  1. 1.Department of PsychiatryOxford University, Warneford HospitalOxfordUK

Personalised recommendations