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Cannabinoids pp 719–756Cite as

Human Studies of Cannabinoids and Medicinal Cannabis

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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

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References

  • Abel EL (1980) Outlawing marihuana. In: Marihuana: the First twelve thousand years. Plenum Press, New York, pp 237–247

    Google Scholar 

  • Abrahamov A, Abrahamov A, Mechoulam R (1995) An efficient new cannabinoids antiemetic in pediatric oncology. Life Sci 56:2097–2102

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 139:258–266

    PubMed  CAS  Google Scholar 

  • Advisory Council on the Misuse of Drugs (2002) The classification of cannabis under the Misuse of Drugs Act 1971. Home Office, London

    Google Scholar 

  • Arseneault L, Cannon M, Witton J, et al (2004) Causal association between cannabis and psychosis: examination of the evidence. Br J Psychiatry 184:110–117

    PubMed  CrossRef  Google Scholar 

  • Ashworth B (1964) Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 192:540–542

    PubMed  CAS  Google Scholar 

  • Astley SJ, Little RE (1990) Maternal Maijuana use during lactation and infant development at one year. Neurotoxicol Teratol 12:161–168

    PubMed  CrossRef  CAS  Google Scholar 

  • Baker D, Pryce G, Croxford JL, et al (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404:84–87

    PubMed  CrossRef  CAS  Google Scholar 

  • Baker D, Pryce G, Croxford JL, et al (2001) Endocannabinoids control spasticity in a multiple sclerosis model. FASEB J 15:300–302

    PubMed  CAS  Google Scholar 

  • 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 10:89–97

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 14:7–14

    PubMed  CrossRef  CAS  Google Scholar 

  • Benowitz NL, Jones RT (1981) Cardiovascular and metabolic considerations in prolonged cannabinoid administration in man. J Clin Pharmacol 21:214–223S

    CAS  Google Scholar 

  • 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 56

    Google Scholar 

  • 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–89S

    PubMed  CAS  Google Scholar 

  • 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 34:446–452

    Google Scholar 

  • 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 133:586–594

    PubMed  CrossRef  CAS  Google Scholar 

  • Brotchie JM (2000) The neural mechanisms underlying levodopa-induced dyskinesia. Ann Neurol 47:105–114S

    Google Scholar 

  • Budney AJ, Moore BA, Vandrey RG, et al (2003) The time course and significance of cannabis withdrawal. J Abnorm Psychol 112:393–402

    PubMed  CrossRef  Google Scholar 

  • Buggy DJ, Toogood L, Maric S, et al (2003) Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. Pain 106:169–172

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 323:13–16

    CAS  Google Scholar 

  • 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, 505–515

    Google Scholar 

  • 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 79:946–952

    PubMed  CAS  Google Scholar 

  • 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 91:819–830

    PubMed  CAS  Google Scholar 

  • Chaperon F, Thiebot MH (1999) Behavioural effects of cannabinoid agents in animals. Crit Rev Neurobiol 13:243–281

    PubMed  CAS  Google Scholar 

  • Cichewicz DL, McCarthy EA (2003) Antinociceptive synergy between delta-9-tetrahydrocannabinol and opioids after oral administration. J Pharmacol Exp Ther 304:1010–1015

    PubMed  CAS  Google Scholar 

  • 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 305:812–817

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 40

    Google Scholar 

  • Clifford DB (1983) THC for tremor in multiple sclerosis. Ann Neurol 13:669–671

    PubMed  CrossRef  CAS  Google Scholar 

  • Consroe P, Snider SR (1986) Therapeutic potential of cannabinoids in neurological disorders. In: Mechoulam E (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, 21–49

    Google Scholar 

  • Consroe P, Sandyk R, Snider SR (1986) Open label evaluation of cannabidiol in dystonic movement disorders. Int J NeuroSci 30:277–282C

    PubMed  CAS  CrossRef  Google Scholar 

  • Consroe P, Laguna J, Allender J, et al (1991) Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav 40:701–708C

    PubMed  CAS  Google Scholar 

  • Consroe P, Musty R, Rein J, Tillery W, Pertwee RG (1997) The Perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol 38:44–48

    PubMed  CAS  Google Scholar 

  • Consroe PF, Wood GC, Buchsbaum H (1975) Anticonvulsant nature of marihuana smoking. J Am Med Assoc 234:306–307

    CrossRef  CAS  Google Scholar 

  • Cunha JM, Carlini EA, Pereira AE, et al (1980) Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21:175–185

    PubMed  CAS  Google Scholar 

  • Dahl V, Raeder JC (2000) Non-opioid postoperative analgesia. Acta Anaesthesiol Scand 44:1191–1203

    PubMed  CrossRef  CAS  Google Scholar 

  • Dalzell AM, Bartlett H, Lilleyman JS (1986) Nabilone: an alternative antiemetic for cancer chemotherapy. Arch Dis Child 61:502–505

    PubMed  CAS  Google Scholar 

  • Degenhardt L, Hall W (2002) Cannabis and psychosis. Curr Psychiatry Rep 4:191–196

    PubMed  Google Scholar 

  • Dunn M, Davis R (1974) The perceived effects of marijuana on spinal cord injured males. Paraplegia 12:175

    PubMed  CAS  Google Scholar 

  • Einhorn LH, Nagy C, Furnas B, et al (1981) Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol 21:64S–69S

    PubMed  CAS  Google Scholar 

  • Fabre LF, McLendon D (1981) The efficacy and safety of nabilone (a synthetic cannabinoid) in the treatment of anxiety. J Clin Pharmacol 21:377S–382S

    PubMed  CAS  Google Scholar 

  • Foltin RW, Fischman MW, Byrne MF (1986) Behavioural analysis of marijuana effects on food intake in humans. Pharmacol Biochem Behav 25:577–582

    PubMed  CrossRef  CAS  Google Scholar 

  • Formukong EA, Evans AT, Evans FJ (1989) The medicinal use of cannabis and its constituents. Phyto Ther Res 3:219–231

    CAS  Google Scholar 

  • 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 92:91–100

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 17:145–149

    PubMed  Google Scholar 

  • Georgotas A, Zeidenberg P (1979) Observations on the effects of heavy marijuana smoking on group interaction and individual behaviour. Compr Psychiatry 20:427–432

    PubMed  CrossRef  CAS  Google Scholar 

  • Gonzalez R, Carey C, Grant I (2002) Nonacute (residual) effects of cannabis use: a qualitative analysis and systematic review. J Clin Pharmacol 42:48–57S

    Google Scholar 

  • 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 9:679–689

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 55:324–328

    PubMed  CAS  CrossRef  Google Scholar 

  • Greenwald MK, Stitzer ML (2000) Antinociceptive, subjective and behavioural effects of smoked marijuana in humans. Drug Alcohol Depend 59:261–275

    PubMed  CAS  Google Scholar 

  • Grinspoon L, Bakalar JB (1993) The history of cannabis. In: Marihuana: the forbidden medicine. Yale University Press, New Haven, pp 1–23

    Google Scholar 

  • 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 30:171–177

    PubMed  CAS  Google Scholar 

  • 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, 389–395

    Google Scholar 

  • Guzmán M (2003) Cannabinoids: potential anticancer agents. Nat Rev Cancer 3:745–755

    PubMed  Google Scholar 

  • 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, 329–365

    Google Scholar 

  • 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 10

    Google Scholar 

  • Hall W, Solowij N, Lemon J (1994) The health and social consequences of cannabis use. Monograph series No. 25. Australian Government Publishing Service, Canberra

    Google Scholar 

  • Hampson A, Grimaldi M, Axelrod J, et al (1998) Cannabidiol and delta-9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci USA 95:8268–8273

    PubMed  CrossRef  CAS  Google Scholar 

  • Hanigan WC, Destree R, Truong XT (1985) The effect of delta-9-THC on human spasticity. Clin Pharmacol Ther 35:198

    Google Scholar 

  • Hemming M, Yellowlees PM (1993) Effective treatment of Tourette’s syndrome with marijuana. J Clin Pharmacol 7:389–391

    Google Scholar 

  • Hepler RS, Frank IM (1971) Marihuana smoking and intraocular pressure. JAMA 217:1392

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 815–824

    Google Scholar 

  • Herkenham M, Lynn AB, Little MD, et al (1990) Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA 87:1932–1936

    PubMed  CAS  Google Scholar 

  • Hinderer SR, Gupta S (1996) Functional outcome measures to assess interventions for spasticity. Arch Phys Med Rehabil 77:1083–1089

    PubMed  CrossRef  CAS  Google Scholar 

  • Hodges C (1992) Very alternative medicine. Spectator, 1 August 1992, p 18

    Google Scholar 

  • 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 308:446–453

    PubMed  CAS  Google Scholar 

  • Holdcroft A, Smith M, Jacklin A, et al (1997) Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia 5:483–486

    Google Scholar 

  • Hollister LE (1971) Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine. Clin Pharmacol Ther 12:44–49

    PubMed  CAS  Google Scholar 

  • House of Lords Select Committee on Science and Technology (1998) Ninth Report. London

    Google Scholar 

  • Ilaria RL, Thornby JI, Fann WE (1981) Nabilone, a cannabinoid derivative, in the treatment of anxiety neurosis. Curr Ther Res Clin Exp 29:943–949

    Google Scholar 

  • 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, 137–191

    Google Scholar 

  • Iversen L (2001) Few well controlled trials of cannabis exist for systematic review. Br Med J 323:1250

    CAS  Google Scholar 

  • Jain AK, Ryan JR, McMahon FG, Smith G (1981) Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. J Clin Pharmacol 21:320S–326S

    PubMed  CAS  Google Scholar 

  • Jarvinen T, Pate D, Laine K (2002) Cannabinoids in the treatment of glaucoma. Pharmacol Ther 95:203–220

    PubMed  CAS  Google Scholar 

  • Jatoi A, Windshitl HE, Loprinzi CL, et al (2002) Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia. J Clin Oncol 20:567–573

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 141

    Google Scholar 

  • Johns A (2001) Psychiatric effects of cannabis. Br J Psychiatry 178:116–122

    PubMed  CrossRef  CAS  Google Scholar 

  • Jones RT (2002) Cardiovascular system effects of marijuana. J Clin Pharmacol 42:58–63S

    Google Scholar 

  • Jones RT, Benowitz NL, Herning RL (1981) Clinical relevance of cannabis tolerance and dependence. J Clin Pharmacol 21:143S–152S

    PubMed  CAS  Google Scholar 

  • 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 9:45–48S

    PubMed  Google Scholar 

  • Karler R, Turkanis SA (1981) The cannabinoids as potential antiepileptics. J Clin Pharmacol 21:437S–448S

    PubMed  CAS  Google Scholar 

  • Karniol IG, Carlini EA (1973) Pharmacological interaction between cannabidiol and delta-9-THC. Psychopharmacologia 33:53–70

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 290:1757–1762

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 261:3424–3429

    PubMed  CrossRef  CAS  Google Scholar 

  • Keeler MH, Reifler CB (1967) Grand mal convulsions subsequent to marihuana smoking. Dis Nerv Syst 18:474–475

    Google Scholar 

  • Killestein J, Hoogervorst EL, Reif M, et al (2002) Safety, tolerability, and efficacy of orally administered cannabinoids in MS. Neurology 58:1404–1407

    PubMed  CAS  Google Scholar 

  • Kirkham TC (2003) Endogenous cannabinoids: a new target in the treatment of obesity. Am J Physiol Regul Integr Comp Physiol 284:R343–R344

    PubMed  CAS  Google Scholar 

  • Kirkham TC, Williams CM (2001) Endogenous cannabinoids and appetite. Nutr Res Rev 14:65–86

    CrossRef  CAS  PubMed  Google Scholar 

  • 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 30:548–554

    PubMed  CAS  Google Scholar 

  • Levitt M (1986) Cannabinoids as antiemetics in cancer chemotherapy. In: Mechoulam R (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, 71–83

    Google Scholar 

  • Leweke FM, Giuffrida A, Wurster U, et al (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10:1665–1669

    PubMed  CAS  Google Scholar 

  • Malec J, Harvey RF, Cayner JJ (1982) Cannabis effect on spasticity in spinal cord injury. Arch Phys Med Rehabil 63:116–118

    PubMed  CAS  Google Scholar 

  • 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 97:9561–9566

    PubMed  CrossRef  CAS  Google Scholar 

  • Marsicano G, Wotjak CT, Azad SC, et al (2002) Endogenous cannabinoid system controls extinction aversive memories. Nature 418:530–534

    PubMed  CrossRef  CAS  Google Scholar 

  • Martyn CN, Illis LS, Thom J (1995) Nabilone in the treatment of multiple sclerosis. Lancet 345:579

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 18:327–336

    CrossRef  Google Scholar 

  • 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 240:1–4

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 45

    Google Scholar 

  • McPartland J, Russo E (2001) Cannabis and cannabis extracts: greater than the sum of their parts? J Cannabis Ther 1:103–132

    CAS  Google Scholar 

  • 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, London

    Google Scholar 

  • Mechoulam R (1986) The pharmacohistory of cannabis sativa. In: Mechoulam R (ed) Cannabinoids as therapeutic agents. CRC Press, Boca Raton, pp 1–19

    Google Scholar 

  • Meinck HM, Schonle PW, Conrad B (1989) Effect of cannabinoids on spasticity and ataxia in multiple scleroris. J Neurol 236:120–122

    PubMed  CrossRef  CAS  Google Scholar 

  • Merritt JC, Crawford WJ, Alexander PC, et al (1980) Effect of marihuana on intraocular and blood pressure in glaucoma. Ophthalmology 87:222–228

    PubMed  CAS  Google Scholar 

  • Merritt JC, Olsen JL, Armstrong PC, et al (1981) Topical delta-9-THC in hypertensive glaucomas. J Pharm Pharmacol 33:40–41

    PubMed  CAS  Google Scholar 

  • Metz L, Page S (2003) Oral cannabinoids for spasticity in multiple sclerosis: will attitude continue to limit use? (editorial). Lancet 362:1513

    PubMed  CrossRef  Google Scholar 

  • Mittleman MA, Lewis RA, Maclure M, et al (2001) Triggering myocardial infarction by marijuana. Circulation 103:2805–2809

    PubMed  CAS  Google Scholar 

  • Muller-Vahl K, Schneider U, Kolbe H, et al (1999) Treatment of Tourette’s syndrome with delta-9-tetrahydrocannabinol. Am J Psychiatry 156:495

    PubMed  CAS  Google Scholar 

  • 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 64:459–465

    PubMed  CrossRef  Google Scholar 

  • 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.pdf

    Google Scholar 

  • 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 10:14–18

    PubMed  CAS  Google Scholar 

  • 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 

  • 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 64:362–365

    PubMed  CAS  Google Scholar 

  • Niiranen A, Mattson K (1985) A cross-over comparison of nabilone and prochlorperazine for emesis induced by cancer chemotherapy. Am J Clin Oncol 8:336–340

    PubMed  CAS  Google Scholar 

  • Notcutt W, Price M, Chapman G (1997) Clinical experience with nabilone for chronic pain. Pharm Sci 3:551–555

    CAS  Google Scholar 

  • 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 55

    Google Scholar 

  • Noyes R, Brunk SF, Baram DA, Canter A (1975a) Analgesic effects of delta-9-THC. J Clin Pharmacol 15:139–143

    PubMed  Google Scholar 

  • Noyes R, Brunk SF, Avery DH, Canter A (1975b) The analgesic properties of delta-9-THC and codeine. Clin Pharmacol Ther 18:84–89

    PubMed  Google Scholar 

  • O’shaughnessy WB (1843) On the cannabis indica or Indian hemp. Pharmacol J 2:594

    Google Scholar 

  • 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–80S

    CAS  Google Scholar 

  • 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, 441–442

    Google Scholar 

  • 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 13:567–570

    PubMed  CAS  Google Scholar 

  • 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 Congress

    Google Scholar 

  • 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–22S

    PubMed  CAS  Google Scholar 

  • 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 829–832

    Google Scholar 

  • Pertwee RG (2001) Cannabinoids and the gastrointestinal tract. Gut 48:859–867

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 

  • Petro DJ (1980) Marihuana as a therapeutic agent for muscle spasm or spasticity. Psychosomatics 21:81–85C

    PubMed  CAS  Google Scholar 

  • Petro DJ, Ellenberger C (1981) Treatment of human spasticity with delta-9-THC. J Clin Pharmacol 21:413S–416S

    PubMed  CAS  Google Scholar 

  • Plasse TF, Gorter RW, Krasnow SH, et al (1991) Recent clinical experience with dronabinol. Pharmacol Biochem Behav 40:695–700

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 17:285–288

    PubMed  CrossRef  CAS  Google Scholar 

  • Pope HG, Gruber AJ, Hudson JI, et al (2002) Cognitive measures in long-term cannabis users. J Clin Pharmacol 42:41–47S

    Google Scholar 

  • Portenoy RK (1990) Chronic opioid therapy in non-malignant pain. J Pain Symptom Manage 5(Suppl 1):46–62

    Google Scholar 

  • Porter J, Jick H (1980) Addiction rare in patients treated with narcotics (letter). N Engl J Med 302:123

    PubMed  CAS  Google Scholar 

  • Prunte C, Orgul S, Flammer J (1998) Abnormalities of microcirculation in glaucoma: facts and hints. Curr Opin Ophthalmol 9:50–55

    PubMed  CAS  Google Scholar 

  • Pryce G, Ahmed Z, Hankey DJR, et al (2003) Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126:2191–2202

    PubMed  CrossRef  Google Scholar 

  • 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–R353

    Google Scholar 

  • 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 763–776

    Google Scholar 

  • 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 264:2511–2518

    CrossRef  CAS  Google Scholar 

  • Reynolds JR (1890) Therapeutic uses and toxic effects of cannabis indica. Lancet 1:637–638

    Google Scholar 

  • Robson P, Bruce M (1997) A comparison of’ visible’ and’ invisible’ users of amphetamine, cocaine and heroin: two distinct populations? Addiction 92:1729–1736

    PubMed  CrossRef  CAS  Google Scholar 

  • 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, London

    Google Scholar 

  • Robson PJ (1999) Drug policy— time for change? In: Forbidden drugs. Oxford University Press, Oxford, pp 239–259

    Google Scholar 

  • Russo E (2001) Hemp for headache: an in-depth historical and scientific review of cannabis in migraine treatment. J Cannabis Ther 1:21–92

    Google Scholar 

  • 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 61

    Google Scholar 

  • Sandyk R, Awerbuch G (1988) Marijuana and Tourette’s syndrome. J Clin PsychoPharmacol 8:444–445

    PubMed  CAS  Google Scholar 

  • 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, London

    Google Scholar 

  • Sidney S (2001) Marijuana use in HIV-positive and AIDS patients: results of an anonymous mail survey. J Cannabis Ther 1:35–43

    Google Scholar 

  • Sidney S, Beck JE, Tekawa IS, et al (1997) Marijuana use and mortality. Am J Public Health 87:585–590

    PubMed  CAS  Google Scholar 

  • Sieradzan KA, Fox SH, Hill M, et al (2001) Cannabinoids reduce levodopa-induced dyskinesia in Parkinson2019;s disease: a pilot study. Neurology 57:2108–2111

    PubMed  CAS  Google Scholar 

  • Solowij N (1998) Acute effects of cannabis on cognitive functioning In: Cannabis and cognitive functioning. Cambridge University Press, Cambridge, pp 29–38

    Google Scholar 

  • Solowij N, Stephens RS, Roffman RA, et al (2002) Cognitive functioning of long-term heavy cannabis users seeking treatment. JAMA 287:1123–1131

    PubMed  CrossRef  Google Scholar 

  • 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 243:838–843

    PubMed  CrossRef  CAS  Google Scholar 

  • 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, Prague

    Google Scholar 

  • 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 109:420–428

    PubMed  CAS  Google Scholar 

  • 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 115:57–65

    PubMed  CAS  Google Scholar 

  • Taylor PC (2001) Anti-TNF therapy for rheumatoid arthritis and other inflammatory diseases. Mol Biotechnol 19:153–168

    PubMed  CrossRef  CAS  Google Scholar 

  • Thomas H (1993) Psychiatric symptoms in cannabis users. Br J Psychiatry 163:141–149

    PubMed  CAS  Google Scholar 

  • Thompson AJ, Baker D (2002) Cannabinoids in MS: potentially useful but not just yet? Editorial. Neurology 58:1323–1324

    PubMed  Google Scholar 

  • 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 2004

    Google Scholar 

  • Ungerleider T, Andrysiak T, Fairbanks L, et al (1982) Cannabis and cancer chemotherapy: a comparison of oral delta-9-THC and prochlorperazine. Cancer 50:636–645

    PubMed  CAS  Google Scholar 

  • 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 57

    Google Scholar 

  • 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 145

    Google Scholar 

  • 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 12:913–919

    PubMed  CAS  Google Scholar 

  • 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 17:18–26

    Google Scholar 

  • 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 10:434–442

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 307:129–137

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 139

    Google Scholar 

  • Whittle BA, Guy GW, Robson P (2001) Prospects for new cannabis-based prescription medicines. J Cannabis Ther 1:183–205

    CAS  Google Scholar 

  • Williams CM, Kirkham TC (1999) Anandamide induces overeating: mediation by central cannabinoid (CB1) receptors. Psychopharmacology (Berl) 143:315–317

    PubMed  CrossRef  CAS  Google Scholar 

  • Williams SJ, Hartley JPR, Graham JDP (1976) Bronchodilator effect of delta-9-THC administered by aerosol to asthmatic patients. Thorax 31:720–723

    PubMed  CAS  CrossRef  Google Scholar 

  • Wisbeck GA, Schuckit MA, Kalmijn JA (1996) An evaluation of the history of a marijuana withdrawal syndrome in a large population. Addiction 91:1469–1478

    Google Scholar 

  • 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 25

    Google Scholar 

  • 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, Prague

    Google Scholar 

  • Young RR (1994) Spasticity: a review. Neurology 44:S12–S20

    PubMed  CAS  Google Scholar 

  • 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 362:1517–1526

    PubMed  CrossRef  CAS  Google Scholar 

  • 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 133–141

    Google Scholar 

  • 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) 76:245–250

    PubMed  CrossRef  CAS  Google Scholar 

  • Zuardi AW, Rogdrigues JA, Cunha JM (1991) Effects of cannabidiol in animal models predictive of antipsychotic activity. Psychopharmacology (Berl) 104:260–264

    PubMed  CrossRef  CAS  Google Scholar 

  • Zuardi AW, Cosme RA, Graeff FG, Guimaraes FS (1993) Effects of ipsapirone and cannabidiol on human experimental anxiety. J PsychoPharmacol 7:82–88

    CAS  Google Scholar 

  • Zuardi AW, Morais SL, Guimaraes FS, Mechoulam R (1995) Antipsychotic effect of cannabidiol. J Clin Psychiatry 56:485–486

    PubMed  CAS  Google Scholar 

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Robson, P. (2005). Human Studies of Cannabinoids and Medicinal Cannabis. In: Pertwee, R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26573-2_25

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