THE MEDICAL VALUE
OF MARIJUANA AND RELATED SUBSTANCES
Chapter 4 - Continued
Table 4.1. Studies on the Effects of Marijuana and Cannabinoids in Multiple Sclerosis
Drug and Dose | Study Design |
Results |
Reference |
Marijuana | Mail survey 112/233 MS patients | Survey was mailed to 233 MS patients, of whom 112 (48 %) responded. 97% of respondents reported improved spasticity and reduced pain. | Consroe and coworkers, 1997 |
Marijuana | Clinical trial 1 MS patient | Reduction in spasticity and improved ataxia | Meinck, 1989 |
Marijuana | Double-blind, placebo-controlled 10 MS patients; 10 normal individuals | MS patients felt they were improved, but posture and balance were impaired. | Greenberg, 1994 |
Oral THC 5-15 mg 6 hourly, up to 18 hours | Open trial 8 MS patients |
5 patients experienced subjective, but not objective improvement in motor coordination; objective improvement in tremor demonstrated in 2 of the 8 patients. | Clifford, 1983 |
Oral THC 5 and 10 mg, single doses |
Double-blind, placebo controlled 9 MS patients | Spasticity was improved based on examiner ratings | Petro and Ellenberger, 1981 |
Oral THC 2.5 - 15 mg, once or twice daily for 5 days |
Double-blind, placebo controlled, crossover 13 MS patients |
Patients reported subjective decreases in spasticity at doses of 7.5 mg or greater, but no changes in objective measures of spasticity or weakness were observed. |
Ungerleider, 1987 |
Nabilone (THC analogue) | Placebo controlled 1 MS patient |
The patient reported increased well-being; less frequent nocturia, and reduced severity of muscle spasticity during nabilone treatment (Figure 4.2). | Martyn, 1995 |
4.27
Spinal Cord Injury
In 1990 there were approximately 15 million patients worldwide with spinal cord injury, and an estimated 10,000 new cases are reported each year in the United States alone.136 140 Approximately 60 percent of these injuries are to those younger than 35 years. Most of these patients will need long-term, and some life-long care.118
Therapy for Muscle Spasticity
Present Therapy
Present therapy for spasticity includes the various medications listed in table 4.2 below.
TABLE 4.2 Classes of Anti-spasticity Drugs
Drug Class | Drug |
GABAB receptor agonists | baclofen |
a-receptor agonists | tizanidine |
non-competitive GABAA receptor agonists | benzodiazepines, including diazepam |
calcium blockers in skeletal muscle | dantrolene |
4.28
Future Therapy
Conclusion
4.29
Movement Disorders
Dystonia
No controlled study of marijuana in patients with dystonia has been published, and the only study on cannabinoids was a preliminary open trial using cannabidiol which suggested modest dose-related improvements in the five dystonic patients studied.31 In mutant dystonic hamsters, however, the cannabinoid receptor agonist, WIN 55,212-2, can produce antidystonic effects.155
Huntington's Disease
h Spasmodic torticollis is defined by contractions of the neck and shoulder muscles, producing recurrent head turning, head extensions and, in some cases, shoulder elevations.
4.30
over study on 15 Huntington's disease patients who were not taking any neuroleptic drugs. The symptoms neither improved nor worsened with CBD treatment.28 167
Parkinson's Disease
Tourette's Syndrome
4.31
Therapy for Movement Disorders
i Dyskinesia is the development of irreversible, involuntary dyskinetic movements.
4.32
TABLE 4.3 Drugs Used to Treat Movement Disorders
___________________________________________
Huntington's chorea Parkinson's disease reserpine levodopa/carbidopacombinatior j tetrabenazine amantadine haloperidol bromocriptine pergolide pramipexole ropinirole selegiline Dystonia trihexyphenidyl benzodiazepines benztropine tetrabenazine intramuscular botulinum toxin anticholinergics Tourette 's Syndrome Tics baclofen pimozide clonidine haloperidol
___________________________________________
Summary
Compared to the abundance of anecdotal reports concerning the beneficial effects of marijuana on muscle spasticity, there are relatively few claims that marijuana is useful for treating movement disorders. This might reflect a lack of effect or a lack of individuals with movement disorders who have tried marijuana. In any case, while there are a few isolated reports of individuals with movement disorders who report a benefit from marijuana, there are, as yet, no published surveys indicating that a substantial percent of patients with movement disorders find relief from marijuana. Existing studies involve too few patients from which to draw conclusions. The most promising reports involve symptomatic treatment of spasticity. If the reported neuroprotective effects of cannabinoids discussed in chapter 2 prove to be therapeutically useful, this could benefit patients with
j Tablet contains both drugs = combination therapy.
4.33
movement disorders - although, at this point, such is highly speculative. Since stress often transiently exacerbates movement disorders, it is reasonable to hypothesize that the anxiolytic effects of marijuana or cannabinoids might be beneficial to some patients with movement disorders. However, chronic marijuana smoking is a health risk that could increase the burden of chronic conditions such as movement disorders.
Epilepsy
4.34
Cannabinoids in Epilepsy
4.35
Table 4.4 Clinical Trials of Cannabidiol in Epileptics
Study Design | Results | Reference |
Double-blind placebo-controlled trial - 8 epileptic patients were given 200-300 mg CBD/day in conjunction with standard antiepileptic therapies. | Four out of 8 remained almost free of convulsions. Three of the 4 were partially improved for up to 4.5 months. | Cunha et al35 |
Double-blind placebo-controlled study - 12 epileptic patients were given 200-300 mg CBD/day along with standard antiepileptic drugs | CBD had no effect on seizure frequency. | Ames4 |
Double-blind placebo-controlled, add-on cross-over trial - 10 epileptic
patients were given 300mg. CBD/day for 6 months. Open trial |
CBD had no effect on seizures. Seizure frequency was reduced in the patient. |
Trembly et al.188 (reviewed in Consroe, 199230) |
Therapy for Epilepsy
Present Therapy
4.36
TABLE 4.5 Anticonvulsant Drugs for Various Types of Seizures5
____________________________________________________
Generalized grand mal Partial (focal) carbamazepine carbamazepine valproate phenytoin phenytoin valproate phenobarbital phenobarbital clonazepam Generalized petit mal gabapentin ethosuximide lamotrigine clonazepam tiagabine (as adjunct valproate therapy) ____________________________________________________
Future Therapy
Alzheimer's Disease
4.37
of each treatment). The dronabinol treatment resulted in significant weight gains and declines in disturbed behavior.194 No serious side effects were observed. One patient had a seizure and was removed from the study, but it is not clear that this was due to the dronabinol. Recurrent seizures develop without any precipitating events in 20 percent of patients with advanced dementia of the Alzheimer's type.193 Nevertheless, these results are encouraging enough to recommend further clinical research with cannabinoids.
Glaucoma
k The cornea and lens of an eye must be optically clear, which means there cannot be blood circulation in these tissues. The aqueous humor is a clear fluid that functions as alternative circulation across the rear of the cornea and to the lens to provide nutrients and remove waste from these tissues.
4.38
consequent blindness.72 Because elevated IOP is the only known major risk factor that can be controlled, most treatments have been designed to reduce IOP. Unfortunately, reducing IOP does not always arrest or slow the progression of visual loss.21, 113
Marijuana and Cannabinoids in Glaucoma
4.39
pressure reduced to manageable and acceptable levels through medication, but this does not seem to affect IOP. In contrast, there is evidence that reduction in blood pressure below normal levels (considerably below) will influence IOP, and particularly ocular blood flow.48 78, 144 Hence' an eye with elevated IOP, or an optic nerve in poor condition with susceptibility to increased IOP, reduced blood flow to the optic nerve could compromise a functional retina and be a factor in the progression of glaucoma.
Therapy for Glaucoma
Present Therapy
TABLE 4.6 Classes of Glaucoma Drugs
_______________________________________________________
Cholinergic Agonists Carbonic Anhydrase Inhibitors pilocarpine acetazolamide dorzolamide (TrusoptŪ) B2- Adrenergic Agonists epinephrine Prostaglandin-F2a Analogs dipivefrin latanoprost unoprostone B2-Adrenergic Antagonists timolol betaxolol (Betoptic(R) a2-Adrenergic Agonists aproclonidine brimonidine
_____________________________________________________
4.40
Summary
4.41
Summary
4.42
assessment of the scientific data on the medical value of marijuana and its constituent cannabinoids is but one component of attaining that balance.
CONCLUSION: Scientific data indicate the potential therapeutic value of cannabinoid drugs, primarily THC, for pain relief, control of nausea and vomiting, and appetite stimulation; smoked marijuana, however, is a crude THC delivery system that also delivers harmful substances.
RECOMMENDATION: Clinical trials of cannabinoid drugs for symptom management should be conducted with the goal of developing rapid onset reliable, and safe delivery systems.
RECOMMENDATION: Clinical trials of marijuana use for medical purposes should be conducted under the following limited circumstances: trials should be approved by institutional review boards; involve only short-term marijuana use (less than 6 months); be conducted in patients with conditions for which there is reasonable expectation of efficacy; and collect data about efficacy.
4.43
RECOMMENDATION: Short-term use of smoked marijuana (less than six months) for patients with debilitating symptoms (such as intractable pain or vomiting) must meet the following conditions:
* failure of all approved medications to provide relief has been documented;
* the symptoms can reasonably be expected to be relieved by rapid-onset cannabinoid drugs;
* such treatment is administered under medical supervision in a manner that allows for assessment of treatment effectiveness;
* and involves an oversight strategy comparable to an institutional review board process that could provide guidance within 24 hours of a submission by a physician to provide marijuana to a patient for a specified use.
Other Reports on Marijuana as Medicine
4.44
4.45
References
1. Alm A, Camras CB1 Watson PG. 1997. Phase III latanoprost studies in Scandinavia, the United Kingdom and the United States. Survey of Ophthalmology 41 Suppl 2:S105-S110.
2. Alward WL. 1998. Medical management of glaucoma. The New England Journal Of Medicine 339:1298-1307.
3. AMA (American Medical Association Council on Scientific Affairs). 1997. Report to the AMA House Of Delegates. AMA.
4. Ames FR. 1986. Anticonvulsant effect of cannabidiol. South African Medical Journal 69:14.
5. Andreoli TE, Carpenter CC, Bennet CJ, Plum F. Editors. 1997. Cecil Essentials of Medicine. Fourth Edition. Philadelphia: W.B. Saunders Co.
6. Andrews PL, Davis CJ. 1995. The physiology of emesis induced by anti-cancer therapy. In: Reynolds DJ, Andrews PL, Davis CJ, Editors Serotonin and the scientific basis of anti-emetic therapy. Oxford; Oxford Clinical Communications. Pp. 2549.
7. Bankes JL, Perkins ES, Tsolakis S. Wright JE. 1968. Bedford glaucoma survey. British Medical Journal 1(595):791-796.
8. Bayer R O'Connell TJ, Lapey JD. 1997. Medicinal Uses of Marijuana (To the Editor). Annals of Internal Medicine 127: 1134-1135.
9. Beal JE, Olson RLL, Morales JO, Bellman P. Yangco B. Lefkowitz L, Plasse TF, Shepard KV. 1995. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. Journal of Pain and Symptom Management 10:89-97.
10. Beal JE, Olson R. Lefkowitz L, Laubenstein L, Bellman P. Yangco B. Morales JO, Murphy R. Powderly W. Plasse TF, Mosdell KW, Shepard KV. 1997. Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia. Journal of Pain and Symptom Management 14:7-14.
11. Bhasin S. Storer T W. Asbel-Sethi N. Kilbourne A, Hays R. Sinha-Hikim I, Shen R. Arver S. Beall G. 1998. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. Journal Clinical of Endocrinology and Metabolism 83:3155-62.
12. Billingsley KG, Alexander HR. 1996. The pathophysiology of cachexia in advanced cancer and AIDS. In: Bruera E, Higginson I, Editors Cachexia-Anorexia in Cancer Patients. New York: Oxford University Press In. Pp. 1-22.
13. Borison HL, McCarthy LE. 1983. Neuropharmacology of chemotherapy-induced emesis. Drugs 25:8-17.
14. British Medical Association. 1997. Therapeutic uses of cannabis. Amsterdam, The Netherlands: Harwood Academic Publishers.
4.46
15. Bruera E. 1998. Pharmacological treatment of cachexia: any progress? Supportive Care of Cancer 6-109-1 13.
16. Calignano A, La Rana C, Giuffrida A. Piomelli D. 1998. Control of pain initiation by endogenous cannabinoids. Nature 394:277-281.
17. Camras CB, Alm A, Watson P. Stjernschantz J. 1996. Latanoprost, a prostaglandin analog, for glaucoma therapy: Efficacy and safety after I year of treatment in 198 patients. Latanoprost Study Groups. Ophthalmology 103:1916-1924.
18. (CDC) Centers for Disease Control. 1992. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR (Morbidity Mortality Weekly Report) 41 :(RR- 17): 1 - 19 .
19. Chang AK, Shiling DJ, Stillman RC, et al. 1979. Delta-9-tetrahydrocannabinol as an Antiemetic in patients receiving high-dose methotrexate: A prospective, randomized evaluation. Annals of Internal Medicine 91:819-824.
20. Chang AK, Shiling DJ, Stillman RC, Goldberg NH, Seipp CA, Barofsky I, Rosenberg SA. 1981. A prospective evaluation of delta-9-tetrahydrocannabinol as an antiemetic in patients receiving adriamycin and cytoxan chemotherapy. Cancer 47:1746-51.
21. Chanhan BC, Drance SM. 1992. The relationship between intraocular pressure and visual field progression in glaucoma. Graefes Archives of Clinical and Experimental Ophthalmology 230:521-526.
22. Clark RA, Tyson LB, Frisone M. 1985. A correlation of objective and subjective parameters in assessing antiemetic regimens. Proceedings of the Tenth Anniversary Congress of the Oncology Nursing Society 2:96.
23. Clark WC, Janal MN, Zeidenberg P. Nahas GG. 1981. Effects of moderate and high doses of marihuana on thermal pain: a sensory decision theory analysis. Journal of Clinical Pharmacology 21:299S-310S.
24. Clarke RC. 1995. Marijuana Botany An Advanced Study: The Propagation and Breeding of Distinctive Cannabis. Berkeley, CA: Ronin Publishing.
25. Clifford DB. 1983. Tetrahydrocannabinol for tremor in multiple sclerosis. Annals of Neurology 13:669-671.
26. Consroe P. l 998a. Clinical and Experimental Reports of Marijuana and Cannabinoids in Spastic Disorders.
27. Consroe P. 1998b. Brain cannabinoid systems as target for the treatment of neurological disorders. Neurobiology of Disease 5
28. Consroe P. Laguna J. Allender J. Snider S. Stern L, Sandyk R. Kennedy K, Schram K. 1991. Controlled clinical trial of cannabidiol in Huntington's disease. Pharmacology, Biochemistry and Behavior (New York) 40:701-708.
29. Consroe P. Musty R. Rein J. Tillery W. Pertwee RG. 1997. The perceived effects of smoked cannabis on patients with multiple sclerosis. European Neurology 38:44-48.
4.47
30. Consroe P. Sandyk R. 1992. Potential role of cannabinoids for therapy of neurological disorders. In: Bartke A, Murphy LL, Editors Marijuana/Cannabinoids: Neurobiology and Neurophysiology. Boca Raton: CRC Press Inc. Pp. 459-524.
31. Consroe P. Sandyk R. Snider SR. 1986. Open label evaluation of cannabidiol in dystonic movement disorders. International Journal of Neuroscience 30:277-282.
32. Cooler P. Gregg JM. 1977. Effect of delta-9-tetrahydrocannabinol on intraocular pressure in humans. Southern Medical Journal 70:951 -954.
33. Crawford WJ, Merritt JC. 1979. Effects of Tetrahydrocannabinol on arterial and intraocular hypertension. International Journal of Clinical Pharmacology and Biopharmacy 17:191-196.
34. Crow S. 1997. Investigational drugs for eating disorders. Expert Opinion on Investigational Drugs 6:427-436.
35. Cunha JM, Carlini EA, Pereira AK, Ramos OL, Pimentel C, Gagliardi R. Sanvito WL, Lander N. Mechoulam R. 1980. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 21: 175- 185.
36. Davis CJ. 1995. Emesis research: A concise history of the critical concepts and experiments. In: Reynolds DJ' Andrews PL, Davis CJ, Editors. Serotonin and the scientific basis of anti-emetic therapy. Oxford: Oxford Clinical Communications. Pp. 9-24.
37. DeLong M R. Georgopoulos A P. Crutcher M D, Mitchell S J. Richardson R T. Alexander G E. 1984. Functional organization of the basal ganglia: contributions of single-cell recording studies. CIBA Foundation Symposium 107:64-82.
38. DeMulder PH, Seynaeve C, Vermorker JB, et al. 1990. Ondansetron compared with highdose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting: A multicenter, randomized, double-blind, crossover study. Annals of Internal Medicine 113:834-840.
39. Doblin R. Kleiman MA. 1995. The medical use of marijuana: the case for clinical trials [editorial; comment]. Journal of Addictive Diseases 14:5-14. Comment on J Addict Dis 1994;13(1):53-65.
40. Doblin R. Kleiman M. 1991. Marijuana as Antiemetic Medicine: A Survey of Oncologists' Experiences and Attitudes. Journal of Clinical Oncology 9:1314-1319.
41. Dunlop R. 1996. Clinical epidemiology of cancer cachexia. In: Bruera E, Higginson I, Editors Cachexia-anorexia in cancer patients. 5. Oxford: Oxford University Press. Pp. 76-82.
42. Dunn M, Davis R. 1974. The perceived effects of marijuana on spinal cord injured males. Paraplegia 12:175.
43. Eidelberg D., Moeller JR, Antonini A., Kazumata K, Dhawan V, Budman C, Feigin A. 1997. The metabolic anatomy of Tourette's syndrome. Neurology 48:927-934.
44. El-Mallakh RS. 1987. Marijuana and migraine. Headache 27:442-443.
4.48
45. Endicott JN, Skipper P. Hernandez L. 1993. Marijuana and head and neck cancer. In: Friedman et al, Editors Drugs of Abuse, Immunity and AIDS. New York: Plenum Press. Pp. 107- 113.
46. Engelson E S. Rabkin J G. Rabkin R. Kotler D P. I 996. Effects of testosterone upon body composition.. Journal of Acquired immune Deficiency Syndrome and Human Retrovirology 11:510-511.
47. Enoch M, Kaye WH, Rotondo A, Greenberg BD, Murphy DL, Goldman D. 1998. 5-HT2A promoter polymorphism-1438G/A, anorexia nervosa, and obsessive-compulsive disorder. The Lancet 351: 1785-1786.
48. Follmann P. Paltotas C, Suveges 1, Petrovits A. 1996-1997. Nocturnal blood pressure and intraocular pressure measurement in glaucoma patients and healthy controls International Ophthalmology 20:83-87.
49. Foltin R W. Fischman M W. Byrne M F. 1988. Effects of smoked marijuana on food intake and body weight of humans living in a residential laboratory. Appetite 11 :1-14.
50. Fozard JR. 1984. Neuronal 5-HT receptors in the periphery. Neuropharmacology 23: 14731486.
51. Frankel JP, Hughes A, Lees AT, Stern GM. 1990. Marijuana for Parkinsonian Tremor. Journal of Neurology, Neurosurgery and Psychiatry 53:436.
52. French ED. 1997. Delta-9-tetrahydrocannabinol excites rat VTA dopamine neurons through activation of cannabinoid CB1 but not opioid receptors. Neuroscience Letters 226: 159-162.
53. French J. 1998. The art of antiepileptic trial design. Advances in Neurology 76:113- 123.
54. Frytak S. Moertel CG, O'Fallon J. et al. 1979. Delta-9-tetrahydrocannabinol as an antiemetic in patients treated with cancer chemotherapy: a double comparison with prochloperazine and a placebo. Annals of Internal Medicine 91 :825-830.
55. Glass M, Dragunow M, Faull RLM. 1997. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77:299-318.
56. Goadsby PJ, Gundlach AL. 1991. Localization of [3H]-dihydroergotamine binding sites in the cat central nervous system: Relevance to migraine. Annals of Neurology 29:91-, 94.
57 Gonzalez EC, Brownlee HJ. 1998. Movement disorders. In: Taylor RB, Editor Family Medicine: Principles and Practice. 5th Edition. New York: Springer-Verlag. Pp. 565-573.
58. Gorter R. 1991. Management of anorexia-cachexia associated with cancer and HIV infection. Oncology (Supplement) 5: 13-17.
59. Gralla RJ, Itri LM, Pisko SE, et al. 1981. Antiemetic efficacy of high dose metoclopramide: randomized trials with placebo and prochlorperazine in patients with chemotherapy induced nausea vomiting. New England Journal of Medicine 305:905-909.
4.49
60. Gralla RJ, Navari RM, Hesketh PJ, et al. 1998. Single-dose oral granisetron has equivalent antiemetic efficacy to intravenous ondansetron for highly emetogenic cisplatin based chemotherapy. Journal of Clinical Oncology 16:1-7.
61. Gralla RJ, Rittenberg CN, Lettow LA, et al. 1995. A unique all-oral, single-dose, combination antiemetic regimen with high efficacy and marked cost saving potential. Proceedings of the American Society for Clinical Oncology 14:526.
62 Gralla RJ, Tyson LB, Borden LB, et al. 1984. Antiemetic therapy a review of recent studies and a report of a random assignment trial comparing metoclopramide with delta-9-tetrahydrocannabinol. Cancer Treatment Reports 68:163-172.
63. Grandara DR, Roila F. Warr D, Edelman MJ, Perez EA, Gralla RJ. 1998 Consensus proposal for 5HT3 antagonists in the prevention of acute emesis related to highly emetogenic chemotherapy. Dose, schedule, and route of administration. Supportive Care in Cancer 6:237-243.
64. Green K, Roth M. 1982. Ocular effects of topical administration of delta-9- Tetrahydrocannabinol in man. Archives of Ophthalmology 100:265-267.
65. Greenberg HS, Werness SA, Pugh JE, Andrus RO, Anderson DJ, Domino EF. 1994. Short term effects of smoking marijuana on balance in patients with multiple sclerosis and normal volunteers. Clinical Pharmacology and Therapeutics 55:324-328.
66. Grinspoon L, Bakalar JB. 1993. Marijuana, the forbidden medicine. New Haven: Yale University Press.
67. Grinspoon L, Bakalar JB, Zimmer L, Morgan JP. 1997. Marijuana addiction [letter]. Science 277:749; discussion 750-2.
68. Grinspoon S. Corcoran C, Askari H. Schoenfeld D, Wolf L, Burrows B. Walsh M, Hayden D, Parlman K, Anderson E, Basgoz N. Klibanski A. 1998. Effects of androgen administration in men with the AIDS wasting syndrome. Annals of Internal Medicine 129:18-26.
69. Gross H. Egbert MH, Faden VB, Godberg SC, Kaye WH, Caine ED, Hawks R. Zinberg NE. 1983. A double-blind trial of delta-9-THC in primary anorexia nervosa. Journal of Clinical Psychopharmacology 3:165-171.
70. Guyatt GH, Keller JL, Jaeschke R. Rosenbloom D, Adachi ID, Newhouse MT. 1990. The N-of--1 randomized controlled trial - clinical usefulness: our three-year experience. Annals of internal Medicine 112:293-299.
71. Guyatt GH, Sackett D, Taylor DW, Chong J. Roberts R. Pugsley S. 1986. Determining optimal therapy: randomized trials in individual patients. New England Journal of Medicine 314:889-892.
72. Guyton AC. 1986. Textbook of Medical Physiology. Seventh Edition. Philadelphia: WB Saunders Company.
73. Hall W. 1997. An Ongoing Debate. Science 278:75.
74. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. 1999. Abstinence symptoms following oral THC administration to humans. Psychopharmacology 141:385-394.
4.50
75. Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. 1999. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology 141 :395-404.
76. Hanigan WC, Destree R. Truong XT. 1986. The effect of delta-9-THC on human spasticity. Clinical Pharmacology and Therapeutics 39:198.
77. Hardin TC. 1993. Cytokine mediators of malnutrition: Clinical implications. Nutrition in Clinical Practice 8:55-59.
78. Hayreh SS, Zimmerman MB, Podhajsky P. Alward W. 1994. Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders. American Journal of Ophthalmology 117:603-624.
79. Hemming M, Yellowlees PM. 1993. Effective treatment of Tourette's syndrome with marijuana. Journal of Psychopharmacology 7:389-391.
80. Hepler RS, Frank IM, Petrus R. 1976 Ocular effects of marijuana smoking. In: Braude MC, Szara S. Editors The Pharmacology of Marijuana. New York: Raven Press. Pp. 815-824.
81 Hepler RS, Frank in 1971. Marihuana smoking and intraocular pressure. Journal of the American Medical Association 217(10):1392.
82. Herkenham M, Lynn AB, de Costa BR, Richfield EK. 1991a. Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Research 547:267-274.
83. Herkenham M, Lynn AB, Johnson MR, Melvin LS, de Costa BR, Rice KC. l991b. Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study. Journal of Neuroscience 11 :563-583.
84. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. 1990. Cannabinoid receptor localization in the brain. Proceedings of the National Academy of Sciences of the United States of America 87:1932- 1936.
85. Herrstedt J. Aapro MS, Smyth JF, Del Favero A. 1998. Corticosteroids, dopamine antagonists and other drugs. Support Care in Cancer 6:204-214.
86. Hesketh PJ, Gralla RJ, duBois A, Tonato M. 1998. Methodology of antiemetic trials: response assessment, evaluation of new agents and definition of chemotherapy emetogenicity. Supportive Care in Cancer 6:221-227.
87. Hesketh PJ, Kris MG, Grunberg SM, Beck T. Hainsworth ID, Harker G. Aapro MS, Gandara D, Lindley CM. 1997. Proposal for classifying the acute emetogenicity of cancer chemotherapy. Journal of Clinical Oncology 15:103-109.
88. Hill SY. Schwin R. Goodwin DW, Powell BJ. 1974. Marihuana and pain. Journal of Pharmacology and Experimental Therapeutics 188:415-418.
89. Holdcroft A, Smith M, Jacklin A, Hodgson H. Smith B. Newton M, Evans F. 1997. Pain relief with oral cannabinoids in familial Mediterranean fever. Anaesthesia 5:483486.
4.51
90. Homesley HD. Gainey JM, Jobson VN, et al. 1982. Double-blind placebo-controlled study of metoclopramide in cisplatin-induced emesis New England Journal of Medicine 307:250-251.
91. Huestis MA, Henningfield JE, Cone EJ. 1992. Blood Cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. Journal of Analytical Toxicology 16:276-282.
92. Italian Group for Antiemetic Trials. 1995. Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. New England Journal of Medicine 332:332-337.
93. Jain AK, Ryan JR, McMahon FG, Smith G. 1981. Evaluation of intramuscular
levonantradol
and placebo in acute postoperative pain. Journal of Clinical Pharmacology 21
:320S-326S.
94. Jay WM, Green K. 1983. Multiple-drop study of topically applied I % D9 Tetrahydrocannabinol in human eyes. Archives of Ophthalmology 101 :591-593.
95. Jones RT, Benowitz NL, Herning RI. 1981. Clinical relevance of cannabis tolerance and dependence. Journal of Clinical Pharmacology 21:143S-152S.
96. Kass MA, Gordon MO, Hoff MR, Pardinson JM, Kolker AK, Hart WM, Becker B. 1989. Topical timolol administration reduces the incidence of glaucomatous damage in ocular hypertensive individuals. A randomized, double-masked, long-term clinical trial. Archives of Ophthalmology 107:1590-1598.
97. Kaufman P. Mittag TW. 1994. Medical therapy of glaucoma. In: Kaufman P. Mittag TW, Editors Textbook of Ophthalmology. Volume 7. London: Mosby-Year.
98. Kotler DP. 1997. Wasting Syndrome Pathogenesis and Clinical Markers. Institute of Medicine Workshop. Irvine, CA, December 15, 1997, Pp.56-66. Washington, DC: Institute of Medicine.
99. Kotler DP, Gaetz HP, Klein EB, Lange M, Holt PR. 1984. Enteropathy associated with the acquired immunodeficiency syndrome. Annals of Internal Medicine 101 :421-428.
100. Kotler DP, Tierney AR, Culpepper-Morgan JA, Wang J. Peirson RN. 1990. Effect of home total parental nutrition on body composition in patients with acquired immunodeficiency syndrome. Journal of Parenteral Nutrition 14:454-458.
101. Kotler DP, Tierney AR, Dilmanian FA, Kamen Y. Wang J. Pierson Jr RN, Weber D. 1991. Correlation between total body potassium and total body nitrogen in patients with acquired immunodeficiency syndrome. Clinical Research 39:649A.
102. Kotler DP, Tierney AR, Ferraro R. et al. 1991. Enteral alimentation and repletion of body cell mass in malnourished patients with acquired immunodeficiency syndrome. American Journal of Clinical Nutrition 53:149-154.
103. Kotler DP, Tierney AR, Wang J. Pierson RN. 1989. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. American Journal of Clinical Nutrition 50:444-447.
4.52
104. Kotler DP, Wang J. Pierson RN. 1985. Studies of body composition in patients with the acquired immunodeficiency syndrome. American Journal of Clinical Nutrition 42: 1255-1265.
105. Kris MG, Gralla RJ, Clark RA, et al. 1987. Antiemetic control and prevention of side effects of anticancer therapy with lorazepam or diphenhydramine when used in combination with metoclopramide plus dexamethasone: a double-blind randomized trial. Cancer 60:2816-2822.
106. Kris MG, Radford JE, Pizzo BA, et al. 1997. Use of an NK-1 receptor antagonist to prevent delayed emesis following cisplatin. Journal of the National Cancer Institute 89:817-818.
107. Kris MG, Roila F. De Mulder PH, Marty M. 1998. Delayed emesis following anticancer chemotherapy. Supportive Care in Cancer 6:228-232.
108. Lang IM, Sarna SK. 1989. Motor and myoelectric activity associated with vomiting, regurgitation, and nausea. In: Wood JD, Editor Handbook of Physiology, the Gastrointestinal System. 1, Motility and Circulation. Bethesda. American Physiological Society. Pp. 1179-1198.
109. Larson EB, Ellsworth AJ, Oas J. 1993. Randomized clinical trials in single patients during a 2-year period. Journal of American Medical Association 270:2708-2712.
110 Leske MC, Connell AM, Schachat AP, Hyman L 1994 The Barbados Eye Study: Prevalence of open angle glaucoma. Archives of Ophthalmology 112:821-829.
111. Levitt M, Faiman C, Hawks R. et al. 1984. Randomized double-blind comparison of delta-9- THC and marijuana as chemotherapy antiemetics. Proceedings of the American Society for Clinical Oncology 3:91.
112. Libman E, Stern MH. 1985. The effects of delta-9-tetrahydrocannabinol on cutaneous sensitivity and its relation to personality. Personality, Individuality and Difference 6: 169-174.
113. Lichter PR. 1988. A wolf in sheep's clothing. Ophthalmology 95:149-150.
114. Lindgren JE, Ohlsson A, Agurell S. Hollister LE, Gillespie H. 1981. Clinical effects and plasma levels of delta 9-tetrahydrocannabinol (delta 9-THC) in heavy and light users of cannabis. Psychopharmacology (Berl) 74:208-12.
115. Macallan DC, Noble C, Baldwin C, Foskett M, McManus T. Griffin GE. 1993. Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection. American Journal of Clinical Nutrition 58:417-424.
116. Malec J. Harvey RF, Cayner JJ. 1982. Cannabis effect on spasticity in spinal cord injury. Archives of Physical Medicine and Rehabilitation 63: 116- 118.
117. Mao LK, Stewart WC, Shields M. 1991. Correlation between intraocular pressure control and progressive glaucomatous damage in primary open-angle glaucoma. American Journal of Ophthalamology 111:51-55.
118. Marotta JT. 1995. Spinal injury. In: Rowland LP, Editor Merrit's Textbook of Neurology. 9th Edition. Philadelphia: Lea and Febiger. Pp. 440-447.
4.53
119. Martyn CN, Illis LS, Thom J. 1995. Nabilone in the treatment of multiple sclerosis [letter]. Lancet 345:579.
120. Mathew NT. 1997. Serotonin 1D (5-MT 1D) agonists and other agents in acute migraine. Neurologic Clinics 15:61-83.
121 Mattes Rn, Engelman K, Shaw LM, Elsohly MA. 1994. Cannabinoids and appetite stimulation. Pharmacology, Biochemistry and Behavior 49:187-195.
122. Maurer M, Henn V, Dittrich A, Hoffman A. 1990. Delta-9-tetrahydrocannabinol shows antispastic and analgesic effects in a single case double-blind trial. European Archives of Psychiatry and Clinical Neuroscience 240: 1-4.
123. McCarthy LE, Flora KP, Vishnuvajjala BR. 1984. Antiemetic properties and plasma concentrations of delta-9-tetrahydrocannabinol against cisplatin vomiting in cats. In: Agurell S. Dewey WL, Willette RE, Editors The Cannabinoids: Chemical, Pharmacologic and Therapeutic Aspects. Orlando, FL: Academic Press. Pp. 859- 870.
124. McQuay H. Carroll D Moore A. 1996 Variation in the placebo effect in randomised controlled trials of analgesics: all is as blind as it seems. Pain 64:331-335.
125. Meinck HM, Schonle PW, Conrad B. 1989. Effect of cannabinoids on spasticity and ataxia in multiple sclerosis. Journal of Neurology 236:120-122.
126 Merritt JC, Cook CE, Davis KH. l982. Orthostatic hypotension after delta 9-tetrahydrocannabinol marihuana inhalation. Ophthalmic Research 14:124-128.
127. Merritt JC, Crawford WJ, Alexander PC, Anduze AL, Gelbart SS. 1980. Effect of marihuana on intrasocular and blood pressure in glaucoma. Ophthalmology 87:222-228.
128. Mertens TE' Low-Beer D 1996. HIV and AIDS: where is the epidemic going? Bulletin of the World Health Organization 74: 121 - 129.
129. Miller AD. 1998. Nausea and vomiting: Underlying mechanisms and upcoming treatments Journal of the Japan Broncho-Esophagological Society 49:57-64.
130. Miller AD, Nonaka S. Siniaia MS, Jakus J. 1995. Multifunctional ventral respiratory group: Bulospinal expiratory neurons play a role in pudendal discharge during vomiting. Journal of the Autonomic Nervous System 54:253-260.
131. Miller AS, Walker JM. 1995. Effects of a cannabinoid on spontaneous and evoked neuronal activity in the substantia nigra pars reticulate. European Journal of Pharmacology 279: 179-185.
132. Miller AS, Walker JM. 1996. Electrophysiological effects of a cannabinoid on neural activity in the globus pallidus. European Journal of Pharmacology 304:29-35.
133. Moertel CG, Taylor WF, Roth A, Tyce FA. 1976. Who responds to sugar pills? Mayo Clinic Proceedings 51 :96-100.
134. Moldawer LL, Andersson C, Gelin J. Lundholm KG. 1988. Regulation of food intake and hepatic protein synthesis by recombinant-derived cytokines. American Journal of Physiology 254:G450-G456.
4.54
135. Mulligan K, Tai VW, Schambelan M. 1997. Cross-sectional and longitudinal evaluation of body composition in men with HIV infection. Journal of Acquired Immunodeficiency Syndromes 15 :43-48.
136. Murray C J L, Lopez A D. 1996. Global Health Statistics. A compendium of incidence, prevalence, and mortality estimates for over 200 conditions. Global Burden of Disease and Injury Series, Volume II. Boston, MA: The Harvard School of Public Health.
137. Navari RM, Reinhardt RR, Gralla RJ, Kris MG, Hesketh PJ, et al. 1999. Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. The New England Journal of Medicine 340: 190-195.
138. Newell FW, Stark P. Jay WM, Schanzlin DJ. 1979. Nabilone: a pressure-reducing synthetic benzopyran in open-angle glaucoma. Ophthalmology 86:156-160.
139. Ng SKC, Brust JCM, Hauser WA, Susser M. 1990. Illicit drug use and the risk of new-onset seizures. American Journal of Epidemiology 132: 47-57.
140. NIH. 1997. Spinal cord injury: Emerging concepts: An NIH workshop. Proceedings of an NIH Workshop on Spinal Cord Injury. Bethesda, MD, September 30-October 1, 1996. Bethesda, MD: National Institute of Neurological Disorders and Stroke.
141. Noyes R. Jr, Brunk SF, Avery DH, Canter A. 1975b. The analgesic properties of delta-9- Tetrahydrocannabinol and codeine. Clinical Pharmacology and Therapeutics 18:84- 89.
142. Noyes R Jr. Brunk SF, Baram DA, Canter A. 1975a. Analgesic effect of delta-9-tetrahydrocannabinol. Journal of Clinical Pharmacology 15:139-143.
143. Ohlsson A, Lindgren J-E, Wahlen A, Agurell S. Hollister L E, Gillespie HK. 1980. Plasma delta-9-tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clinical Pharmacology and Therapeutics 28:409-416.
144. Orgul S. Kaiser HJ, Flammer J. Gasser P. 1995. Systemic blood pressure and capillary blood-cell velocity in glaucoma patients: a preliminary study. European Journal of Ophthalmology 5:88-91.
145. Orr LE, McKernan JF, Bloome B. 1980. Antiemetic effect of Tetrahydrocannabinol. Compared with placebo and prochlorperazine in chemotherapy-associated nausea and emesis. Archives of Internal Medicine 140:1431 -3.
146. Ott M, Lambke B. Fischer H. Jagre R. Polat H. Geier H. Rech M, Staszeswki S. Helm EB, Caspary WF 1993. Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition. American Journal of Clinical Nutrition 57:15-19.
147. Perez EA, Chawla SP, Kaywin PK, et al. 1997. Efficacy and safety of oral granisetron versus IV ondansetron in prevention of moderately emetogenic chemotherapy-induced nausea and vomiting. Proceedings of the American Society for Clinical Oncology 16:43.
4.55
148. Perez-Reyes M, Wagner D, Wall ME, Davis KH. 1976. Intravenous administration of cannabinoids and intraocular pressure. In: The Pharmacology of Marihuana, New York: Raven Press. Pp. 829-832.
149. Peroutka SJ. 1996. Drugs effective in the therapy of migraine. In: Hardman JG, Limbird LE, Editors Goodman and Gilman's The Pharmacological Basis of Therapeutics. 9th Edition. New York: McGraw-Hill. Pp. 487-502.
150. Petro D, Ellenberger Jr C. 1981. Treatment of human spasticity with delta 9- tetrahydrocannabinol. Journal of Clinical Pharmacology 21:413S-416S.
151. Quigley HA. 1996. Number of people with glaucoma worldwide. British Journal of Ophthalmology 80:389-393.
152. Raft D, Gregg J. Ghia J. Harris L. 1977. Effects of intravenous tetrahydrocannabinol on experimental and surgical pain: Psychological correlates of the analgesic response. Clinical Pharmacology and Therapeutics 21 :26-33.
153. Razdan RK. 1986. Structure-activity relationships in cannabinoids. Pharmacology Review 38:75-149.
154. Richfield E K, Herkenham M. 1994. Selective vulnerability in Huntington's disease: preferential loss of cannabinoid receptors in lateral globus pallidus . Annals of Neurology: 577-584.
155. Richter A, Loscher W. 1994. (+)-WIN55,212-2 a novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters European Journal of Pharmacology 264:371-377.
156. Rodriguez de Fonseca F. Carrera MRA, Navarro M, Koob G. Weiss F. 1997. Activation of corticotrophin-releasing factor in the limbic system during cannabinoid withdrawal [see comments Science 1997. 276: 1967- 1968]. Science 276:2050-2054.
157. Roila F. Tonato M, Cognetti F. et al. 1991. Prevention of cisplatin-induced emesis: a double- blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone. Journal of Clinical Oncology 9:674-678.
158. Rosenzweig MR, Leiman AL, Breedlove SM. 1996. Biological Psychology. Sunderland, MA: Sinauer Associates, Inc.
159. Roth R I, Owen R L, Keren D F. Volberding P A. 1985. Intestinal infection with Mycobacterium avium in acquired immune deficiency syndrome (AIDS). Histological and clinical comparison with Whipple's disease. Digestive Disease science 30:497-504
160. Russo E. 1998. Cannabis for Migraine Treatment: The Once and Future Prescription?: An Historical and Scientific Review. Pain 76
161. Suttmann U. Ockenga J. Selberg O. Hoogestraat L, Deicher H. Muller MJ. 1995. Incidence and prognostic value of malnutrition and wasting in human irnmunodeficiency virus - infected outpatients. Journal of Acquired immune Deficiency Syndromes and Human Retrovirology 8:239-246.
4.56
162. Sackett D, Rosenberg W. Haynes B. Richardson S. 1997. Evidence-based medicine: How to practice and teach EBM. New York: Churchhill Livingston.
163. Sallan SE, Cronin CM, Zelen M, et al. 1980. Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of delta-9-tetrahydrocannabinol and prochlorperazine. New England Journal of Medicine 302: 135 - 138.
164. Sallan SE, Zinberg NE, Frei E. 1975. Antiemetic effect of delta-9-THC in patients receiving cancer chemotherapy. New England Journal of Medicine 293 :795-797.
165. SAMHSA (Substance Abuse and Mental Health Services Administration). 1998. National Household Survey on Drug Abuse: Population Estimates 1997. DHHS Pub No. (SMA) 98-3250. Rockville, MD: SAMHSA, Office of Applied Studies.
166. Sandyk R. Awerbuch G. 198X. Marijuana and Tourette's syndrome. Journal of Clinical Psychopharmacology 8:444-445.
167. Sandyk R. Consroe P. Stern P. Biklen D. 1988. Preliminary trial of cannabidiol in Huntington's disease. Marijuana: An International Research Report Editors Chesher G. Consroe P. Musty R. Canberra: Australian Government Publishing Service.
168. Sanudo-Pena MC, Patrick SL, Patrick RL, Walker JM l 996 Effects of intranigral cannabinoids on rotational behavior in rats: Interactions with the dopaminergic system. Neuroscience Letters 206:21 -24.
169. Sanudo-Pena MC, Tsou K, and Walker JM. Cannabinoid dopamine interactions in the basal ganglia in an animal model of Parkinson disease. (in preparation).
170. Sanudo-Pena MC, Tsou K, and Walker JM. Superior colliculus and turning: dopamine and cannabinoids. (in preparation).
171. Sanudo-Pena MC, Walker JM. 1997. Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat. Journal of Neurophysiology 77: 1635-1638.
172. Sanudo-Pena MC, Walker JM. 1998. Effects of intrastriatal cannabinoids on rotational behavior in rats: interactions with the dopaminergic system . Synapse 30:221 -226.
173. Schambelan M, Mulligan K, Grunfeld C, Daar ES, LaMarca A, Kotler DP. 1996. Recombinant human growth hormone in patients with HIV-associated wasting: a randomized, placebo-controlled trial: Serostim Study Group. Annals of Internal Medicine 125:873-882.
174. Schwartz RH, Beveridge RA. 1994. Marijuana as an antiemetic drug: how useful is it today? Opinions from clinical oncologists [see comments]. Journal of Addictive Diseases 13:53-65.
175 Schwartz RH, Voth EA. 1995. Marijuana as Medicine: Making a Silk Purse Out of a Sow's Ear. Journal of Addictive Diseases 14: 15-21.
176. Shields MB. 1998. Textbook of glaucoma. 4th. Baltimore, MD: Williams & Wilkins.
177. Sommer A, Tielsch JM, Katz J. Quigley HA, Gottsch JD, Javitt J. Singh K. 1991. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: The Baltimore Eye Survey. Archives of Ophthalmology 109: 1090-1095.
4.57
178. Staquet M, Gantt C, Machin D. 1978. Effect of a nitrogen analog of tetrahydrocannabinol on cancer pain. Clinical Pharmacology and Therapeutics 23:397401.
179. Steele N. Gralla RJ, Braun DW, Jr. 1980. Double-blind comparison of the antiemetic effects of nabilone and prochlorperazine on chemotherapy-induced emesis. Cancer Treatments Report 64:219-224.
180. Stimmel B. 1995. Medical marijuana: to prescribe or not to prescribe, that is the question [editorial]. Journal of Addictive Diseases 14: 1-3.
181. Strassman RJ. 1998. Marijuana: The forbidden medicine (book review). Journal of the American Medical Association 279:963-964.
182. Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV, Ries K, Evans TG. 1993. Effect of dronabinol on nutritional status in HIV infection. Annals of Pharmacotherapy 27;827-31.
183. Swift RM, 1994. Marijuana: The forbidden medicine (book review). The New England Journal of Medicine 331 :749-750.
184. Tanda G. Pontieri FE, Di Chiara G. 1997. Cannabinoid and heroin activation of mesolimbic dopamine transmission by a common u1 opioid receptor mechanism. Science 276:2048-2049.
185. Tiedeman JS, Shields MB, Weber PA, Crow JW, Cocchetto DM, Harris WA, Howes JF. 1981. Effect of synthetic cannabinoids on elevated intraocular pressure. Ophthalmology 88:270-277.
186. Tielsch JM, Sommer A, Katz J. Royall RM, Quigley HA, Javitt J. 1991. Racial variations in the prevalence of primary open-angle glaucoma: The Baltimore Eye Survey. Journal of the American Medical Association 266:369-374.
187. Timpone JG, Wright DJ, Li N. Egorin MJ, Enama ME, Mayers J. Galetto G. DATRI 004 Study Group. 1997. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 study group. AIDS Research and Human Retroviruses 13:305-15.
188. Trembly B. Sherman M. 1990. Double-blind clinical study of cannabidiol as a secondary anticonvulsant. Marijuana '90 International Conference on Cannabis and Cannabinoids. Kolympari, Crete, July 8-11, 1990. Unpublished manuscript presented at the conference.
189. Tyson LB, Gralla RJ, Clark RA, et al. 1985. Phase I trial of levonantradol in chemotherapy- induced emesis. American Journal of Clinical Oncology 8:528-532.
190. UNAIDS, WHO. 1998. Report on the Global HIV/AIDS Epidemic, June 1998.
191. Ungerleider JT, Andrysiak TA, Fairbanks L, Ellison GW, Myers LW. 1987. Delta-9-THC in the treatment of spasticity associated with multiple sclerosis. Adv Alcohol Subst Abuse 7:39-50.
4.58
192. Vinciguerra V, Moore T. Brennan E. 1988. Inhalation marijuana as an antiemetic for cancer chemotherapy. New York State Journal of Medicine 88:525-527.
193. Volicer L, Smith S. Volicer BJ. 1995. Effect of seizures on progression of dementia of the Alzheimer type. Dementia 6:258-263.
194. 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. International Journal of Geriatric psychiatry 12:913-919.
195. Voth E A, Schwartz R. H. 1997. Medicinal applications of delta-9-tetrahydrocannabinol and marijuana. Annals of Internal Medicine 126:791-798.
196. Wall PD, Melzack R. 1994. Textbook of Pain. Edinburgh: Churchill Livingstone.
197. Walters TR. 1996. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, Efficacy dose response, and dosing studies. Survey of Ophthalmology 41 Suppl 1 :S19-S26.
198. Wang ZM, Visser M, Ma R. Baumgartner RN, Kotler DP, Gallagher D, Heymsfield SB. 1996. Skeletal muscle mass: Validation of neutron activation and dual energy X-ray absorptiometry methods by computerized tomography. Journal of Applied Physiology 80:824-831.
199. Whitney EN. 1994. Nutrition and Wasting Disorders: Cancer and AIDS. In: Whitney EN, Cataldo CB1 Rolfes SR, Editors Understanding Normal and Clinical Nutrition. Minneapolis: West Publishing Co. Pp. 948-977.
200. Wood. 1998. HIV-protease inhibitors. Drug Therapy 338:1281-1292.
201. Yoles E, Belkin M, Schwartz M. 1996. HU-211, a nonpsychotropic cannabinoid, produces short- and long-term neuroprotection after optic nerve axotomy. Journal of Neurotrauma 13:49-57.
202. Zimmer L, Morgan JP. 1997. Marijuana myths marijuana facts. New York, NY: The Lindesmith Center.
4.59