s of Papers, 188th Meet. American Chemical Soc., Philadelphia, August 1984, American Chemical Society, Washington, D.C., 1984; Abstr. MEDI,45. 35. Melvin, L. S., Johnson, M. R., and Milne, G. M., CP-55,244: a cannabinoid derived analgetic, in Abstracts of Papers, 186th Meet. American Chemical Soc., Washington, D.C., August 1983, American Chemical Society, Washington, D.C., 1983; Abstr. MEDI, 22. 36. Johnson, M. R., Eggler, J. F., Melvin, L. S., and Milne, G. M., Cannabinoid-derived therapeutants: further studies in the search for non-addicting drugs to relieve pain and discomfort, in Abstracts of Papers, 186th Meet, of the American Chemical Soc., Washington, D.C., Aug. 1983, American Chemical Society, Washington, D.C., 1983; Abstr. MEDI, 1. 37. Yaksh, T. L., The antinociceptive effects of intrathecally administered levonantradol and desacetyllevonantradol in the rat, /. Clin. Pharmacol.,21, 334s, 1981. 38. Dykstra, L. A., Effects of morphine, levonantradol and N-methyllevonantradol on shock intensity discrimination, J. Clin. Pharmacol.,21, 341s, 1981. 39. Smith, J. B., Effects of morphine and two cannabinoid-related analgesics on responding under schedules of electric-shock titration, Fed. Proc., 39, 761, 1980. 40. Gilbert, P. E., A comparison of THC, nantradol, nabilone and morphine in the chronic spinal dog, J. Clin. Pharmacol.,2\, 311s, 1981. 41. Jain, A. K., Ryan, J. R., McMahon, F. G., and Smith, G., Evaluation of intramuscular levonantradol and placebo in acute postoperative pain, /. Clin. Pharmacol.,2[, 320s, 1981. 42. Lai, H., Bennett, D. A., Shearman, G. T., McCarten, M. D., Murphy, R., and Angeja, A., Effectiveness of nantradol in blocking narcotic withdrawal signs through nonnarcotic mechanisms, J. Clin. Pharmacol.,21, 361s, 1981. 43. Collier, H. O. J. and Roy, A. C., Morphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenate, Nature (London), 248, 24, 1974. 44. Johnson, M. R., Schaaf, T. K., Constantine, J. W., and Hess, H.-J., Structure activity studies leading to a tissue-selective hypotensive prostaglandin analog, 13,14-dihydro-16-phenyl-w-tetranor PGE2, Prostaglandins, 20, 515, 1980. 45. Bordner, J., University of North Carolina, personal communication, 1979. 46. Edmonds, J. W. and Duax, W. L., Molecular conformation of prostaglandin Ez, Prostaglandins, 5, 275, 1974. 47. McCarthy, L. E. and Borison, H. L., Antiemetic activity of N-methyllevonantradol and nabilone in cisplatin-treated cats, J. Clin. Pharmacol.,21, 30s, 1981. 48. Cronin, C. M., Sallan, S. E., Gelber, R., Lucas, V. S., and Laszlo, J., Antiemetic effect of intramuscular levonantradol in patients receiving anticancer chemotherapy, J. Clin. Pharmacol.,21, 43s, 1981. 49. Embrey, M. P., Killer, K., and Mahendran, P., Termination of pregnancy by extraamniotic prostaglandins and the synergistic action of oxytocin, Adv. Biosci., 9, 507, 1973. 50. Craft, L, Oral prostaglandin E2 and amniotomy for induction of labor, Adv. Biosci., 9, 593, 1973. 51. Rich, W. M., Abdulhayoglu, G., and DiSaia, P. J., Methylprednisolone as an antiemetic during cancer chemotherapy — a pilot study, Gynecol. Oncol., 9, 193, 1980. 52. Home, W. C., Desacetyl-1-nantradol: a selective prostaglandin antagonist, Prostaglandins Leukotrienes and Med., 15, 129, 1984. 53. Hillard, C. J. and Bloom, A. S., Possible role of prostaglandins in the effects of the cannabinoids on adenylate cyclase activity, Eur. J. Pharmacol.,91, 21, 1983. 54. Loscher, W., 3-Mercaptopropionic acid: convulsant properties, effects on enzymes of the y-aminobutyrate system in mouse brain and antagonism by certain anticonvulsant drugs, aminooxyacetic acid and gabaculine, Biochem. Pharmacol.,28, 1397, 1979. 55. Revuelta, A. V., Cheney, D. L., Wood, P. L., and Costa, E., GABAergic mediation in the inhibition of hippocampal acetylcholine turnover rate elicited by A'-tetrahydrocannabinol, Neuropharmacology, 18, 525, 1979. 56. Leader, J. P., Koe, B. K., and Weissman, A., GABA-like actions of levonantradol, J. Clin. Pharmacol.,2\, 262s, 1981. 57. Koe, B. K. and Weissman, A., Facilitation of benzodiazepine binding by levonantradol, J. Clin. Pharmacol.,21, 397s, 1981. 58. Costa, E., Cheney, D. L., and Murray, T. F., Levonantradol-induced inhibition of acetylcholine turnover in rat hippocampus and striatum, J. Clin. Pharmacol.,21, 256s, 1981. 59. Koe, B. K., Milne, G. M., Weissman, A., Johnson, M. R., and Melvin, L. S., Enhancement of brain LHJFIunitrazepam binding and analgesic activity of synthetic cannabimimetics, Eur. J. Pharmacol., 109, 201, 1985. 60. Citron, M. L., Herman, T. S., Fossieck, B. E., Jr., Krasnow, S. H., Vreeland, F., and Harwood, S., Double blind, randomized, crossover study of the antiemetic effect of levonantradol (LVN) versus tetrahydrocannabinol (THC), Proc. Am. Assoc. Cancer Res., 24, 165, 1983. 61. Earhart, R. H. and Koeller, J. M., Levonantradol vs. prochlorperazine as parenteral antiemetics in cancer patients receiving cisplatin chemotherapy, Proc. Am. Assoc. Cancer Res., 24, 163, 1983. 62. Stuart-Harris, R. C., Mooney, C. A., and Smith, I. E., Levonantradol: a synthetic cannabinoid in the treatment of severe chemotherapy-induced nausea and vomiting resistant to conventional antiemetic therapy, Clin. Oncol.,9, 143, 1983. 63. Stuart-Harris, R., Mooney, C., and Smith, I. E., Levonantradol (LN) in the treatment of chemotherapy induced nausea and vomiting, refractory to conventional anti-emetics, Br. J. Cancer, 47, 568, 1983. 64. Hutcheon, A. W., Palmer, J. B., Soukop, M., Cunningham, D., McArdle, C., Welsh, J., Stuart, F., Sangster, G., Kaye, S., Charlton, D., and Cash, H., A randomized multicenter single blind comparison of a cannabinoid anti-emetic (levonantradol) with chlorpromazine in patients receiving their first cytotoxic chemotherapy, Eur. J. Cancer Clin. Oncol., 19, 1087, 1983. 65. Gerhartz, H. H., Binsack, T., and Hiller, E., Levonantradol for the treatment of chemotherapyinduced nausea and vomiting, Klin. Wochenscfir.,61, 719, 1983. 66. Welsh, J., Stuart, F., Sangster, G., Milstead, R., Kaye, S., Cash, H., Charlton, D., and Caiman, K., Oral levonantradol in the control of cancer chemotherapy-induced emesis, Cancer Chemother. Pharmacol., 11, 66, 1983. 67. Sheidler, V. R., Ettinger, D. S., Diasio, R. B., Enterline, J. P., and Brown, M. D., Double-blind multiple-dose crossover study of the antiemetic effect of intramuscular levonantradol compared to prochlorperazine, /. Clin. Pharmacol.,24, 155, 1984. 68. Heim, M. E. and Queisser, W., Treatment of refractory cytostatic agent-induced vomiting with the synthetic cannabinoid levonantradol, Onkologie,S, 94, 1982. 69. Heim, M. E., Romer, W., and Queisser, W., Clinical experience with levonantradol hydrochloride in the prevention of cancer chemotherapy-induced nausea and vomiting, J. Clin. Pharmacol., 21, 86s, 1981. 70. Diasio, R. B., Ettinger, D. S., and Satterwhite, B. E., Oral levonantradol in the treatment of chemotherapy-induced emesis: preliminary observations, J. Clin. Pharmacol.,21, 81s, 1981. 71. Laszlo, J., Lucas, V. S., Jr., Hanson, D. C., Cronin, C. M., and S. E. Sallan, Levonantradol for chemotherapy-induced emesis: phase I-II oral administration, J. Clin. Pharmacol., 21, 51s, 1981. 1. Shapiro, B. J., Tashkin, D. P., and Vachon, L., THC as a bronchodilator. Why bother?, Chest, 71, 558, 1977. 2. Perez-Reyes, N., Lipton, M. A., Timmous, M. C., Wall, M. E., Brine, D. R., and Davis, K. H., Pharmacology of orally administered A'-THC, /. Clin. Pharm. Ther., 14, 48, 1973. 3. Abboud, R. T. and Sanders, H. D., Effect of oral administration of A'-THC on airways mechanics in normal and asthmatic subjects, Chest, 70, 480, 1976. 4. Davies, B. H., Radcliffe, S., Seaton, A., and Graham, J. D. P., A trial of oral A'-THC in reversible airways obstruction, Thorax, 30, 80, 1975. 5. Perez Reyes, M., Timmons, M. C., Davis, K. H., and Wall, M. C., A comparison of the pharmacological activity in man of intravenously administered A'-tetrahydrocannabinol, cannabinol, and cannabidiol, Experientia,29, 1368, 1973. 6. Malit, L. A., Johnstone, R. E., Bourke, D. L, Kulp, R. A., Klein, V., and Smith, T. C., Intravenous A'-THC: effects on ventilatory control and cardiovascular dynamics, Anaesthesiology, 42, 666, 1975. 7. Smith, T. C. and Kulp, R. A., Respiratory and cardiovascular effects of A'-THC alone and in combination with oxymorphone, pentobarbital and diazepam, in Therapeutic Potential of Marijuana, Cohen, S. and Stillman, R. C., Eds., Plenum Press, New York, 1976, 123. 8. Olsen, J. L., Lodge, J. W., Shapiro, B. J., and Tashkin, D. P., An inhalation aerosol of A'-THC, J. Pharm. Pharmacol., 28, 86, 1976. 9. Williams, S. J., Hartley, J. P. R., and Graham, J. D. P., Bronchodilator effect of A'-THC administered by aerosol to asthmatic patients, Thorax, 31, 720, 1976. 10. Vachon, L., The smoke in marijuana smoking, N. Engl. J. Med., 294, 160, 1976. 11. Vachon, L., Fitzgerald, M. X., Solliday, N. H., Gould, I. A., and Gaensler, E. A., Single dose effect of marijuana smoke, N. Engl. J. Med., 288, 985, 1973. 12. Tashkin, D. R., Shapiro, B. J., and Frank, I. M., Acute pulmonary physiological effects of smoked marijuana and oral A'-tetrahydrocannabinol in healthy young men, New Engl. J. Med., 289, 336, 1973. 13. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E., Effects of smoked marijuana in experimentally induced asthma, Am. Rev. Resp. Dis., 112, 337, 1975. 14. Tashkin, D. P., Shapiro, B. J., Lee, Y. E., and Harper, C. E., Subacute effects of heavy marijuana smoking on pulmonary function in healthy men, New Engl. J. Med., 294, 125, 1976. 15. Avakian, E. V., Horvath, S. M., Michael, E. D., and Jacobs, S., Effect of marijuana on cardiorespiratory responses to submaximal exercise, din. Pharmacol. Ther.,26, 77, 1979. 16. Tashkin, D. P., Calvarese, B. M., Simmons, S., and Shapiro, B. J., Respiratory status of seventy four habitual marijuana smokers, Chest, 78, 699, 1980. 17. Tashkin, D. P., Calv

Cannabinoids As Therapeutic Agents

Determination of sub-microgram levels of α-tocopherol in serum by gas—liquid chromatography with solid injection

Muscular dystrophy in mice after chronic subcutaneous treatment with cannabinoids

Neutralization of the effect of Δ9-tetrahydrocannabinol on barbiturate sleeping time by specific active immunization

The i.v. administration of 10 mg ofΔ9-THC in rabbits produced, after 24 h, a 50% reduction of the initial values of serum alpha-tocopherol.

Decrease of serum alpha-tocopherol levels in rabbits after acute treatment with delta9-tetrahydrocannabinol.

After chronic treatment with Δ9-THC at behavioural doses, a muscular dystrophy was demonstrated in adult mice, on the basis of histological and biochemical data and of functional tests on muscle.

M. Passatore

Papers

Muscular dystrophy in adult mice chronically treated with delta9-THC at behavioural doses.

Muscular dystrophy in mice after chronic subcutaneous treatment with cannabinoids