Advertisement

Drugs of Abuse pp 319-371 | Cite as

Cannabis: Structure-Activity Relationships

  • R. Duane Sofia
Part of the Handbook of Psychopharmacology book series (HBKPS)

Abstract

Cannabis sativa or marihuana most likely is one of man’s oldest and most widely used drugs (Mikuriya, 1969). The earliest record of its use and description was in China in 2737 b.c. Its use as an intoxicant spread to India and North Africa and from there to Europe, probably as a result of the expedition of Napoleon during his Egyptian campaign around 1800. In the Western Hemisphere marihuana has been known for centuries in South and Central America, but it was not used in the United States to any significant degree until the early 1900s.

Keywords

Analgesic Activity Anticonvulsant Activity Paradoxical Sleep Spontaneous Locomotor Activity Audiogenic Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abel, F. L., 1969, Effects of the marihuana homologue, pyrahexyl, on a conditioned emotional response, Psychon. Sci. 16:44.Google Scholar
  2. Abel, E. L., 1970, Effects of the marihuana-homologue, pyrahexyl, on open field behaviour in the rat, J. Pharm. Pharmacol. 22:785.PubMedCrossRefGoogle Scholar
  3. Abel, E. L., 1971, Effects of marihuana on the solution of anagrams, memory and appetite, Nature 231:260–261.PubMedCrossRefGoogle Scholar
  4. Abel, E. L., and Schiff, B. B., 1969, Effects of the marihuana homologue, pyrahexyl, on food and water intake and curiosity in the rat, Psychon. Sci. 16:38.Google Scholar
  5. Adams, R., and Baker, B. R., 1940, Structure of cannabidiol. VII. A method of synthesis of a tetrahydrocannabinol which possesses marihuana activity, J. Am. Cheem. Soc. 62:2405–2408.CrossRefGoogle Scholar
  6. Adams, H. R., and Sofia, R. D., 1973, Interaction of chloramphenicol and Δ 1-tetrahydrocannabinol in barbital-anesthetized mice, Experientia 29:181–182.PubMedCrossRefGoogle Scholar
  7. Agurell, S., Nilsson, I. M., Ohlsson, A., and Sandberg, F., 1969, Elimination of tritiumlabelled cannabinols in the rat with special reference to the development of tests for the identification of cannabis users, Biochem. Pharmacol. 18:1195–1201.PubMedCrossRefGoogle Scholar
  8. Agurell, S., Nilsson, I. M., Ohlsson, A., and Sandberg, F., 1970, On the metabolism of tritium-labelled Δ 1-tetrahydrocannabinol in the rabbit, Biochem. Pharmacol. 19:1333–1339.PubMedCrossRefGoogle Scholar
  9. Allentuck, S., and Bowman, K. M., 1942, The psychiatric aspects of marihuana intoxication, Am. J. Psychiat. 99:248–251.Google Scholar
  10. Ames, F., 1958, A clinical and metabolic study of acute intoxication with Cannabis sativa and its role in the model psychoses, J. Ment. Sci. 104:972–999.PubMedGoogle Scholar
  11. Askew, W. E., and Ho, B. T., 1974, Effects of tetrahydrocannabinols on cyclic AMP levels in rat brain areas, Experientia 30:879–880.PubMedCrossRefGoogle Scholar
  12. Banerjee, S. P., Snyder, S. H., and Mechoulam, R., 1975, Cannabinoids: Influence on neurotransmitter uptake in rat brain synaptosomes, J. Pharmacol. Exp. Ther. 194:74–81.PubMedGoogle Scholar
  13. Barry, H., III, and Kubena, R. K., 1969, Acclimation to laboratory alters response of rats to Δ 1-tetrahydrocannabinol, in: Proceedings of the 77th Annual Convention of the American Psychological Association, Vol. 4, Part 2, pp. 865–866, American Psychological Association Press, Washington, D.C.Google Scholar
  14. Barry, H., III, and Kubena, R. K., 1971, Repeated high doses of Δ 1-tetrahydrocannabinol enhance acquisition of shock avoidance in rats, in: Proceedings of the 79th Annual Convention of the American Psychological Association, Vol. 6, Part 2, pp. 747–748, American Psychological Association Press, Washington, D.C.Google Scholar
  15. Bicher, H. I., and Mechoulam, R., 1968, Pharmacological effects of two active constituents of marihuana, Arch. Int. Pharmacodyn. 172:24–31.PubMedGoogle Scholar
  16. Black, M. B., Woods, J. H., and Domino, E. F., 1970, Some effects of (—p)-Δ9 -trans-tetrahydrocannabinol and other cannabis derivatives on schedule-controlled behavior, Pharmacologist 12:258.Google Scholar
  17. Boggan, W. O., Steele, R. A., and Freedman, D. X., 1973, Δ9-Tetrahydrocannabinol Effect on Audiogenic Seizure Susceptibility, Psychopharmacologia 29:101–106.PubMedCrossRefGoogle Scholar
  18. Borgen, L. A., and Shumway, J., 1974, Comparative effects of Δ9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), and cannabinol (CBN) on timing behavior in rats, Pharmacologist 16:260.Google Scholar
  19. Borgen, L. A., Davis, W. M., and Pace, H. B., 1971, Effects of synthetic Δ9-tetrahydrocan-nabinol on pregnancy and offspring in the rat, Tox. Appl. Pharmacol. 40:480–486.CrossRefGoogle Scholar
  20. Boyd, E. S., and Meritt, D. A., 1965, Effects of thiopental and a tetrahydrocannabinol derivative on arousal and recruiting in the cat, J. Pharmacol. Exp. Ther. 149:138–145.PubMedGoogle Scholar
  21. Boyd, E. S., and Meritt, D. A., 1966, Effects of barbiturates and a tetrahydrocannabinol derivative on recovery cycles of medial lemniscus, thalamus and reticular formation in the cat, J. Pharmacol. Exp. Ther. 151:376–384.PubMedGoogle Scholar
  22. Boyd, E. S., Hutchinson, E. D., Gardner, L. C., and Meritt, D. A., 1963, Effects of tetrahydrocannabinols and other drugs on operant behavior in rats, Arch. Int. Pharmacodyn. 144:533–554.PubMedGoogle Scholar
  23. Brown, H., 1972, Possible anticholinesterase-like effects of trans (—)Δ8-and Δ9tetrahydrocannabinol as observed in the general motor activity of mice, Psychopharmacologia 27:111–116.PubMedCrossRefGoogle Scholar
  24. Brown, O. M., 1973, Effects of Δ9-tetrahydrocannabinol (THC) on rat brain acetylcholine levels, Pharmacologist 15:200.Google Scholar
  25. Burstein, S. H., and Kupfer, D., 1971, Hydroxylation of trans- Δ1-tetrahydrocannabinol by a hepatic microsomal monooxygenase, Chem. Biol. Interact. 3:316.PubMedCrossRefGoogle Scholar
  26. Burstein, S., and Varanelli, C., 1975, Transformations of cannabinol in the mouse, Res. Comm. Chem. Pathol. Pharmacol. 11:343–354.Google Scholar
  27. Burstein, S. H., Menezes, F., Williamson, E., and Mechoulam, R., 1970, Metabolism of Δ1(16)-Tetrahydrocannabinol, an active marihuana constituent, Nature 225:87–88.PubMedCrossRefGoogle Scholar
  28. Burstein, S., Rosenfeld, J., and Wittstruck, T., 1972, Isolation and characterization of two major urinary metabolites of Δ1-tetrahydrocannabinol, Science 176:422–423.PubMedCrossRefGoogle Scholar
  29. Buxbaum, D. M., 1972, Analgesic activity of Δ9-tetrahydrocannabinol in the rat and mouse, Psychopharmacologia 25:275–280.PubMedCrossRefGoogle Scholar
  30. Byck, R., and Ritchie, J. M., 1973, Δ9-Tetrahydrocannabinol: Effects on mammalian nonmyelinated nerve fibers, Science 180:84–85.PubMedCrossRefGoogle Scholar
  31. Chesher, G. B., Dahl, C. J., Everingham, M., Jackson, D. M., Marchant-Williams, H., and Starmer, G. A., 1973, The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice, Br. J. Pharmacol. 49:588–594.PubMedGoogle Scholar
  32. Chesher, G. B., Jackson, D. M., and Starmer, G. A., 1974, Interaction of cannabis and general anaesthetic agents in mice, Br. J. Pharmacol. 50:593–599.PubMedGoogle Scholar
  33. Chesher, G. B., and Jackson, D. M., 1974, Anticonvulsant effects of cannabinoids in mice: Drug interactions within cannabinoids and cannabinoid interactions with phenytoin, Psychopharmacologia 37:255–264.PubMedCrossRefGoogle Scholar
  34. Christensen, H. D., Freudenthal, R. I., Gidley, J. T., Rosenfeld, R., Boegli, G., Testino, L., Brine, D. R., Pitt, C. G., and Wall, M. E., 1971, Activity of Δ8-and Δ9-Tetrahydrocannabinol and related compounds in the mouse, Science 172:165–167.PubMedCrossRefGoogle Scholar
  35. Christiansen, J., and Rafaelsen, O. J., 1969, Cannabis metabolites in urine after oral administration, Psychopharmacologia 15:60–63.PubMedCrossRefGoogle Scholar
  36. Coldwell, B. B., Bailey, K., Paul, C. J., and Anderson, G., 1974, Interaction of cannabinoids with pentobarbital in rats, Tox. Appl. Pharmacol. 29:59–69.CrossRefGoogle Scholar
  37. Conrad, D. C., Elsmore, T. F., and Sodetz, F. J., 1972, Δ9-Tetrahydrocannabinol: Doserelated effects on timing behavior in chimpanzee, Science 175:547–550.PubMedCrossRefGoogle Scholar
  38. Consroe, P. F., and Man, D. P., 1973, Effects of Δ8-and Δ8-Tetrahydrocannabinol on experimentally induced seizures, Life Sci. 13:429–439.CrossRefGoogle Scholar
  39. Consroe, P. F., Man, D. P., Chin, L., and Picchioni, A. L., 1973, Reduction of audiogenic seizure by Δ8-and Δ9-Tetrahydrocannabinols, J. Pharm. Pharmacol. 25:764–765.PubMedCrossRefGoogle Scholar
  40. Coper, H., and Fernandes, M., 1973, Interaction between cannabis and other drugs, in: Bayer Symposium IV, Psychic Dependence (L. Goldberg and F. Hoffmeister, eds.), pp. 135–141, Springer-Verlag, New York.Google Scholar
  41. Corcoran, M. E., Mccaughran, J. A., Jr., and Wada, J. A., 1973, Acute antiepileptic effects of Δ9-tetrahydrocannabinol in rats with kindled seizures, Exp. Neurol. 40:471–483.PubMedCrossRefGoogle Scholar
  42. Corcoran, M. E., Bolotow, I., Amit, Z., and Mccaughran, J. A., Jr., 1974, Conditioned taste aversions produced by active and inactive cannabinoids, Pharmacol. Biochem. Behav. 2:725–728.PubMedCrossRefGoogle Scholar
  43. Dagirmanjian, R., and Boyd, E. S., 1962, Some pharmacological effects of two tetrahydrocannabinols, J. Pharmacol. Exp. Ther. 135:25–33.PubMedGoogle Scholar
  44. Davis, W. M., and Borgen, L. A., 1974, Effects of cannabidiol and Δ9-tetrahydrocannabinol on operant behavior, Res. Comm. Chem. Pathol. Pharmacol. 9:453–462.Google Scholar
  45. Delini-Stula, A., 1973, Suppression of conditioned avoidance behavior and the development of tolerance to Δ8-Tetrahydrocannabinol and dimethylheptylpyran in rats, Pharmakopsychiat. Neuro-Psychopharmacol. 6:189–197.Google Scholar
  46. Dewey, W. L., Kennedy, J. S., and Howes, J. F., 1970, Some autonomic, gastrointestinal, and metabolic effects of two constituents of marihuana, Fed. Proc. 29:650.Google Scholar
  47. Dewey, W. L., Harris, L. S., and Kennedy, J. S., 1972, Some pharmacological and toxicological effects of 1-trans-Δ8- and 1-trans9-tetrahydrocannabinol in laboratory rodents, Arch. Int. Pharmacodyn. Ther. 196:133–145.PubMedGoogle Scholar
  48. De Zeeuw, R. A., Wijsbeek, J., Breimer, D. D., Vree, T. B., Van Ginneken, C. A. M., and Van Rossum, J. M., 1972, Cannabinoids with a propyl side chain in cannabis: Occurrence and chromatographic behavior, Science 175:778–779.PubMedCrossRefGoogle Scholar
  49. De Zeeuw, R. A., Vree, T. B., Breimer, D. D., and Van Ginneken, C. A. M., 1973, Cannabivarichromene, a new cannabinoid with a propyl side chain in cannabis, Experientia 29:260–261.PubMedCrossRefGoogle Scholar
  50. Dingell, J. V., Miller, K. W., Heath, E. C., and Klausner, H. A., 1973, The intracellular localization of Δ9-tetrahydrocannabinol in liver and its effects on drug metabolism in vitro, Biochem. Pharmacol. 22:949–958.PubMedCrossRefGoogle Scholar
  51. Dolby, T. W., and Kleinsmith, L. J., 1974, Effects of Δ9-tetrahydrocannabinol on the levels of cyclic adenosine 3′,5′-Monophosphate in mouse brain, Biochem. Pharmacol. 23:1817–1825.PubMedCrossRefGoogle Scholar
  52. dubinsky, B., Robichaud, R. C, and Goldberg, M. E., 1973, Effects of (—) Δ9-rans-tetrahydrocannabinol and its selectivity in several models of aggressive behavior, Pharmacology 9:204–216.CrossRefGoogle Scholar
  53. Dykstra, L. A., Mcmillan, D. E., and Harris, L. S., 1975, Effects of Δ9-THC and a water soluble ester of Δ9-THC on schedule-controlled behavior, Pharmacol. Biochem. Behav. 3:29–32.PubMedCrossRefGoogle Scholar
  54. Edery, H., and Gottesfeld, Z., 1975, The γ-aminobutyric acid system in rat cerebellum during cannabinoid-induced cataleptoid state, Brit. J. Pharmacol. 54:406–408.Google Scholar
  55. Edery, H., Grunfeld, Y., Porath, G., Ben-Zvi, Z., Shani, A., and Mechoulam, R., 1972, Structure-activity relationships in the tetrahydrocannabinol series, Arzneim.-Forsch. 22:1995–2003.Google Scholar
  56. Elsmore, T. F., 1972, Effects of delta-9-tetrahydrocannabinol on temporal and auditory discrimination performances of monkeys, Psychopharmacologia 26:62–72.PubMedCrossRefGoogle Scholar
  57. Elsmore, T. F., and Fletcher, G. V., 1972, Δ9-Tetrahydrocannabinol: Aversive effects in rat at high doses, Science 175:911–912.PubMedCrossRefGoogle Scholar
  58. Estevez, V. S., Englert, L. F., and Ho, B. T., 1973, A new methylated metabolite of (—)-1 l-hydroxy-Δ8-tetrahydrocannabinol in rats, Res. Comm. Chem. Pathol. Pharmacol. 6:821–827.Google Scholar
  59. Estevez, V. S., Englert, L. F., and Ho, B. T., 1974, Effect of SKF-525-A on the metabolism of (—)-Δ9-tetrahydrocannabinol in the rat brain and liver, Res. Comm. Chem. Pathol. Pharmacol. 8:389–392.Google Scholar
  60. Fernandes, M., Warning, N., Christ, W., and Hill, R., 1973, Interactions of several cannabinoids with the hepatic drug metabolizing system, Biochem. Pharmacol. 22:2981–2987.PubMedCrossRefGoogle Scholar
  61. Ferraro D. P., and Billings, D. K.,1972, Comparison of behavioral effects of synthetic (—)-Δ9 -trans-tetrahydrocannabinol and marihuana extract distillate in chimpanzees, Psychopharmacologia 25:169–174.PubMedCrossRefGoogle Scholar
  62. Ferraro, D. P., Lynch, W. C., and Grilly, D. M., 1972, Behavioral effects of small oral doses of marihuana extract in chimpanzees, Pharmacology 7:273–282.PubMedCrossRefGoogle Scholar
  63. Ferraro, D. P., Gluck, J. P., and Herndon, G. B., 1974, Acquisition and extinction of variable interval schedule behavior by rats under Δ9-tetrahydrocannabinol, Pharmacol. Biochem. Behav. 2:487–491.PubMedCrossRefGoogle Scholar
  64. Fetterman, P. S., and Turner, C. F., 1972, Constituents of Cannabis sativa L. I: Propyl homologs of cannabinoids from an Indian variant, J. Pharm. Sci. 61:1476–1477.PubMedCrossRefGoogle Scholar
  65. Foltz, R. L., Fentiman, A. F., Jr., Leighty, E. G., Walter, J. L., Drewes, H. R., Schwartz, W. E., Page, T. F., Jr., and Truitt, E. B., Jr., 1970, Metabolite of (—)-trans-Δ8-tetrahydrocannabinol: Identification and synthesis, Science 168:844–845.PubMedCrossRefGoogle Scholar
  66. Forney, R. B., 1971, Toxicology of marihuana, Pharmacol. Rev. 23:279–284.PubMedGoogle Scholar
  67. Frankenheim, J. M., 1974, Effects of repeated doses of 1-Δ8 -trans-tetrahydrocannabinol on schedule-controlled temporally-spaced responding of rats, Psychopharmacologia 38:125–144.PubMedCrossRefGoogle Scholar
  68. Frankenheim, J. M., Mcmillan, D. E., and Harris, L. S., 1971, Effects of 1-Δ9-and 1-Δ8-trans-tetrahydrocannabinol and cannabinol on schedule-controlled behavior of pigeons and rats, J. Pharmacol. Exp. Ther. 178:241–252.PubMedGoogle Scholar
  69. Friedman, E., and Gershon, S., 1974, Tetrahydrocannabinols: Inhibition in acetylcholine synthesis in regional rat brain slices, Pharmacologist 16:286.Google Scholar
  70. Gaoni, Y., and Mechoulam, R., 1964, Isolation, structure, and partial synthesis of an active constituent of hashish, J. Amer. Chem. Soc. 86:1646–1647.CrossRefGoogle Scholar
  71. Gaoni, Y., and Mechoulam, R., 1971, The isolation and structure of Δ1-tetrahydrocannabinol and other neutral cannabinoids from hashish, J. Amer. Chem. Soc. 93:217–224.CrossRefGoogle Scholar
  72. Garriott, J. C, King, L. J., Forney, R. B., and Hughes, F. W., 1967, Effects of some tetrahydrocannabinols on hexobarbital sleeping time and amphetamine-induced hyperactivity in mice, Life Sci. 6:2119–2128.PubMedCrossRefGoogle Scholar
  73. Garriott, J. C, Forney, R. B., Hughes, F. W., and Richards, A. B., 1968, Pharmacologic properties of some cannabis related compounds, Arch. Int. Pharmacodyn. 171:425–434.PubMedGoogle Scholar
  74. Gill, E. W., and Jones, G., 1972, Brain levels of Δ1-tetrahydrocannabinol and its metabolites in mice—Correlation with behaviour, and the effect of the metabolic inhibitors SKF 525-A and piperonyl butoxide, Biochem. Pharmacol 21:2237–2248.PubMedCrossRefGoogle Scholar
  75. Gill, E. W., Paton, W. D. M., and Pertwee, R. G., 1970, Preliminary experiments in the chemistry and pharmacology of cannabis, Nature 228:134–136.PubMedCrossRefGoogle Scholar
  76. Gill, E. W., Jones, G., and Lawrence, D. K., 1973, Contribution of the metabolite 7-hydroxy-Δ1tetrahydrocannabinol towards the pharmacological activity of A′-tetrahydrocannabinol in mice, Biochem. Pharmacol. 22:175–184.PubMedCrossRefGoogle Scholar
  77. Glick, S. D., and Milloy, S., 1972, Increased and decreased eating following THC administration, Psychon. Sci. 29:6.Google Scholar
  78. Grinspoon, L., 1971, Marihuana Reconsidered, Harvard University Press, Cambridge, Mass.Google Scholar
  79. Grunfeld, Y., and Edery, H., 1969, Psychopharmacological activity of the active constituents of hashish and some related cannabinoids, Psychopharmacologia 14:200–210.PubMedCrossRefGoogle Scholar
  80. GuRny, O., Maynard, D. E., Pitcher, R. G., and Kierstead, R. W., 1972, Novel in vitro metabolites of (—)-Δ8-and (—)-Δ9-tetrahydrocannabinol (THC), 5th Intl. Cong. Pharmacol, p. 92.Google Scholar
  81. Haavik, C. O., and Hardman, H. F., 1973a, Evaluation of the hypothermic action of tetrahydrocannabinols in mice and squirrel monkeys, J. Pharmacol. Exp. Ther. 187:568–574.PubMedGoogle Scholar
  82. Haavik, C. O., and Hardman, H. F., 1973b, Hypothermic action of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol and 1 l-hydroxy-Δ8-tetrahydrocannabinol in mice, Life Sci. 13:1771–1778.PubMedCrossRefGoogle Scholar
  83. Harris, R. T., Waters, W., and Mclendon, D., 1972, Behavioral effects in rhesus monkeys of repeated intravenous doses of Δ9-tetrahydrocannabinol, Psychopharmacologia 26:297–306.PubMedCrossRefGoogle Scholar
  84. Hine, B., Friedman, E., Torrelio, M., and Gershon, S., 1975a, Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol, Science 187:443–445.PubMedCrossRefGoogle Scholar
  85. Hine, B., Friedman, E., Torrelio, M., and Gershon, S., 1975b, Tetrahydrocannabinolattenuated abstinence and induced rotation in morphine-dependent rats: Possible involvement of dopamine, Neuropharmacology 14:607–610.PubMedCrossRefGoogle Scholar
  86. Ho, B. T., Fritchie, G. F., Kralik, P. M., Englert, L. F., Mcisaac, W. M., and Idanpaan-Heikkila, J., 1970, Distribution of tritiated-1-Δ9-tetrahydrocannabinol in rat tissues after inhalation, J. Pharm. Pharmacol. 22:538–539.PubMedCrossRefGoogle Scholar
  87. Ho, B. T., Estevez, V., Englert, L. F., and Mcisaac, W. M., 1972a, Δ9-Tetrahydrocannabi-nol and its metabolites in monkey brains, J. Pharm. Pharmacol. 24:414–416.PubMedCrossRefGoogle Scholar
  88. Ho, B. T., Taylor, D., Fritchie, G. E., Englert, L. F., and Mcisaac, W. M., 1972b, Neuropharmacological study of Δ9-and Δ8-1-tetrahydrocannabinols in monkeys and mice, Brain Res. 38:163–170.PubMedCrossRefGoogle Scholar
  89. Ho, B. T., Estevez, V. S., and Englert, L. F., 1973a, The uptake and metabolic fate of cannabinoids in rat brains, J. Pharm. Pharmacol. 25:488–490.PubMedCrossRefGoogle Scholar
  90. Ho, B. T., Estevez, V. S., and Englert, L. F., 1973b, Effect of repeated administration on the metabolism of (—)-Δ9-tetrahydrocannabinols in rats, Res. Comm. Chem. Path. Pharmacol. 5:215–218.Google Scholar
  91. Ho, B. T., Taylor, D., and Englert, L. F., 1973c, The effect of repeated administration of (—)-Δ9-tetrahydrocannabinol on the biosynthesis of brain amines, Res. Comm. Chem. Path. Pharmacol. 5:851–854.Google Scholar
  92. Hockman, C. H., Perrin, R. G., and Kalant, H., 1971, Electroencephalographic and behavioral alterations produced by Δ1-tetrahydrocannabinol, Science 172:968–970.PubMedCrossRefGoogle Scholar
  93. Hollister, L. E., 1971, Hunger and appetite after single doses of marihuana, alcohol, and dextroamphetamine, Clin. Pharmacol. Therap. 12:44–49.Google Scholar
  94. Holtzman, D., Lovell, R. A., Jaffe, J. H., and Freedman, D. X., 1969, 1Δ9-Tetrahydrocannabinol: neurochemical and behavioral effects in the mouse, Science 163:1464–1467.PubMedCrossRefGoogle Scholar
  95. Howes, J. F., 1970, A study of two water soluble derivatives of Δ9-tetrahydrocannabinol, Pharmacologist 12:758.Google Scholar
  96. Jarbe, T. U. C., and Henriksson, B. G., 1973, Effects of Δ8-THC, and Δ9-THC on the acquisition of a discriminative positional habit in rats, Psychopharmacologia 31:321–332.PubMedCrossRefGoogle Scholar
  97. Jarbe, T. U. C., and Henriksson, B. G., 1974, Discriminative response control produced with hashish, tetrahydrocannabinols (Δ8-THC and Δ9-THC), and other drugs, Psychopharmacologia 40:1–16.PubMedCrossRefGoogle Scholar
  98. Johnson, K. M., and Dewey, W. L., 1975, Structure-activity relationships of the cannabinoids in blocking synaptosomal serotonin uptake, Pharmacologist 17:182.Google Scholar
  99. Just, W. W., Erdmann, G., Thel, S., Werner, G., and Wiechmann, M., 1975, Metabolism and autoradiographic distribution of Δ8-and Δ9-tetrahydrocannabinol in some organs of the monkey Callithrix jacchus, N.-S. Arch. Pharmacol. 287:219–225.CrossRefGoogle Scholar
  100. Karbowski, M., Jagoda, A., Dewey, W. L., and Harris, L. S., 1975, Effect of Δ9-THC on the level and turnover of acetylcholine in mouse brain, Pharmacologist 17:254.Google Scholar
  101. Karler, R., Cely, W., and Turkanis, S. A., 1973, The anticonvulsant activity of cannabidiol and cannabinol, Life Sci. 13:1527–1531.PubMedCrossRefGoogle Scholar
  102. Karler, R., Cely, W., and Turkanis, S. A., 1974a, Anticonvulsant properties of Δ9-tetrahydrocannabinol and other cannabinoids, Life Sci. 15:931–947.PubMedCrossRefGoogle Scholar
  103. Karler, R., Cely, W., and Turkanis, S. A., 1974b, A study of the development of tolerance to an anticonvulsant effect of Δ9-tetrahydrocannabinol and cannabidiol Res. Coram. Chem. Pathol. Pharmacol. 9:23–39.Google Scholar
  104. Karler, R., Cely, W., and Turkanis, S. A., 1974c, A study of the relative anticonvulsant and toxic activities of Δ9-tetrahydrocannabinol and its congeners, Res. Comm. Chem. Pathol. Pharmacol. 7:353–358.Google Scholar
  105. Karniol, I. G., and Carlini, E. A., 1973a, Comparative studies in man and in laboratory animals on Δ8-and Δ9-trans-tetrahydrocannabinol, Pharmacology 9:115–126.PubMedCrossRefGoogle Scholar
  106. Karniol, I. G., and Carlini, E. A., 1973b, Pharmacological interaction between cannabidiol and Δ9-tetrahydrocannabinol, Psychopharmacologia 33:53–70.PubMedCrossRefGoogle Scholar
  107. Karniol, I. G., Takahashi, R. N., and Musty, R. E., 1974, Effects of Δ9tetrahydrocannabinol and cannabinol on operant performance in rats, Arch. Int. Pharmacodyn. Ther. 212:230–237.PubMedGoogle Scholar
  108. Kayaalp, S. O., Kaymakcalan, S., Verimer, T., Ilhan, M., and Onur, R., 1974, In vitro neuromuscular effects of Δ9-trans-tetrahydrocannabinol (THC), Arch. Int. Pharmacodyn. Ther. 212:67–75.PubMedGoogle Scholar
  109. Kaymakcalan, S., and Deneau, G. A., 1971, Some pharmacological effects of synthetic Δ9-tetrahydrocannabinol, Pharmacologist 13:247.Google Scholar
  110. Kaymakcalan, S., Turker, R. K., and Turker, M. N., 1974, Analgesic effect of Δ9-tetrahydrocannabinol in the dog, Psychopharmacologia 35:123–128.PubMedCrossRefGoogle Scholar
  111. Killam, K. F., and Killam, E. K., 1972, The action of tetrahydrocannabinol on EEG and photomyoclonic seizures in the baboon, 5th Intl. Cong. Pharmacol., p. 124.Google Scholar
  112. King, L. J., and Forney, R. H., 1967, The absorption and excretion of the marihuana constituents, cannabinol and tetrahydrocannabinol, Fed. Proc. 26:540.Google Scholar
  113. Klausner, H. A., and Dingell, J. V., 1971, The metabolism and excretion of Δ9-tetrahydrocannabinol in the rat, Life Sci. 10:49–59.CrossRefGoogle Scholar
  114. Klausner, H. A., Wilcox, H. G., and Dingell, J. V., 1971, Studies on the interaction of Δ9-tetrahydrocannabinol with plasma lipoproteins, Acta Pharmaceut. Suecica 8:705–706.Google Scholar
  115. Klausner, H. A., Wilcox, H. G., and Dingell, J. V., 1975, The use of zonal ultracentrifugation in the investigation of the binding of Δ9-tetrahydrocannabinol by plasma lipoproteins, Drug Metab. Disp. 3:314–319.Google Scholar
  116. Kosersky, D. S., Mcmillan, D. E., and Harris, L. S., 1974, Δ9-Tetrahydrocannabinol and 11-hydroxy-Δ9-tetrahydrocannabinol: Behavioral effects and tolerance development, J. Pharmacol. Exp. Ther. 189:61–65.PubMedGoogle Scholar
  117. Kreuz, D. S., and Axelrod, J., 1973, Delta-9-tetrahydrocannabinol: Localization in body fat, Science 179:391–393.PubMedCrossRefGoogle Scholar
  118. Kubena, R. K., 1970, Behavioral and physiological effects of delta-1-tetrahydrocannabinol, Ph.D. Thesis, University of Pittsburgh, pp. 82-86.Google Scholar
  119. Kubena, R. K., and Barry, H., III, 1970, Interactions of Δ9tetrahydrocannabinol with barbiturates and methamphetamine, J. Pharmacol. Exp. Ther. 173:94–100.PubMedGoogle Scholar
  120. Kubena, R. K., and Barry, H., III, 1972, Stimulus characteristics of marihuana components, Nature 235:397–398.PubMedCrossRefGoogle Scholar
  121. Lapa, A. J., Sampaio, C. A. M., Timo-Iaria, C., and Valle, J. R., 1968, Blocking action of tetrahydrocannabinol upon transmission in the trigeminal system of the cat, J. Pharm. Pharmacol. 20:373–376.PubMedCrossRefGoogle Scholar
  122. Lemberger, L., Silberstein, S. D., Axelrod, J., and Kopin, I. J., 1970, Marihuana: Studies on the disposition and metabolism of delta-9-tetrahydrocannabinol in man, Science 170:1320–1322.PubMedCrossRefGoogle Scholar
  123. Lemberger, L., Crabtree, R. E., and Rowe, H. M., 1972, 11-Hydroxy-Δ9-Tetrahydrocannabinol: Pharmacology, disposition, and metabolism of a major metabolite of marihuana in man, Science 177:62–64.PubMedCrossRefGoogle Scholar
  124. Lemberger, L., Mcmahon, R. E., Archer, R. A., Matsumoto, K., and Rowe, H., 1973, The in vitro and in vivo metabolism of Δ6a,10a dimethyl heptal tetrahydrocannabinol (DMHP), J. Pharmacol. Exp. Ther. 187:169–175.PubMedGoogle Scholar
  125. Leonard, B. E., 1971, The effect of Δ1,6-tetrahydrocannabinol on biogenic amines and their amino acid precursors in the rat brain, Pharmacol. Res. Comm. 3:139–145.CrossRefGoogle Scholar
  126. Lpparini, F., Scotti de Carolis, A., and Longo, V. G., 1969, A neuropharmacological investigation of some trans-tetrahydrocannabinol derivatives, Physiol. Behav. 4:527–532.CrossRefGoogle Scholar
  127. Liu, R. K., 1974, Hypothermic effects of marihuana, marihuana derivatives and chlorpromazine in laboratory mice, Res. Comm. Chem. Path. Pharmacol. 9:215–228.Google Scholar
  128. Loev, B., Bender, P. E., Dowalo, F., Macro, E., and Fowler, P. J., 1973, Cannabinoids. Structure-activity studies related to 1,2-dimethylheptyl derivatives, J. Med. Chem. 16:1200–1206.PubMedCrossRefGoogle Scholar
  129. Loewe, S., 1946, Studies on the pharmacology and acute toxicity of compounds with marihuana activity, J. Pharmacol. Exp. Ther. 88:154–161.PubMedGoogle Scholar
  130. Lomax, P., 1971, Acute tolerance to the hypothermic effect of marihuana in the rat, Res. Comm. Chem. Pathol. Pharmacol. 2:159–167.Google Scholar
  131. Maitre, L., 1971, Effects of some cannabinols on biosynthesis of brain amines and on pituitary response in the rat, Acta Pharmaceut. Suecica 8:693–694.Google Scholar
  132. Maitre, L., Staehelin, M., and Bein, H. J., 1970, Effect of an extract of cannabis and of some cannabinols on catecholamine metabolism in rat brain and heart, Agents and Actions 1:136–143.PubMedCrossRefGoogle Scholar
  133. Manning, F. J., Mcdonough, J. H., JR., Elsmore, T. F., Saller, C., and Sodetz, F. J., 1971, Inhibition of normal growth by chronic administration of Δ9-tetrahydrocannabinol, Science 174:424–426.PubMedCrossRefGoogle Scholar
  134. Marihuana And Health, Fourth Report to the United States Congress, From the Secretary of Health, Education and Welfare, United States Government Printing Office, 1974, pp. 15-29.Google Scholar
  135. Masur, J., and Khazan, N., 1970, Induction by Cannabis sativa (marihuana) of rhythmic spike discharges overriding REM sleep electrocorticogram in the rat, Life Sci. 9:1275–1280.CrossRefGoogle Scholar
  136. Maynard, D. E., Gurny, O., Pitcher, R. G., and Kierstead, R. W., 1971, (—)-Δ8-Tetrahydrocannabinol: Two novel in vitro metabolites, Experientia 27:1154–1155.PubMedCrossRefGoogle Scholar
  137. Mccaughran, J. A., Jr., Corcoran, M. E., and Wada, J. A., 1974, Anticonvulsant activity of Δ8-and Δ9-tetrahydrocannabinol in rats, Pharmacol. Biochem. Behav. 2:227–233.PubMedCrossRefGoogle Scholar
  138. Mcmillan, D. E., Harris, L. S., Frankenheim, J. M., and Kennedy, J. S., 1970, 1-Δ9-trans-Tetrahydrocannabinol in pigeons: Tolerance to the behavioral effects, Science 169:501–503.CrossRefGoogle Scholar
  139. Mcmillan, D. E., Ford, R. D., Frankenheim, J. M., Harris, R. A., and Harris, L. S., 1972, Tolerance to active constituents of marihuana, Arch. Int. Pharmacodyn. Ther. 198:132–144.PubMedGoogle Scholar
  140. Mcmillan, D. E., Dewey, W. L., Turk, R. F., Harris, L. S., and Mcneil, J. H., Jr., 1973, Blood levels of 3H-Δ9-tetrahydrocannabinol and its metabolites in tolerant and nontolerant pigeons, Biochem. Pharmacol. 22:383–397.PubMedCrossRefGoogle Scholar
  141. Mechoulam, R., 1970, Marihuana chemistry, Science 168:1 159–1166.Google Scholar
  142. Mechoulam, R., 1973, Marijuana Chemistry, Pharmacology, Metabolism and Clinical Effects, Academic Press, New York.Google Scholar
  143. Mikes, F., Hofmann, A., and Waser, P. G., 1971, Identification of (—)-Δ9-6a,10a-trans-tetrahydrocannabinol and two of its metabolites in rats by use of combination gas chromatography-mass spectrometry and mass fragmentography, Biochem. Pharmacol. 20:2469–2476.PubMedCrossRefGoogle Scholar
  144. Mikuriya, T. H., 1969, Marijuana in medicine: Past, present and future, Calif. Med. 110:34–40.PubMedGoogle Scholar
  145. Moreton, J. E., and Davis, W. M., 1970 Effects of Δ9-tetrahydrocannabinol on locomotor activity and on phases of sleep. Pharmacologist 12:258.Google Scholar
  146. Nahas, G. G., 1973, Marihuana—Deceptive Weed, Raven Press, New York.Google Scholar
  147. Nilsson, I. M., Agurell, S., Nilsson, J. L. G., Ohlsson, A., Sandberg, F., and Wahlqvist, M., 1970, Δ1-Tetrahydrocannabinol: Structure of a major metabolite, Science 168:1228–1229.PubMedCrossRefGoogle Scholar
  148. Nilsson, I. M., Agurell, S., Nilsson, J. L. G., Ohlsson, A., Lindgren, J.-E., and Mechoulam, R., 1973a, Metabolism of 7-hydroxy-Δ1(16)-tetrahydrocannabinol in the rabbit, Acta Pharmaceut. Suecica 10:97–106.Google Scholar
  149. Nilsson, I., Agurell, S., Nilsson, J. L. G., Widman, M., and Leander, K., 1973b, Two cannabidiol metabolites formed by rat liver, J. Pharm. Pharmacol. 25:486–487.PubMedCrossRefGoogle Scholar
  150. Nordqvist, M., and Widman, M., 1975, Metabolism of Δ1-tetrahydrocannabinol by lung and liver from dog, Sixth Intl. Cong. Pharmacol, p. 266.Google Scholar
  151. Nordqvist, M., Agurell, S., Binder, M., et al. Nilsson, I. M., 1974, Structure of an acidic metabolite of Δ1tetrahydrocannabinol isolated from rabbit urine, J. Pharm. Pharmacol. 26:471–473.PubMedCrossRefGoogle Scholar
  152. Page, J. G., and West, L. E., 1975, Acute tolerance to hypothermia in rats produced by dl-3-(l,l-dimethylheptyl)-6aβ, 7, 8, 10, 10aα hexahydro-1-hydroxy-6,6-dimethyl-9H-dibenzo b,d pyran-9-One (Lilly Compound 109514), Pharmacologist 17:211.Google Scholar
  153. Pars, H. G., Granchelli, F. E., Razdan, R. K., Keller, J. K., Teiger, D. C., Rosenberg, F. J., and Harris, L. S., 1976, Drugs derived from cannabinoids—Part I. Nitrogen analogs: benzopyranopyridines and benzopyranopyrroles, J. Med. Chem. 19:445–454.PubMedCrossRefGoogle Scholar
  154. Paton, W. D. M., 1975, Pharmacology of marijuana, Ann. Rev. Pharmacol 15:191–220.PubMedCrossRefGoogle Scholar
  155. Paton, W. D. M., and Crown, J., 1972, Cannabis and Its Derivatives, Pharmacology and Applied Psychology, Oxford Univ. Press, London.Google Scholar
  156. Petrzilka, T., and Sikemeier, C., 1967, Compounds of hashish. II. Synthesis of (-)-delta-6,1-3,4 trans-tetrahydrocannabinol and (+)-delta-6,1-3,4 trans-tetrahydrocannabinol, Helv. Chim. Acta 50:2111–2113.PubMedCrossRefGoogle Scholar
  157. Phillips, R. N., Brown, D. J., and Forney, R. B., 1971a, Enhancement of depressant properties of alcohol or barbiturate in combination with aqueous suspended Δ9-tetrahydrocannabinol in rats, J. Forensic Sci. 16:152–161.PubMedGoogle Scholar
  158. Phillips, R. N., Neel, M. A., Brown, D. J., and Forney, R. B., 1971b, Enhancement of caffeine or methamphetamine stimulation in mice with aqueous-suspended Δ9-tetrahydrocannabinol, Pharmacologist 13:297.Google Scholar
  159. Phillips, R. N., Brown, D. J., Martz, R., Hubbard, J. D., and Forney, R. B., 1972, Subacute toxicity of aqueous-suspended Δ9-tetrahydrocannabinol in rats, Tox. Appl. Pharmacol 22:45–49.CrossRefGoogle Scholar
  160. Rating, E., Broermann, I., Honecker, H., Kluwe, S., and Coper, H., 1972, Effect of subchronic treatment with (—) Δ9-trans-tetrahydrocannabinol (Δ8-THC) on food intake, body temperature, hexobarbital sleeping time and hexobarbital elimination in rats, Psychopharmacologia 27:349–357.PubMedCrossRefGoogle Scholar
  161. Razdan, R. K., Handrick, C. R., Dalzell, H. C, Howes, J. F., Winn, M., Plotnikoff, N. P., Dodge, P. W., and Dren, A. T., 1976a, Drugs derived from cannabinoids, IV: Effect of alkyl substitution in sulfur and carbocyclic analogs, J. Med. Chem. 19:552–554.PubMedCrossRefGoogle Scholar
  162. Razdan, R. K., Zitko Terris, B., Handrick, G. R., Dalzell, H. C., Pars, H. G., Howes, J. F., Plotnikoff, N., Dodge, P., Dren, A., Kyncl, J., Shoer, L., and Thompson, W. R., 1976b, Drugs derived from cannabinoids, III: Sulfur analogs: thiopyranobenzopyrans and thienobenzopyrans, J. Med. Chem. 19:549–551.PubMedCrossRefGoogle Scholar
  163. Razdan, R. K., Zitko Terris, B., Pars, H. G., Plotnikoff, N. P., Dodge, P. W., Dren, A. T., Kyncl, J., and Somani, P., 1976c, Drugs derived from cannabinoids, II: Basic esters of nitrogen and carbocyclic analogs, J. Med. Chem. 19:454–461.PubMedCrossRefGoogle Scholar
  164. Ryrfeldt, A., and Ramsay, C. H., 1973, Whole-body autoradiography of Δ1-tetrahydrocannabinol and Δ1(16)-tetrahydrocannabinol in mouse, Acta Pharmaceut. Suedca 10:13–28.Google Scholar
  165. Sampaio, C. A. M., Lapa, A. J., and Valle, J. R., 1967, Influence of cannabis, tetrahydrocannabinol and pyrahexyl on the linguomandibular reflex of the dog, J. Pharm. Pharmacol 19:552–554.PubMedCrossRefGoogle Scholar
  166. Sasman, M., 1938, Cannabis indica in pharmaceuticals, J. Med. Soc. N. J. 35:51–52.Google Scholar
  167. scheckel, C. L., Boff, E., Dahlen, P., and Smart, T., 1968, Behavioral effects in monkeys of racemates of two biologically active marijuana constituents, Science 160:1467–1469.PubMedCrossRefGoogle Scholar
  168. Schildkraut, J. J., and Efron, D. H., 1971, The effects of Δ9-tetrahydrocannabinol on the metabolism of norepinephrine in rat brain, Psychopharmacologia 20:191–196.PubMedCrossRefGoogle Scholar
  169. Segal, M., 1974, Central implantation of cannabinoids: Induction of epileptiform discharges, Europ. J. Pharmacol. 27:40–45.CrossRefGoogle Scholar
  170. Segal, M., and Kenney, A. F., 1972, Δ1-and Δ9-Tetrahydrocannabinol: Preliminary observations on similarities and differences in central pharmacological effects in the cat, Experientia 28:816–819.PubMedCrossRefGoogle Scholar
  171. Segelman, A. B., Sofia, R. D., Segelman, F. P., Harakal, J. J., and Knobloch, L. C., 1974, Cannabis sativa L. (marijuana) V: Pharmacological evaluation of marijuana aqueous extract and volatile oil, J. Pharm. Sci. 63:962–964.PubMedCrossRefGoogle Scholar
  172. Siemens, A. J., and Kalant, H., 1974, Metabolism of Δ1-tetrahydrocannabinol by rats tolerant to cannabis, Can. J. Physiol. Pharmacol. 52:1154–1166.PubMedCrossRefGoogle Scholar
  173. Siemens, A. J., and Kalant, H., 1975, Metabolism of Δ1-tetrahydrocannabinol by the rat in vivo and in vitro, Biochem. Pharmacol. 24:755–762.PubMedCrossRefGoogle Scholar
  174. Siemens, A. J., Kalant, H., Khanna, J. M., Marshman, J., and Ho, G., 1974, Effect of cannabis on pentobarbital-induced sleeping time and pentobarbital metabolism in the rat, Biochem. Pharmacol. 23:477–488.PubMedCrossRefGoogle Scholar
  175. Siemens, A. J., de Nie, L. C, Kalant, H., and Khanna, J. M., 1975, Effects of various psychoactive drugs on the metabolism of Δ1-tetrahydrocannabinol by rats in vitro and in vivo, Europ. J. Pharmacol 31:136–147.CrossRefGoogle Scholar
  176. Sigg, E. B., Keim, K. L., Kovacs, J. L., and Sigg, T. D., 1973, Selective effect of psychotropic agents on preganglionic sympathetic outflow in cat, Fed. Proc. 32:221.Google Scholar
  177. Sjoden, P.-O., Jarbe, T. U. C, and Henriksson, B. G., 1973, Influence of tetrahydrocannabinols (Δ8-THC and Δ9-THC) on body weight, food, and water intake in rats, Pharmacol. Biochem. Behav. 1:395–399.PubMedCrossRefGoogle Scholar
  178. Sofia, R. D., 1972, A paradoxical effect for Δ1-tetrahydrocannabinol on rectal temperature in rats, Res. Comm. Chem. Path. Pharmacol. 4:281–288.Google Scholar
  179. Sofia, R. D., 1974, The lethal effects of Δ9-tetrahydrocannabinol in mice enhanced by pretreatment with SKF 525-A or chloramphenicol, Europ. J. Pharmacol. 26:383–385.CrossRefGoogle Scholar
  180. Sofia, R. D., and Barry, H., III, 1970, Depressant effect of Δ1-tetrahydrocannabinol enhanced by inhibition of its metabolism, Europ. J. Pharmacol. 13:134–137.CrossRefGoogle Scholar
  181. Sofia, R. D., and Barry, H., III, 1972, The influence of SKF 525-A on the analgesic actions of Δ1-tetrahydrocannabinol, Fed. Proc. 31:506.Google Scholar
  182. Sofia, R. D., and Barry, H., III, 1973, Interactions of chronic and acute Δ1-tetrahydrocannabinol pretreatment with zoxazolamine and barbiturates, Res. Comm. Chem. Path. Pharmacol. 5:91–98.Google Scholar
  183. Sofia, R. D., and Barry, H., III, 1974, Acute and chronic effects of Δ9-tetrahydrocannabinol on food intake by rats, Psychopharmacologia 39:213–222.PubMedCrossRefGoogle Scholar
  184. Sofia, R. D., and Knobloch, L. C, 1973, The interaction of Δ9-tetrahydrocannabinol pretreatment with various sedative-hypnotic drugs, Psychopharmacologia 30:185–194.PubMedCrossRefGoogle Scholar
  185. Sofia, R. D., and Knobloch, L. C, 1974, The effect of Δ9-tetrahydrocannabinol pretreatment on ketamine, thiopental or CT-1341-induced loss of righting reflex in mice, Arch. Int. Pharmacodyn. Ther. 207:270–281.PubMedGoogle Scholar
  186. Sofia, R. D., and Knobloch, L. C, 1976, Comparative effects of various naturally occurring cannabinoids on food, sucrose and water consumption by rats, Pharmacol. Biochem. Behav. 4:591–599.PubMedCrossRefGoogle Scholar
  187. Sofia, R. D., Dixit, B. N., and Barry, H., III, 1971a, The effect of Δ1-tetrahydrocannabinol on serotonin metabolism in the rat brain, Life Sci. 10:425–436.CrossRefGoogle Scholar
  188. Sofia, R. D., Ertel, R. J., Dixit, B. N., and Barry, H., III, 1971b, The effect of Δ1-tetrahydrocannabinol on the uptake of serotonin by rat brain homogenates, Europ. J. Pharmacol 16:257–259.CrossRefGoogle Scholar
  189. Sofia, R. D., Nalepa, S. D., Harakal, J. J., and Vassar, H. B., 1973, Anti-edema and analgesic properties of Δ9-tetrahydrocannabinol (THC), J. Pharmacol. Exp. Ther. 186:646–655.PubMedGoogle Scholar
  190. Sofia, R. D., Solomon, T. A., and Barry, H., III, 1976, Anticonvulsant activity of Δ9-tetrahydrocannabinol compared with three other drugs, Europ. J. Pharmacol. 35:7–16.CrossRefGoogle Scholar
  191. Sofia, R. D., Vassar, H. B., and Knobloch, L. C., 1975, Comparative analgesic activity of various naturally occurring cannabinoids in mice and rats, Psychopharmacologia 40:285–295.PubMedCrossRefGoogle Scholar
  192. Stark, P., and Archer, R. A., 1975, Preclinical pharmacologic profile of a psychoactive cannabinoid, Pharmacologist 17:210.Google Scholar
  193. Stoelting, R. K., Martz, R. C., Gartner, J., Creasser, C., Brown, D. J., and Forney, R. B., 1973, Effects of delta-9-tetrahydrocannabinol on halothane MAC in dogs, Anesthesiology 38:521–524.PubMedCrossRefGoogle Scholar
  194. Ten Ham, M., and Van Noordwijk, J., 1973, Lack of tolerance to the effect of two tetrahydrocannabinols on aggressiveness, Psychopharmacologia 29:171–176.PubMedCrossRefGoogle Scholar
  195. Ten Ham, M., and De Jong, Y., 1974, Tolerance to the hypothermic and aggressionattenuating effect of Δ8-and Δ9tetrahydrocannabinol in mice, Europ. J. Pharmacol. 28:144–148.CrossRefGoogle Scholar
  196. Ten Ham, M., and De Jong, Y., 1975, Absence of interaction between Δ9-tetrahydrocannabi-nol (Δ9-THC) and cannabidiol (CBD) in aggression, muscle control and body temperature experiments in mice, Psychopharmacologia 41:169–174.PubMedCrossRefGoogle Scholar
  197. Ten Ham, M., Loskota, W. J., and Lomax, P., 1975, Acute and chronic effects of Δ9-tetrahydrocannabinol on seizures in the gerbil, Europ. J. Pharmacol. 31:148–152.CrossRefGoogle Scholar
  198. Truitt, E. B., Jr., 1971, Biological disposition of tetrahydrocannabinols, Pharmacol. Rev. 23:273–278.PubMedGoogle Scholar
  199. Truitt, E. B., Jr., and Braude, M. C., 1974, Preclinical pharmacology of marihuana, in Research Advances in Alcohol and Drug Problems, Vol. 1 (R. J. Gibbins, Y. Israel, H. Kalant, R. E. Popham, W. Schmidt, and R. G. Smart, eds.), pp. 199–242, Wiley, New York.Google Scholar
  200. Vitez, T. S., Way, W. L., Millter, R. D., and Eger, E. I., II, 1973, Effects of delta-9-tetrahydrocannabinol on cyclopropane MAC in the rat, Anesthesiology 38:525–527.PubMedCrossRefGoogle Scholar
  201. Vree, T. B., Breimer, D. D., Van Ginneken, C. A. M., and Van Rossum, J. M., 1972, Identification in hashish of tetrahydrocannabinol, cannabidiol and cannabinol analogues with a methyl side-chain, J. Pharm. Pharmacol. 24:7–12.PubMedCrossRefGoogle Scholar
  202. Wahlqvist, M., Nilsson, I. M., Sandberg, F., Agurell, S., and Granstrand, B., 1970, Binding of Δ9tetrahydrocannabinol to human plasma proteins, Biochem. Pharmacol. 19:2579–2584.PubMedCrossRefGoogle Scholar
  203. Wall, E., 1971, The in vitro and in vivo metabolism of tetrahydrocannabinol (THC), Ann. N.Y. Acad. Sci. 191:23–29.CrossRefGoogle Scholar
  204. Wall, M. E., Brine, D. R., and Perez-Reyes, M., 1975, Metabolism and excretion of cannabidiol and cannabinol in man, Sixth International Congress of Pharmacology, p. 450.Google Scholar
  205. Wallach, M. B., and Gershon, S., 1973, The effects of Δ8-THC on the EEG, reticular multiple unit activity and sleep of cats, Europ. J. Pharmacol. 24:172–178.CrossRefGoogle Scholar
  206. Welch, B. L., Welch, A. S., Messiha, F. S., and Berger, H. J., 1971, Rapid depletion of adrenal epinephrine and elevation of telencephalic serotonin by (—)-trans-Δ9-tetrahydrocannabinol in mice, Res. Comm. Chem. Path. Pharmacol. 2:382–391.Google Scholar
  207. Widman, M., Nilsson, I. M., Nilsson, J. L. G., Agurell, S., and Leander, K., 1971, Metabolism of cannabis. IX. Cannabinol: Structure of a major metabolite formed in rat liver, Life Sci. 10:157–162.CrossRefGoogle Scholar
  208. Widman, M., Nilsson, I. M., Nilsson, J. L. G., Agurell, S., Borg, H., and Granstrand, B., 1973, Plasma protein binding of 7-hydroxy-Δ9-tetrahydrocannabinol: An active Δ1-tetrahydrocannabinol metabolite, J. Pharm. Pharmacol. 25:453–457.PubMedCrossRefGoogle Scholar
  209. Widman, M., Agurell, S., Ehrnebo, M., and Jones, G., 1974a, Binding of (+)-and (—)-Δ1-tetrahydrocannabinols and (—)-7-hydroxy-Δ9tetrahydrocannabinol to blood cells and plasma proteins in man, J. Pharm. Pharmacol. 26:914–916.PubMedCrossRefGoogle Scholar
  210. Widman, M., Nordqvist, M., Agurell, S., Lindgren, J.-E., and Sandberg, F., 1974b, Biliary excretion of Δ1tetrahydrocannabinol and its metabolites in the rat, Biochem. Pharmacol. 23:1163–1172.PubMedCrossRefGoogle Scholar
  211. Willinsky, M. D., Scotti de Carolis, A., and Longo, V. G., 1973, EEG and behavioral effects of natural, synthetic and biosynthetic cannabinoids, Psychopharmacologia 31:365–374.PubMedCrossRefGoogle Scholar
  212. Willinsky, M. D., Kalant, H., Meresz, C., Endrenyi, L., and Woo, N., 1974, Distribution and metabolism in vivo of 14C-tetrahydrocannabinol in the rat, Europ. J. Pharmacol. 27:106–119.CrossRefGoogle Scholar
  213. Wilson, R. S., and May, E. L., 1975, Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs, J. Med. Chem. 17:700–703.CrossRefGoogle Scholar
  214. Winn, M., Arendsen, D., Dodge, P., Dren, A., Dunnigan, D., Hallas, R., Hwang, K., Kyncl, J., Lee, Y.-H., Plotnikoff, N., Young, P., Zaugg, H., Dalzell, H., and Razdan, R. K., 1976, Drugs derived from cannabinoids, V: Δ6a,10a-tetrahydrocannabinol and heterocyclic analogs containing aromatic side chains, J. Med. Chem. 19:461–471.PubMedCrossRefGoogle Scholar
  215. Zitko, B. A., Howes, J. F., Razdan, R. K., Dalzell, B. C., Dalzell, H. C., Sheehan, J. C, Pars, H. G., Dewey, W. L., and Harris, L. S., 1972, Water-soluble derivatives of Δ1-tetrahydrocannabinol, Science 177:442–444.PubMedCrossRefGoogle Scholar
  216. Zunin, L. M., 1969, Marijuana: The drug and the problem, Mil. Med, 134:104–110.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1978

Authors and Affiliations

  • R. Duane Sofia
    • 1
  1. 1.Biological ResearchWallace LaboratoriesCranburyUSA

Personalised recommendations