Pharmacology of Cannabis

  • Allyn C. Howlett
Chapter

Abstract

The biological actions of cannabinoid compounds in humans have received the attention of several excellent reviews within the last 20 years (Abood & Martin, 1992; Bhargava, 1978; Dewey, 1986; Hollister, 1986; Lemberger, 1980; Paton, 1975). It is now believed that many of the effects of cannabimimetic compounds can be attributed to their actions via two receptors, the CB1 and the CB2 cannabinoid receptors. The central nervous system (CNS) responses to cannabinoid compounds are believed to be mediated by the CB1 subtype. The CB1 subtype also exists as a splice variant isoform, CB1(b), which is truncated at an extracellular site and whose mRNA is found in much lower abundance (Rinaldi-Carmona et al, 1996; Shire et al, 1995). The CB1(a) and CB1(b) isoforms exhibit relatively similar pharmacological properties when expressed in Chinese hamster ovary (CHO) cells (Rinaldi-Carmona et al, 1996). The CB1 receptor is a G protein coupled receptor that inhibits adenylate cyclase activity and regulates ion channels. Several recent reviews have described the pharmacology, biochemistry, and CNS distribution of this receptor subtype (Abood & Martin, 1992; Howlett, Bidaut-Russell, et al, 1990; Howlett, Evans, & Houston, 1992; R. Pertwee, 1993). The CB2 receptor is found in immune tissue, and is also a G protein coupled receptor that mediates inhibition of cyclic AMP synthesis. As discussed in reviews by Howlett (1995a), Martin (1986), and Pertwee (1988), certain in vitro effects of cannabinoid drugs have been reported that may not be mediated by a receptor mechanism.

Keywords

Adenylate Cyclase Phospholipid Headgroups Arachidonoyl Ethanolamide Inhibit Adenylate Cyclase Activity Central Nervous System Distribution 
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.

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References

  1. Abood, M. E., & Martin, B. R. (1992). Neurobiology of marijuana abuse. Trends in Pharmacological Sciences, 13, 201–206.PubMedCrossRefGoogle Scholar
  2. Aceto, M. D., Scates, S. M., Lowe, J. A., & Martin, B. R. (1995). Cannabinoid precipitated withdrawal by the selective cannabinoid receptor antagonist, SR 141716A. European Journal of Pharmacology, 282, R 1 — R2.Google Scholar
  3. Adler, M. W., & Geller, E. B. (1986). Ocular effects of cannabinoids. In R. Mechoulam (Ed.), Cannabinoids as therapeutic agents (pp. 51–70 ). Boca Raton, FL: CRC.Google Scholar
  4. Agurell, S., Hal!din, M., Lindgren, J. E., Ohlsson, A., Widman, M., Gillespie, H., & Hollister, L. (1986). Pharmacokinetics and metabolism of delta I-tetrahydrocannabinol and other cannabinoids with emphasis on man. Pharmacological Reviews, 38, 21–43.Google Scholar
  5. Bhargava, H. N. (1978). Potential therapeutic applications of naturally occurring and synthetic cannabinoids. General Pharmacology, 9, 195–213.PubMedCrossRefGoogle Scholar
  6. Bidaut-Russell. M., & Howlett, A. C. (1991). Cannabinoid receptor-regulated cyclic AMP accumulation in the rat striatum. Journal of Neurochemistry, 57, 1769–1773.Google Scholar
  7. Bidaut-Russell, M., Devane, W. A., & Howlett, A. C. (1990). Cannabinoid receptors and modulation of cyclic AMP accumulation in the rat brain. Journal of Neurochemistry, 55, 21–26.PubMedCrossRefGoogle Scholar
  8. Bloom, A. S., Dewey, W. L., Harris, L. S., & Brosius, K. K. (1977). 9-nor-93-Hydroxyhexahydrocannabinol, a cannabinoid with potent antinociceptive activity: Comparisons with morphine. Journal of Pharmacology and Experimental Therapeutics, 200, 263–270.Google Scholar
  9. Bornheim, L. M., Kim, K. Y., Chen, B., & Correia, M. A. (1993). The effect of cannabidiol on mouse hepatic microsomal cytochrome P450-dependent anandamide metabolism. Biochemical and Biophysical Research Communications, 197, 740–746.PubMedCrossRefGoogle Scholar
  10. Bornheim, L. M., Kim, K. Y., Chen, B., & Correia, M. A. (1995). Microsomal cytochrome P450-mediated liver and brain anandamide metabolism. Biochemical Pharmacology, 50, 677–686.PubMedCrossRefGoogle Scholar
  11. Bouaboula, M., Rinaldi, M., Carayon, P, Carillon, C., Delpech, B., Shire, D., Le Fur, G., & Casellas, P. (1993). Cannabinoid-receptor expression in human leukocytes. European Journal of Biochemistry, 214, 173–180.CrossRefGoogle Scholar
  12. Campbell, K. A., Foster, T. C., Hampson, R. E., & Deadwyler, S. (1986a). 49-Tetrahydrocannabinol differentially affects sensory-evoked potentials in the rat dentate gyrus. Journal of Pharmacology and Experimental Therapeutics, 239, 936–940.Google Scholar
  13. Campbell, K. A., Foster, T. C., Hampson, R. E., & Deadwyler, S. A. (1986b). Effects of A°-tetrahydrocannabinol on sensory-evoked discharges of granule cells in the dentate gyrus of behaving rats. Journal of Pharmacology and Experimental Therapeutics, 239, 941–945.PubMedGoogle Scholar
  14. Caulfield, M. P., & Brown, D. A. (1992). Cannabinoid receptor agonists inhibit Ca current in NG 108–15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. British Journal of Pharmacology, 106, 231–232.PubMedCrossRefGoogle Scholar
  15. Chait, L. D., & Pierri, J. (1992). Effects of smoked marijuana on human performance: A critical review. In L. Murphy & A. Bartke (Eds.), Marijuana/cannabinoids neurobiology and neurophysiology (pp. 387–424 ). Boca Raton, FL: CRC.Google Scholar
  16. Childers, S. R., & Deadwyler, S. A. (1996). Role of cyclic AMP in the actions of cannabinoid receptors. Biochemical Pharmacology, 52, 819–827.PubMedCrossRefGoogle Scholar
  17. Compton, D. R., Rice, K. C., De Costa, B. R., Razdan, R. K., Melvin, L. S., Johnson, M. R., & Martin, B. R. (1993). Cannabinoid structure-activity relationships: Correlation of receptor binding and in vivo activities. Journal of Pharmacology and Experimental Therapeutics, 265, 218–226.PubMedGoogle Scholar
  18. Compton, D. R., Aceto, M. D., Lowe, J., & Martin, B. R. (1996). In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): Inhibition of 4°-tetrahydrocannabinol-induced responses and apparent agonist activity. Journal of Pharmacology and Experimental Therapeutics, 277, 586–594.PubMedGoogle Scholar
  19. Deadwyler, S. A., Hampson, R. E., Bennett, B. A., Edwards, T. A., Mu, J., Pacheco, M. A., Ward, S. J., & Childers, S. R. (1993). Cannabinoids modulate potassium current in cultured hippocampal neurons. Receptors and Channels, I, 121–134.Google Scholar
  20. Desarnaud, F., Cadas, H., & Piomelli, D. (1995). Anandamide amidohydrolase activity in rat brain microsomes: Identification and partial characterization. Journal of Biological Chemistry 270, 6030–6035.PubMedCrossRefGoogle Scholar
  21. Deutsch, D. G., & Chin, S. A. (1993). Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochemical Pharmacology, 46, 791–796.PubMedCrossRefGoogle Scholar
  22. Devane, W. A., & Axelrod, J. (1994). Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes. Proceedings of the National Academy of Sciences of the United States ofAmerica, 91, 6698–6701.CrossRefGoogle Scholar
  23. Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S., & Howlett, A. C. (1988). Determination and characterization of a cannabinoid receptor in rat brain. Molecular Pharmacology, 34, 605–613.PubMedGoogle Scholar
  24. Devane, W. A., Breuer, A., Sheskin, T., Jarbe, T. U. C., Eisen, M. S., & Mechoulam, R. (1992). A novel probe for the cannabinoid receptor. Journal of Medicinal Chemistry, 35, 2065–2069.PubMedCrossRefGoogle Scholar
  25. Dewey, W. L. (1986). Cannabinoid pharmacology. Pharmacological Reviews, 38, 151–178.PubMedGoogle Scholar
  26. Dewey, W L., Peng, T. C, & Harris, L. S. (1970). The effect of I-trans-4°-tetrahydrocannabinol on the hypothalamo-hypophyseal-adrenal axis of rats. European Journal of Pharmacology, 12, 382–384.Google Scholar
  27. DiMarzo, V, & Fontana, A. (1995). Anandamide, an endogenous cannabinomimetic eicosanoid: “Killing two birds with one stone” Prostaglandins Leukotrienes and Essential Fatty Acids, 53, 1–11.CrossRefGoogle Scholar
  28. DiMarzo, V., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D. (1994). Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature, 372, 686–691.CrossRefGoogle Scholar
  29. Eldridge, J. C., Murphy, L. L., & Landfield, P. W. (1991). Cannabinoids and the hippocampal glucocorticoid receptor: Recent findings and possible significance. Steroids, 56, 226–231.PubMedCrossRefGoogle Scholar
  30. Felder, C. C., Joyce, K. E., Briley, E. M., Mansouri, J., Mackie, K., Blond, O., Lai, Y., Ma, A. L., & Mitchell, R. L. (1995). Comparison of the pharmacology and signal transduction of the human cannabinoid CBI and CB2 receptors. Molecular Pharmacology, 48, 443–450.PubMedGoogle Scholar
  31. Ferraro, D. P. (1980). Acute effects of marijuana on human memory and cognition. In R. C. Peterson (Ed.), Marijuana research findings: 1980 (NIDA Research Monograph Series No. 31, pp. 98–119). Bethesda, MD: National Institute on Drug Abuse.Google Scholar
  32. Galiegue, S., Sophie, M., Marchand, J., Dussossoy, D., Carriere, D., Carayon, E, Bouaboula, M., Shire, D., LeFur, G., & Casellas, P. (1995). Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. European Journal of Biochemistry, 232, 54–61.PubMedCrossRefGoogle Scholar
  33. Gough, A. L., & O11ey, J. E. (1978). Catalepsy induced by intrastriatal injections of delta9-THC and 11-OHdelta9-THC in the rat. Neuropharmacology, 17, 137–144.PubMedCrossRefGoogle Scholar
  34. Hampson, R. E., Foster, T. C., & Deadwyler, S. A. (1989). Effects of 49-tetrahydrocannabinol on sensory evoked hippocampal activity in the rat: Principal components analysis and sequential dependency. Journal of Pharmacology and Experimental Therapeutics, 251, 870–877.PubMedGoogle Scholar
  35. Hampson, R. E., Evans, G. J. O., Mu, J., Zhuang, S., King, V. C., Childers, S. R., & Deadwyler, S. A. (1995). Role of cyclic AMP dependent protein kinase in cannabinoid receptor modulation of potassium “A-current” in cultured rat hippocampal neurons. Life Sciences, 56, 2081–2088.PubMedCrossRefGoogle Scholar
  36. Hansen, H. S., Lauritzen, L., Strand, A. M., Moesgaard, B., & Frandsen, A. (1995). Glutamate stimulates the formation of N-acylphosphatidylethanolamine and N-acylethanolamine in cortical neurons in culture. Biochimica Et Biophysica Acta, 1258, 303–308.PubMedCrossRefGoogle Scholar
  37. Hanus, L., Gopher, A., Almog, S., & Mechoulam, R. (1993). Two new unsaturated fatty acid ethanolamides in brain that bind to the cannabinoid receptor. Journal of Medicinal Chemistry, 36, 3032–3034.PubMedCrossRefGoogle Scholar
  38. Henry, D. J., & Chavkin, C. (1995). Activation of inwardly rectifying potassium channels (GIRKI) by co-expressed rat brain cannabinoid receptors in Xenopus oocytes. Neuroscience Letters, 186, 91–94.PubMedCrossRefGoogle Scholar
  39. Herkenham, M., Lynn, A. B., Little, M. D., Johnson, M. R., Melvin, L. S., de Costa, B. R., & Rice, K. C. (1990). Cannabinoid receptor localization in brain. Proceedings of the National Academy of Sciences of the United States of America, 87, 1932–1936.PubMedCrossRefGoogle Scholar
  40. Herkenham, M., Groen, B. G., Lynn, A. B., De Costa, B. R., & Richfield, E. K. (1991). Neuronal localization of cannabinoid receptors and second messengers in mutant mouse cerebellum. Brain Research, 552, 301–310.PubMedCrossRefGoogle Scholar
  41. Herkenham, M., Lynn, A. B., De Costa, B. R., & Richfield, E. K. (1991). Neuronal localization of cannabinoid receptors in the basal ganglia of the rat. Brain Research, 547, 267–274.PubMedCrossRefGoogle Scholar
  42. Herkenham, M., Lynn, A. B., Johnson, M. R., Melvin, L. S., de Costa, B. R., & Rice, K. C. (1991). Characterization and localization of cannabinoid receptors in rat brain: A quantitative in vitro autoradiographic study. Journal of Neuroscience, 11, 563–583.PubMedGoogle Scholar
  43. Heyser, C. J., Hampson, R. E., & Deadwyler, S. A. (1993). Effects of 4°-tetrahydrocannabinol on delayed match to sample performance in rats: Alterations in short-term memory associated with changes in task specific firing of hippocampal cells. Journal of Pharmacology and Experimental Therapeutics, 264, 294–307.PubMedGoogle Scholar
  44. Hillard, C. J., & Bloom, A. S. (1983). Possible role of prostaglandins in the effects of the cannabinoids on adenylate cyclase activity. European Journal of Pharmacology, 91, 21–27.PubMedCrossRefGoogle Scholar
  45. Hillard, C. J., Farber, N. E., Hagen, T. C., & Bloom, A. S. (1984). The effects of 49-tetrahydrocannabinol on serum thyrotropin levels in the rat. Pharmacology, Biochemistry and Behavior, 20, 547–550.CrossRefGoogle Scholar
  46. Hillard C. J., Harris, R. A., & Bloom, A. S. (1985). Effects of the cannabinoids on physical properties of brain membranes and phospholipid vesicles: Fluorescence studies. Journal of Pharmacology and Experimental Therapeutics, 232, 579–588.PubMedGoogle Scholar
  47. Hillard, C. J., Pounds, J. J., Boyer, D. R., & Bloom, A. S. (1990). Studies of the role of membrane lipid order in the effects of delta 9-tetrahydrocannabinol on adenylate cyclase activation in heart. Journal of Pharmacology and Experimental Therapeutics, 252, 1075–1082.PubMedGoogle Scholar
  48. Hillard, C. J.. Wilkison, D. M., Edgemond, W. S., & Campbell, W. B. (1995). Characterization of the kinetics and distribution of N-arachidonylethanolamine (anandamide) hydrolysis by rat brain. Biochimica Et Biophysica Acta, 1257, 249–256.Google Scholar
  49. Hollister, L. E. (1986). Health aspects of cannabis. Pharmacological Reviews, 38, 1–20.PubMedGoogle Scholar
  50. Hollister, L. E., & Gillespie, H. K. (1973). Delta-8- and delta-9-tetrahydrocannabinol comparison in man by oral and intravenous administration. Clinical Pharmacology and Therapeutics, 14, 353–357.PubMedGoogle Scholar
  51. Hosko, M. J., Schmeling, W. T., & Hardman, H. F. (1984). 49-tetrahydrocannabinol: Site of action for autonomic effects. In S. Agurell, W. L. Dewey, & R. E. Willette (Eds.), The cannabinoids: Chemical, pharmacologic and therapeutic aspects (pp. 635–648 ). New York: Academic Press.Google Scholar
  52. Houslay, M. D., & Gordon, L. M. (1983). The activity of adenylate cyclase is regulated by the nature of its lipid environment. Current Topics Membranes and Transport, 18, 179–231.Google Scholar
  53. Howlett, A. C. (1987). Cannabinoid inhibition of adenylate cyclase: Relative activity of constituents and metabolites of marihuana. Neuropharmacology, 26, 507–512.PubMedCrossRefGoogle Scholar
  54. Howlett, A. C. (1995a). Cannabinoid compounds and signal transduction mechanisms. In R. G. Pertwee (Ed.), Cannabinoid receptors: Molecular biology and phar- macology (pp. 167–204 ). London: Academic Press.Google Scholar
  55. Howlett, A. C. (19956). Pharmacology of cannabinoid receptors. Annual Review of Pharmacology and Toxicology, 35, 607–634.Google Scholar
  56. Howlett, A. C., Bidaut-Russell, M., Devane, W. A., Melvin, L. S., Johnson, M. R., & Herkenham, M. (1990). The cannabinoid receptor: Biochemical, anatomical and behavioral characterization. Trends in Neurosciences, 13, 420–423.PubMedCrossRefGoogle Scholar
  57. Howlett, A. C., Champion, T. M., Wilken, G. H., & Mechoulam, R. (1990). Stereochemical effects of Il–OH-delta 8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. Neuropharmacology, 29, 161–165.PubMedCrossRefGoogle Scholar
  58. Howlett, A. C., Evans, D. M., & Houston, D. B. (1992). The cannabinoid receptor. In L. Murphy & A. Bartke (Eds.), Marijuana/cannabinoids: Neurobiology and neurophysiology (pp. 35–72 ). Boca Raton, FL: CRC.Google Scholar
  59. Howlett, A. C., Berglund, B. A., & Melvin, L. S. (1995). Cannabinoid receptor agonists and antagonists. Current Pharmaceutical Design, 1, 343–354.Google Scholar
  60. Jain, A. K., Ryan, J. R., McMahon, F. G., & Smith, G. (1981). Evaluation of intramuscular levonantradol and placebo in acute postoperative pain. Journal of Clinical Pharmacology, 21, 3205–3265.Google Scholar
  61. Jansen, E. M., Haycock, D. A., Ward, S. J., & Seybold, V. S. (1992). Distribution of cannabinoid receptors in rat brain determined with aminoalkylindoles. Brain Research, 575, 93–102.PubMedCrossRefGoogle Scholar
  62. Johnson, M. R., & Melvin, L. S. (1986). The discovery of nonclassical cannabinoid analgetics. In R. Mechoulam (Ed.), cannabinoids as therapeutic agents (pp. 121–145 ). Boca Raton, FL: CRC.Google Scholar
  63. Jones, R. T. (1985). Cardiovascular effects of cannabinoids. In D. J. Harvey (Ed.), Marihuana ‘84 (pp. 325–334 ). Oxford, England: IRL.Google Scholar
  64. Kempe, K., Hsu, E F., Bohrer, A., & Turk, J. (1996). Isotope dilution mass spectrometric measurements indicate that arachidonylethanolamide, the proposed endogenous ligand of the cannabinoid receptor, accumulates in rat brain tissue post mortem but is contained at low levels in or is absent from fresh tissue. Journal of Biological Chemistry, 271, 17287–17295.PubMedCrossRefGoogle Scholar
  65. Kokka, N., & Garcia, Y. E (1974). Effects of A9-tetrahydrocannabinol on growth hormone and adrenocorticotrophic hormone secretions in rats. Life Sciences, 15, 329–338.PubMedCrossRefGoogle Scholar
  66. Koutek, B., Prestwich, G. D., Howlett, A. C., Chin, S. A., Salehani, D., Akhavan, N., & Deutsch, D. G. (1994). Inhibitors of arachidonoyl ethanolamide hydrolysis. Journal of Biological Chemistry, 269, 22937–22940.PubMedGoogle Scholar
  67. Kruszka, K. K., & Gross, R. W. (1994). The ATP- and CoA-independent synthesis of arachidonoylethanolamide. Journal of Biological Chemistry, 269, 14345–14348.PubMedGoogle Scholar
  68. Kuster, J. E., Stevenson, J. I., Ward, S. J., D’Ambra, T. E., & Haycock, D. A. (1993). Aminoalkylindole binding in rat cerebellum: Selective displacement by natural and synthetic cannabinoids. Journal of Pharmacol- ogy and Experimental Therapeutics, 264, 1352–1363.Google Scholar
  69. Lawrence, D. K., & Gill, E. W. (1975). The effects of deltal-tetrahydrocannabinol and other cannabinoids on spin-labeled liposomes and their relationship to mechanisms of general anesthesia. Molecular Pharmacology, 11, 595–602.PubMedGoogle Scholar
  70. Lemberger, L. (1980). Potential therapeutic usefulness of marijuana. Annual Review of Pharmacology and Toxicology, 20, 151–172.PubMedCrossRefGoogle Scholar
  71. Lichtman, A. H., & Martin, B. R. (1991a). Cannabinoidinduced antinociception is mediated by a spinal alpha 2-noradrenergic mechanism. Brain Research, 559, 309–314.PubMedCrossRefGoogle Scholar
  72. Lichtman, A. H., & Martin, B. R. (1991b). Spinal and supraspinal components of cannabinoid-induced antinociception. Journal of Pharmacology and Experimental Therapeutics, 258, 517–523.PubMedGoogle Scholar
  73. Lichtman, A. H., Cook, S. A., & Martin, B. R. (1996). Investigation of brain sites mediating cannabinoidinduced antinociception in rats: Evidence supporting periaqueductal gray involvement. Journal of Pharmacology and Experimental Therapeutics, 276, 585–593.PubMedGoogle Scholar
  74. Lichtman, A. R., Dimen, K. R., & Martin, B. R. (1995). Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats. Psychopharmacology, 119, 282–290.PubMedCrossRefGoogle Scholar
  75. Little, P. J., Compton, D. R., Mechoulam, R., & Martin, B. R. (1989). Stereochemical Effects of II-OH-AsTHC-dimethytheptyl in mice and dogs. Pharmacology, Biochemistry and Behavior, 32, 661–666.CrossRefGoogle Scholar
  76. Lynn, A. B., & Herkenham, M. (1994). Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: Implications for receptor-mediated immune modulation by cannabinoids. Journal of Pharmacology and Experimental Therapeutics, 268, 1612–1623.PubMedGoogle Scholar
  77. Mackie, K., & Hille, B. (1992). Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proceedings of the National Academy of Sciences of the United States ofAmerica, 89, 3825–3829.CrossRefGoogle Scholar
  78. Mackie, K.. Lai, Y., Westenbroek, R., & Mitchell, R. (1995). Cannabinoids activate an inwardly rectifying potassium conductance and inhibit Q-type calcium currents in AtT20 cells transfected with rat brain cannabinoid receptor. Journal of Neuroscience, 15, 6552–6561.Google Scholar
  79. Mailleux, P., & Vanderhaeghen, J.-J. (1992a). Distribution of neuronal cannabinoid receptor in the adult rat brain: A comparative receptor binding radioautography and in situ hybridization histochemistry. Neuroscience, 48, 655–668.PubMedCrossRefGoogle Scholar
  80. Mailleux, P., & Vanderhaeghen, J. J. (1992b). Localization of cannabinoid receptor in the human developing and adult basal ganglia. Higher levels in the striatonigral neurons. Neuroscience Letters, 148, 173–176.PubMedCrossRefGoogle Scholar
  81. Mailleux, P., Parmentier, M., & Vanderhaeghen, J. J. (1992). Distribution of cannabinoid receptor messenger RNA in the human brain: An in situ hybridization histochemistry with oligonucleotides. Neuroscience Letters, 143, 200–204.PubMedCrossRefGoogle Scholar
  82. Mailleux, P., Verslijpe, M., & Vanderhaeghen, J.-J. (1992). Initial observations on the distribution of cannabinoid receptor binding sites in the human adult basal ganglia using autoradiography. Neuroscience Letters, 139, 7–9.PubMedCrossRefGoogle Scholar
  83. Martin, B. R. (1986). Cellular effects of cannabinoids. Pharmacological Reviews, 38, 45–74.PubMedGoogle Scholar
  84. Martin, B. R., Balster, R. L., Razdan, R. K., Harris, L. S., & Dewey, W. L. (1981). Behavioral comparisons of the stereoisomers of tetrahydrocannabinols. Life Sciences, 29, 565–574.PubMedCrossRefGoogle Scholar
  85. Martin, B. R., Compton, D. R., Thomas, B. F., Prescott, W. R., Little, P. J, Razdan, R. K., Johnson, M. R., Melvin, L. S., Mechoulam, R., & Ward, S. J. (1991). Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs. Pharmacology, Biochemistry and Behavior, 40, 471–478.Google Scholar
  86. Martin, W. J., Lai, N. K., Patrick, S. L., Tsou, P. K., & Walker, J. M. (1993). Antinociceptive actions of cannabinoids following intraventricular administration in rats. Brain Research, 629, 300–304.PubMedCrossRefGoogle Scholar
  87. Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned eDNA. Nature, 346, 561–564.PubMedCrossRefGoogle Scholar
  88. Matsuda, L. A., Bonner, T. I., & Lolait, S. J. (1993). Localization of cannabinoid receptor mRNA in rat brain. Journal of Comparative Neurology 327, 535–550.PubMedCrossRefGoogle Scholar
  89. Mavromoustakos, T., Yang, D. P., Charalambous, A., Her-bette, L. G., & Makriyannis, A. (1990). Study of the topography of cannabinoids in model membranes using X-ray diffraction. Biochimica Et Biophysica Acta, 1024, 336–344.PubMedCrossRefGoogle Scholar
  90. Mavromoustakos, T., Yang, D. E, Broderick, W., Fournier, D., & Makriyannis, A. (1991). Small angle x-ray diffraction studies on the topography of cannabinoids in synaptic plasma membranes. Pharmacology, Biochemistry and Behavior, 40, 547–552.CrossRefGoogle Scholar
  91. Mechoulam, R., Hanus, L., & Martin, B. R. (1994). Search for endogenous ligands of the cannabinoid receptor. Biochemical Pharmacology, 48, 1537–1544.PubMedCrossRefGoogle Scholar
  92. Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N. E., Schatz, A. R., Gopher, A., Almog, S., Martin, B. R., Compton, D. R., Pertwee, R. G., Griffin, G., Bayewitch, M., Barg, J., & Vogel, Z. (1995). Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochemical Pharmacology, 50, 83–90.PubMedCrossRefGoogle Scholar
  93. Miller, L. L. (1984). Marijuana: Acute effects on human memory. In S. Agurell, W. L. Dewey, & R. E. Willette (Eds.), The cannabinoids: Chemical, pharmacological, and therapeutic aspects (pp. 21–46 ). Orlando, FL: Academic Press.Google Scholar
  94. Mons, N., & Cooper, D. M. E. (1995). Adenylate cyclases: Critical foci in neuronal signaling. Trends in Neurosciences, 18, 536–542.PubMedCrossRefGoogle Scholar
  95. Moss, D. E., McMaster, S. B., & Rogers, J. (1981). Tetrahydrocannabinol potentiates reserpine-induced hypokinesia. Pharmacology, Biochemistry and Behavior, 15, 779–783.CrossRefGoogle Scholar
  96. Moss, D. E., Manderscheid, P Z., Kobayashi, H., & Montgomery, S. P. (1988). Evidence for the nicotinic cholinergic hypothesis of cannabinoid action within the central nervous system: Extrapyramidal motor behaviors. In G. Chesher, P. Consroe, & R. Musty (Eds.), Marijuana: An international research report (pp. 359–364 ). Canberra, Australia: Australian Government Publishing Service.Google Scholar
  97. Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61–65.PubMedCrossRefGoogle Scholar
  98. Murphy, L. L., Steger, R. W, & Bartke, A. (1990). Psychoactive and nonpsychoactive cannabinoids and their effects on reproductive neuroendocrine parameters. In R. R. Watson (Ed.), Biochemistry and physiology of substance abuse (Vol. 2, pp. 73–93 ). Boca Raton, FL: CRC.Google Scholar
  99. Okey, A. B., & Bondy, G. P. (1977). Is delta-9-tetrahydrocannabinol estrogenic? [Letter]. Science, 195, 904–906.PubMedCrossRefGoogle Scholar
  100. Pacheco, M., Childers, S. R., Arnold, R., Casiano, F., & Ward, S. J. (1991). Aminoalkylindoles: Actions on specific G-protein-linked receptors. Journal of Pharmacology and Experimental Therapeutics, 257, 170–183.Google Scholar
  101. Pacheco, M. A., Ward, S. J., & Childers, S. R. (1993). Identification of cannabinoid receptors in cultures of rat cerebellar granule cells. Brain Research, 603, 102–110.PubMedCrossRefGoogle Scholar
  102. Pacheco, M. A., Ward, S. J., & Childers, S. R. (1994). Differential requirements of sodium for coupling of cannabinoid receptors to adenylyl cyclase in rat brain membranes. Journal of Neurochemistry, 62, 1773–1782.PubMedCrossRefGoogle Scholar
  103. Pan, X., Ikeda, S. R., & Lewis, D. L. (1996). Rat brain cannabinoid receptor modulates N-type Ca’ channels in a neuronal expression system. Molecular Pharmacology 49, 707–714.PubMedGoogle Scholar
  104. Paton, W. D. (1975). Pharmacology of marijuana. Annual Review of Pharmacology, 15, 191–220.PubMedCrossRefGoogle Scholar
  105. Pertwee, R. (1993). The evidence for the existence of cannabinoid receptors. General Pharmacology, 24, 811–824.PubMedCrossRefGoogle Scholar
  106. Pertwee, R. G. (1985). Effects of cannabinoids on thermoregulation: A brief review. In D. J. Harvey (Ed.), Marihuana ‘84 (pp. 263–277 ). Oxford, England: IRL.Google Scholar
  107. Pertwee, R. G. (1988). The central neuropharmacology of psychotropic cannabinoids. Pharmacology & Therapeutics, 36, 189–261.Google Scholar
  108. Pertwee, R. G., & Greentree, S. G. (1988). A’ -tetrahydrocannabinol-induced catalepsy in mice is enhanced by pretreatment with flurazepam or chlordiazepoxide. Neuropharmacology, 27, 485–491.PubMedCrossRefGoogle Scholar
  109. Pertwee, R. G., & Ross, T M. (1991). Drugs which stimulate or facilitate central cholinergic transmission interact synergistically with delta-9-tetrahydrocannabinol to produce marked catalepsy in mice. Neumpharmacology, 30, 67–71.CrossRefGoogle Scholar
  110. Pertwee, R. G., Greentree, S. G., & Swift, P. A. (1988). Drugs which stimulate or facilitate central GABAergic transmission interact synergistically with 4°tetrahydrocannabinol to produce marked catalepsy in mice. Neuropharmacology, 27, 1265–1270.PubMedCrossRefGoogle Scholar
  111. Pertwee, R. G., Stevenson, L. A., Elrick, D. B., Mechoulam, R., & Corbett, A. D. (1992). Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and the myenteric plexus preparation of guinea-pig small intestine. British Journal of Pharmacology, 105, 980–984.PubMedCrossRefGoogle Scholar
  112. Priller, J., Briley, E. M., Mansouri, J., Devane, W. A., Mackie, K., & Felder, C. C. (1995). Mead ethanolamide, a novel eicosanoid, is an agonist for the central (CBI) and peripheral (CB2) cannabinoid receptors. Molecular Pharmacology, 48, 288–292.PubMedGoogle Scholar
  113. Rawitch, A. B., Schultz, G. S., Ebner, K. E., & Vardaris, R. M. (1977). Competition of delta 9-tetrahydrocannabinol with estrogen in rat uterine estrogen receptor binding. Science, 197, 1189–1191.PubMedCrossRefGoogle Scholar
  114. Razdan, R. K. (1986). Structure—activity relationships in cannabinoids. Pharmacological Reviews, 38, 75–149.PubMedGoogle Scholar
  115. Rinaldi-Carmona, M., Barth, F., Heaulme, M., Shire, D., Calandra, B., Congy, C., Martinez, S., Maruani, J., Neliat, G., Caput, D., Ferrara, P, Soubrie, P., Breliere, J. C., & LeFur, G. (1994). SR I417I 6A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Letters, 350, 240–244.PubMedCrossRefGoogle Scholar
  116. Rinaldi-Carmona, M., Barth, E, Heaulme, M., Alonso, R., Shire, D., Congy, C., Soubrie, P., Breliere, J.-C., & LeFur, G. (1995). Biochemical and pharmacological characterization of SR141716A, the first potent and selective brain cannabinoid receptor antagonist. Life Sciences, 56, 1941–1947.PubMedCrossRefGoogle Scholar
  117. Rinaldi-Carmona, M., Calandra, B., Shire, D., Bouaboula, M., Oustric, D., Barth, E, Casellas, P., Ferrara, P, & LeFur, G. (1996). Characterization of two cloned human CBI cannabinoid receptor isoforms. Journal of Pharmacology and Experimental Therapeutics, 278, 871–878.PubMedGoogle Scholar
  118. Rosell, S., Agurell, S., & Martin, B. (1976). Effects of cannabinoids on isolated smooth muscle preparations. In G. G. Nahas (Ed.), Marihuana: Chemistry, biochemistry and cellular effects (pp. 397–406 ). New York: Springer-Verlag.Google Scholar
  119. Roth, S. H. (1978). Stereospecific presynaptic inhibitory effect of A°-tetrahydrocannabinol on cholinergic transmission in the myenteric plexus of the guinea pig. Canadian Journal of Physiology and Pharmacology 56, 968–975.PubMedCrossRefGoogle Scholar
  120. Rowley, J. T., & Rowley, P. T. (1990). Tetrahydrocannabinol inhibits adenyl cyclase in human leukemia cells. Life Sciences, 46, 217–222.PubMedCrossRefGoogle Scholar
  121. Ruh, M. E, Taylor, J. A., Howlett, A. C., & Welshons, W. V. (1997). Cannabinoid compounds fail to stimulate estrogen receptors. Biochemical Pharmacology, 53, 35–41.PubMedCrossRefGoogle Scholar
  122. Sauer, M. A., Rifka, S. M., Hawks. R. L., Cutler, G. B., Jr., & Loriaux, D. L. (1983). Marijuana: Interaction with the estrogen receptor. Journal of Pharmacology and Experimental Therapeutics, 224, 404–407.Google Scholar
  123. Schatz, A. R., Kessler, F. K., & Kaminski, N. E. (1992). Inhibition of adenylate cyclase by 49-tetrahydrocannabinol in mouse spleen cells: A potential mechanism for cannabinoid-mediated immunosuppression. Life Sciences, 51, PL25–PL30.Google Scholar
  124. Schmid, H. H. O., Schmid, P. C., & Natarajan, V. (1990). N-Acylated glycerophospholipids and their derivatives. Progress in Lipid Research, 29, 1–43.PubMedCrossRefGoogle Scholar
  125. Seeman, P., Chau-Wong, M., & Moyyen, S. (1972). The membrane binding of morphine, diphenylhydantoin, and tetrahydrocannabinol. Canadian Journal of Physiology and Pharmacology, 50, 1193–1200.PubMedCrossRefGoogle Scholar
  126. Selley, D. E., Stark, S., & Childers, S. R. (1996). Cannabinoid receptor stimulation of [’’S]GTPyS binding in rat brain membranes. Life Sciences, 59, 659–668.PubMedCrossRefGoogle Scholar
  127. Shire, D., Carillon, C., Kaghad, M., Calandra, B., RinaldiCarmona, M., LeFur, G., Caput, D., & Ferrara, P. (1995). An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. Journal of Biological Chemistry, 270, 3726–3731.PubMedCrossRefGoogle Scholar
  128. Sim, L. J., Selley, D. E., & Childers, S. R. (1995). In vitro autoradiography of receptor-activated G proteins in rat brain by agonist-stimulated guanylyl 5’[y[“S]thio]-triphosphate binding. Proceedings of the National Acadenry of Sciences of the United States of America, 92, 7242–7246.CrossRefGoogle Scholar
  129. Smith, P. B., Welch, S. P., & Martin, B. R. (1994). Interactions between 49-tetrahydrocannabinol and kappa opioids in mice. Journal of Pharmacology and Experimental Therapeutics, 268, 1381–1387.PubMedGoogle Scholar
  130. Sugiura, T., Kondo, S., Sukagawa, A., Nakane, S., Shinoda, A., Itoh, K., Yamashita, A., & Waku, K. (1995). 2-arachidonoylglycerol: A possible endogenous cannabinoid receptor ligand in brain. Biochemical and Biophysical Research Communications, 215, 89–97.Google Scholar
  131. Sunahara, R. K., Dessauer, C. W., & Gilman, A. G. (1996). Complexity and diversity of mammalian adenylate cyclases. Annual Review of Pharmacology and Toxicology, 36, 461–480.PubMedCrossRefGoogle Scholar
  132. Thomas, B. F., Wei, X., & Martin, 13. R. (1992). Characterization and autoradiographic localization of the cannabinoid binding site in rat brain using [3H]I IOH-A°-THC-DMH. Journal of Pharmacology and Experimental Therapeutics, 263, 1383–1390.Google Scholar
  133. Tsou, K., Patrick, S. L., & Walker, J. M. (1995). Physical withdrawal in rats tolerant to 4°-tetrahydrocannabinol precipitated by a cannabinoid receptor antagonist. European Journal of Pharmacology, 280, R13 - R15.PubMedCrossRefGoogle Scholar
  134. Ueda, N., Kurahashi, Y., Yamamoto, S., & Tokunaga, T. (1995). Partial purification and characterization of the porcine brain enzyme hydrolyzing and synthesizing anandamide. Journal of Biological Chemistry, 270, 23823–23827.PubMedCrossRefGoogle Scholar
  135. Vincent, B. J., McQuiston, D. J., Einhorn, L. H., Nagy, C. M., & Brames, M. J. (1983). Review of cannabinoids and their antiemetic effectiveness. Drugs, 25, 52–62.PubMedCrossRefGoogle Scholar
  136. Welch, S. P. (1993). Blockade of cannabinoid-induced antinociception by norbinaltorphimine, but not N,N-diallyl-tyrosine-aib-phenylalanine-leucine, ICI 174,864 or naloxone in mice. Journal of Pharmacology and Experimental Therapeutics, 265, 633–640.PubMedGoogle Scholar
  137. Welch, S. P., & Stevens, D. L. (1992). Antinociceptive activity of intrathecally administered cannabinoids alone, and in combination with morphine, in mice. Journal of Pharmacology and Experimental Therapeutics, 262, 10–18.PubMedGoogle Scholar
  138. Wenger, T., Croix, D., Tramu, G., & Leonardelli, J. (1992). Effects of e-tetrahydrocannabinol on pregnancy, puberty, and the neuroendocrine system. In L. Murphy & A. Bartke (Eds.), Marijuana /cannabinoids. Neurobiology and neurophysiology (pp. 539–560 ). Boca Raton, FL: CRC.Google Scholar
  139. Wiley, J. L., Barrett, R. L., Lowe, J., Balster, R. L., & Martin, B. R. (1995). Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats. Neuropharmacology, 34, 669–676.PubMedCrossRefGoogle Scholar
  140. Wiley, J. L., Lowe, J. A., Balster, R. L., & Martin, B. R. (1995). Antagonism of the discriminative stimulus effects of L1°-tetrahydrocannabinol in rats and rhesus monkeys. Journal of Pharmacology and Experimental Therapeutics, 275, 1–6.PubMedGoogle Scholar
  141. Wilson, R. S., & May, E. L. (1975). Analgesic properties of the tetrahydrocannabinols, their metabolites, and analogs. Journal of Medicinal Chemistry, 18, 700–703.PubMedCrossRefGoogle Scholar
  142. Wilson, R. S., May, E. L., Martin, B. R., & Dewey, W. L. (1976). 9-Nor-9-hydroxyhexahydrocannabinols: Synthesis, some behavioral and analgesic properties, and comparison with the tetrahydrocannabinols. Journal of Medicinal Chemistry, 19, 1165–1167.Google Scholar
  143. Yaksh, T. L. (1981). The antinociceptive effects of intrathecally administered levonantradol and desacetyllevonantradol in the rat. Journal of Clinical Pharmacology, 21, 334S - 340S.Google Scholar
  144. Yang, D. P., Banijamali, A., Charalambous, A., Marciniak, G., & Makriyannis, A. (1991). Solid state 2H-NMR as a method for determining the orientation of cannabinoid analogs in membranes. Pharmacology, Biochemistry and Behavior, 40, 553–557.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Allyn C. Howlett
    • 1
  1. 1.Saint Louis University School of MedicineSt. LouisUSA

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