Clinical Reviews in Allergy & Immunology

, Volume 46, Issue 1, pp 65–81 | Cite as

Marijuana: Respiratory Tract Effects

  • Kelly P. OwenEmail author
  • Mark E. Sutter
  • Timothy E. Albertson


Marijuana is the most commonly used drug of abuse in the USA. It is commonly abused through inhalation and therefore has effects on the lung that are similar to tobacco smoke, including increased cough, sputum production, hyperinflation, and upper lobe emphysematous changes. However, at this time, it does not appear that marijuana smoke contributes to the development of chronic obstructive pulmonary disease. Marijuana can have multiple physiologic effects such as tachycardia, peripheral vasodilatation, behavioral and emotional changes, and possible prolonged cognitive impairment. The carcinogenic effects of marijuana are unclear at this time. Studies are mixed on the ability of marijuana smoke to increase the risk for head and neck squamous cell carcinoma, lung cancer, prostate cancer, and cervical cancer. Some studies show that marijuana is protective for development of malignancy. Marijuana smoke has been shown to have an inhibitory effect on the immune system. Components of cannabis are under investigation as treatment for autoimmune diseases and malignancy. As marijuana becomes legalized in many states for medical and recreational use, other forms of tetrahydrocannabinol (THC) have been developed, such as food products and beverages. As most research on marijuana at this time has been on whole marijuana smoke, rather than THC, it is difficult to determine if the currently available data is applicable to these newer products.


Marijuana Chronic obstructive pulmonary disease Malignancy Chronic bronchitis Immune system 


  1. 1.
    US Department of Justice (2013) Accessed 10 Feb 2013
  2. 2.
  3. 3.
    Ashton CH (2001) Pharmacology and effects of cannabis: a brief review. Br J Psychiatry 178:101–106PubMedGoogle Scholar
  4. 4.
    Mechoulam R, Gaoni Y (1965) A total synthesis of delta-1-tetrahydrocannabinol, the active constituent of hashish. J Am Chem Soc 87:3273–3275PubMedGoogle Scholar
  5. 5.
    Mechoulam R, Parker LA, Gallily R (2002) Cannabidiol: an overview of some pharmacological aspects. J Clin Pharmacol 42:11S–19SPubMedGoogle Scholar
  6. 6.
    Mehmedic Z, Chandra S, Slade D, Denham H, Foster S, Patel AS et al (2010) Potency trends of Delta9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008. J Forensic Sci 55:1209–1217PubMedGoogle Scholar
  7. 7.
    Maykut MO (1985) Health consequences of acute and chronic marihuana use. Prog Neuropsychopharmacol Biol Psychiatry 9:209–238PubMedGoogle Scholar
  8. 8.
    Huber GL, First MW, Grubner O (1991) Marijuana and tobacco smoke gas-phase cytotoxins. Pharmacol Biochem Behav 40:629–636PubMedGoogle Scholar
  9. 9.
    Busch FW, Seid DA, Wei ET (1979) Mutagenic activity of marihuana smoke condensates. Cancer Lett 6:319–324PubMedGoogle Scholar
  10. 10.
    Fentiman AF Jr, Foltz RL, Kinzer GW (1973) Identification of noncannabinoid phenols in marihuana smoke condensate using chemical ionization mass spectrometry. Anal Chem 45:580–583PubMedGoogle Scholar
  11. 11.
    Haq MZ, Rose SJ, Deiderich LR, Patel AR (1974) Identification and quantitative measurement of some N-heterocyclics in marijuana smoke condensates. Anal Chem 46:1781–1784PubMedGoogle Scholar
  12. 12.
    Kettenes-van den Bosch JJ, Salemink CA (1977) Cannabis. XVI. Constituents of marihuana smoke condensate. J Chromatogr 131:422–424PubMedGoogle Scholar
  13. 13.
    Kier LD, Yamasaki E, Ames BN (1974) Detection of mutagenic activity in cigarette smoke condensates. Proc Natl Acad Sci U S A 71:4159–4163PubMedCentralPubMedGoogle Scholar
  14. 14.
    Lee ML, Novotny M, Bartle KD (1976) Gas chromatography/mass spectrometric and nuclear magnetic resonance spectrometric studies of carcinogenic polynuclear aromatic hydrocarbons in tobacco and marijuana smoke condensates. Anal Chem 48:405–416PubMedGoogle Scholar
  15. 15.
    Mann PE, Cohen AB, Finley TN, Ladman AJ (1971) Alveolar macrophages. Structural and functional differences between nonsmokers and smokers of marijuana and tobacco. Lab Invest 25:111–120PubMedGoogle Scholar
  16. 16.
    Novotny M, Lee ML, Bartle KD (1976) A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke. Experientia 32:280–282PubMedGoogle Scholar
  17. 17.
    Novotny M, Lee ML, Low CE, Raymond A (1976) Analysis of marijuana samples from different origins by high-resolution gas–liquid chromatography for forensic application. Anal Chem 48:24–29PubMedGoogle Scholar
  18. 18.
    Okamoto T, Chan PC, So BT (1972) Effect of tobacco, marijuana and benzo(a)pyrene on aryl hydrocarbon hydroxylase in hamster lung. Life Sci II 11:733–741PubMedGoogle Scholar
  19. 19.
    Patel AR, Gori GB (1975) Preparation and monitoring of marijuana smoke condensate samples. Bull Narc 27:47–54PubMedGoogle Scholar
  20. 20.
    Rickert WS, Robinson JC, Rogers B (1982) A comparison of tar, carbon monoxide and pH levels in smoke from marihuana and tobacco cigarettes. Can J Public Health 73:386–391PubMedGoogle Scholar
  21. 21.
    Stedman RL (1968) The chemical composition of tobacco and tobacco smoke. Chem Rev 68:153–207PubMedGoogle Scholar
  22. 22.
    Swain AP, Cooper JE, Stedman RL (1969) Large-scale fractionation of cigarette smoke condensate for chemical and biologic investigations. Cancer Res 29:579–583PubMedGoogle Scholar
  23. 23.
    Tomkins BA, Jenkins RA, Griest WH, Reagan RR, Holladay SK (1985) Liquid chromatographic determination of benzo[a]pyrene in total particulate matter of cigarette smoke. J Assoc Off Anal Chem 68:935–940PubMedGoogle Scholar
  24. 24.
    Wehner FC, van Rensburg SJ, Thiel PG (1980) Mutagenicity of marijuana and Transkei tobacco smoke condensates in the Salmonella/microsome assay. Mutat Res 77:135–142PubMedGoogle Scholar
  25. 25.
    Hoffmann DBK, Gori GB, Wynder EL (1975) On the carcinogenicity of marijuana smoke. Recent Adv Phytochem 9:63–81Google Scholar
  26. 26.
    Moir D, Rickert WS, Levasseur G, Larose Y, Maertens R, White P et al (2008) A comparison of mainstream and sidestream marijuana and tobacco cigarette smoke produced under two machine smoking conditions. Chem Res Toxicol 21:494–502PubMedGoogle Scholar
  27. 27.
    Simmons MS, Tashkin DP (1995) The relationship of tobacco and marijuana smoking characteristics. Life Sci 56:2185–2191PubMedGoogle Scholar
  28. 28.
    Wu TC, Tashkin DP, Djahed B, Rose JE (1988) Pulmonary hazards of smoking marijuana as compared with tobacco. N Engl J Med 318:347–351PubMedGoogle Scholar
  29. 29.
    Tashkin DP, Gliederer F, Rose J, Chang P, Hui KK, Yu JL et al (1991) Tar, CO and delta 9THC delivery from the 1st and 2nd halves of a marijuana cigarette. Pharmacol Biochem Behav 40:657–661PubMedGoogle Scholar
  30. 30.
    Hashibe M, Straif K, Tashkin DP, Morgenstern H, Greenland S, Zhang ZF (2005) Epidemiologic review of marijuana use and cancer risk. Alcohol 35:265–275PubMedGoogle Scholar
  31. 31.
    Hazekamp A, Ruhaak R, Zuurman L, van Gerven J, Verpoorte R (2006) Evaluation of a vaporizing device (Volcano) for the pulmonary administration of tetrahydrocannabinol. J Pharm Sci 95:1308–1317PubMedGoogle Scholar
  32. 32.
    Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL (2007) Vaporization as a smokeless cannabis delivery system: a pilot study. Clin Pharmacol Ther 82:572–578PubMedGoogle Scholar
  33. 33.
    Pomahacova B, Van der Kooy F, Verpoorte R (2009) Cannabis smoke condensate III: the cannabinoid content of vaporised Cannabis sativa. Inhal Toxicol 21:1108–1112PubMedGoogle Scholar
  34. 34.
    Van Dam NT, Earleywine M (2010) Pulmonary function in cannabis users: support for a clinical trial of the vaporizer. Int J Drug Policy 21:511–513PubMedGoogle Scholar
  35. 35.
    Hollister LE, Gillespie HK, Ohlsson A, Lindgren JE, Wahlen A, Agurell S (1981) Do plasma concentrations of delta 9-tetrahydrocannabinol reflect the degree of intoxication? J Clin Pharmacol 21:171S–177SPubMedGoogle Scholar
  36. 36.
    Huestis MA, Henningfield JE, Cone EJ (1992) Blood cannabinoids. I. Absorption of THC and formation of 11-OH-THC and THCCOOH during and after smoking marijuana. J Anal Toxicol 16:276–282PubMedGoogle Scholar
  37. 37.
    Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK (1980) Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 28:409–416PubMedGoogle Scholar
  38. 38.
    Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I (2007) Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci 80:1415–1419PubMedGoogle Scholar
  39. 39.
    Bornheim LM, Lasker JM, Raucy JL (1992) Human hepatic microsomal metabolism of delta 1-tetrahydrocannabinol. Drug Metab Dispos 20:241–246PubMedGoogle Scholar
  40. 40.
    Watanabe K, Matsunaga T, Yamamoto I, Funae Y, Yoshimura H (1995) Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman. Biol Pharm Bull 18:1138–1141PubMedGoogle Scholar
  41. 41.
    Mazur A, Lichti CF, Prather PL, Zielinska AK, Bratton SM, Gallus-Zawada A et al (2009) Characterization of human hepatic and extrahepatic UDP-glucuronosyltransferase enzymes involved in the metabolism of classic cannabinoids. Drug Metab Dispos 37:1496–1504PubMedGoogle Scholar
  42. 42.
    Hunt CA, Jones RT (1980) Tolerance and disposition of tetrahydrocannabinol in man. J Pharmacol Exp Ther 215:35–44PubMedGoogle Scholar
  43. 43.
    Yamaori S, Okamoto Y, Yamamoto I, Watanabe K (2011) Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos 39:2049–2056PubMedGoogle Scholar
  44. 44.
    Jiang R, Yamaori S, Okamoto Y, Yamamoto I, Watanabe K (2013) Cannabidiol is a potent inhibitor of the catalytic activity of cytochrome P450 2C19. Drug Metab Pharmacokinet (in press)Google Scholar
  45. 45.
    Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564PubMedGoogle Scholar
  46. 46.
    Chakrabarti A, Onaivi ES, Chaudhuri G (1995) Cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein. DNA Seq 5:385–388PubMedGoogle Scholar
  47. 47.
    Abood ME, Ditto KE, Noel MA, Showalter VM, Tao Q (1997) Isolation and expression of a mouse CB1 cannabinoid receptor gene. Comparison of binding properties with those of native CB1 receptors in mouse brain and N18TG2 neuroblastoma cells. Biochem Pharmacol 53:207–214PubMedGoogle Scholar
  48. 48.
    Gebremedhin D, Lange AR, Campbell WB, Hillard CJ, Harder DR (1999) Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current. Am J Physiol 276:H2085–2093PubMedGoogle Scholar
  49. 49.
    Stefano GB, Salzet B, Salzet M (1997) Identification and characterization of the leech CNS cannabinoid receptor: coupling to nitric oxide release. Brain Res 753:219–224PubMedGoogle Scholar
  50. 50.
    Yamaguchi F, Macrae AD, Brenner S (1996) Molecular cloning of two cannabinoid type 1-like receptor genes from the puffer fish Fugu rubripes. Genomics 35:603–605PubMedGoogle Scholar
  51. 51.
    Soderstrom K, Leid M, Moore FL, Murray TF (2000) Behaviroal, pharmacological, and molecular characterization of an amphibian cannabinoid receptor. J Neurochem 75:413–423PubMedGoogle Scholar
  52. 52.
    Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G et al (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949PubMedGoogle Scholar
  53. 53.
    Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR et al (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90PubMedGoogle Scholar
  54. 54.
    Sugiura T, Kondo S, Sukagawa A, Nakane S, Shinoda A, Itoh K et al (1995) 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem Biophys Res Commun 215:89–97PubMedGoogle Scholar
  55. 55.
    Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE et al (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci U S A 98:3662–3665PubMedCentralPubMedGoogle Scholar
  56. 56.
    Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279(Pt 1):129–134PubMedGoogle Scholar
  57. 57.
    Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65PubMedGoogle Scholar
  58. 58.
    Hirst RA, Lambert DG, Notcutt WG (1998) Pharmacology and potential therapeutic uses of cannabis. Br J Anaesth 81:77–84PubMedGoogle Scholar
  59. 59.
    Mechoulam R, Parker LA (2013) The endocannabinoid system and the brain. Annu Rev Psychol 64:21–47PubMedGoogle Scholar
  60. 60.
    Onaivi ES (2009) Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications. Int Rev Neurobiol 88:335–369PubMedGoogle Scholar
  61. 61.
    Howlett AC, Barth F, Bonner TI, Cabral G, Casellas P, Devane WA et al (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol Rev 54:161–202PubMedGoogle Scholar
  62. 62.
    Mackie K, Devane WA, Hille B (1993) Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N18 neuroblastoma cells. Mol Pharmacol 44:498–503PubMedGoogle Scholar
  63. 63.
    Mackie K, Hille B (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci U S A 89:3825–3829PubMedCentralPubMedGoogle Scholar
  64. 64.
    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. J Neurosci 15:6552–6561PubMedGoogle Scholar
  65. 65.
    Caulfield MP, Brown DA (1992) Cannabinoid receptor agonists inhibit Ca current in NG108-15 neuroblastoma cells via a pertussis toxin-sensitive mechanism. Br J Pharmacol 106:231–232PubMedGoogle Scholar
  66. 66.
    Childers SR, Deadwyler SA (1996) Role of cyclic AMP in the actions of cannabinoid receptors. Biochem Pharmacol 52:819–827PubMedGoogle Scholar
  67. 67.
    Pacher P, Mechoulam R (2011) Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog Lipid Res 50:193–211PubMedCentralPubMedGoogle Scholar
  68. 68.
    Klein TW, Newton C, Larsen K, Lu L, Perkins I et al (2003) The cannabinoid system and immune modulation. J Leukoc Biol 74:486–496PubMedGoogle Scholar
  69. 69.
    Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O et al (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48:443–450PubMedGoogle Scholar
  70. 70.
    Zhang PW, Ishiguro H, Ohtsuki T, Hess J, Carillo F, Walther D et al (2004) Human cannabinoid receptor 1: 5' exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse. Mol Psychiatry 9:916–931PubMedGoogle Scholar
  71. 71.
    Comings DE, Muhleman D, Gade R, Johnson P, Verde R, Saucier G et al (1997) Cannabinoid receptor gene (CNR1): association with i.v. drug use. Mol Psychiatry 2:161–168PubMedGoogle Scholar
  72. 72.
    Benyamina A, Kebir O, Blecha L, Reynaud M, Krebs MO (2011) CNR1 gene polymorphisms in addictive disorders: a systematic review and a meta-analysis. Addict Biol 16:1–6PubMedGoogle Scholar
  73. 73.
    Hopfer CJ, Young SE, Purcell S, Crowley TJ, Stallings MC, Corley RP et al (2006) Cannabis receptor haplotype associated with fewer cannabis dependence symptoms in adolescents. Am J Med Genet B Neuropsychiatr Genet 141B:895–901PubMedCentralPubMedGoogle Scholar
  74. 74.
    Vardakou I, Pistos C, Spiliopoulou C (2010) Spice drugs as a new trend: mode of action, identification and legislation. Toxicol Lett 197:157–162PubMedGoogle Scholar
  75. 75.
    Pertwee RG (2006) Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 147(Suppl 1):S163–171PubMedGoogle Scholar
  76. 76.
    Einhorn LH, Nagy C, Furnas B, Williams SD (1981) Nabilone: an effective antiemetic in patients receiving cancer chemotherapy. J Clin Pharmacol 21:64S–69SPubMedGoogle Scholar
  77. 77.
    Ungerleider JT, Sarna G, Fairbanks LA, Goodnight J, Andrysiak T, Jamison K (1985) THC or compazine for the cancer chemotherapy patient—the UCLA study. Part II: patient drug preference. Am J Clin Oncol 8:142–147PubMedGoogle Scholar
  78. 78.
    Struwe M, Kaempfer SH, Geiger CJ, Pavia AT, Plasse TF, Shepard KV et al (1993) Effect of dronabinol on nutritional status in HIV infection. Ann Pharmacother 27:827–831PubMedGoogle Scholar
  79. 79.
    Smith PF (2004) GW-1000. GW pharmaceuticals. Curr Opin Investig Drugs 5:748–754PubMedGoogle Scholar
  80. 80.
    Pope HG Jr, Gruber AJ, Hudson JI, Huestis MA, Yurgelun-Todd D (2002) Cognitive measures in long-term cannabis users. J Clin Pharmacol 42:41S–47SPubMedGoogle Scholar
  81. 81.
    Bolla KI, Eldreth DA, Matochik JA, Cadet JL (2005) Neural substrates of faulty decision-making in abstinent marijuana users. NeuroImage 26:480–492PubMedGoogle Scholar
  82. 82.
    Crean RD, Crane NA, Mason BJ (2011) An evidence based review of acute and long-term effects of cannabis use on executive cognitive functions. J Addict Med 5:1–8PubMedCentralPubMedGoogle Scholar
  83. 83.
    Sarne Y, Asaf F, Fishbein M, Gafni M, Keren O (2011) The dual neuroprotective-neurotoxic profile of cannabinoid drugs. Br J Pharmacol 163:1391–1401PubMedGoogle Scholar
  84. 84.
    Eubanks LM, Rogers CJ, Beuscher AE IV, Koob GF, Olson AJ, Dickerson TJ et al (2006) A molecular link between the active component of marijuana and Alzheimer's disease pathology. Mol Pharm 3:773–777PubMedCentralPubMedGoogle Scholar
  85. 85.
    Saito VM, Rezende RM, Teixeira AL (2012) Cannabinoid modulation of neuroinflammatory disorders. Curr Neuropharmacol 10:159–166PubMedGoogle Scholar
  86. 86.
    Stefanis NC, Dragovic M, Power BD, Jablensky A, Castle D, Morgan VA (2013) Age at initiation of cannabis use predicts age at onset of psychosis: the 7- to 8-year trend. Schizophr Bull 39:251–254PubMedGoogle Scholar
  87. 87.
    Galvez-Buccollini JA, Proal AC, Tomaselli V, Trachtenberg M, Coconcea C, Chun J et al (2012) Association between age at onset of psychosis and age at onset of cannabis use in non-affective psychosis. Schizophr Res 139:157–160PubMedCentralPubMedGoogle Scholar
  88. 88.
    Dragt S, Nieman DH, Schultze-Lutter F, van der Meer F, Becker H, de Haan L et al (2012) Cannabis use and age at onset of symptoms in subjects at clinical high risk for psychosis. Acta Psychiatr Scand 125:45–53PubMedGoogle Scholar
  89. 89.
    Zuardi AW, Crippa JA, Hallak JE, Moreira FA, Guimaraes FS (2006) Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug. Braz J Med Biol Res 39:421–429PubMedGoogle Scholar
  90. 90.
    Deiana S (2013) Medical use of cannabis. Cannabidiol: a new light for schizophrenia? Drug Test Anal 5:46–51PubMedGoogle Scholar
  91. 91.
    Van Hoozen BE, Cross CE (1997) Marijuana. Respiratory tract effects. Clin Rev Allergy Immunol 15:243–269PubMedGoogle Scholar
  92. 92.
    Tashkin DP, Reiss S, Shapiro BJ, Calvarese B, Olsen JL, Lodge JW (1977) Bronchial effects of aerosolized delta 9-tetrahydrocannabinol in healthy and asthmatic subjects. Am Rev Respir Dis 115:57–65PubMedGoogle Scholar
  93. 93.
    Tashkin DP, Shapiro BJ, Frank IM (1973) Acute pulmonary physiologic effects of smoked marijuana and oral 9-tetrahydrocannabinol in healthy young men. N Engl J Med 289:336–341PubMedGoogle Scholar
  94. 94.
    Tashkin DP, Shapiro BJ, Lee YE, Harper CE (1975) Effects of smoked marijuana in experimentally induced asthma. Am Rev Respir Dis 112:377–386PubMedGoogle Scholar
  95. 95.
    Tashkin DP, Shapiro BJ, Lee YE, Harper CE (1976) Subacute effects of heavy marihuana smoking on pulmonary function in healthy men. N Engl J Med 294:125–129PubMedGoogle Scholar
  96. 96.
    Vachon L, FitzGerald MX, Solliday NH, Gould IA, Gaensler EA (1973) Single-dose effects of marihuana smoke. Bronchial dynamics and respiratory-center sensitivity in normal subjects. N Engl J Med 288:985–989PubMedGoogle Scholar
  97. 97.
    Wu HD, Wright RS, Sassoon CS, Tashkin DP (1992) Effects of smoked marijuana of varying potency on ventilatory drive and metabolic rate. Am Rev Respir Dis 146:716–721PubMedGoogle Scholar
  98. 98.
    Vachon L, Sulkowski A, Rich E (1974) Marihuana effects on learning, attention and time estimation. Psychopharmacologia 39:1–11PubMedGoogle Scholar
  99. 99.
    Tashkin DP, Shapiro BJ, Frank IM (1974) Acute effects of smoked marijuana and oral delta9-tetrahydrocannabinol on specific airway conductance in asthmatic subjects. Am Rev Respir Dis 109:420–428PubMedGoogle Scholar
  100. 100.
    Bernstein JG, Kuehnle JC, Mendelson JH (1976) Medical implications of marijuana use. Am J Drug Alcohol Abuse 3:347–361PubMedGoogle Scholar
  101. 101.
    Laviolette M, Belanger J (1986) Role of prostaglandins in marihuana-induced bronchodilation. Respiration 49:10–15PubMedGoogle Scholar
  102. 102.
    Renaud AM, Cormier Y (1986) Acute effects of marihuana smoking on maximal exercise performance. Med Sci Sports Exerc 18:685–689PubMedGoogle Scholar
  103. 103.
    Steadward RD, Singh M (1975) The effects of smoking marihuana on physical performance. Med Sci Sports 7:309–311PubMedGoogle Scholar
  104. 104.
    Steffens S, Pacher P (2012) Targeting cannabinoid receptor CB(2) in cardiovascular disorders: promises and controversies. Br J Pharmacol 167:313–323PubMedGoogle Scholar
  105. 105.
    Gong H Jr, Fligiel S, Tashkin DP, Barbers RG (1987) Tracheobronchial changes in habitual, heavy smokers of marijuana with and without tobacco. Am Rev Respir Dis 136:142–149PubMedGoogle Scholar
  106. 106.
    Roth MD, Arora A, Barsky SH, Kleerup EC, Simmons M, Tashkin DP (1998) Airway inflammation in young marijuana and tobacco smokers. Am J Respir Crit Care Med 157:928–937PubMedGoogle Scholar
  107. 107.
    Fligiel SE, Beals TF, Tashkin DP, Paule MG, Scallet AC, Ali SF et al (1991) Marijuana exposure and pulmonary alterations in primates. Pharmacol Biochem Behav 40:637–642PubMedGoogle Scholar
  108. 108.
    Barbers RG, Gong H Jr, Tashkin DP, Oishi J, Wallace JM (1987) Differential examination of bronchoalveolar lavage cells in tobacco cigarette and marijuana smokers. Am Rev Respir Dis 135:1271–1275PubMedGoogle Scholar
  109. 109.
    Barbers RG, Evans MJ, Gong H Jr, Tashkin DP (1991) Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers. Am Rev Respir Dis 143:1092–1095PubMedGoogle Scholar
  110. 110.
    Wallace JM, Oishi JS, Barbers RG, Simmons MS, Tashkin DP (1994) Lymphocytic subpopulation profiles in bronchoalveolar lavage fluid and peripheral blood from tobacco and marijuana smokers. Chest 105:847–852PubMedGoogle Scholar
  111. 111.
    Sarafian TA, Kouyoumjian S, Khoshaghideh F, Tashkin DP, Roth MD (2003) Delta 9-tetrahydrocannabinol disrupts mitochondrial function and cell energetics. Am J Physiol Lung Cell Mol Physiol 284:L298–306PubMedGoogle Scholar
  112. 112.
    Sarafian TA, Magallanes JA, Shau H, Tashkin D, Roth MD (1999) Oxidative stress produced by marijuana smoke. An adverse effect enhanced by cannabinoids. Am J Respir Cell Mol Biol 20:1286–1293PubMedGoogle Scholar
  113. 113.
    Sarafian TA, Tashkin DP, Roth MD (2001) Marijuana smoke and delta(9)-tetrahydrocannabinol promote necrotic cell death but inhibit Fas-mediated apoptosis. Toxicol Appl Pharmacol 174:264–272PubMedGoogle Scholar
  114. 114.
    Sarafian T, Habib N, Mao JT, Tsu IH, Yamamoto ML, Hsu E et al (2005) Gene expression changes in human small airway epithelial cells exposed to delta9-tetrahydrocannabinol. Toxicol Lett 158:95–107PubMedGoogle Scholar
  115. 115.
    Bloom JW, Kaltenborn WT, Paoletti P, Camilli A, Lebowitz MD (1987) Respiratory effects of non-tobacco cigarettes. Br Med J (Clin Res Ed) 295:1516–1518Google Scholar
  116. 116.
    Sherrill DL, Krzyzanowski M, Bloom JW, Lebowitz MD (1991) Respiratory effects of non-tobacco cigarettes: a longitudinal study in general population. Int J Epidemiol 20:132–137PubMedGoogle Scholar
  117. 117.
    Taylor DR, Poulton R, Moffitt TE, Ramankutty P, Sears MR (2000) The respiratory effects of cannabis dependence in young adults. Addiction 95:1669–1677PubMedGoogle Scholar
  118. 118.
    Aldington S, Williams M, Nowitz M, Weatherall M, Pritchard A, McNaughton A et al (2007) Effects of cannabis on pulmonary structure, function and symptoms. Thorax 62:1058–1063PubMedGoogle Scholar
  119. 119.
    Tashkin DP, Simmons MS, Sherrill DL, Coulson AH (1997) Heavy habitual marijuana smoking does not cause an accelerated decline in FEV1 with age. Am J Respir Crit Care Med 155:141–148PubMedGoogle Scholar
  120. 120.
    Taylor DR, Fergusson DM, Milne BJ, Horwood LJ, Moffitt TE, Sears MR et al (2002) A longitudinal study of the effects of tobacco and cannabis exposure on lung function in young adults. Addiction 97:1055–1061PubMedGoogle Scholar
  121. 121.
    Moore BA, Augustson EM, Moser RP, Budney AJ (2005) Respiratory effects of marijuana and tobacco use in a U.S. sample. J Gen Intern Med 20:33–37PubMedCentralPubMedGoogle Scholar
  122. 122.
    Tetrault JM, Crothers K, Moore BA, Mehra R, Concato J, Fiellin DA (2007) Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review. Arch Intern Med 167:221–228PubMedCentralPubMedGoogle Scholar
  123. 123.
    Tan WC, Lo C, Jong A, Xing L, Fitzgerald MJ, Vollmer MJ et al (2009) Marijuana and chronic obstructive lung disease: a population-based study. CMAJ 180:814–820PubMedCentralPubMedGoogle Scholar
  124. 124.
    Tashkin DP (2009) Does smoking marijuana increase the risk of chronic obstructive pulmonary disease? CMAJ 180:797–798PubMedCentralPubMedGoogle Scholar
  125. 125.
    Hancox RJ, Poulton R, Ely M, Welch D, Taylor DR, McLachlan CR et al (2010) Effects of cannabis on lung function: a population-based cohort study. Eur Respir J 35:42–47PubMedCentralPubMedGoogle Scholar
  126. 126.
    Pletcher MJ, Vittinghoff E, Kalhan R, Richman J, Safford M, Sidney S et al (2012) Association between marijuana exposure and pulmonary function over 20 years. JAMA 307:173–181PubMedGoogle Scholar
  127. 127.
    Lee MH, Hancox RJ (2011) Effects of smoking cannabis on lung function. Expert Rev Respir Med 5:537–546 (quiz 547)PubMedGoogle Scholar
  128. 128.
    Tashkin DP, Simmons MS, Tseng CH (2012) Impact of changes in regular use of marijuana and/or tobacco on chronic bronchitis. COPD 9:367–374PubMedGoogle Scholar
  129. 129.
    Tashkin DP, Coulson AH, Clark VA, Simmons M, Bourque LB, Duann S et al (1987) Respiratory symptoms and lung function in habitual heavy smokers of marijuana alone, smokers of marijuana and tobacco, smokers of tobacco alone, and nonsmokers. Am Rev Respir Dis 135:209–216PubMedGoogle Scholar
  130. 130.
    Henderson RL, Tennant FS, Guerry R (1972) Respiratory manifestations of hashish smoking. Arch Otolaryngol 95:248–251PubMedGoogle Scholar
  131. 131.
    Chopra GS (1973) Studies on psycho-clinical aspects of long-term marihuana use in 124 cases. Int J Addict 8:1015–1026PubMedGoogle Scholar
  132. 132.
    Boulougouris JC, Panayiotopoulos CP, Antypas E, Liakos A, Stefanis C (1976) Effects of chronic hashish use on medical status in 44 users compared with 38 controls. Ann N Y Acad Sci 282:168–172PubMedGoogle Scholar
  133. 133.
    Sparacino CM, Hyldburg PA, Hughes TJ (1990) Chemical and biological analysis of marijuana smoke condensate. NIDA Res Monogr 99:121–140PubMedGoogle Scholar
  134. 134.
    Cottrell JC, Sohn SS, Vogel WH (1973) Toxic effects of marihuana tar on mouse skin. Arch Environ Health 26:277–278PubMedGoogle Scholar
  135. 135.
    Walaszek Z, Hanausek M, Slaga TJ (2007) The role of skin painting in predicting lung cancer. Int J Toxicol 26:345–351PubMedGoogle Scholar
  136. 136.
    Leuchtenberger C, Leuchtenberger R, Ritter U, Inui N (1973) Effects of marijuana and tobacco smoke on DNA and chromosomal complement in human lung explants. Nature 242:403–404PubMedGoogle Scholar
  137. 137.
    Sherman MP, Aeberhard EE, Wong VZ, Simmons MS, Roth MD, Tashkin DP (1995) Effects of smoking marijuana, tobacco or cocaine alone or in combination on DNA damage in human alveolar macrophages. Life Sci 56:2201–2207PubMedGoogle Scholar
  138. 138.
    Chan PC, Sills RC, Braun AG, Haseman JK, Bucher JR (1996) Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice. Fundam Appl Toxicol 30:109–117PubMedGoogle Scholar
  139. 139.
    Hall W, MacPhee D (2002) Cannabis use and cancer. Addiction 97:243–247PubMedGoogle Scholar
  140. 140.
    Talaska G, Schamer M, Bailey JR, Ali SF, Scallet AC, Slikker W et al (1992) No increase in carcinogen-DNA adducts in the lungs of monkeys exposed chronically to marijuana smoke. Toxicol Lett 63:321–332PubMedGoogle Scholar
  141. 141.
    Zhang ZF, Morgenstern H, Spitz MR, Tashkin DP, Yu GP, Marshall JR et al (1999) Marijuana use and increased risk of squamous cell carcinoma of the head and neck. Cancer Epidemiol Biomarkers Prev 8:1071–1078PubMedGoogle Scholar
  142. 142.
    Feng BJ, Khyatti M, Ben-Ayoub W, Dahmoul S, Ayad M, Maachi F et al (2009) Cannabis, tobacco and domestic fumes intake are associated with nasopharyngeal carcinoma in North Africa. Br J Cancer 101:1207–1212PubMedCentralPubMedGoogle Scholar
  143. 143.
    Gillison ML, D'Souza G, Westra W, Sugar E, Xiao W, Begum S et al (2008) Distinct risk factor profiles for human papillomavirus type 16-positive and human papillomavirus type 16-negative head and neck cancers. J Natl Cancer Inst 100:407–420PubMedGoogle Scholar
  144. 144.
    Llewellyn CD, Linklater K, Bell J, Johnson NW, Warnakulasuriya S (2004) An analysis of risk factors for oral cancer in young people: a case–control study. Oral Oncol 40:304–313PubMedGoogle Scholar
  145. 145.
    Llewellyn CD, Johnson NW, Warnakulasuriya KA (2004) Risk factors for oral cancer in newly diagnosed patients aged 45 years and younger: a case–control study in Southern England. J Oral Pathol Med 33:525–532PubMedGoogle Scholar
  146. 146.
    Aldington S, Harwood M, Cox B, Weatherall M, Beckert L, Hansell A et al (2008) Cannabis use and cancer of the head and neck: case–control study. Otolaryngol Head Neck Surg 138:374–380PubMedCentralPubMedGoogle Scholar
  147. 147.
    Rosenblatt KA, Daling JR, Chen C, Sherman KJ, Schwartz SM (2004) Marijuana use and risk of oral squamous cell carcinoma. Cancer Res 64:4049–4054PubMedGoogle Scholar
  148. 148.
    Hashibe M, Morgenstern H, Cui Y, Tashkin DP, Zhang ZF, Cozen W et al (2006) Marijuana use and the risk of lung and upper aerodigestive tract cancers: results of a population-based case–control study. Cancer Epidemiol Biomarkers Prev 15:1829–1834PubMedGoogle Scholar
  149. 149.
    Berthiller J, Lee YC, Boffetta P, Wei Q, Sturgis EM, Greenland S et al (2009) Marijuana smoking and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Cancer Epidemiol Biomarkers Prev 18:1544–1551PubMedCentralPubMedGoogle Scholar
  150. 150.
    Liang C, McClean MD, Marsit C, Christensen B, Peters E, Nelson HH et al (2009) A population-based case–control study of marijuana use and head and neck squamous cell carcinoma. Cancer Prev Res (Phila) 2:759–768Google Scholar
  151. 151.
    Mehra R, Moore BA, Crothers K, Tetrault J, Fiellin DA (2006) The association between marijuana smoking and lung cancer: a systematic review. Arch Intern Med 166:1359–1367PubMedGoogle Scholar
  152. 152.
    Aldington S, Harwood M, Cox B, Weatherall M, Beckert L, Hansell A et al (2008) Cannabis use and risk of lung cancer: a case–control study. Eur Respir J 31:280–286PubMedCentralPubMedGoogle Scholar
  153. 153.
    Chen AL, Chen TJ, Braverman ER, Acuri V, Kemer M, Varshavskiy M et al (2008) Hypothesizing that marijuana smokers are at a significantly lower risk of carcinogenicity relative to tobacco-non-marijuana smokers: evidenced based on statistical reevaluation of current literature. J Psychoactive Drugs 40:263–272PubMedGoogle Scholar
  154. 154.
    Sidney S, Quesenberry CP Jr, Friedman GD, Tekawa IS (1997) Marijuana use and cancer incidence (California, United States). Cancer Causes Control 8:722–728PubMedGoogle Scholar
  155. 155.
    Daling JR, Doody DR, Sun X, Trabert BL, Weiss NS, Chen C et al (2009) Association of marijuana use and the incidence of testicular germ cell tumors. Cancer 115:1215–1223PubMedCentralPubMedGoogle Scholar
  156. 156.
    Trabert B, Sigurdson AJ, SweeneyAM SSS, McGlynn KA (2011) Marijuana use and testicular germ cell tumors. Cancer 117:848–853PubMedCentralPubMedGoogle Scholar
  157. 157.
    Lacson JC, Carroll JD, Tuazon E, Castelao EJ, Bernstein L, Cortessis VK (2012) Population-based case–control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer 118:5374–5383PubMedCentralPubMedGoogle Scholar
  158. 158.
    Efird JT, Friedman GD, Sidney S, Klatsky A, Habel LA, Udaltsova NV et al (2004) The risk for malignant primary adult-onset glioma in a large, multiethnic, managed-care cohort: cigarette smoking and other lifestyle behaviors. J Neurooncol 68:57–69PubMedGoogle Scholar
  159. 159.
    Munson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA (1975) Antineoplastic activity of cannabinoids. J Natl Cancer Inst 55:597–602PubMedGoogle Scholar
  160. 160.
    Guindon J, Hohmann AG (2011) The endocannabinoid system and cancer: therapeutic implication. Br J Pharmacol 163:1447–1463PubMedGoogle Scholar
  161. 161.
    Torres S, Lorente M, Rodriguez-Fornes F, Hernandez-Tiedra S, Salazar M, Garcia-Taboada E et al (2011) A combined preclinical therapy of cannabinoids and temozolomide against glioma. Mol Cancer Ther 10:90–103PubMedGoogle Scholar
  162. 162.
    Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P et al (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61PubMedGoogle Scholar
  163. 163.
    Croxford JL, Yamamura T (2005) Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol 166:3–18PubMedGoogle Scholar
  164. 164.
    Klein TW, Newton C, Friedman H (1998) Cannabinoid receptors and immunity. Immunol Today 19:373–381PubMedGoogle Scholar
  165. 165.
    Lau RJ, Tubergen DG, Barr M Jr, Domino EF, Benowitz N, Jones RT (1976) Phytohemagglutinin-induced lymphocyte transformation in humans receiving delta9-tetrahydrocannabinol. Science 192:805–807PubMedGoogle Scholar
  166. 166.
    White SC, Brin SC, Janicki BW (1975) Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers. Science 188:71–72PubMedGoogle Scholar
  167. 167.
    Nahas GG, Suciu-Foca N, Armand JP, Morishima A (1974) Inhibition of cellular mediated immunity in marihuana smokers. Science 183:419–420PubMedGoogle Scholar
  168. 168.
    El-Gohary M, Eid MA (2004) Effect of cannabinoid ingestion (in the form of bhang) on the immune system of high school and university students. Hum Exp Toxicol 23:149–156PubMedGoogle Scholar
  169. 169.
    Rachelefsky GS, Opelz G, Mickey MR, Lessin P, Kiuchi M, Silverstein MJ et al (1976) Intact humoral and cell-mediated immunity in chronic marijuana smoking. J Allergy Clin Immunol 58:483–490PubMedGoogle Scholar
  170. 170.
    Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT et al (2003) Short-term effects of cannabinoids in patients with HIV-1 infection: a randomized, placebo-controlled clinical trial. Ann Intern Med 139:258–266PubMedGoogle Scholar
  171. 171.
    Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH (2009) Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol 60(Suppl 3):99–103PubMedGoogle Scholar
  172. 172.
    Cabral GA, Stinnett AL, Bailey J, Ali SF, Paule MG, Scallet AC et al (1991) Chronic marijuana smoke alters alveolar macrophage morphology and protein expression. Pharmacol Biochem Behav 40:643–649PubMedGoogle Scholar
  173. 173.
    Roth MD, Whittaker K, Salehi K, Tashkin DP, Baldwin GC (2004) Mechanisms for impaired effector function in alveolar macrophages from marijuana and cocaine smokers. J Neuroimmunol 147:82–86PubMedGoogle Scholar
  174. 174.
    Kusher DI, Dawson LO, Taylor AC, Djeu JY (1994) Effect of the psychoactive metabolite of marijuana, delta 9-tetrahydrocannabinol (THC), on the synthesis of tumor necrosis factor by human large granular lymphocytes. Cell Immunol 154:99–108PubMedGoogle Scholar
  175. 175.
    Kawakami Y, Klein TW, Newton C, Djeu JY, Dennert G, Specter S et al (1988) Suppression by cannabinoids of a cloned cell line with natural killer cell activity. Proc Soc Exp Biol Med 187:355–359PubMedGoogle Scholar
  176. 176.
    Specter SC, Klein TW, Newton C, Mondragon M, Widen R, Friedman H (1986) Marijuana effects on immunity: suppression of human natural killer cell activity of delta-9-tetrahydrocannabinol. Int J Immunopharmacol 8:741–745PubMedGoogle Scholar
  177. 177.
    Wang M, Richards AL, Friedman H, Djeu JY (1991) Selective inhibition of natural killer but not natural cytotoxic activity in a cloned cell line by delta-9-tetrahydrocannabinol. J Leukoc Biol 50:192–197PubMedGoogle Scholar
  178. 178.
    Shivers SC, Newton C, Friedman H, Klein TW (1994) Delta 9-Tetrahydrocannabinol (THC) modulates IL-1 bioactivity in human monocyte/macrophage cell lines. Life Sci 54:1281–1289PubMedGoogle Scholar
  179. 179.
    Zhu W, Newton C, Daaka Y, Friedman H, Klein TW (1994) Delta 9-tetrahydrocannabinol enhances the secretion of interleukin 1 from endotoxin-stimulated macrophages. J Pharmacol Exp Ther 270:1334–1339PubMedGoogle Scholar
  180. 180.
    Zheng ZM, Specter S, Friedman H (1992) Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages. Int J Immunopharmacol 14:1445–1452PubMedGoogle Scholar
  181. 181.
    Fischer-Stenger K, Dove Pettit DA, Cabral GA (1993) Delta 9-tetrahydrocannabinol inhibition of tumor necrosis factor-alpha: suppression of post-translational events. J Pharmacol Exp Ther 267:1558–1565PubMedGoogle Scholar
  182. 182.
    Blanchard DK, Newton C, Klein TW, Stewart WE 2nd, Friedman H (1986) In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells. Int J Immunopharmacol 8:819–824PubMedGoogle Scholar
  183. 183.
    Cabral GA, Lockmuller JC, Mishkin EM (1986) Delta 9-tetrahydrocannabinol decreases alpha/beta interferon response to herpes simplex virus type 2 in the B6C3F1 mouse. Proc Soc Exp Biol Med 181:305–311PubMedGoogle Scholar
  184. 184.
    Zhu W, Igarashi T, Friedman H, Klein TW (1995) Delta 9-tetrahydrocannabinol (THC) causes the variable expression of IL2 receptor subunits. J Pharmacol Exp Ther 274:1001–1007PubMedGoogle Scholar
  185. 185.
    Beshay M, Kaiser H, Niedhart D, Reymond MA, Schmid RA (2007) Emphysema and secondary pneumothorax in young adults smoking cannabis. Eur J Cardiothorac Surg 32:834–838PubMedGoogle Scholar
  186. 186.
    Hii SW, Tam JD, Thompson BR, Naughton MT (2008) Bullous lung disease due to marijuana. Respirology 13:122–127PubMedGoogle Scholar
  187. 187.
    Hii S, Naughton MT, Young A (2006) Marijuana lung. Intern Med J 36:270–271PubMedGoogle Scholar
  188. 188.
    Gao Z, Wood-Baker R, Harle R, Muller K, Hauser J, Reid DW (2010) “Bong lung” in cystic fibrosis: a case report. J Med Case Rep 4:371PubMedCentralPubMedGoogle Scholar
  189. 189.
    Hazouard E, Koninck JC, Attucci S, Fauchier-Rolland F, Brunereau L, Diot P (2001) Pneumorachis and pneumomediastinum caused by repeated Muller's maneuvers: complications of marijuana smoking. Ann Emerg Med 38:694–697PubMedGoogle Scholar
  190. 190.
    Luque MA 3rd, Cavallaro DL, Torres M, Emmanual P, Hillman JV (1987) Pneumomediastinum, pneumothorax, and subcutaneous emphysema after alternate cocaine inhalation and marijuana smoking. Pediatr Emerg Care 3:107–109PubMedGoogle Scholar
  191. 191.
    Kagen SL (1981) Aspergillus: an inhalable contaminant of marihuana. N Engl J Med 304:483–484PubMedGoogle Scholar
  192. 192.
    Gargani Y, Bishop P, Denning DW (2011) Too many mouldy joints—marijuana and chronic pulmonary aspergillosis. Mediterr J Hematol Infect Dis 3:e2011005PubMedCentralPubMedGoogle Scholar
  193. 193.
    Schwartz IS (1985) Marijuana and fungal infection. Am J Clin Pathol 84:256PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Kelly P. Owen
    • 1
    Email author
  • Mark E. Sutter
    • 1
  • Timothy E. Albertson
    • 2
    • 3
  1. 1.Department of Emergency MedicineUniversity of California Davis Medical CenterSacramentoUSA
  2. 2.Department of Internal MedicineUniversity of California Davis Medical CenterSacramentoUSA
  3. 3.Department of MedicineVeterans Administration Northern California Health Care SystemMatherUSA

Personalised recommendations