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Human Laboratory Models of Cannabis Use Disorder

  • Caroline A. AroutEmail author
  • Evan Herrmann
  • Margaret Haney
Chapter

Abstract

This chapter describes the use of human laboratory procedures to characterize key behavioral features of cannabis use disorder (CUD). First, we provide a brief overview of recent shifts in cannabis policy in the United States and how these policy changes may affect CUD prevalence. This overview is followed by sections describing the scientific rationale, and methodologies used, for studying discrete behavioral features of CUD (intoxication, positive reinforcing effects, tolerance, withdrawal, abstinence initiation, and relapse) under carefully controlled human laboratory conditions. The methodological primer is followed by sections that summarize studies that have used human laboratory models to examine various classes of medications as potential treatments for CUD. We then conclude with a discussion that synthesizes the results of these studies into the broader CUD treatment development literature, examining potential ways in which human laboratory and clinical trial research methodologies could be further refined.

Keywords

Human laboratory Intoxication Positive reinforcing effects Tolerance Withdrawal Abstinence initiation Relapse 

References

  1. 1.
    Allsop DJ, Norberg MM, Copeland J, Fu S, Budney AJ. The cannabis withdrawal scale development: patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend. 2011;119:123–9.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev. 2001;7:249–64.PubMedCrossRefGoogle Scholar
  3. 3.
    Ashton CH. Pharmacology and effects of cannabis: a brief review. Br J Psychiatry. 2001;178:101–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Association A. P. The Diagnostic and statistical manual of mental disorders: DSM 5: BookpointUS; 2013.Google Scholar
  5. 5.
    Bigelow G, Griffiths R, Liebson I. Experimental models for the modification of human drug self-administration: methodological developments in the study of ethanol self-administration by alcoholics. Fed Proc. 1975;34:1785–92.PubMedPubMedCentralGoogle Scholar
  6. 6.
    Bigelow GE, Griffiths RR, Liebson IA. Pharmacological influences upon human ethanol self-administration. In:Alcohol intoxication and withdrawal—IIIb. Boston: Springer; 1977. p. 523–38.CrossRefGoogle Scholar
  7. 7.
    Brezing CA, Levin FR. The current state of pharmacological treatments for cannabis use disorder and withdrawal. Neuropsychopharmacology. 2018;43(1):173.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Budney AJ, Novy PL, Hughes JR. Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction. 1999;94:1311–22.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Budney AJ, Higgins ST, Radonovich KJ, Novy PL. Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. J Consult Clin Psychol. 2000;68:1051–61.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Budney AJ, Hughes JR, Moore BA, Novy PL. Marijuana abstinence effects in marijuana smokers maintained in their home environment. Arch Gen Psychiatry. 2001;58:917–24.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Budney AJ, Moore BA, Vandrey RG, Hughes JR. The time course and significance of cannabis withdrawal. J Abnorm Psychol. 2003;112:393.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Budney AJ, Hughes JR, Moore BA, Vandrey R. Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry. 2004;161:1967–77.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Budney AJ, Vandrey RG, Hughes JR, Moore BA, Bahrenburg B. Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms. Drug Alcohol Depend. 2007;86:22–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Carpenter KM, McDowell D, Brooks DJ, Cheng WY, Levin FR. A preliminary trial: double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Am J Addict. 2009;18:53–64.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Carroll KM, Easton CJ, Nich C, Hunkele KA, Neavins TM, Sinha R, Ford HL, Vitolo SA, Doebrick CA, Rounsaville BJ. The use of contingency management and motivational/skills-building therapy to treat young adults with marijuana dependence. J Consult Clin Psychol. 2006;74:955–66.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Center for Behavioral Health Statistics and Quality, S. A. A. M. H. S. A. Treatment episode data set (TEDS) for 2015. 2017.Google Scholar
  17. 17.
    Chait LD, Zacny JP. Reinforcing and subjective effects of oral delta 9-THC and smoked marijuana in humans. Psychopharmacology. 1992;107:255–62.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Cooper ZD, Haney M. Opioid antagonism enhances marijuana’s effects in heavy marijuana smokers. Psychopharmacology. 2010;211:141–8.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Cooper ZD, Foltin RW, Hart CL, Vosburg SK, Comer SD, Haney M. A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers. Addict Biol. 2013;18(6):993–1002.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Dalton WS, Martz R, Lemberger L, Rodda BE, Forney RB. Influence of cannabidiol on delta-9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976;19:300–9.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S. Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. N Engl J Med. 2017;376:2011–20.PubMedCrossRefGoogle Scholar
  22. 22.
    Fawcett J, Marcus RN, Anton SF, O’Brien K, Schwiderski U. Response of anxiety and agitation symptoms during nefazodone treatment of major depression. J Clin Psychiatry. 1995;56(Suppl 6):37–42.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Foltin RW, Brady JV, Fischman MW, Emurian CS, Dominitz J. Effects of smoked marijuana on social interaction in small groups. Drug Alcohol Depend. 1987;20:87–93.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Forray A, Sofuoglu M. Future pharmacological treatments for substance use disorders. Br J Clin Pharmacol. 2014;77:382–400.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Huestis MA. The cannabinoid CB1 receptor antagonist rimonabant attenuates the hypotensive effect of smoked marijuana in male smokers. Am Heart J. 2006;151:754.e1–5.CrossRefGoogle Scholar
  26. 26.
    Griffiths RR, Bigelow G, Liebson I. Human drug self-administration: double-blind comparison of pentobarbital, diazepam, chlorpromazine and placebo. J Pharmacol Exp Ther. 1979;210:301–10.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Haney M. Self-administration of cocaine, cannabis and heroin in the human laboratory: benefits and pitfalls. Addict Biol. 2009;14:9–21.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Haney M, Spealman R. Controversies in translational research: drug self-administration. Psychopharmacology (Berl). 2008;199(3):403–19.  https://doi.org/10.1007/s00213-008-1079-x.CrossRefGoogle Scholar
  29. 29.
    Haney M, Comer SD, Ward AS, Foltin RW, Fischman MW. Factors influencing marijuana self-administration by humans. Behav Pharmacol. 1997;8:101–12.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following oral THC administration to humans. Psychopharmacology. 1999a;141:385–94.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW. Abstinence symptoms following smoked marijuana in humans. Psychopharmacology. 1999b;141:395–404.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW. Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology. 2001;155:171.PubMedCrossRefGoogle Scholar
  33. 33.
    Haney M, Hart CL, Ward AS, Foltin RW. Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology. 2003;165:157–65.PubMedCrossRefGoogle Scholar
  34. 34.
    Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, Foltin RW. Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacology. 2004;29:158.PubMedCrossRefGoogle Scholar
  35. 35.
    Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW. Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology. 2008;197:157–68.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD, Foltin RW. Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology. 2010;211:233–44.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW. Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology. 2013;38:1557–65.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Haney M, Ramesh D, Glass A, Pavlicova M, Bedi G, Cooper ZD. Naltrexone maintenance decreases cannabis self-administration and subjective effects in daily cannabis smokers. Neuropsychopharmacology. 2015;40:2489.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Haney M, Malcolm RJ, Babalonis S, Nuzzo PA, Cooper ZD, Bedi G, Gray KM, McRae-Clark A, Lofwall MR, Sparenborg S. Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology. 2016;41:1974–82.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Hart CL, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW. Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology. 2002;164:407–15.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Hasin DS. U.S. epidemiology of cannabis use and associated problems. Neuropsychopharmacology. 2017;43(1):195–212.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Hasin DS, Keyes KM, Alderson D, Wang S, Aharonovich E, Grant BF. Cannabis withdrawal in the United States: a general population study. J Clin Psychiatry. 2008;69(9):1354–63.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Hasin D, O’Brien CP, Auriacombe M, Borges G, Bucholz K, Budney A, Compton WM, Crowley T, Ling W, Petry NM. DSM-5 criteria for substance use disorders: recommendations and rationale. Am J Psychiatr. 2013;170:834–51.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Hasin DS, Sarvet AL, Cerda M, Keyes KM, Stohl M, Galea S, Wall MM. US adult illicit cannabis use, cannabis use disorder, and medical marijuana laws: 1991-1992 to 2012-2013. JAMA Psychiat. 2017;74:579–88.CrossRefGoogle Scholar
  45. 45.
    Heishman SJ, Singleton EG, Liguori A. Marijuana craving questionnaire: development and initial validation of a self-report instrument. Addiction. 2001;96:1023–34.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Herrmann ES, Cooper ZD, Bedi G, Ramesh D, Reed SC, Comer SD, Foltin RW, Haney M. Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users. Psychopharmacology. 2016;233:2469–78.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Hill KP. Medical marijuana for treatment of chronic pain and other medical and psychiatric problems: a clinical review. JAMA. 2015;313:2474–83.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4:1770–804.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, Frank RA. Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry. 2001;58:322–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Huestis MA, Boyd SJ, Heishman SJ, Preston KL, Bonnet D, Le Fur G, Gorelick DA. Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology. 2007;194:505–15.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Hughes JR, Higgins ST, Bickel WK. Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities. Addiction. 1994;89:1461–70.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Hurd YL. Cannabidiol: swinging the marijuana pendulum from ‘weed’ to medication to treat the opioid epidemic. Trends Neurosci. 2017;40:124–7.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Hurd YL, Yoon M, Manini AF, Hernandez S, Olmedo R, Ostman M, Jutras-Aswad D. Early phase in the development of cannabidiol as a treatment for addiction: opioid relapse takes initial center stage. Neurotherapeutics. 2015;12:807–15.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Jensen KP, Devito EE, Valentine G, Gueorguieva R, Sofuoglu M. Intravenous nicotine self-administration in smokers: dose-response function and sex differences. Neuropsychopharmacology. 2016;41:2034–40.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Juckel G, Roser P, Nadulski T, Stadelmann AM, Gallinat J. Acute effects of Delta9-tetrahydrocannabinol and standardized cannabis extract on the auditory evoked mismatch negativity. Schizophr Res. 2007;97:109–17.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Kampman KM, Rukstalis M, Ehrman R, Mcginnis DE, Gariti P, Volpicelli JR, Pettinati H, O’Brien CP. Open trials as a method of prioritizing medications for inclusion in controlled trials for cocaine dependence. Addict Behav. 1999;24(2):287–91.PubMedCrossRefPubMedCentralGoogle Scholar
  57. 57.
    Kouri EM, Pope HG Jr, Lukas SE. Changes in aggressive behavior during withdrawal from long-term marijuana use. Psychopharmacology. 1999;143:302–8.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Lee D, Schroeder JR, Karschner EL, Goodwin RS, Hirvonen J, Gorelick DA, Huestis MA. Cannabis withdrawal in chronic, frequent cannabis smokers during sustained abstinence within a closed residential environment. Am J Addict. 2014;23:234–42.PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Lemberger L, Rubin A, Wolen R, Desante K, Rowe H, Forney R, Pence P. Pharmacokinetics, metabolism and drug-abuse potential of nabilone. Cancer Treat Rev. 1982;9:17–23.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Levin FR, Mcdowell D, Evans SM, Nunes E, Akerele E, Donovan S, Vosburg SK. Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict. 2004;13:21–32.PubMedCrossRefGoogle Scholar
  61. 61.
    Levin KH, Copersino ML, Heishman SJ, Liu F, Kelly DL, Boggs DL, Gorelick DA. Cannabis withdrawal symptoms in non-treatment-seeking adult cannabis smokers. Drug Alcohol Depend. 2010;111:120–7.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV. Dronabinol for the treatment of cannabis dependence: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2011;116:142–50.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Levin FR, Mariani JJ, Pavlicova M, Brooks D, Glass A, Mahony A, Nunes EV, Bisaga A, Dakwar E, Carpenter KM. Dronabinol and lofexidine for cannabis use disorder: a randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend. 2016;159:53–60.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Liappas J, Paparrigopoulos T, Tzavellas E, Rabavilas A. Mirtazapine and venlafaxine in the management of collateral psychopathology during alcohol detoxification. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29(1):55–60.CrossRefGoogle Scholar
  65. 65.
    Litt MD, Kadden RM, Kabela-Cormier E, Petry NM. Coping skills training and contingency management treatments for marijuana dependence: exploring mechanisms of behavior change. Addiction. 2008;103:638–48.PubMedPubMedCentralCrossRefGoogle Scholar
  66. 66.
    Mannucci C, Navarra M, Calapai F, Spagnolo EV, Busardo FP, Cas RD, Ippolito FM, Calapai G. Neurological aspects of medical use of cannabidiol. CNS Neurol Disord Drug Targets. 2017;16:541–53.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Mariani JJ, Pavlicova M, Mamczur AK, Bisaga A, Nunes EV, Levin FR. Open-label pilot study of quetiapine treatment for cannabis dependence. Am J Drug Alcohol Abuse. 2014;40:280–4.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    McClure EA, Stitzer ML, Vandrey R. Characterizing smoking topography of cannabis in heavy users. Psychopharmacology. 2012;220:309–18.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, White KG, Brady KT. A placebo-controlled trial of atomoxetine in marijuana-dependent individuals with attention deficit hyperactivity disorder. Am J Addict. 2010;19:481–9.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Mendelson JH, Mello NK. Reinforcing properties of oral delta 9-tetrahydrocannabinol, smoked marijuana, and nabilone: influence of previous marijuana use. Psychopharmacology. 1984a;83:351–6.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Mendelson JH, Mello NK. Reinforcing properties of oral Δ 9-tetrahydrocannabinol, smoked marijuana, and nabilone: influence of previous marijuana use. Psychopharmacology. 1984b;83:351–6.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Moreira FA, Crippa JAS. The psychiatric side-effects of rimonabant. Rev Bras Psiquiatr. 2009;31:145–53.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Penetar DM, Looby AR, Ryan ET, Maywalt MA, Lukas SE. Bupropion reduces some of the symptoms of marihuana withdrawal in chronic marihuana users: a pilot study. Subst Abuse Res Treat. 2012;6:63.Google Scholar
  74. 74.
    Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA. International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB(1) and CB(2). Pharmacol Rev. 2010;62:588–631.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Petrakis IL, Ralevski E, Gueorguieva R, O’Malley SS, Arias A, Sevarino KA, Jane JS, O’Brien E, Krystal JH. Mecamylamine treatment for alcohol dependence: a randomized controlled trial. Addiction. 2017;113(1):6–14.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Prud’homme M, Cata R, Jutras-Aswad D. Cannabidiol as an intervention for addictive behaviors: a systematic review of the evidence. Subst Abuse Res Treat. 2015;9:33.Google Scholar
  77. 77.
    Roser P, Gallinat J, Weinberg G, Juckel G, Gorynia I, Stadelmann AM. Psychomotor performance in relation to acute oral administration of Delta9-tetrahydrocannabinol and standardized cannabis extract in healthy human subjects. Eur Arch Psychiatry Clin Neurosci. 2009;259:284–92.PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Roux P, Sullivan MA, Cohen J, Fugon L, Jones JD, Vosburg SK, Cooper ZD, Manubay JM, Mogali S, Comer SD. Buprenorphine/naloxone as a promising therapeutic option for opioid abusing patients with chronic pain: reduction of pain, opioid withdrawal symptoms, and abuse liability of oral oxycodone. Pain. 2013;154:1442–8.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Schuster RM, Hanly A, Gilman J, Budney A, Vandrey R, Evins AE. A contingency management method for 30-days abstinence in non-treatment seeking young adult cannabis users. Drug Alcohol Depend. 2016;167:199–206.PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Sofuoglu M, Carroll KM. Effects of galantamine on cocaine use in chronic cocaine users. Am J Addict. 2011;20:302–3.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Sofuoglu M, Yoo S, Hill KP, Mooney M. Self-administration of intravenous nicotine in male and female cigarette smokers. Neuropsychopharmacology. 2008;33:715–20.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Stott CG, White L, Wright S, Wilbraham D, Guy GW. A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray. Eur J Clin Pharmacol. 2013;69:1135–47.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Tirado CF, Goldman M, Lynch K, Kampman KM, Obrien CP. Atomoxetine for treatment of marijuana dependence: a report on the efficacy and high incidence of gastrointestinal adverse events in a pilot study. Drug Alcohol Depend. 2008;94:254–7.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Turnbull D, Hodge JG Jr. Driving under the influence of marijuana laws and the public’s health: public health and the law. J Law Med Ethics. 2017;45:280–3.CrossRefGoogle Scholar
  85. 85.
    Vandrey R, Budney AJ, Kamon JL, Stanger C. Cannabis withdrawal in adolescent treatment seekers. Drug Alcohol Depend. 2005a;78:205–10.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Vandrey RG, Budney AJ, Moore BA, Hughes JR. A cross-study comparison of cannabis and tobacco withdrawal. Am J Addict. 2005b;14:54–63.PubMedCrossRefPubMedCentralGoogle Scholar
  87. 87.
    Vandrey RG, Budney AJ, Hughes JR, Liguori A. A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend. 2008;92:48–54.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Vandrey R, Smith MT, McCann UD, Budney AJ, Curran EM. Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend. 2011;117:38–44.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Vandrey R, Stitzer ML, Mintzer MZ, Huestis MA, Murray JA, Lee D. The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend. 2013;128:64–70.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;370:2219–27.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Ward AS, Comer SD, Haney M, Foltin RW, Fischman MW. The effects of a monetary alternative on marijuana self-administration. Behav Pharmacol. 1997;8:275–86.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Yoon SJ, Pae CU, Kim DJ, Namkoong K, Lee E, Oh DY, Lee YS, Shin DH, Jeong YC, Kim JH, Choi SB. Mirtazapine for patients with alcohol dependence and comorbid depressive disorders: a multicentre, open label study. Prog Neuro-Psychopharmacol Biol Psychiatry. 2006;30(7):1196–201.CrossRefGoogle Scholar
  93. 93.
    Zhornitsky S, Potvin S. Cannabidiol in humans—the quest for therapeutic targets. Pharmaceuticals. 2012;5:529–52.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Zuardi AW, Shirakawa I, Finkelfarb E, Karniol IG. Action of cannabidiol on the anxiety and other effects produced by delta 9-THC in normal subjects. Psychopharmacology. 1982;76:245–50.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Caroline A. Arout
    • 1
    Email author
  • Evan Herrmann
    • 2
  • Margaret Haney
    • 1
  1. 1.Department of Psychiatry, New York State Psychiatric Institute, Columbia University Medical CenterNew YorkUSA
  2. 2.Public Health Center for Substance Use Research, Battelle Memorial InstituteBaltimoreUSA

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