The Current State of Pharmacological Treatments for Cannabis Use Disorder and Withdrawal

Neuropsychopharmacology

Volumn 43, Issue 1, 2018, Pages 173-194

  Brezing, Christina A ^a,b   Levin, Frances R ^a,b  

^a NEW YORK STATE PSYCHIATRIC INSTITUTE   (United States)

^b Surg of Columbia University ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID RECEPTOR STIMULATING AGENT; ACETYLCYSTEINE; ADRENERGIC RECEPTOR BLOCKING AGENT; CANNABINOID; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID 1 RECEPTOR ANTAGONIST; DRUGS USED IN THE TREATMENT OF ADDICTION; LITHIUM CARBONATE; NALTREXONE; OXYTOCIN; QUETIAPINE; SEROTONIN AGONIST; CANNABIS;

CANNABIS ADDICTION; CANNABIS USE; HUMAN; PRIORITY JOURNAL; PSYCHOPHARMACOTHERAPY; REVIEW; SMOKING CESSATION; WITHDRAWAL SYNDROME;

CANNABIS; HUMANS; MARIJUANA ABUSE; SUBSTANCE WITHDRAWAL SYNDROME;

EID: 85036621383     PISSN: 0893133X     EISSN: 1740634X     Source Type: Journal    
DOI: 10.1038/npp.2017.212     Document Type: Review

References (107)

1. Addolorato G, Caputo F, Capristo E, Colombo G, Gessa GL, Gasbarrini G (2000). Ability of baclofen in reducing alcohol craving and intake: II-preliminary clinical evidence. Alcohol Clin Exp Res 24: 67-71.
2. Allsop DJ, Copeland J, Norberg MM, Fu S, Molnar A, Lewis J, et al (2012). Quantifying the clinical significance of cannabis withdrawal. PLoS ONE 7: E44864.
3. Allsop DJ, Norberg MM, Copeland J, Fu S, Budney AJ (2011). The Cannabis Withdrawal Scale development: Patterns and predictors of cannabis withdrawal and distress. Drug Alcohol Depend 119: 123-129.
4. Allsop DJ, Bartlett DJ, Johnston J, Helliwell D, Winstock A, McGregor IS, et al (2015). The effects of lithium carbonate supplemented with nitrazepam on sleep disturbance during cannabis abstinence. J Clin Sleep Med 11: 1153-1162.
5. Allsop DJ, Copeland J, Lintzeris N, Dunlop AJ, Montebello M, Sadler C, et al (2014). Nabiximols as an agonist replacement therapy during cannabis withdrawal: A randomized clinical trial. JAMA Psychiatry 71: 281-291.
6. Anthenelli RM, Heffner JL, Wong E, Tibbs J, Russell K, Isgro M, et al (2017). A randomized trial evaluating whether topiramate aids smoking cessation and prevents alcohol relapse in recovering alcohol-dependent men. Alcohol Clin Exp Res 41: 197-206.
7. APA (2013). Diagnostic and Statistical Manual of Mental Disorders. American Psychiatric Association: Arlington, VA, USA.
8. Balter RE, Cooper ZD, Haney M (2014). Novel pharmacologic approaches to treating cannabis use disorder. Curr Addict Rep 1: 137-143.
9. Bedi G, Cooper ZD, Haney M (2013). Subjective, cognitive and cardiovascular doseeffect profile of nabilone and dronabinol in marijuana smokers. Addict Biol 18: 872-881.
10. Benn A, Robinson ES (2017). Differential roles for cortical versus sub-cortical noradrenaline and modulation of impulsivity in the rat. Psychopharmacology 234: 255-266.
11. Bentzley JP, Tomko RL, Gray KM (2016). Low pretreatment impulsivity and high medication adherence increase the odds of abstinence in a trial of N-acetylcysteine in adolescents with cannabis use disorder. J Subst Abuse Treat 63: 72-77.
12. Bonnet U, Preuss UW (2017). The cannabis withdrawal syndrome: Current insights. Subst Abuse Rehabil 8: 9-37.
13. Buckner JD, Carroll KM (2010). Effect of anxiety on treatment presentation and outcome: Results from the Marijuana Treatment Project. Psychiatry Res 178: 493-500.
14. Buckner JD, Schmidt NB, Lang AR, Small JW, Schlauch RC, Lewinsohn PM (2008). Specificity of social anxiety disorder as a risk factor for alcohol and cannabis dependence. J Psychiatric Res 42: 230-239.
15. Budney AJ, Novy PL, Hughes JR (1999). Marijuana withdrawal among adults seeking treatment for marijuana dependence. Addiction 94: 1311-1322.
16. Budney AJ, Higgins ST, Radonovich KJ, Novy PL (2000). Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. J Consult Clin Psychol 68: 1051-1061.
17. Budney AJ, Moore BA, Rocha HL, Higgins ST (2006). Clinical trial of abstinencebased vouchers and cognitive-behavioral therapy for cannabis dependence. J Consult Clin Psychol 74: 307-316.
18. Budney AJ, Vandrey RG, Hughes JR, Moore BA, Bahrenburg B (2007). Oral delta-9-tetrahydrocannabinol suppresses cannabis withdrawal symptoms. Drug Alcohol Depend 86: 22-29.
19. Budney AJ, Vandrey RG, Hughes JR, Thostenson JD, Bursac Z (2008). Comparison of cannabis and tobacco withdrawal: Severity and contribution to relapse. J Subst Abuse Treat 35: 362-368.
20. Carpenter KM, McDowell D, Brooks DJ, Cheng WY, Levin FR (2009). A preliminary trial: Double-blind comparison of nefazodone, bupropion-SR, and placebo in the treatment of cannabis dependence. Am J Addict 18: 53-64.
21. Cooper ZD, Foltin RW, Hart CL, Vosburg SK, Comer SD, Haney M (2013). A human laboratory study investigating the effects of quetiapine on marijuana withdrawal and relapse in daily marijuana smokers. Addict Biol 18: 993-1002.
22. Cooper ZD, Haney M (2010). Opioid antagonism enhances marijuana's effects in heavy marijuana smokers. Psychopharmacology 211: 141-148.
23. Cooper ZD, Haney M (2016). Sex-dependent effects of cannabis-induced analgesia. Drug Alcohol Depend 167: 112-120.
24. Copeland J, Swift W, Roffman R, Stephens R (2001). A randomized controlled trial of brief cognitive-behavioral interventions for cannabis use disorder. J Subst Abuse Treat 21: 55-64 discussion 65-56.
25. Cornelius JR, Bukstein OG, Douaihy AB, Clark DB, Chung TA, Daley DC, et al (2010). Double-blind fluoxetine trial in comorbid MDD-CUD youth and young adults. Drug Alcohol Depend 112: 39-45.
26. Cui SS, Bowen RC, Gu GB, Hannesson DK, Yu PH, Zhang X (2001). Prevention of cannabinoid withdrawal syndrome by lithium: Involvement of oxytocinergic neuronal activation. J Neurosci 21: 9867-9876.
27. Degenhardt L, Ferrari AJ, Calabria B, Hall WD, Norman RE, McGrath J, et al (2013). The global epidemiology and contribution of cannabis use and dependence to the global burden of disease: Results from the GBD 2010 study. PLoS ONE 8: E76635.
28. Dennis M, Babor TF, Roebuck MC, Donaldson J (2002). Changing the focus: The case for recognizing and treating cannabis use disorders. Addiction 97(Suppl 1): 4-15.
29. Garbutt JC, West SL, Carey TS, Lohr KN, Crews FT (1999). Pharmacological treatment of alcohol dependence: A review of the evidence. JAMA 281: 1318-1325.
30. Gates PJ, Sabioni P, Copeland J, Le Foll B, Gowing L (2016). Psychosocial interventions for cannabis use disorder. Cochrane Database Syst Rev CD005336.
31. Ghaemi SN, Katzow JJ, Desai SP, Goodwin FK (1998). Gabapentin treatment of mood disorders: A preliminary study. J Clin Psychiatry 59: 426-429.
32. Gomes FV, Resstel LB, Guimaraes FS (2011). The anxiolytic-like effects of cannabidiol injected into the bed nucleus of the stria terminalis are mediated by 5-HT1A receptors. Psychopharmacology 213: 465-473.
33. Gorelick DA (2016). Pharmacological treatment of cannabis-related disorders: A narrative review. Curr Pharm Des 22: 6409-6419.
34. Gray KM, Carpenter MJ, Baker NL, DeSantis SM, Kryway E, Hartwell KJ, et al (2012). A double-blind randomized controlled trial of N-acetylcysteine in cannabisdependent adolescents. Am J Psychiatry 169: 805-812.
35. Gray KM, Sonne SC, McClure EA, Ghitza UE, Matthews AG, McRae-Clark AL, et al (2017). A randomized placebo-controlled trial of N-acetylcysteine for cannabis use disorder in adults. Drug Alcohol Depend 177: 249-257.
36. Gray KM, Watson NL, Carpenter MJ, Larowe SD (2010). N-acetylcysteine (NAC) in young marijuana users: An open-label pilot study. Am J Addict 19: 187-189.
37. Gueye AB, Pryslawsky Y, Trigo JM, Poulia N, Delis F, Antoniou K, et al (2016). The CB1 neutral antagonist AM4113 retains the therapeutic efficacy of the inverse agonist rimonabant for nicotine dependence and weight loss with better psychiatric tolerability. Int J Neuropsychopharmacol 19: 1-11.
38. Haney M, Hart CL, Foltin RW (2006). Effects of baclofen on cocaine selfadministration: Opioid-A nd nonopioid-dependent volunteers. Neuropsychopharmacology 31: 1814-1821.
39. Haney M, Bedi G, Cooper ZD, Glass A, Vosburg SK, Comer SD, et al (2013a). Predictors of marijuana relapse in the human laboratory: Robust impact of tobacco cigarette smoking status. Biol Psychiatry 73: 242-248.
40. Haney M, Cooper ZD, Bedi G, Vosburg SK, Comer SD, Foltin RW (2013b). Nabilone decreases marijuana withdrawal and a laboratory measure of marijuana relapse. Neuropsychopharmacology 38: 1557-1565.
41. Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Cooper ZD, et al (2010). Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology 211: 233-244.
42. Haney M, Hart CL, Vosburg SK, Comer SD, Reed SC, Foltin RW (2008). Effects of THC and lofexidine in a human laboratory model of marijuana withdrawal and relapse. Psychopharmacology 197: 157-168.
43. Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, et al (2004). Marijuana withdrawal in humans: Effects of oral THC or divalproex. Neuropsychopharmacology 29: 158-170.
44. Haney M, Hart CL, Ward AS, Foltin RW (2003). Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacology 165: 157-165.
45. Haney M, Malcolm RJ, Babalonis S, Nuzzo PA, Cooper ZD, Bedi G, et al (2016). Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology 41: 1974-1982.
46. Haney M, Ramesh D, Glass A, Pavlicova M, Bedi G, Cooper ZD (2015). Naltrexone maintenance decreases cannabis self-administration and subjective effects in daily cannabis smokers. Neuropsychopharmacology 40: 2489-2498.
47. Haney M, Spealman R (2008). Controversies in translational research: Drug selfadministration. Psychopharmacology 199: 403-419.
48. Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001). Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacology 155: 171-179.
49. Hart CL, Haney M, Vosburg SK, Comer SD, Foltin RW (2005). Reinforcing effects of oral Delta9-THC in male marijuana smokers in a laboratory choice procedure. Psychopharmacology 181: 237-243.
50. Hart CL, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW (2002). Comparison of smoked marijuana and oral Delta(9)-tetrahydrocannabinol in humans. Psychopharmacology 164: 407-415.
51. Herrmann ES, Cooper ZD, Bedi G, Ramesh D, Reed SC, Comer SD, et al (2016). Effects of zolpidem alone and in combination with nabilone on cannabis withdrawal and a laboratory model of relapse in cannabis users. Psychopharmacology 233: 2469-2478.
52. Hill MN, Sun JC, Tse MT, Gorzalka BB (2006). Altered responsiveness of serotonin receptor subtypes following long-term cannabinoid treatment. Int J Neuropsychopharmacol 9: 277-286.
53. Huestis MA, Boyd SJ, Heishman SJ, Preston KL, Bonnet D, Le Fur G, et al (2007). Single and multiple doses of rimonabant antagonize acute effects of smoked cannabis in male cannabis users. Psychopharmacology 194: 505-515.
54. Huestis MA, Gorelick DA, Heishman SJ, Preston KL, Nelson RA, Moolchan ET, et al (2001). Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716. Arch Gen Psychiatry 58: 322-328.
55. Hughes JR, Naud S, Budney AJ, Fingar JR, Callas PW (2016). Attempts to stop or reduce daily cannabis use: An intensive natural history study. Psychol Addict Behav 30: 389-397.
56. Hughes JR, Peters EN, Callas PW, Budney AJ, Livingston AE (2008). Attempts to stop or reduce marijuana use in non-treatment seekers. Drug Alcohol Depend 97: 180-184.
57. Johnston J, Lintzeris N, Allsop DJ, Suraev A, Booth J, Carson DS, et al (2014). Lithium carbonate in the management of cannabis withdrawal: A randomized placebocontrolled trial in an inpatient setting. Psychopharmacology 231: 4623-4636.
58. Kampman KM, Rukstalis M, Ehrman R, McGinnis DE, Gariti P, Volpicelli JR, et al (1999). Open trials as a method of prioritizing medications for inclusion in controlled trials for cocaine dependence. Addict Behav 24: 287-291.
59. Kelly MA, Pavlicova M, Glass A, Mariani JJ, Bisaga A, Sullivan MA, et al (2014). Do withdrawal-like symptoms mediate increased marijuana smoking in individuals treated with venlafaxine-XR Drug Alcohol Depend 144: 42-46.
60. Keuroghlian AS, Barry AS, Weiss RD (2012). Circadian dysregulation, zolpidem dependence, and withdrawal seizure in a resident physician performing shift work. Am J Addict 21: 576-577.
61. Lee D, Vandrey R, Mendu DR, Murray JA, Barnes AJ, Huestis MA (2015). Oral fluid cannabinoids in chronic frequent cannabis smokers during ad libitum cannabis smoking. Drug Test Anal 7: 494-501.
62. Levin FR, Mariani J, Brooks DJ, Pavlicova M, Nunes EV, Agosti V, et al (2013). A randomized double-blind, placebo-controlled trial of venlafaxine-extended release for co-occurring cannabis dependence and depressive disorders. Addiction 108: 1084-1094.
63. Levin FR, Mariani JJ, Brooks DJ, Pavlicova M, Cheng W, Nunes EV (2011). Dronabinol for the treatment of cannabis dependence: A randomized, doubleblind, placebo-controlled trial. Drug Alcohol Depend 116: 142-150.
64. Levin FR, Mariani JJ, Pavlicova M, Brooks D, Glass A, Mahony A, et al (2016). Dronabinol and lofexidine for cannabis use disorder: A randomized, double-blind, placebo-controlled trial. Drug Alcohol Depend 159: 53-60.
65. Levin FR, McDowell D, Evans SM, Nunes E, Akerele E, Donovan S, et al (2004). Pharmacotherapy for marijuana dependence: A double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict 13: 21-32.
66. Lo HS, Yang CM, Lo HG, Lee CY, Ting H, Tzang BS (2010). Treatment effects of gabapentin for primary insomnia. Clin Neuropharmacol 33: 84-90.
67. Mason BJ, Light JM, Williams LD, Drobes DJ (2009). Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: Effects of gabapentin. Addict Biol 14: 73-83.
68. Mariani JJ, Pavlicova M, Mamczur AK, Bisaga A, Nunes EV, Levin FR (2014). Openlabel pilot study of quetiapine treatment for cannabis dependence. Am J Drug Alcohol Abuse 14: 280-284.
69. Martino S, Ball SA, Nich C, Frankforter TL, Carroll KM (2009). Informal discussions in substance abuse treatment sessions. J Subst Abuse Treat 36: 366-375.
70. Mason BJ, Crean R, Goodell V, Light JM, Quello S, Shadan F, et al (2012). A proofof-concept randomized controlled study of gabapentin: Effects on cannabis use, withdrawal and executive function deficits in cannabis-dependent adults. Neuropsychopharmacology 37: 1689-1698.
71. McRae-Clark AL, Baker NL, Gray KM, Killeen T, Hartwell KJ, Simonian SJ (2016). Vilazodone for cannabis dependence: A randomized, controlled pilot trial. Am J Addict 25: 69-75.
72. McRae-Clark AL, Baker NL, Gray KM, Killeen TK, Wagner AM, Brady KT, et al (2015). Buspirone treatment of cannabis dependence: A randomized, placebocontrolled trial. Drug Alcohol Depend 156: 29-37.
73. McRae-Clark AL, Baker NL, Maria MM, Brady KT (2013). Effect of oxytocin on craving and stress response in marijuana-dependent individuals: A pilot study. Psychopharmacology 228: 623-631.
74. McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, Wahlquist AE, Simpson SA, et al (2009). A placebo-controlled trial of buspirone for the treatment of marijuana dependence. Drug Alcohol Depend 105: 132-138.
75. McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, White KG, Brady KT (2010). A placebo-controlled trial of atomoxetine in marijuana-dependent individuals with attention deficit hyperactivity disorder. Am J Addict 19: 481-489.
76. Mills EJ, Wu P, Lockhart I, Thorlund K, Puhan M, Ebbert JO (2012). Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: A systematic review and multiple treatment meta-analysis. Ann Med 44: 588-597.
77. Miranda R Jr, Treloar H, Blanchard A, Justus A, Monti PM, Chun T, et al (2016). Topiramate and motivational enhancement therapy for cannabis use among youth: A randomized placebo-controlled pilot study. Addict Biol 22: 779-790.
78. Morales P, Reggio PH, Jagerovic N (2017). An overview on medicinal chemistry of synthetic and natural derivatives of cannabidiol. Front Pharmacol 8: 422.
79. Moss HB, Chen CM, Yi HY (2012). Measures of substance consumption among substance users, DSM-IV abusers, and those with DSM-IV dependence disorders in a nationally representative sample. J Stud Alcohol Drugs 73: 820-828.
80. Olmstead TA, Abraham AJ, Martino S, Roman PM (2012). Counselor training in several evidence-based psychosocial addiction treatments in private US substance abuse treatment centers. Drug Alcohol Depend 120: 149-154.
81. Pacek LR, Vandrey R (2014). Cannabis use history and characteristics of quit attempts: A comparison study of treatment-seeking and non-treatment-seeking cannabis users. Exp Clin Psychopharmacol 22: 517-523.
82. Penetar DM, Looby AR, Ryan ET, Maywalt MA, Lukas SE (2012). Bupropion reduces some of the symptoms of marihuana withdrawal in chronic marihuana users: A pilot study. Subst Abuse 6: 63-71.
83. Perkonigg A, Goodwin RD, Fiedler A, Behrendt S, Beesdo K, Lieb R, et al (2008). The natural course of cannabis use, abuse and dependence during the first decades of life. Addiction 103: 439-449 discussion 450-451.
84. Roberfroid D, Lachat C, Lucet C (2010). Termination of the CRESCENDO trial. Lancet 376: 1983-1984 author reply 1984-1985.
85. Roberto M, Gilpin NW, O'Dell LE, Cruz MT, Morse AC, Siggins GR, et al (2008). Cellular and behavioral interactions of gabapentin with alcohol dependence. J Neurosci 28: 5762-5771.
86. SAMHSA (2015). Behavioral Health Trends in the United States: Results from the 2014 National Survey on Drug Use and Health NSDUH Series H-50 Center for Behavioral Health Statistics and Quality: Rockville, MD, USA.
87. SAMHSA (2016). Treatment Episode Data Set (TEDS): 2004-2014. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality: Rockville, MD, USA.
88. Santa Ana EJ, Martino S, Ball SA, Nich C, Frankforter TL, Carroll KM (2008). What is usual about "treatment-as-usual" Data from two multisite effectiveness trials. J Subst Abuse Treat 35: 369-379.
89. Sherman BJ, Baker NL, McRae-Clark AL (2017). Effect of oxytocin pretreatment on cannabis outcomes in a brief motivational intervention. Psychiatry Res 249: 318-320.
90. Sherman BJ, McRae-Clark AL (2016). Treatment of cannabis use disorder: Current science and future outlook. Pharmacotherapy 36: 511-535.
91. Simoneau H, Brochu S (2017). ASI profile of persons who re-enter treatment for substance use disorders. Subst Abuse 1-6.
92. Smith ML, Barnes AJ, Huestis MA (2009). Identifying new cannabis use with urine creatinine-normalized THCCOOH concentrations and time intervals between specimen collections. J Anal Toxicol 33: 185-189.
93. Stead LF, Perera R, Bullen C, Mant D, Lancaster T (2008). Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev CD000146.
94. Tait RJ, Spijkerman R, Riper H (2013). Internet and computer based interventions for cannabis use: A meta-analysis. Drug Alcohol Depend 133: 295-304.
95. Tirado CF, Goldman M, Lynch K, Kampman KM, Obrien CP (2008). 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 94: 254-257.
96. Trigo JM, Lagzdins D, Rehm J, Selby P, Gamaleddin I, Fischer B, et al (2016a). Effects of fixed or self-titrated dosages of Sativex on cannabis withdrawal and cravings. Drug Alcohol Depend 161: 298-306.
97. Trigo JM, Soliman A, Staios G, Quilty L, Fischer B, George TP, et al (2016b). Sativex associated with behavioral-relapse prevention strategy as treatment for cannabis dependence: A case series. J Addict Med 10: 274-279.
98. United Nations Office on Drugs and Crime (2015). World Drug Report 2015. United Nations Publication: Vienna, Austria
99. Vandrey R, Haney M (2009). Pharmacotherapy for cannabis dependence: How close are we CNS Drugs, 23, 543-553.
100. Vandrey R, Smith MT, McCann UD, Budney AJ, Curran EM (2011). Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal. Drug Alcohol Depend 117: 38-44.
101. Vandrey R, Stitzer ML, Mintzer MZ, Huestis MA, Murray JA, Lee D (2013). The dose effects of short-term dronabinol (oral THC) maintenance in daily cannabis users. Drug Alcohol Depend 128: 64-70.
102. Vandrey RG, Budney AJ, Hughes JR, Liguori A (2008). A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances. Drug Alcohol Depend 92: 48-54.
103. Vermersch P (2011). Sativex((R)) (tetrahydrocannabinol+cannabidiol), an endocannabinoid system modulator: Basic features and main clinical data. Expert Rev Neurother 11: 15-19.
104. Wei D, Lee D, Cox CD, Karsten CA, Penagarikano O, Geschwind DH, et al (2015). Endocannabinoid signaling mediates oxytocin-driven social reward. Proc Natl Acad Sci USA 112: 14084-14089.
105. Weinstein AM, Miller H, Bluvstein I, Rapoport E, Schreiber S, Bar-Hamburger R, et al (2014). Treatment of cannabis dependence using escitalopram in combination with cognitive-behavior therapy: A double-blind placebo-controlled study. Am J Drug Alcohol Abuse 40: 16-22.
106. Winstock AR, Lea T, Copeland J (2009). Lithium carbonate in the management of cannabis withdrawal in humans: An open-label study. J Psychopharmacol 23: 84-93.
107. Zanelati TV, Biojone C, Moreira FA, Guimaraes FS, Joca SR (2010). Antidepressantlike effects of cannabidiol in mice: Possible involvement of 5-HT1A receptors. Br J Pharmacol 159: 122-128.