Abstract
Rationale
Only a small percentage of individuals seeking treatment for their marijuana use achieves sustained abstinence, suggesting more treatment options are needed.
Objectives
We investigated the effects of baclofen (study 1) and mirtazapine (study 2) in a human laboratory model of marijuana intoxication, withdrawal, and relapse.
Methods
In study 1, daily marijuana smokers (n = 10), averaging 9.4 (±3.9) marijuana cigarettes/day, were maintained on placebo and each baclofen dose (60, 90 mg/day) for 16 days. In study 2, daily marijuana smokers (n = 11), averaging 11.9 (±5.3) marijuana cigarettes/day, were maintained on placebo and mirtazapine (30 mg/day) for 14 days each. Medication administration began outpatient prior to each 8-day inpatient phase. On the first inpatient day of each medication condition, participants smoked active marijuana (study 1: 3.3% THC; study 2: 6.2% THC). For the next 3 days, they could self-administer placebo marijuana (abstinence phase), followed by 4 days in which they could self-administer active marijuana (relapse phase); participants paid for self-administered marijuana using study earnings.
Results
In study 1, during active marijuana smoking, baclofen dose-dependently decreased craving for tobacco and marijuana, but had little effect on mood during abstinence and did not decrease relapse. Baclofen also worsened cognitive performance regardless of marijuana condition. In study 2, mirtazapine improved sleep during abstinence, and robustly increased food intake, but had no effect on withdrawal symptoms and did not decrease marijuana relapse.
Conclusions
Overall, this human laboratory study did not find evidence to suggest that either baclofen or mirtazapine showed promise for the potential treatment of marijuana dependence.
Similar content being viewed by others
References
Akhondzadeh S, Ahmadi-Abhari SA, Assadi SM, Shabestari OL, Kashani AR, Farzanehgan ZM (2000) Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiate withdrawal. J Clin Pharm Ther 25:347–353
Bolla KI, Lesage SR, Gamaldo CE, Neubauer DN, Funderburk FR, Cadet JL, David PM, Verdejo-Garcia A, Benbrook AR (2008) Sleep disturbance in heavy marijuana users. Sleep 31:901–908
Budney AJ, Hughes JR, Moore BA, Vandrey R (2004) Review of the validity and significance of cannabis withdrawal syndrome. Am J Psychiatry 161:1967–1977
Budney AJ, Moore BA, Rocha HL, Higgins ST (2006) Clinical trial of abstinence-based vouchers and cognitive-behavioral therapy for cannabis dependence. J Consult Clin Psychol 74:307–316
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
Carpenter KM, McDowell D, Brooks DJ, Cheng W, 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
Cooper ZD, Haney M (2009) Comparison of subjective, pharmacokinetic, and physiological effects of marijuana smoked as joints and blunts. Drug Alcohol Depend 103:107–113
Copeland J, Swift W (2009) Cannabis use disorder: epidemiology and management. Int Rev Psychiatry 21:96–103
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
Cousins MS, Roberts DCS, de Wit H (2002) GABAB receptor agonists for the treatment of drug addiction: a review of recent findings. Drug Alcohol Depend 65:209–220
Epstein DH, Preston KL, Stewart J, Shaham Y (2006) Toward a model of drug relapse: an assessment of validity of the reinstatement procedure. Psychopharmacology 189:1–16
Foltin RW, Fischman MW, Pedroso JJ, Pearlson GD (1987) Marijuana and cocaine interactions in humans: cardiovascular consequences. Pharmacol Biochem Behav 28:459–464
Foltin RW, Haney M, Comer SD, Fischman MW (1996) Effects of fenfluramine in food intake, mood, and performance of humans living in a residential laboratory. Physiol Behav 59:295–305
Franklin TR, Harper D, Kampman K, Kildea-McCrea S, Jens W, Lynch KG, O’Brien CP, Childress AR (2009) The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebo-controlled smoking reduction study. Drug Alcohol Depend 103:30–36
Haney M (2005) The marijuana withdrawal syndrome: diagnosis and treatment. Curr Psychiatry Rep 7:360–366
Haney M, Spealman R (2008) Controversies in translational research: drug self-administration. Psychopharmacol 199:403–419
Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999a) Abstinence symptoms following oral THC administration to humans. Psychopharmacol 141:385–394
Haney M, Ward AS, Comer SD, Foltin RW, Fischman MW (1999b) Abstinence symptoms following smoked marijuana in humans. Psychopharmacol 141:395–404
Haney M, Ward AS, Comer SD, Hart CL, Foltin RW, Fischman MW (2001) Bupropion SR worsens mood during marijuana withdrawal in humans. Psychopharmacol 155:171–179
Haney M, Hart CL, Ward AS, Foltin RW (2003) Nefazodone decreases anxiety during marijuana withdrawal in humans. Psychopharmacol 165:157–165
Haney M, Hart CL, Vosburg SK, Nasser J, Bennett A, Zubaran C, Foltin RW (2004) Marijuana withdrawal in humans: effects of oral THC or divalproex. Neuropsychopharmacol 29:158–170
Haney M, Hart CL, Foltin RW (2006) Effects of baclofen on cocaine self-administration: opiod- and nonopioid-dependent volunteers. Neuropsychopharmacol 31:1814–1821
Haney M, Gunderson GW, Rabkin J, Hart CL, Vosburg SK, Comer SD, Foltin RW (2007) Dronabinol and marijuana in HIV-positive marijuana smokers. J Acquir Immune Defic Syndr 45:545–554
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. Psychopharmacol 197:157–168
Hart C, Ward AS, Haney M, Comer SD, Foltin RW, Fischman MW (2002) Comparison of smoked marijuana and oral delta(9)-tetrahydrocannabinol in humans. Psychopharmacol 164:407–415
Heishman SJ, Stizer ML, Yingling JE (1989) Effects of tetrahydrocannabidiol content on marijuana smoking behavior, subjective reports and performance. Pharmacol Biochem Behav 34:173–179
Kadden RM, Litt MD, Kabela-Cormier E, Petry NM (2007) Abstinence rates following behavioral treatments for marijuana dependence. Addict Behav 32:1220–1236
Koob GF, Lloyd GK, Mason BJ (2009) Development of pharmacotherapies for drug addiction: a Rosetta Stone approach. Nat Rev Drug Discov 8:500–515
Kouri EM, Pope HG Jr (2000) Abstinence symptoms during withdrawal from chronic marijuana use. Exp Clin Psychopharmacol 8:483–492
Laimer M, Kramer-Reinstadler K, Rauchenzauner M, Lechner-Schoner T, Strauss R, Engl J, Deisenhammer EA, Hinterhuber H, Patsch JR, Ebenbichler CF (2006) Effect of mirtazapine treatment on body composition and metabolism. J Clin Psychiatry 67:421–424
Levin FR, McDowell D, Evans SM, Nunes E, Akerele E, Donovan S, Vosburg SK (2004) Pharmacotherapy for marijuana dependence: a double-blind, placebo-controlled pilot study of divalproex sodium. Am J Addict 13:21–32
Levin FR, Brooks DJ, Bisaga A, Raby W, Rubin E, Aharonovich E, Nunez E (2006) Severity of dependence and motivation for treatment: comparison of marijuana- and cocaine-dependent treatment seekers. J Addict Dis 25:33–41
Liappas J, Paparrigopoulos T, Tzavellas E, Rabavilas A (2005) Mirtazapine and venlafaxine in the management of collateral psychopathology during alcohol detoxification. Prog Neuropsychopharmacol 29:55–60
Lichtman AH, Fisher J, Martin BR (2001) Precipitated cannabinoid withdrawal is reversed by delta(9)-tetrahydrocannabinol or clonidine. Pharmacol Biochem Behav 69:181–188
Marijuana Treatment Project Research Group (2004) Brief treatments for cannabis dependence: findings from a randomized multisite trial. J Consult Clin Psychol 72:455–466
McRae-Clark AL, Carter RE, Killeen TK, Carpenter MJ, Wahlquist AE, Simpson SA, Brady KT (2009) A placebo-controlled trial of buspirone for the treatment of marijuana dependence. Drug Alcohol Depend 105:132–138
Substance Abuse and Mental Health Services Administration (2007) Results from the 2006 National Survey on Drug Use and Health: National Findings (Office of Applied Studies, NSDUH series h-32, DHHS Publication No. SMA 07-4293). Rockville, MD
Moore BA, Budney AJ (2003) Relapse in outpatient treatment for marijuana dependence. J Subst Abuse Treat 25:85–89
Papakostas GI, Homberger CH, Fava M (2008) A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder. J Psychopharmacol 22:843–848
Sandyk R, Gillman MA (1985) Baclofen-induced memory impairment. Clin Neuropharmacol 8:294–295
Schierenbeck T, Riemann D, Berger M, Hornyak M (2008) Effect of illicit recreational drugs upon sleep: cocaine, ecstasy, and marijuana. Sleep Med Rev 12:381–389
Schmid DA, Wichniak A, Uhr M, Ising M, Brunner H, Held K, Weikel JC, Sonntag A, Steiger A (2006) Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacol 31:832–844
Stephens RS, Roffman RA, Simpson EE (1994) Treating adult marijuana dependence: a test of the relapse prevention model. J Consult Clin Psychol 62:92–99
Stephens RS, Roffman RA, Curtin L (2000) Extended versus brief treatment for marijuana use. J Consult Clin Psychol 68:898–908
Stinson FS, Ruan WJ, Pickering R, Grant BF (2006) Cannabis use disorders in the USA: prevalence, correlates and co-morbidity. Psychol Med 36:1447–1460
Teesson M, Lynskey M, Manor B, Baillie A (2002) The structure of cannabis dependence in the community. Drug Alcohol Depend 68:255–262
Yoon SJ, Pae CU, Kim DJ, Namkoong K, Lee E, Oh DY, Lee YS, Shin DH, Jeong YC, Kim JH, Choi SB, Hwang IB, Shin YC, Cho SN, Lee HK, Lee CT (2006) Mirtazapine for patients with alcohol dependence and comorbid depressive disorders: a multicentre, open label study. Prog Neuropsychopharmacol 30:1196–1201
Acknowledgment
The U.S. National Institute on Drug Abuse (NIDA) supported this research (DA19239, DA09236) supplied the marijuana cigarettes. The authors have no conflicts of interest. We are grateful to Brooke Roe, Diana Paksarian, Michael Rubin, Danielle Lion, and Matthew Pecht for their superb assistance in data collection.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Haney, M., Hart, C.L., Vosburg, S.K. et al. Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology 211, 233–244 (2010). https://doi.org/10.1007/s00213-010-1888-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-010-1888-6