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Baclofen in Cannabis Dependence Syndrome
CORRESPONDENCE Baclofen in Cannabis Dependence Syndrome To the Editor: annabis, like other drugs of abuse, produces its reinforcing effects by activating the brain “reward” pathways comprising dopamine (DA) neurons in the ventral tegmental area that project to the nucleus accumbens and by increasing DA levels in the shell of the nucleus accumbens. Discontinuation of cannabis use results in a recognized withdrawal syndrome that develops within 24 to 48 hours of abstinence, peaks within 6 days, and lasts from 1 to 3 weeks (1). Relapse is very common (2), and the symptoms associated with cessation strongly contribute to relapse. Treating the symptoms of cannabis withdrawal may improve the likelihood of prolonged abstinence (3). However, there are no approved medications for withdrawal or relapse prevention in this population. Baclofen, a selective gamma aminobutyric acid B receptor agonist that inhibits the release of several neurotransmitters, including DA, noradrenaline, glutamate (4), and serotonin (5), has been shown to be effective in suppressing alcohol withdrawal and delaying relapse (6), and there is preliminary evidence of efficacy in cocaine (7) and inhalant dependence
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(8). In rodents, pretreatment with baclofen reduces dopamine release evoked by nicotine, morphine, and cocaine in the shell of the nucleus accumbens. Based on the above findings, we hypothesize that baclofen may be beneficial in the treatment of symptoms of cannabis withdrawal as well as in reducing craving. We present a case series of six male subjects (Table 1) with cannabis dependence and nicotine dependence without any other comorbid psychiatric diagnosis, treated with baclofen at a standard dose of 40 mg/day in divided doses (9). All subjects were assessed using the Cannabis Withdrawal Assessment Scale (10) at intake, 1 week, and monthly intervals. Urine toxicology screening for cannabis was conducted at intake and monthly. Baclofen significantly improved the symptoms of cannabis withdrawal and also appeared to appreciably delay relapse. The common side effects reported were sedation and lethargy, which were self-limiting and did not require discontinuation. All the subjects remained abstinent for periods ranging from at least 1 to 13 months. The dose of baclofen used was the same as in the previous studies with alcohol (6) and inhalants (8).
Table 1. Case Summariesa CWAS Score—1 Week
Intensity of Cannabis Use and Duration
Withdrawal Symptoms; Baseline Urine Screen
Baseline CWAS Score
20 Years
10 joints of marijuana per day for 1 year
Insomnia, irritability, restlessness, and craving; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺4
26 Years
8 to 10 joints of marijuana per day for 6 years
Craving, mood swings, insomnia, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺3
24 Years
6 joints of marijuana per day for 5 years
Intense craving, irritability, unreality feeling, insomnia, anorexia, and anger; Urine toxicology screen⫺positive
CWAS score⫺18
1 week CWAS score⫺6
21 Years
4 to 5 joints of marijuana per day for 4 years
Craving, mood swings, insomnia, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺5
33 Years
6 joints of marijuana per day for 7 years
Craving, insomnia, restlessness, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺2
21 Years
6 joints of marijuana per day for 4 years
Intense craving, irritability, insomnia, and anorexia; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺3
Age
Period of Definite Abstinence; Urine Screen; Outcome Abstinent for 390 days with a lapse (14 follow-up visits); Urine toxicology screen—negative (ten); Lost to follow-up after 390 days Abstinent for 120 days (three follow-up visits); Urine toxicology screen—negative (twice); Lost to follow-up after 120 days Abstinent for 90 days (four followup visits); Urine toxicology screen—negative (thrice); Lost to follow-up after 90 days Abstinent for 60 days (three follow-up visits); Urine toxicology screen—negative (twice); Lost to follow-up after 60 days Abstinent for 40 days (two follow-up visits); Urine toxicology screen—negative (once); Relapsed with stopping of medication with decrease in frequency. Lost to follow-up after 60 days Abstinent for 30 days (two followup visits); Urine toxicology screen—negative (once); Lost to follow-up after 30 days
CWAS, Cannabis Withdrawal Assessment Scale. Informed consent was obtained in all the cases before starting of the medications.
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0006-3223/$36.00
BIOL PSYCHIATRY 2010;68:e9 – e10 © 2010 Society of Biological Psychiatry
e10 BIOL PSYCHIATRY 2010;68:e9 – e10 The subjects were not on any other prescribed medications during this period. These findings provide preliminary support for the use of baclofen in the management of patients with cannabis dependence. However, larger randomized, controlled trials are required before baclofen can be widely recommended in the treatment of cannabis dependence. The authors report no biomedical financial interests or potential conflicts of interest. Subodh Bhagyalakshmi Nanjayya Senior Resident Department of Psychiatry National Institute of Mental Health and Neuro Sciences Bangalore, India 560029 E-mail: [email protected] Madhusudhan Shivappa Prabhat Kumar Chand Pratima Murthy Vivek Benegal De-Addiction Centre Department of Psychiatry National Institute of Mental Health and Neuro Sciences Bangalore, Republic of India 1. Budney AJ, Hughes JR (2006): The cannabis withdrawal syndrome. Curr Opin Psychiatry 19:233–238.
www.sobp.org/journal
Correspondence 2. Perkonigg A, Goodwin RD, Fiedler A, Behrendt S, Beesdo K, Lieb R, Wittchen HU (2008): The natural course of cannabis use, abuse and dependence during the first decades of life. Addiction 103:439 – 449. 3. Clapper JR, Mangieri RA, Piomelli D (2009): The endocannabinoid system as a target for the treatment of cannabis dependence. Neuropharmacology 5:235–243. 4. Huston E, Cullen GP, Burley JR, Dolphin AC (1995): The involvement of multiple calcium channel sub-types in glutamate release from cerebellar granule cells and its modulation by GABAB receptor activation. Neuroscience 68:465– 478. 5. Wojcik WJ, Holopainen I (1992): Role of central GABAB receptors in physiology and pathology. Neuropsychopharmacology 6:201–214. 6. Addolorato G, Leggio L, Agabio R, Colombo G, Gasbarrini G (2006): Baclofen: A new drug for the treatment of alcohol dependence. Int J Clin Pract 60:1003–1008. 7. Shoptaw S, Yang X, Rotheram-Fuller EJ, Hsieh YC, Kintaudi PC, Charuvastra VC, Ling W (2003): Randomized placebo-controlled trial of baclofen for cocaine dependence: Preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 64:1440 – 1448. 8. Muralidharan K, Rajkumar RP, Mulla U, Nayak RB, Benegal V (2008): Baclofen in the management of inhalant withdrawal: A case series. Prim Care Companion J Clin Psychiatry 10:48 –51. 9. Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. (2007): Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: Randomised, double-blind controlled study. Lancet 370:1915–1922. 10. de Crespigny C, Talmet J, Modystack K, Cusack L, Watkinson J (2003): Alcohol, Tobacco & Other Drugs Guidelines for Nurses and Midwives: Clinical Guidelines. Adelaide, South Australia: Flinders University and Drug & Alcohol Services Council, 209 –210.
doi:10.1016/j.biopsych.2010.03.033
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(8). In rodents, pretreatment with baclofen reduces dopamine release evoked by nicotine, morphine, and cocaine in the shell of the nucleus accumbens. Based on the above findings, we hypothesize that baclofen may be beneficial in the treatment of symptoms of cannabis withdrawal as well as in reducing craving. We present a case series of six male subjects (Table 1) with cannabis dependence and nicotine dependence without any other comorbid psychiatric diagnosis, treated with baclofen at a standard dose of 40 mg/day in divided doses (9). All subjects were assessed using the Cannabis Withdrawal Assessment Scale (10) at intake, 1 week, and monthly intervals. Urine toxicology screening for cannabis was conducted at intake and monthly. Baclofen significantly improved the symptoms of cannabis withdrawal and also appeared to appreciably delay relapse. The common side effects reported were sedation and lethargy, which were self-limiting and did not require discontinuation. All the subjects remained abstinent for periods ranging from at least 1 to 13 months. The dose of baclofen used was the same as in the previous studies with alcohol (6) and inhalants (8).
Table 1. Case Summariesa CWAS Score—1 Week
Intensity of Cannabis Use and Duration
Withdrawal Symptoms; Baseline Urine Screen
Baseline CWAS Score
20 Years
10 joints of marijuana per day for 1 year
Insomnia, irritability, restlessness, and craving; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺4
26 Years
8 to 10 joints of marijuana per day for 6 years
Craving, mood swings, insomnia, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺3
24 Years
6 joints of marijuana per day for 5 years
Intense craving, irritability, unreality feeling, insomnia, anorexia, and anger; Urine toxicology screen⫺positive
CWAS score⫺18
1 week CWAS score⫺6
21 Years
4 to 5 joints of marijuana per day for 4 years
Craving, mood swings, insomnia, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺5
33 Years
6 joints of marijuana per day for 7 years
Craving, insomnia, restlessness, and decreased appetite; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺2
21 Years
6 joints of marijuana per day for 4 years
Intense craving, irritability, insomnia, and anorexia; Urine toxicology screen⫺positive
CWAS score⫺15
1 week CWAS score⫺3
Age
Period of Definite Abstinence; Urine Screen; Outcome Abstinent for 390 days with a lapse (14 follow-up visits); Urine toxicology screen—negative (ten); Lost to follow-up after 390 days Abstinent for 120 days (three follow-up visits); Urine toxicology screen—negative (twice); Lost to follow-up after 120 days Abstinent for 90 days (four followup visits); Urine toxicology screen—negative (thrice); Lost to follow-up after 90 days Abstinent for 60 days (three follow-up visits); Urine toxicology screen—negative (twice); Lost to follow-up after 60 days Abstinent for 40 days (two follow-up visits); Urine toxicology screen—negative (once); Relapsed with stopping of medication with decrease in frequency. Lost to follow-up after 60 days Abstinent for 30 days (two followup visits); Urine toxicology screen—negative (once); Lost to follow-up after 30 days
CWAS, Cannabis Withdrawal Assessment Scale. Informed consent was obtained in all the cases before starting of the medications.
a
0006-3223/$36.00
BIOL PSYCHIATRY 2010;68:e9 – e10 © 2010 Society of Biological Psychiatry
e10 BIOL PSYCHIATRY 2010;68:e9 – e10 The subjects were not on any other prescribed medications during this period. These findings provide preliminary support for the use of baclofen in the management of patients with cannabis dependence. However, larger randomized, controlled trials are required before baclofen can be widely recommended in the treatment of cannabis dependence. The authors report no biomedical financial interests or potential conflicts of interest. Subodh Bhagyalakshmi Nanjayya Senior Resident Department of Psychiatry National Institute of Mental Health and Neuro Sciences Bangalore, India 560029 E-mail: [email protected] Madhusudhan Shivappa Prabhat Kumar Chand Pratima Murthy Vivek Benegal De-Addiction Centre Department of Psychiatry National Institute of Mental Health and Neuro Sciences Bangalore, Republic of India 1. Budney AJ, Hughes JR (2006): The cannabis withdrawal syndrome. Curr Opin Psychiatry 19:233–238.
www.sobp.org/journal
Correspondence 2. Perkonigg A, Goodwin RD, Fiedler A, Behrendt S, Beesdo K, Lieb R, Wittchen HU (2008): The natural course of cannabis use, abuse and dependence during the first decades of life. Addiction 103:439 – 449. 3. Clapper JR, Mangieri RA, Piomelli D (2009): The endocannabinoid system as a target for the treatment of cannabis dependence. Neuropharmacology 5:235–243. 4. Huston E, Cullen GP, Burley JR, Dolphin AC (1995): The involvement of multiple calcium channel sub-types in glutamate release from cerebellar granule cells and its modulation by GABAB receptor activation. Neuroscience 68:465– 478. 5. Wojcik WJ, Holopainen I (1992): Role of central GABAB receptors in physiology and pathology. Neuropsychopharmacology 6:201–214. 6. Addolorato G, Leggio L, Agabio R, Colombo G, Gasbarrini G (2006): Baclofen: A new drug for the treatment of alcohol dependence. Int J Clin Pract 60:1003–1008. 7. Shoptaw S, Yang X, Rotheram-Fuller EJ, Hsieh YC, Kintaudi PC, Charuvastra VC, Ling W (2003): Randomized placebo-controlled trial of baclofen for cocaine dependence: Preliminary effects for individuals with chronic patterns of cocaine use. J Clin Psychiatry 64:1440 – 1448. 8. Muralidharan K, Rajkumar RP, Mulla U, Nayak RB, Benegal V (2008): Baclofen in the management of inhalant withdrawal: A case series. Prim Care Companion J Clin Psychiatry 10:48 –51. 9. Addolorato G, Leggio L, Ferrulli A, Cardone S, Vonghia L, Mirijello A, et al. (2007): Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: Randomised, double-blind controlled study. Lancet 370:1915–1922. 10. de Crespigny C, Talmet J, Modystack K, Cusack L, Watkinson J (2003): Alcohol, Tobacco & Other Drugs Guidelines for Nurses and Midwives: Clinical Guidelines. Adelaide, South Australia: Flinders University and Drug & Alcohol Services Council, 209 –210.
doi:10.1016/j.biopsych.2010.03.033