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2014 ; 12
(12
): CD008940
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Pharmacotherapies for cannabis dependence
#MMPMID25515775
Marshall K
; Gowing L
; Ali R
; Le Foll B
Cochrane Database Syst Rev
2014[]; 12
(12
): CD008940
PMID25515775
show ga
BACKGROUND: Cannabis is the most prevalent illicit drug in the world. Demand for
treatment of cannabis use disorders is increasing. There are currently no
pharmacotherapies approved for treatment of cannabis use disorders. OBJECTIVES:
To assess the effectiveness and safety of pharmacotherapies as compared with each
other, placebo or supportive care for reducing symptoms of cannabis withdrawal
and promoting cessation or reduction of cannabis use. SEARCH METHODS: We searched
the Cochrane Central Register of Controlled Trials (CENTRAL) (to 4 March 2014),
MEDLINE (to week 3 February 2014), EMBASE (to 3 March 2014) and PsycINFO (to week
4 February 2014). We also searched reference lists of articles, electronic
sources of ongoing trials and conference proceedings, and contacted selected
researchers active in the area. SELECTION CRITERIA: Randomised and
quasi-randomised controlled trials involving the use of medications to reduce the
symptoms and signs of cannabis withdrawal or to promote cessation or reduction of
cannabis use, or both, in comparison with other medications, placebo or no
medication (supportive care) in participants diagnosed as cannabis dependent or
who were likely to be dependent. DATA COLLECTION AND ANALYSIS: We used standard
methodological procedures expected by The Cochrane Collaboration. Two review
authors assessed studies for inclusion and extracted data. All review authors
confirmed the inclusion decisions and the overall process. MAIN RESULTS: We
included 14 randomised controlled trials involving 958 participants. For 10
studies the average age was 33 years; two studies targeted young people; and age
data were not available for two studies. Approximately 80% of study participants
were male. The studies were at low risk of selection, performance, detection and
selective outcome reporting bias. Three studies were at risk of attrition
bias.All studies involved comparison of active medication and placebo. The
medications included preparations containing tetrahydrocannabinol (THC) (two
studies), selective serotonin reuptake inhibitor (SSRI) antidepressants (two
studies), mixed action antidepressants (three studies), anticonvulsants and mood
stabilisers (three studies), an atypical antidepressant (two studies), an
anxiolytic (one study), a norepinephrine reuptake inhibitor (one study) and a
glutamatergic modulator (one study). One study examined more than one medication.
Diversity in the medications and the outcomes reported limited the extent that
analysis was possible. Insufficient data were available to assess the utility of
most of the medications to promote cannabis abstinence at the end of
treatment.There was moderate quality evidence that completion of treatment was
more likely with preparations containing THC compared to placebo (RR 1.29, 95% CI
1.08 to 1.55; 2 studies, 207 participants, P = 0.006). There was some evidence
that treatment with preparations containing THC was associated with reduced
cannabis withdrawal symptoms and craving, but this latter outcome could not be
quantified. For mixed action antidepressants compared with placebo (2 studies,
179 participants) there was very low quality evidence on the likelihood of
abstinence from cannabis at the end of follow-up (RR 0.82, 95% CI 0.12 to 5.41),
and moderate quality evidence on the likelihood of treatment completion (RR 0.93,
95% CI 0.71 to 1.21). For this same outcome there was very low quality evidence
for the effects of SSRI antidepressants (RR 0.82, 95% CI 0.44 to 1.53; 2 studies,
122 participants), anticonvulsants and mood stabilisers (RR 0.78, 95% CI 0.42 to
1.46; 2 studies, 75 participants), and the atypical antidepressant, bupropion (RR
1.06, 95% CI 0.67 to 1.67; 2 studies, 92 participants). Available evidence on
gabapentin (anticonvulsant) and N-acetylcysteine (glutamatergic modulator) was
insufficient for quantitative estimates of their effectiveness, but these
medications may be worth further investigation. AUTHORS' CONCLUSIONS: There is
incomplete evidence for all of the pharmacotherapies investigated, and for many
of the outcomes the quality was downgraded due to small sample sizes,
inconsistency and risk of attrition bias. The quantitative analyses that were
possible, combined with general findings of the studies reviewed, indicate that
SSRI antidepressants, mixed action antidepressants, atypical antidepressants
(bupropion), anxiolytics (buspirone) and norepinephrine reuptake inhibitors
(atomoxetine) are probably of little value in the treatment of cannabis
dependence. Preparations containing THC are of potential value but, given the
limited evidence, this application of THC preparations should be considered still
experimental. Further studies should compare different preparations of THC, dose
and duration of treatment, adjunct medications and therapies. The evidence base
for the anticonvulsant gabapentin and the glutamatergic modulator
N-acetylcysteine is weak, but these medications are also worth further
investigation.
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