Reduced Cannabis Use After Low-Dose Naltrexone Addition to Opioid Detoxification

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To the Editors:
Although the influence of cannabis use on the abuse of other drugs or their treatment may vary,1,2 the increasing severity of cannabis use and its resistance to treatment warrant looking for more effective intervention strategies.3 Multiple interactions exist between opioid and cannabinoid systems; opioid antagonist medications such as naltrexone (NTX) at low doses have been proposed to reduce cannabis reinforcement and consumption.4 In a randomized, double-blind, placebo-controlled clinical trial, we found that daily addition to methadone taper of very-low-dose NTX (VLNTX, 0.125 mg/d, 0.250 mg/d) was associated with attenuated opioid withdrawal during inpatient detoxification and with reduced use of opioids and cannabis, measured by urine drug testing and self-report the day after discharge (D1) and 1 week later (D7).5 The study was carried out in accordance with the Declaration of Helsinki and was approved by the institutional review boards of Duke University, Durham, NC, and Thomas Jefferson University, Philadelphia, Pa.
We examined follow-up data to explore factors associated with cannabis use after detoxification, in addition to VLNTX treatment, and determine whether such use affected short-term outcomes after discharge.
It is difficult to identify new cannabis use with urine testing at weekly intervals, because of the long excretion half-life in urine of cannabinoid metabolites.6 As self-reported use of other drugs was reliably associated with urine test results in this sample (Fisher exact test: opioids, P = 0.01; cocaine, P = 0.001), self-reports were utilized as the primary data source for cannabis use at follow-up. Of 120 subjects completing detoxification, 96 were evaluated on D1, 48 of whom were using cannabis at study entry. Among the 61 evaluated on D7, 27 were positive for cannabis at admission. There was no significant difference in proportion of cannabis users randomized to VLNTX or placebo treatment groups (NTX 0.125 mg = 26.9%, NTX 0.25 mg = 35.9%, placebo = 37.2%). There were no significant differences in demographic or clinical characteristics between subjects lost to follow-up and those who participated in the evaluation (data not shown). There were no significant differences at admission between cannabis users receiving different treatments and between users and nonusers who participated in follow-up evaluations in terms of demographic, other drug use, and clinical characteristics, or proportion of subjects lost to follow-up (data not shown), except that cannabis users reported less frequent alcohol use (χ22 = 7.0, P = 0.03).
Cannabis use was detected in 22.9% of all patients on D1 and 34.5% on D7. Cannabis use on D1 was significantly associated with cannabis use at admission (Fisher exact test, P = 0.03), with cannabis use by D7 (Fisher exact test, P = 0.001), and with opioid use on D1 (Fisher exact test, P = 0.001) and D7 (Fisher exact test, P = 0.001). Cannabis use was not significantly associated with alcohol or any other drug use (data not shown). Cannabis use on D1 was also significantly associated with opioid withdrawal and craving intensity, measured by the Subjective and Objective Opioid Withdrawal Scales,7 after adjusting for admission ratings by analysis of covariance: subjective (F1,94 = 20.4, P = 0.001), objective (F1,93 = 16.4, P = 0.001), and craving (F1,89 = 9.9, P = 0.002).
Very-low-dose NTX addition to detoxification was associated with significantly less cannabis use, both on D1 (χ22 = 42.3, P = 0.001) and D7 (χ22 = 28.4, P = 0.001). Fifty-one percent of subjects receiving placebo used cannabis within 24 hours after treatment completion versus 12% of the VLNTX-treated patients.
At D7, 41% (25/61) of subjects were attending drug-free structured outpatient programs. Fifty-six percent (14/25) of subjects in treatment were using drugs; no polysubstance use was detected.
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