The effects of dronabinol during detoxification and the initiation of treatment with extended release naltrexone

Abstract

Background Evidence suggests that the cannabinoid system is involved in the maintenance of opioid dependence. We examined whether dronabinol, a cannabinoid receptor type 1 partial agonist, reduces opioid withdrawal and increases retention in treatment with extended release naltrexone (XR-naltrexone). Methods Opioid dependent participants were randomized to receive dronabinol 30 mg/d (n=40) or placebo (n=20), under double-blind conditions, while they underwent inpatient detoxification and naltrexone induction. Before discharge all participants received an injection of XR-naltrexone, with an additional dose given four weeks later. Dronabinol or placebo was given while inpatient and for 5 weeks afterwards. The primary outcomes were the severity of opioid withdrawal, measured with the Subjective Opioid Withdrawal Scale, and retention in treatment at the end of the inpatient phase and at the end of the 8-week trial. Results The severity of opioid withdrawal during inpatient phase was lower in the dronabinol group relative to placebo group (p=0.006). Rates of successful induction onto XR-naltrexone (dronabinol 66%, placebo 55%) and completion of treatment (dronabinol 35%, placebo 35%) were not significantly different. Post-hoc analysis showed that the 32% of participants who smoked marijuana regularly during the outpatient phase had significantly lower ratings of insomnia and anxiety and were more likely to complete the 8-week trial. Conclusion Dronabinol reduced the severity of opiate withdrawal during acute detoxification but had no effect on rates of XR-naltrexone treatment induction and retention. Participants who elected to smoke marijuana during the trial were more likely to complete treatment regardless of treatment group assignment.

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies

“…Newer protocols focused on identifying optimal doses and treatment durations of buprenorphine, naltrexone, and clonidine to shorten induction periods, while minimizing the severity of withdrawal. Major changes to earlier protocols involved reducing buprenorphine treatment to 1–2 days, shortening to 1 day the “washout” period before starting naltrexone, and decreasing the first dose of naltrexone from 12.5 to 3 mg, with supportive medications, usually standing doses of clonidine and clonazepam administered at frequent dosing intervals 51, 52, 53, 54, 55, 56, 57. A 2017 study comparing outpatient detoxification regimens showed that an oral naltrexone‐assisted detoxification regimen, compared with a descending buprenorphine taper followed by a 7‐day washout period, was more likely to lead to successful XR‐NTX induction (56% vs. 33%) and a second XR‐NTX dose (50% vs. 27%) 58…”

“…Initiation of treatment with XR‐NTX shortly after completion of opioid withdrawal, or lack of confirmation of the absence of current opioid dependence or recent buprenorphine use, may result in protracted withdrawal‐like symptoms for several weeks 30. Symptoms can include sleep disturbances, low energy, anxiety, irritability, and diarrhea that slowly resolve over days to weeks 52, 57. To alleviate protracted withdrawal, several medication strategies have been proposed, including methylphenidate85 and quetiapine,86 and cannabis may also have a therapeutic benefit 57…”

“…Up to one third of patients who receive XR‐NTX use illicit opioids at some point during treatment, commonly as single episodes to “test” the blocking effect of the medication 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 62. A recent study of patients using opioids during XR‐NTX blockade found that most did not feel euphoria and used lower doses than before receiving XR‐NTX.…”

MicroRNA let-7d is a target of cannabinoid CB 1 receptor and controls cannabinoid signaling

“…In fact, a randomized, double-blind, placebo-controlled, phase III trial has shown that cannabinoids may be useful add-on analgesic drugs for patients with opioid-refractory cancer pain (Portenoy et al, 2012). Although more exhaustive follow-on controlled human studies are indeed necessary, this evidence strongly supports that cannabinoids might be combined with opioids for benefiting patients with pain -and perhaps other diseases (Bisaga et al, 2015;Hurd et al, 2015).…”

The prescription of medical cannabis by a transitional pain service to wean a patient with complex pain from opioid use following liver transplantation: a case report

“…Furthermore, patients who regularly smoked cannabis achieved higher retention rates in the detoxification program compared with noncannabis users. 17 Cellular studies of agonist co-activation of CB1 and mu opioid receptors produced a smaller response than activation of either receptor independently. 11 Partial opioid receptor activation may serve to explain the decreased incidence of withdrawal effect that our patient experienced when tapering off opioids, similar to the opioid agonist-antagonist effect of buprenorphine.…”