The effects of vaped cannabis on the severity of naloxone-precipitated opioid withdrawal

Abstract

Naloxone administration can precipitate opioid withdrawal, concerns about which may result in hesitancy to use this life-saving intervention. Preclinical and clinical research suggests that cannabinoids may reduce the symptoms associated with opioid withdrawal. This proof-of-concept study sought to test the effects of vaporized cannabis pretreatment (T-15 min) on naloxone-precipitated (T0-T+50) withdrawal using the Clinical Opiate Withdrawal Scale (COWS, range = 0-48) as the primary dependent measure. Evaluating the safety of this drug combination was the secondary aim, assessed using vital signs. Before a major methodological redesign, a single participant (male, 52) with opioid use disorder completed testing. The ∼4-week inpatient study began with stabilization on oral morphine (120 mg/day). During testing, the following dose combinations of vaped cannabis (V-CB) and intranasal naloxone (IN-NLX) were tested: (a) IN-NLX 0.0 mg + V-CB 25.0 mg, (b) IN-NLX 4.0 mg + V-CB 0.0 mg, (c) IN-NLX 0.0 mg + V-CB 12.5 mg, (d) IN-NLX 4.0 mg + V-CB 12.5 mg, (e) IN-NLX 0.0 mg + V-CB 0.0 mg, and (f) IN-NLX 4.0 mg + V-CB 25.0 mg. Naloxone alone resulted in a COWS score of 22 at T+30. CB pretreatment (12.5 mg and 25.0 mg) reduced COWS scores at T+30 to 17 and 14, respectively. Active NLX and V-CB administered in combination resulted in elevated heart rate and blood pressure, though not to a greater extent than NLX alone. This study found that the addition of a cannabinoid reduced the severity of NLX-precipitated withdrawal and supported the continued investigation into combined NLX + cannabinoid formulations as overdose reversal agents. (PsycInfo Database Record (c) 2026 APA, all rights reserved).