Abrupt discontinuation of CBD did not lead to a clinically measurable withdrawal syndrome in healthy volunteers.
Summary
n=30 healthy volunteers: CBD 750 mg twice daily (Epidiolex) over 4 weeks, then abrupt discontinuation vs. placebo. No withdrawal syndrome detectable; CWS scores 0–4/190 (Arm 1) vs. 0–0,5/190 (Arm 2); PWC-20 median scores 0/60 in both arms. 97% of volunteers in Part 1 reported AEs; most common: diarrhea (63%). 9 study discontinuations due to AEs in Part 1; no serious AEs.
P
PopulationHealthy volunteers, n=30
I
InterventionPlant-derived pharmaceutical CBD (Epidiolex®/Epidyolex®) 750 mg orally twice daily for 4 weeks, followed by abrupt discontinuation (Arm 1: continued CBD, Arm 2: placebo)
C
ControlMatched placebo (after 4-week CBD intake)
O
OutcomeNo evidence for a withdrawal syndrome; median CWS scores 0,0–4,0 (Arm 1) or 0,0–0,5 (Arm 2) out of max. 190; median PWC-20 scores 0,0 in both arms
Confidence in the evidence
Very lowLowModerateHigh
Moderate
The third of four GRADE levels, the effect estimate is probably reliable.
<h4>Rationale</h4>The rationale of this study was to assess occurrence of withdrawal symptoms induced by abrupt cessation of cannabidiol (CBD) after prolonged administration in healthy volunteers.<h4>Methods</h4>Thirty volunteers were randomized to receive 750 mg of a plant-derived pharmaceutical formulation of highly purified CBD in oral solution (100 mg/mL; Epidiolex® in the United States and Epidyolex® in Europe) twice daily (b.i.d.) for 4 weeks (Part 1) followed by 2 weeks of 750 mg b.i.d. CBD (Part 2, Arm 1) or matched placebo (Part 2, Arm 2). All volunteers completed the Cannabis Withdrawal Scale (CWS) and the 20-item Penn Physician Withdrawal Checklist (PWC-20) on days -1, 21, 28, 31, 35, 42, and at follow-up.<h4>Results</h4>Median CWS and PWC-20 scores slightly decreased from Part 1 to Part 2. Median CWS scores ranged from 0.0 to 4.0 (out of a possible 190) in Arm 1 and 0.0 to 0.5 in Arm 2. Median PWC-20 scores were 0.0 (out of a possible 60) in both arms. Twenty-nine (97%) volunteers in Part 1 reported all-causality treatment-emergent adverse events (AEs); the most commonly reported was diarrhea (63%). In Part 2, Arm 1, 6 (67%) volunteers reported all-causality AEs; the most commonly reported was diarrhea (44%). In Part 2, Arm 2, 9 (75%) volunteers reported all-causality AEs; the most commonly reported was headache (58%). Nine volunteers withdrew because of AEs in Part 1; 1 withdrew in Part 2, Arm 2, because of an AE that began in Part 1. Four severe AEs were reported in Part 1; the remainder were mild or moderate. No serious AEs were reported.<h4>Conclusion</h4>In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.