Abrupt withdrawal of cannabidiol (CBD): A randomized trial

Published:February 07, 2020DOI:


      • Cannabidiol has proven clinical efficacy and a well-characterized safety profile in patients with LGS or DS.
      • Cannabidiol has no interaction with CB1/CB2 receptors; withdrawal symptoms are unlikely with abrupt cessation.
      • Volunteers received 4-weeks CBD, then randomized to cessation (placebo) or continued CBD for 2 weeks.
      • There was no evidence of a physical withdrawal syndrome after abrupt cessation of CBD.
      • Most AEs were mild; there were 10 withdrawals (rash, elevated liver enzymes, muscle injury).



      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.


      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.


      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.


      In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD.


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