PMID- 32036242 OWN - NLM STAT- MEDLINE DCOM- 20201207 LR - 20201214 IS - 1525-5069 (Electronic) IS - 1525-5050 (Linking) VI - 104 IP - Pt A DP - 2020 Mar TI - Abrupt withdrawal of cannabidiol (CBD): A randomized trial. PG - 106938 LID - S1525-5050(19)31116-3 [pii] LID - 10.1016/j.yebeh.2020.106938 [doi] AB - RATIONALE: 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. METHODS: 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(R) in the United States and Epidyolex(R) 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. RESULTS: 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. CONCLUSION: In healthy volunteers, no evidence of withdrawal syndrome was found with abrupt discontinuation of short-term treatment with CBD. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Taylor, Lesley AU - Taylor L AD - GW Research Ltd., Sovereign House, Vision Park, Histon, Cambridge CB24 9BZ, UK. Electronic address: lesley@alchemymedicalwriting.com. FAU - Crockett, Julie AU - Crockett J AD - GW Research Ltd., Sovereign House, Vision Park, Histon, Cambridge CB24 9BZ, UK. Electronic address: JCrockett@gwpharm.com. FAU - Tayo, Bola AU - Tayo B AD - GW Research Ltd., Sovereign House, Vision Park, Histon, Cambridge CB24 9BZ, UK. Electronic address: BTayo@gwpharm.com. FAU - Checketts, Daniel AU - Checketts D AD - GW Research Ltd., Sovereign House, Vision Park, Histon, Cambridge CB24 9BZ, UK. Electronic address: Dchecketts@gwpharm.com. FAU - Sommerville, Kenneth AU - Sommerville K AD - Greenwich Biosciences, Inc., 5750 Fleet Street, Suite 200, Carlsbad, CA 92008, USA. Electronic address: kwsommerville@gmail.com. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20200207 PL - United States TA - Epilepsy Behav JT - Epilepsy & behavior : E&B JID - 100892858 RN - 0 (Anticonvulsants) RN - 19GBJ60SN5 (Cannabidiol) SB - IM MH - Adult MH - Anticonvulsants/*administration & dosage MH - Cannabidiol/*administration & dosage MH - Double-Blind Method MH - Europe/epidemiology MH - Healthy Volunteers MH - Humans MH - Middle Aged MH - Substance Withdrawal Syndrome/*diagnosis/*epidemiology MH - Young Adult OTO - NOTNLM OT - Cannabidiol OT - Cannabinoid OT - Drug withdrawal OT - Epilepsy OT - Seizure COIS- Declaration of competing interest All authors met the International Committee of Medical Journal Editors authorship criteria. Neither honoraria nor payments were made for authorship. Lesley Taylor was an employee of GW Research Ltd. at the time the work was completed. Julie Crockett is an employee of GW Research Ltd. and has share options in the company. Bola Tayo is an employee of GW Research Ltd. and owns shares in the company. Daniel Checketts is an employee of GW Research Ltd. Kenneth Sommerville was an employee of Greenwich Biosciences, Inc. at the time the work was completed. EDAT- 2020/02/10 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/02/10 06:00 PHST- 2019/10/28 00:00 [received] PHST- 2019/12/23 00:00 [revised] PHST- 2020/01/17 00:00 [accepted] PHST- 2020/02/10 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/02/10 06:00 [entrez] AID - S1525-5050(19)31116-3 [pii] AID - 10.1016/j.yebeh.2020.106938 [doi] PST - ppublish SO - Epilepsy Behav. 2020 Mar;104(Pt A):106938. doi: 10.1016/j.yebeh.2020.106938. Epub 2020 Feb 7.