Douglas L Boggs1,2, Toral Surti1,2,3, Aarti Gupta1,2,3, Swapnil Gupta1,2,3, Mark Niciu4, Brian Pittman2,3, Ashley M Schnakenberg Martin1,2,3, Halle Thurnauer1,2,3, Andrew Davies5, Deepak C D'Souza1,2,3, Mohini Ranganathan6,7,8. 1. Schizophrenia and Neuropharmacology Research Group at Yale, VA Connecticut Healthcare System, West Haven, CT, USA. 2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. 3. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA. 4. Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, Bethesda, MD, USA. 5. GW Pharmaceuticals, Cambridge, UK. 6. Schizophrenia and Neuropharmacology Research Group at Yale, VA Connecticut Healthcare System, West Haven, CT, USA. Mohini.Ranganathan@yale.edu. 7. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA. Mohini.Ranganathan@yale.edu. 8. Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, CT, USA. Mohini.Ranganathan@yale.edu.
Abstract
RATIONALE: Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). OBJECTIVE: This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. METHODS: This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. RESULTS: There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. CONCLUSIONS: At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00588731.
RCT Entities:
RATIONALE: Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS). OBJECTIVE: This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial. METHODS: This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly. RESULTS: There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group. CONCLUSIONS: At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00588731.
Authors: Richard S E Keefe; Robert M Bilder; Philip D Harvey; Sonia M Davis; Barton W Palmer; James M Gold; Herbert Y Meltzer; Michael F Green; Del D Miller; Jose M Canive; Lawrence W Adler; Theo C Manschreck; Marvin Swartz; Robert Rosenheck; Diana O Perkins; Trina M Walker; T Scott Stroup; Joseph P McEvoy; Jeffrey A Lieberman Journal: Neuropsychopharmacology Date: 2006-04-19 Impact factor: 7.853
Authors: Deepak Cyril D'Souza; Walid Michel Abi-Saab; Steven Madonick; Kimberlee Forselius-Bielen; Anne Doersch; Gabriel Braley; Ralitza Gueorguieva; Thomas B Cooper; John Harrison Krystal Journal: Biol Psychiatry Date: 2005-03-15 Impact factor: 13.382
Authors: Stefania Risso Bradley; Jelveh Lameh; Linda Ohrmund; Thomas Son; Abhishek Bajpai; Derek Nguyen; Mikael Friberg; Ethan S Burstein; Tracy A Spalding; Thomas R Ott; Hans H Schiffer; Ali Tabatabaei; Krista McFarland; Robert E Davis; Douglas W Bonhaus Journal: Neuropharmacology Date: 2009-10-14 Impact factor: 5.250
Authors: Christopher J O'Donnell; Bruce N Rogers; Brian S Bronk; Dianne K Bryce; Jotham W Coe; Karen K Cook; Allen J Duplantier; Edelweiss Evrard; Mihaly Hajós; William E Hoffmann; Raymond S Hurst; Noha Maklad; Robert J Mather; Stafford McLean; Frank M Nedza; Brian T O'Neill; Langu Peng; Weimin Qian; Melinda M Rottas; Steven B Sands; Anne W Schmidt; Alka V Shrikhande; Douglas K Spracklin; Diane F Wong; Andy Zhang; Lei Zhang Journal: J Med Chem Date: 2010-02-11 Impact factor: 7.446
Authors: Dagmar Koethe; Andrea Giuffrida; Daniela Schreiber; Martin Hellmich; Frauke Schultze-Lutter; Stefan Ruhrmann; Joachim Klosterkötter; Daniele Piomelli; F Markus Leweke Journal: Br J Psychiatry Date: 2009-04 Impact factor: 9.319
Authors: Philip G Tibbo; Kyle A McKee; Jeffrey H Meyer; Candice E Crocker; Katherine J Aitchison; Raymond W Lam; David N Crockford Journal: Can J Psychiatry Date: 2020-09-11 Impact factor: 4.356
Authors: Amedeo Minichino; Morwenna Senior; Natascia Brondino; Sam H Zhang; Beata R Godwlewska; Philip W J Burnet; Andrea Cipriani; Belinda R Lennox Journal: JAMA Psychiatry Date: 2019-09-01 Impact factor: 21.596
Authors: G M Mandolini; M Lazzaretti; A Pigoni; L Oldani; G Delvecchio; P Brambilla Journal: Epidemiol Psychiatr Sci Date: 2018-05-23 Impact factor: 6.892
Authors: Dennis J Sholler; Marilyn A Huestis; Benjamin Amendolara; Ryan Vandrey; Ziva D Cooper Journal: Pharmacol Biochem Behav Date: 2020-10-18 Impact factor: 3.533
Authors: Adina S Fischer; Susan F Tapert; Dexter Lee Louie; Alan F Schatzberg; Manpreet K Singh Journal: Curr Treat Options Psychiatry Date: 2020-04-18
Authors: Anna E Kirkland; Matthew C Fadus; Staci A Gruber; Kevin M Gray; Timothy E Wilens; Lindsay M Squeglia Journal: Psychiatry Res Date: 2021-12-20 Impact factor: 3.222