2. Boggs DL, Surti T, Gupta A, et al. The effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia a randomized placebo controlled trial. Psychopharmacology (Berl). 2018;235(7):1923-1932.
Schizophrenia is associated with cognitive deficits in learning, recall, attention, working memory, and executive function. The cognitive impairments associated with schizophrenia (CIAS) are independent of phase of illness and often persist after other symptoms have been effectively treated. These impairments are the strongest predictor of functional outcome, even more so than psychotic symptoms.
Antipsychotics have limited efficacy for CIAS, which highlights the need for CIAS treatments that target other nondopaminergic neurotransmitter systems. The endocannabinoid system, which has been implicated in schizophrenia and in cognition, is a potential target. Several cannabinoids impair memory and attention. The main psychoactive component of marijuana, THC, is a cannabinoid receptor type 1 (CB1R) partial agonist. Administration of THC produces significant deficits in verbal learning, attention, and working memory.
Researchers have hypothesized that CB1R blockade or modulation of cannabinoid levels may offer a novel target for treating CIAS. Boggs et al5 compared the cognitive, symptomatic, and adverse effects of CBD vs placebo.
- In this 6-week, randomized, placebo-controlled study conducted in Connecticut from September 2009 to May 2012, 36 stable patients with schizophrenia who were treated with antipsychotics were randomized to also receive oral CBD, 600 mg/d, or placebo.
- Cognition was assessed using the t score of the MATRICS Consensus Cognitive Battery (MCCB) composite and subscales at baseline and the end of study. An increase in MCCB t score indicates an improvement in cognitive ability. Psychotic symptoms were assessed using the PANSS at baseline, Week 2, Week 4, and Week 6.
- CBD augmentation did not improve MCCB performance or psychotic symptoms. There was no main effect of time or medication on MCCB composite score, but a significant drug × time effect was observed.
- Post-hoc analyses revealed that only patients who received placebo improved over time. The lack of a similar improvement with CBD might be related to the greater incidence of sedation among the CBD group (20%) vs the placebo group (5%). Both the MCCB composite score and reasoning and problem-solving domain scores were higher at baseline and endpoint for patients who received CBD, which suggests that the observed improvement in the placebo group could represent a regression to the mean.
- There was a significant decrease in PANSS scores over time, but there was no significant drug × time interaction.
- CBD augmentation was not associated with an improvement in MCCB score. This is consistent with data from other clinical trials4,8 that suggested that CBD (at a wide range of doses) does not have significant beneficial effects on cognition in patients with schizophrenia.
- Additionally, CBD did not improve psychotic symptoms. These results are in contrast to published case reports9,10 and 2 published clinical trials3,4 that found CBD (800 mg/d) was as efficacious as amisulpride in reducing positive psychotic symptoms, and a small but statistically significant improvement in PANSS positive scores with CBD (1,000 mg/d) compared with placebo. However, these results are similar to those of a separate study11 that evaluated the same 600-mg/d dose of CBD used by Boggs et al.5 At 600 mg/d, CBD produced very small improvements in PANSS total scores (~2.4) that were not statistically significant. A higher CBD dose may be needed to reduce psychotic symptoms in patients with schizophrenia.
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