White matter integrity after cannabidiol administration for treatment resistant epilepsy

Houston, James T; Nenert, Rodolphe; Allendorfer, Jane B.; Bebin, E. Martina; Gaston, Tyler E.; Goodman, Adam M.; Szaflarski, Jerzy P.

doi:10.1016/j.eplepsyres.2021.106603

Cited by 5 publications

(5 citation statements)

References 28 publications

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“…In addition, a meta-analysis found that patients with refractory epilepsy treated with full-spectrum, high-CBD products reported lower average dose and fewer side effects relative to those treated with CBD isolate products. 54 Findings from the current study demonstrating increased WM coherence following relatively low CBD exposure compared with the previous Epidiolex study 38 provide additional support for the potential entourage effect; additional research is needed to more fully investigate differences between isolates and broad or full-spectrum products.…”

Section: Discussionmentioning

confidence: 65%

“…For example, Houston et al observed increased WM coherence following Epidiolex treatment at doses ranging from 15 to 25 mg/kg per day. 38 However, most MC patients in the current study reported using broad or full-spectrum products with diverse profiles of cannabinoids and other compounds. Research suggests therapeutic response can be achieved at significantly lower doses for broad or full-spectrum products compared with single-compound, purified CBD products, likely due to the entourage effect, a theory that cannabis products containing a variety of constituents (e.g., cannabinoids, terpenoids, flavonoids) may have enhanced effects as a result of the compounds working together synergistically.…”

Section: Discussionmentioning

confidence: 78%

“…These findings are consistent with previous work demonstrating that CBD may be neuroprotective against demyelination in animal models of disease 33–36 and is associated with increased WM coherence in patients with epilepsy. 38 Future research is needed to elucidate the precise mechanism of action for these findings, with preclinical research suggesting potential roles for CBD-related modulation of several receptor subtypes including GPR55, 5-HT1A, TRPV1, and PPAR-γ. 33–36 …”

Section: Discussionmentioning

confidence: 99%

“…Houston et al recently reported increased FA and reduced MD in patients with treatment-resistant epilepsy after taking Epidiolex, a highly purified oral solution of CBD. 38 However, Epidiolex is available only by prescription and is currently FDA approved to treat rare seizure disorders; accordingly, it is not available to most MC patients. Furthermore, single-extracted, purified CBD compounds like Epidiolex are not analogous to products commercially available to MC patients, making it difficult to generalize findings to “real-world” MC patients who report using a range of diverse products.…”

Section: Introductionmentioning

confidence: 99%

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Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment

Dahlgren

Gönenç

Sagar

et al. 2022

Cannabis and Cannabinoid Research

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Background: Previous studies have demonstrated abnormal white matter (WM) microstructure in recreational cannabis consumers; however, the long-term impact of medical cannabis (MC) use on WM coherence is unknown. Accordingly, this study assessed the longitudinal impact of MC treatment on WM coherence. Given results from preclinical studies, we hypothesized that MC treatment would be associated with increased fractional anisotropy (FA) and reduced mean diffusivity (MD). Methods: As part of a larger, longitudinal investigation, patients interested in treating at least one medical condition with commercially available MC products of their choosing were assessed before initiating MC use (baseline n =37; female=25, male=12) and following three ( n =31) and six ( n =22) months of treatment. WM coherence was assessed via diffusion tensor imaging for bilateral regions of interest including the genu of the corpus callosum, anterior limb of the internal capsule, external capsule, and anterior corona radiata, as well as an occipital control region not expected to change over time. Results: In MC patients, FA values significantly increased bilaterally in several callosal regions relative to baseline following both 3 and 6 months of treatment; MD values significantly decreased in all callosal regions but only following 6 months of treatment. No significant changes in WM coherence were observed in the control region or in a pilot sample of treatment-as-usual patients (baseline n =14), suggesting that increased WM coherence observed in MC patients may be attributed to MC treatment as opposed to confounding factors. Interestingly, significant reductions in MD values correlated with higher cannabidiol (CBD) exposure but not Δ-9-tetrahydrocannabinol exposure. Conclusions: Overall, MC treatment was associated with increased WM coherence, which contrasts with prior research examining recreational cannabis consumers, likely related to inherent differences between recreational consumers and MC patients (e.g., product choice, age of onset). In addition, increased CBD exposure was associated with reduced MD following 6 months of treatment, extending evidence from preclinical research indicating that CBD may be neuroprotective against demyelination. However, additional research is needed to elucidate the clinical efficacy of MC treatment and the risks and benefits of long-term MC use.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Increased White Matter Coherence Following Three and Six Months of Medical Cannabis Treatment

Dahlgren

Gönenç

Sagar

et al. 2022

Cannabis and Cannabinoid Research

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“…After the removal of 1350 duplicate records, the remaining 1930 publications were screened, and 61 studies were selected for full-text review (Figure 1). Following the evaluation of these studies for eligibility, 52 were excluded for the following reasons: 48 studies were not RCTs, 2 did not report AEs, and 2 were reanalyses of previously published articles . Finally, a total of 9 articles met the eligibility criteria and were included in the qualitative and quantitative synthesis …”

Section: Resultsmentioning

confidence: 99%

Adverse Events of Cannabidiol Use in Patients With Epilepsy

et al. 2023

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ImportanceEpilepsy is one of the most common neurologic disorders globally. Cannabidiol (CBD) has been approved for the treatment of epilepsy, but its use has been associated with several different adverse events (AEs).ObjectiveTo investigate the frequency and risk of AEs developing in patients with epilepsy who are using CBD.Data SourcesPubMed, Scopus, Web of Science, and Google Scholar were searched for relevant studies published from database inception up to August 4, 2022. The search strategy included a combination of the following keywords: (cannabidiol OR epidiolex) AND (epilepsy OR seizures).Study SelectionThe review included all randomized clinical trials that investigated at least 1 AE from the use of CBD in patients with epilepsy.Data Extraction and SynthesisBasic information about each study was extracted. I2 statistics were calculated using Q statistics to assess the statistical heterogeneity among the included studies. A random-effects model was used in cases of substantial heterogeneity, and a fixed-effects model was used if the I2 statistic for the AEs was lower than 40%. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline.Main Outcomes and MeasuresFrequency of each AE and risk of developing each AE in patients with epilepsy using CBD.ResultsNine studies were included. Overall incidences of 9.7% in the CBD group and 4.0% in the control group were found for any grade AEs. The overall risk ratios (RRs) for any grade and severe grade AEs were 1.12 (95% CI, 1.02-1.23) and 3.39 (95% CI, 1.42-8.09), respectively, for the CBD group compared with the control group. Compared with the control group, the CBD group had a greater risk for incidence of serious AEs (RR, 2.67; 95% CI, 1.83-3.88), AEs resulting in discontinuation (RR, 3.95; 95% CI, 1.86-8.37), and AEs resulting in dose reduction (RR, 9.87; 95% CI, 5.34-14.40). Because most of the included studies had some risk of bias (3 raised some concerns and 3 were at high risk of bias), these findings should be interpreted with some caution.Conclusions and RelevanceIn this systematic review and meta-analysis of clinical trials, the use of CBD to treat patients with epilepsy was associated with an increased risk of several AEs. Additional studies are needed to determine the safe and effective CBD dosage for treating epilepsy.

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