TY - JOUR
T1 - Cannabidiol-enriched oil in children and adults with treatment-resistant epilepsy-does tolerance exist?
AU - Uliel-Sibony, Shimrit
AU - Hausman-Kedem, Moran
AU - Fattal-Valevski, Aviva
AU - Kramer, Uri
N1 - Publisher Copyright:
© 2020 The Japanese Society of Child Neurology
PY - 2021/1
Y1 - 2021/1
N2 - Aim: To evaluate the long-term effectiveness of cannabidiol (CBD)-enriched oil for the treatment of refractory epilepsy and to assess the development of tolerance to its anti-seizure effect. Methods: A prospective study of 92 consecutive patients (age 1–37 years, mean-11.8 years) with treatment resistant epilepsy who were treated with cannabis oil extract (CBD/tetrahydrocannabinol [THC] ratio of 20:1). Mean monthly seizure frequency was reported by the patients/their parents during monthly clinic visits. Tolerance was defined as either the need to increase the dose by ≥30% due to reduced treatment efficacy or as an increase of ≥30% in mean monthly seizure frequency in patients treated for at least 3 months with no change in other anti-seizure medications. Results: Mean follow-up time was 19.8 ± 12.5 months (range 3–45). Mean CBD dose was 11.3 (4–38) mg/kg/day. Twenty-nine (31%) patients discontinued treatment due to lack of effect or adverse reactions, which were reported in 51% (47/87) of the patients. Overall responder rate (>50% seizures reduction) was 54%, whereas 8 patients (9%) became seizure-free. Eighty-four patients were included in the tolerance analysis. Tolerance was observed in 21 (25%) patients after a mean duration of 7.3 ± 5.4 months of CBD-enriched oil treatment. There was a negative correlation between epilepsy duration and tolerance development (p = 0.038). Conclusions: We report for the first time the plausible appearance of tolerance to cannabidiol-enriched oil. This may limit treatment efficacy in the long-term clinical management of refractory epilepsy in both pediatric and adult population. Further studies are needed to investigate potential mechanisms.
AB - Aim: To evaluate the long-term effectiveness of cannabidiol (CBD)-enriched oil for the treatment of refractory epilepsy and to assess the development of tolerance to its anti-seizure effect. Methods: A prospective study of 92 consecutive patients (age 1–37 years, mean-11.8 years) with treatment resistant epilepsy who were treated with cannabis oil extract (CBD/tetrahydrocannabinol [THC] ratio of 20:1). Mean monthly seizure frequency was reported by the patients/their parents during monthly clinic visits. Tolerance was defined as either the need to increase the dose by ≥30% due to reduced treatment efficacy or as an increase of ≥30% in mean monthly seizure frequency in patients treated for at least 3 months with no change in other anti-seizure medications. Results: Mean follow-up time was 19.8 ± 12.5 months (range 3–45). Mean CBD dose was 11.3 (4–38) mg/kg/day. Twenty-nine (31%) patients discontinued treatment due to lack of effect or adverse reactions, which were reported in 51% (47/87) of the patients. Overall responder rate (>50% seizures reduction) was 54%, whereas 8 patients (9%) became seizure-free. Eighty-four patients were included in the tolerance analysis. Tolerance was observed in 21 (25%) patients after a mean duration of 7.3 ± 5.4 months of CBD-enriched oil treatment. There was a negative correlation between epilepsy duration and tolerance development (p = 0.038). Conclusions: We report for the first time the plausible appearance of tolerance to cannabidiol-enriched oil. This may limit treatment efficacy in the long-term clinical management of refractory epilepsy in both pediatric and adult population. Further studies are needed to investigate potential mechanisms.
KW - CBD
KW - CBD-enriched oil
KW - Cannabidiol
KW - Cannabis
KW - Refractory epilepsy
KW - Tolerance
UR - http://www.scopus.com/inward/record.url?scp=85088800260&partnerID=8YFLogxK
U2 - 10.1016/j.braindev.2020.06.018
DO - 10.1016/j.braindev.2020.06.018
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C2 - 32713661
AN - SCOPUS:85088800260
SN - 0387-7604
VL - 43
SP - 89
EP - 96
JO - Brain and Development
JF - Brain and Development
IS - 1
ER -