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Study register · detail Systematische Review (Safety-fokussiert) · Epilepsy · 2017

An Update on Safety and Side Effects of Cannabidiol: A Review of Clinical Data and Relevant Animal Studies

Iffland et al. ·Cannabis and Cannabinoid Research Impact 2.5
Mixed GRADE High 630 citations
SampleSystematische Review
EndpointSafety/side effect profile
Blindingunklar
DesignSystematische Review (Safety-fokussiert)
Cannabinoidcbd
Key finding

CBD shows an overall favourable safety profile, however relevant data gaps remain regarding long-term toxicity and drug interactions.

Summary

Systematic literature review on the safety and side effects of cannabidiol (CBD), focus on clinical studies in epilepsy and psychotic disorders. Most common side effects: fatigue, diarrhoea, appetite/weight changes. CBD shows a more favourable side effect profile compared to other antiepileptics; can reduce clobazam doses in epilepsy and thereby reduce its side effects. Favourable tolerability confirmed.

P
PopulationPatients with epilepsy and psychotic disorders as well as further populations from clinical studies and animal experiments on CBD safety
I
InterventionCannabidiol (CBD), various dosages and forms of application
O
OutcomeCBD showed a favourable safety profile; most common side effects: fatigue, diarrhoea and appetite/weight changes; indications of clinically relevant drug interactions (e.g. CYP enzymes, clobazam dose reduction)
Confidence in the evidence
High

The highest of four GRADE levels, the effect estimate is very reliable.

Quality profile
Sample size —
Blinding —
Effect size Mixed
Citations / year ★★★★★
Authors
Iffland K, Grotenhermen F
DOI 10.1089/can.2016.0034↗
Design: Systematische Review (Safety-fokussiert)
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Indication
Further studies on Epilepsy
All studies →
S Devinsky et al. · 2018 · The New England journal of medicine
973 citations
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.
Clear benefit RCT

Multizentrische Phase-III-RCT bei Lennox-Gastaut-Syndrom (n=225, Alter 2-55 Jahre, 30 Zentren), Cannabidiol 20 mg/kg vs. 10 mg/kg vs. Placebo (14 Wochen). Baseline: median 85 Drop-Seizures/28 Tage. Mediane Reduktion der Drop-Seizure-Frequenz: 41,9% (20 mg/kg, p=0,005 vs. Placebo), 37,2% (10 mg/kg, p=0,002 vs. Placebo), 17,2% (Placebo). Häufigste Nebenwirkungen: Somnolenz, verminderter Appetit, Diarrhö (dosisabhängig); 6 Patienten (20 mg/kg-Gruppe) und 1 Patient (10 mg/kg-Gruppe) brachen wegen Nebenwirkungen ab.

10.1056/nejmoa1714631 View study →
S Devinsky et al. · 2017 · New England Journal of Medicine
1652 citations
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome
Clear benefit RCT

n=120 Dravet-Syndrom (therapierefraktär), CBD 20mg/kg/d vs. Placebo über 14 Wochen; median konvulsive Anfallsreduktion 38,9% (CBD) vs. 13,3% (Placebo), adjustierte Differenz -22,8 Prozentpunkte (95%-CI -41,1 bis -5,4; p=0,01); 5% anfallsfrei (CBD) vs. 0% (Placebo).

10.1056/nejmoa1611618 View study →
S Thiele et al. · 2018 · The Lancet
881 citations
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial
Clear benefit RCT

Phase-III-RCT (GWPCARE4) bei Lennox-Gastaut-Syndrom, n=171 (2–55 Jahre), randomisiert zu CBD 20 mg/kg/d vs. Placebo über 14 Wochen. Primärer Endpunkt: prozentuale Reduktion der monatlichen Drop-Seizure-Frequenz. Multizentrisch (24 Zentren USA, Niederlande, Polen). 14 Patienten in CBD-Gruppe, 1 in Placebo-Gruppe brachen ab. [Numerische Outcomes im Abstract abgeschnitten; Volltext zeigt signifikante Drop-Seizure-Reduktion vs. Placebo].

10.1016/s0140-6736(18)30136-3 View study →

The impediment to action advances action. — Marcus Aurelius