Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials.

Published on Apr 8, 2020in Neuropsychopharmacology7.16
· DOI :10.1038/S41386-020-0667-2
Edward Chesney4
Estimated H-index: 4
('KCL': King's College London),
Dominic Oliver11
Estimated H-index: 11
('KCL': King's College London)
+ 5 AuthorsPhilip McGuire116
Estimated H-index: 116
(NIHR: National Institute for Health Research)
Cannabidiol (CBD) is being investigated as a treatment for several medical disorders but there is uncertainty about its safety. We conducted the first systematic review and meta-analysis of the adverse effects of CBD across all medical indications. Double-blind randomized placebo-controlled clinical trials lasting >/=7 days were included. Twelve trials contributed data from 803 participants to the meta-analysis. Compared with placebo, CBD was associated with an increased likelihood of withdrawal for any reason (OR 2.61, 95% CI: 1.38-4.96) or due to adverse events (OR 2.65, 95% CI: 1.04-6.80), any serious adverse event (OR 2.30, 95% CI: 1.18-4.48), serious adverse events related to abnormal liver function tests (OR 11.19, 95% CI: 2.09-60.02) or pneumonia (OR 5.37, 95% CI: 1.17-24.65), any adverse event (OR 1.55, 95% CI: 1.03-2.33), adverse events due to decreased appetite (OR 3.56, 95% CI: 1.94-6.53), diarrhoea (OR 2.61, 95% CI: 1.46-4.67), somnolence (OR 2.23, 95% CI: 1.07-4.64) and sedation (OR 4.21, 95% CI: 1.18-15.01). Associations with abnormal liver function tests, somnolence, sedation and pneumonia were limited to childhood epilepsy studies, where CBD may have interacted with other medications such as clobazam and/or sodium valproate. After excluding studies in childhood epilepsy, the only adverse outcome associated with CBD treatment was diarrhoea (OR 5.03, 95% CI: 1.44-17.61). In summary, the available data from clinical trials suggest that CBD is well tolerated and has relatively few serious adverse effects, however interactions with other medications should be monitored carefully. Additional safety data from clinical trials outside of childhood epilepsy syndromes and from studies of over-the-counter CBD products are needed to assess whether the conclusions drawn from clinical trials can be applied more broadly.
  • References (35)
  • Citations (3)
📖 Papers frequently viewed together
5 Citations
29 Citations
12 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Geert Jan Groeneveld (LUMC: Leiden University Medical Center)H-Index: 2
#2Jennifer H. Martin (University of Newcastle)H-Index: 32
3 CitationsSource
: GW Pharmaceuticals' formulation of highly purified cannabidiol oral solution is approved in the United States for seizures associated with Lennox-Gastaut and Dravet syndromes in patients aged ≥2 years, for which clobazam, stiripentol, and valproate are commonly used antiepileptic drugs. This open-label, fixed-sequence, drug-drug interaction, healthy volunteer trial investigated the impact of cannabidiol on steady-state pharmacokinetics of clobazam (and N-desmethylclobazam), stiripentol, and va...
31 CitationsSource
The European Medicines Agency (EMA) has approved the first cannabis based medicine to treat two rare and severe forms of childhood onset epilepsy, although hurdles remain before the drug becomes available on the NHS. In August the National Institute for Health and Care Excellence (NICE) published draft guidance saying that on the current evidence it could not recommend cannabidiol as an effective use of NHS resources.1 However, it said it was working with the manufacturer GW Pharmaceuticals to t...
1 CitationsSource
#1Marilyn A. Huestis (Thomas Jefferson University)H-Index: 67
#2Renata Solimini (ISS: Istituto Superiore di Sanità)H-Index: 13
Last. Francesco Paolo Busardò (Marche Polytechnic University)H-Index: 20
view all 6 authors...
BACKGROUND: Currently, there is a great interest in the potential medical use of cannabidiol (CBD), a non-intoxicating cannabinoid. Productive pharmacological research on CBD occurred in the 1970s and intensified recently with many discoveries about the endocannabinoid system. Multiple preclinical and clinical studies led to FDA-approval of Epidiolex®, a purified CBD medicine formulated for oral administration for the treatment of infantile refractory epileptic syndromes, by the US Food and Drug...
1 CitationsSource
#1Tom P. FreemanH-Index: 24
#2Chandni Hindocha (UCL: University College London)H-Index: 14
Last. Michael A P BloomfieldH-Index: 11
view all 4 authors...
### What you need to know Until recently, cannabis and its derivatives were widely restricted under legislation which stated they had no medical value and carried a substantial risk of misuse. Policy is rapidly changing, and cannabis can now be prescribed for medicinal use in many countries, including the UK. This provides important new opportunities for treating patients although these need to be weighed up against potential risks. Several different medicinal products exist, with contrasting me...
8 CitationsSource
OBJECTIVE: Benzodiazepines and benzodiazepine-related drugs (BZRDs) are used to treat various psychiatric diseases. However, there are concerns that BZRDs increase the risk of pneumonia. METHODS: We performed a systematic review and meta-analysis of observational studies to determine whether BZRD use affects the risk of pneumonia. Our analysis included all observational studies that compared pneumonia development among patients receiving BZRD vs those with no treatment. RESULTS: In total, 12 cit...
#1Justin L. Poklis (VCU: Virginia Commonwealth University)H-Index: 23
#2Haley A. Mulder (VCU: Virginia Commonwealth University)H-Index: 4
Last. Michelle R. Peace (VCU: Virginia Commonwealth University)H-Index: 9
view all 3 authors...
Abstract Electronic cigarettes (e-cigarettes) were developed as an alternative method for nicotine delivery and had a significant surge in popularity. E-liquids are formulations used in e-cigarettes, and consist of a ratio of propylene glycol (PG) and vegetable glycerin (VG), a pharmaceutical and/or herbal remedy and, usually, a flavoring agent. Presented is the evaluation of nine cannabidiol (CBD) e-liquids from a single manufacturer for cannabinoids and other psychoactive compounds by Direct A...
6 CitationsSource
#1Simona Lattanzi (Marche Polytechnic University)H-Index: 20
#2Francesco Brigo (University of Verona)H-Index: 26
Last. Mauro Silvestrini (Marche Polytechnic University)H-Index: 40
view all 7 authors...
Background Approximately one-third of patients with epilepsy presents seizures despite adequate treatment. Hence, there is the need to search for new therapeutic options. Cannabidiol (CBD) is a major chemical component of the resin of Cannabis sativa plant, most commonly known as marijuana. The anti-seizure properties of CBD do not relate to the direct action on cannabinoid receptors, but are mediated by a multitude of mechanisms that include the agonist and antagonist effects on ionic channels,...
12 CitationsSource
#1Kerri A. SchoedelH-Index: 15
#2Isabella SzetoH-Index: 2
Last. Kenneth W. SommervilleH-Index: 21
view all 8 authors...
Abstract Rationale Treatment with a highly purified oral solution of cannabidiol (CBD), derived from the plant Cannabis sativa L., demonstrated some evidence of central nervous system (CNS)-related adverse events in patients enrolled in phase 3 trials for treatment of childhood-onset epilepsy. Cannabidiol was categorized as a Schedule 1 substance by the United States Drug Enforcement Administration; therefore, it was important to test CBD for human abuse potential. Methods This was a single-dose...
6 CitationsSource
#1Lesley TaylorH-Index: 2
#2Barry E. Gidal (UW: University of Wisconsin-Madison)H-Index: 40
Last. Gilmour MorrisonH-Index: 1
view all 5 authors...
Background A formal single ascending and multiple dose pharmacokinetic (PK) trial of cannabidiol (CBD) oral solution was required to determine the safety and tolerability of CBD, the maximum tolerated dose, and to examine the effect of food on CBD PK parameters.
18 CitationsSource
Cited By3
#1Miguel Ángel Luján (UPF: Pompeu Fabra University)H-Index: 4
#2Olga Valverde (UPF: Pompeu Fabra University)H-Index: 41
During the last decades, researchers have investigated the functional relevance of adult hippocampal neurogenesis in normal brain function as well as in the pathogenesis of diverse psychiatric conditions. Although the underlying mechanisms of newborn neuron differentiation and circuit integration have yet to be fully elucidated, considerable evidence suggests that the endocannabinoid system plays a pivotal role throughout the processes of adult neurogenesis. Thus, synthetic, and natural cannabin...
#1Irene Braithwaite (Wellington Management Company)H-Index: 13
#2Chiranth Bhagavan (Wellington Management Company)
Last. Giles Newton-Howes (Wellington Management Company)
view all 6 authors...
Regulatory approvals for Epidiolex (purified cannabidiol) in the treatment of childhood drug resistant epilepsy have set a precedent for the use of cannabinoids as a prescribed medicine. Two common reasons cited for the use and prescription of cannabis-based products are pain and insomnia. Unlike drug resistant epilepsy, the level of evidence of efficacy in pain is poorly developed. The lowest quality trials with the greatest methodological shortcomings suggest some benefit, a level of evidence ...
Cannabidiol (CBD) is a naturally occurring, non-psychotropic cannabinoid of the hemp plant Cannabis sativa L. and has been known to induce several physiological and pharmacological effects. While CBD is approved as a medicinal product subject to prescription, it is also widely sold over the counter (OTC) in the form of food supplements, cosmetics and electronic cigarette liquids. However, regulatory difficulties arise from its origin being a narcotic plant or its status as an unapproved novel fo...