Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis

Black, Nicola; Stockings, Emily; Campbell, Gabrielle; Tran, Lucy Thi; Zagic, Dino; Hall, Wayne; Farrell, Michael; Degenhardt, Louisa

doi:10.1016/s2215-0366(19)30401-8

Cited by 381 publications

(236 citation statements)

References 84 publications

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“…A recent meta-analysis identified 83 randomised trials examining cannabis-based medications for the management of a variety of mental health problems but failed to find evidence of the agent's effectiveness in the management of such conditions. 6 Neurologists often found themselves in an awkward position when their patients told them that they accessed cannabis commercially to relieve symptoms such as pain or muscle spasticity. Challenging a patient to stop an agent that relieves a refractory and debilitating symptom is difficult when the physician's natural empathy is mixed with a feeling of guilt and impotence as the options That feeling of guilt is often shared by patients.…”

Section: Practical Implicationsmentioning

confidence: 99%

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

et al. 2020

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IMPORTANCE Clinical evidence supports effectiveness of cannabidiol for treatment-resistant seizures in Dravet syndrome, but this trial is the first to evaluate the 10-mg/kg/d dose.OBJECTIVE To evaluate the efficacy and safety of a pharmaceutical formulation of cannabidiol, 10 and 20 mg/kg/d, vs placebo for adjunctive treatment of convulsive seizures in patients with Dravet syndrome. DESIGN, SETTING, AND PARTICIPANTSThis double-blind, placebo-controlled, randomized clinical trial (GWPCARE2) recruited patients from April 13, 2015, to November 10, 2017, with follow-up completed on April 9, 2018. Of 285 patients screened from 38 centers in the United States, Spain, Poland, the Netherlands, Australia, and Israel, 86 were excluded, and 199 were randomized. Patients were aged 2 to 18 years with a confirmed diagnosis of Dravet syndrome and at least 4 convulsive seizures during the 4-week baseline period while receiving at least 1 antiepileptic drug. Data were analyzed from November 16 (date of unblinding) to December 13 (date of final outputs), 2018, based on intention to treat and per protocol. MAIN OUTCOMES AND MEASURESThe primary outcome was change from baseline in convulsive seizure frequency during the treatment period. Secondary outcomes included change in all seizure frequency, proportion with at least a 50% reduction in convulsive seizure activity, and change in Caregiver Global Impression of Change score. RESULTSOf 198 eligible patients (mean [SD] age, 9.3 [4.4] years; 104 female [52.5%]), 66 were randomized to the CBD10 group, 67 to the CBD20 group, and 65 to the placebo group, and 190 completed treatment. The percentage reduction from baseline in convulsive seizure frequency was 48.7% for CBD10 group and 45.7% for the CBD20 group vs 26.9% for the placebo group; the percentage reduction from placebo was 29.8% (95% CI, 8.4%-46.2%; P = .01) for CBD10 group and 25.7% (95% CI, 2.9%-43.2%; P = .03) for the CBD20 group. The most common adverse events were decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Five patients in the CBD20 group discontinued owing to adverse events. Elevated liver transaminase levels occurred more frequently in the CBD20 (n = 13) than the CBD10 (n = 3) group, with all affected patients given concomitant valproate sodium.CONCLUSIONS AND RELEVANCE Adjunctive cannabidiol at doses of 10 and 20 mg/kg/d led to similar clinically relevant reductions in convulsive seizure frequency with a better safety and tolerability profile for the 10-mg/kg/d dose in children with treatment-resistant Dravet syndrome. Dose increases of cannabidiol to greater than 10 mg/kg/d should be tailored to individual efficacy and safety.

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Section: Practical Implicationsmentioning

confidence: 99%

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

et al. 2020

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“…Similarly, a 2019 systematic review and meta-analysis specifically sought to evaluate the evidence for cannabis and cannabinoids in treating mental health conditions such as depression, anxiety, posttraumatic stress disorder (PTSD), psychosis, and attention-deficit hyperactivity disorder (ADHD) [37]. This study also noted a lack of highquality randomized clinical trials, small sample sizes, and the difficulty of standardizing across studies.…”

Section: Indicationsmentioning

confidence: 99%

“…The meta-analysis found only very lowquality evidence for the use of cannabinoids in treating anxiety disorders in patients with other medical conditions, and no evidence for the other indications studied. The authors succinctly summarized their findings in concluding their study: "In light of the paucity of evidence and absence of good quality evidence, and the known risk of cannabinoids, the use of cannabinoids as treatments for mental disorders cannot be justified at this time" [37].…”

Section: Indicationsmentioning

confidence: 99%

Clinical uses of cannabis and cannabinoids in the United States

Levinsohn

Hill

2020

Journal of the Neurological Sciences

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“…Dans une étude américaine récente, trois fumeurs de cannabis sur 10 remplissent les critères d'un trouble lié à l'usage de cannabis selon les critères du DSM-IV et, la prévalence du trouble lié à l'usage de cannabis évalué sur l'année dernière a doublé chez les adultes américains depuis 2001 [46]. À l'inverse, le cannabidiol pourrait avoir des propriétés « protectrices » [47] mais les résultats à ce jour restent controversés [48,49]. En particulier, un essai a suggéré l'intérêt du CBD pour atténuer les troubles psychotiques [50] mais une autre étude a obtenu des résultats négatifs [51].…”

Section: Complications Psychiatriquesunclassified

Cannabis et neurodéveloppement

Krebs¹,

Demars²,

Frajerman³

et al. 2020

Bulletin de l'Académie Nationale de Médecine

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Le développement cérébral est un phénomène complexe, qui s'étend de la vie foetale à l'adolescence, pendant laquelle la maturation cérébrale suit une série d'événements ordonnés incluant des périodes critiques de plasticité. Le cerveau est particulièrement sensible à l'environnement pendant ces remaniements. Le système endocannabinoïde participe directement et indirectement à ces processus de plasticité et de maturation. Le delta-9tetrahydrocanabinol, principal composant psychoactif du cannabis, diffuse dans le placenta, le lait maternel et le cerveau. Il interagit avec le système endocannabinoïde, notamment par l'activation des récepteurs aux cannabinoïdes 1 CB1R, ce qui peut entraîner des altérations du neurodéveloppement et du fonctionnement des circuits neuronaux. Par conséquent, l'exposition au cannabis in utero, en période périnatale ainsi qu'à l'adolescence est susceptible d'entraîner des perturbations de la maturation cérébrale dont les conséquences, sur le plan cognitif, psychotique et addictif, persistent bien au-delà de la période d'exposition. Plusieurs facteurs modulent le risque de telles complications mais les études réalisées sur des modèles animaux ainsi que chez l'homme ont montré qu'une exposition durant les phases critiques, en particulier durant la phase de développement périnatal et à l'adolescence, constitue en soi un facteur de risque. Les données actuelles incitent à diffuser une information objective aux jeunes, pour prévenir et limiter les consommations précoces. © 2020 Publié par Elsevier Masson SAS au nom de l'Académie nationale de médecine. ଝ Étant donné le contexte sanitaire épidémique lié au Covid-19 du mois de mars 2020, la présentation orale de cette communication en séance à l'Académie a été reportée.Summary. -Brain development is a complex phenomenon, stretching from fetal life to adolescence, during which brain maturation proceeds through a series of ordered events including critical periods of plasticity. The brain is particularly sensitive to the environment during these changes. The endocannabinoid system participates directly and indirectly in these plasticity and maturation processes. The main psychoactive component of cannabis, the delta-9-tetrahydrocanabinol, can cross the placental barrier, is present in breastmilk and diffuses in the brain. It interacts with the endocannabinoid signaling, especially through the activation of cannabinoid receptors 1 CB1R, which can lead to abnormal neurodevelopmental processes and neuronal circuits functions. Therefore, exposure to cannabis in utero, in perinatal phase, as well as during the adolescence disrupts the brain maturation and can cause disturbances on the cognitive, psychotic and addictive levels that persist far beyond the period of exposure. Several factors modulate the risk of such complications, but studies performed in animal models as well as in human cohorts have shown that exposure during both the critical perinatal and adolescence phases is a risk factor per se. Current knowledge encourages the dissemination of obje...

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Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis

Cited by 381 publications

References 84 publications

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome

Clinical uses of cannabis and cannabinoids in the United States

Cannabis et neurodéveloppement

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