CBD: benefits, dosage, contraindications
Scientific name(s)
cannabidiol
Family or group:
Phytosubstances
Indications
Scoring methodology
EFSA approval.
Epilepsy ✪✪✪✪✪
Research into the use of cannabidiol for the treatment of epilepsy has been conducted mainly with a specific oil-based solution, Epidiolex. This product is approved by the FDA for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or the tuberous sclerosis complex in patients one year of age and older. Prescription cannabidiol is generally used as an adjunctive treatment to conventional antiepileptic medications such as clobazam, valproic acid, lamotrigine, levetiracetam and rufinamide.
Posologie
Orally
200 mg
Epidiolex
Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial
Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial
Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomized, double-blind, placebo-controlled phase 3 trial
Long-term safety and efficacy of highly purified cannabidiol for treatment refractory epilepsy
Efficacy and Safety of Cannabidiol in Epilepsy: A Systematic Review and Meta-Analysis
Addictions ✪✪✪✪✪
An observational study conducted among people with alcohol use disorders found that smoking 1 to 3 g of cannabis flower containing approximately 24% cannabidiol (CBD) and 1% tetrahydrocannabinol (THC) for 5 days was associated with a reduction in alcohol consumption compared with smoking cannabis containing equal proportions of CBD (10%) and THC (9%) or with a product having a higher THC level (24% THC vs. 1% CBD). rnrnA small clinical trial in patients with moderate cannabis use disorder shows that taking synthetic cannabidiol oil at 400 mg or 800 mg in two daily doses for 4 weeks appears to reduce overall cannabis use, measured by urinary levels of 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH), compared with placebo. rnrnA small clinical trial conducted in substance-dependent adults with heroin use disorder shows that taking a specific cannabidiol oil-based solution at 400 or 800 mg per day for 3 days reduces drug craving and anxiety for 7 days after the last cannabidiol dose, compared with placebo. rnrnA small clinical trial in cigarette smokers seeking smoking cessation suggests that inhalation of a cannabidiol spray at 400 mcg during a cigarette craving reduces the number of cigarettes smoked over one week by 40% compared with baseline. rnrn
Posologie
Orally
400 µg
oil
Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial
Cannabidiol for the treatment of cannabis use disorder: a Phase 2a, double-blind, placebo-controlled, randomized, adaptive Bayesian trial
THC and CBD effects on alcohol use among alcohol and cannabis co-users
Schizophrenia ✪✪✪✪✪
A small clinical trial in patients with acute paranoid schizophrenia or schizophreniform psychosis shows that taking 400 mg of CBD four times a day for 4 weeks modestly improves psychotic symptoms and cognition compared with baseline and does not appear to be better than taking the antipsychotic amisulpride. Another small clinical trial in patients with schizophrenia shows that adding 1000 mg of CBD per day (as 10 ml of a 100 mg/ml solution) for 6 weeks to standard treatment modestly improves positive symptoms and well-being compared with adding a placebo to standard treatment.
Posologie
Oral
1000 - 1600 mg
oil
Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial
Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia
Anxiety ✪✪✪✪✪
A small clinical study in adolescents with social anxiety disorder found that taking 300 mg of CBD per day for 4 weeks improved anxiety compared with placebo. Other small clinical studies show that taking 300 - 600 mg of CBD as a single dose tends to reduce overall anxiety, but for some people the anxiety reduction was observed only before or after, and not during the speech. These differences may be due to small study sizes, baseline differences in anxiety, and the use of non-standardized products. In addition, cannabidiol does not appear to reduce speech-related anxiety in patients at high risk of psychiatric complications.
Posologie
Oral
300 - 600 mg
oil
Cannabidiol presents an inverted U-shaped dose-response curve in a simulated public speaking test
Effects of short-term cannabidiol treatment on response to social stress in subjects at clinical high risk of developing psychosis
Cannabidiol reduces the anxiety induced by simulated public speaking in treatment-naïve social phobia patients
Anxiolytic Effects of Repeated Cannabidiol Treatment in Teenagers With Social Anxiety Disorders
Effects of ipsapirone and cannabidiol on human experimental anxiety
Dermatoses ✪✪✪✪✪
A small observational study in adults with eczema found that applying a gel containing 1% CBD with dimethicone and polysilicone-11 for 14 days modestly reduced overall symptoms and the severity of itching compared with baseline.
Posologie
Topical
gel, oil
Diabetic neuropathy ✪✪✪✪✪
A small clinical study conducted in adults with peripheral neuropathy of various etiologies shows that the application of an oil-based product containing cannabidiol, camphor and eucalyptus leaf oil to the symptomatic areas for 4 weeks modestly improved severe pain, sharp pain, and sensations of cold and itching compared with a placebo oil. Any benefit from this product may be due to camphor. Camphor is approved by the U.S. Food and Drug Administration (FDA) for topical use as an analgesic and anesthetic.
Posologie
Topical use
oil
Synergies
Properties
Neurological
Clinical research suggests that CBD has effects: - Antiepileptic A number of human trials have demonstrated antiepileptic effects in a variety of syndromes, including Dravet, Lennox-Gastaut, Sturge-Weber, and tuberous sclerosis complex. However, the mechanism of action is not clear. Overall, the therapeutic effects of CBD may be explained by a combination of factors: it increases levels of the antiepileptic medication "clobazam", affects gamma-aminobutyric acid (GABA)-A receptors, and may potentially affect complementary anticonvulsant pathways. - Antipsychotic The exact mechanism of the antipsychotic effects of CBD is not clear. The antipsychotic effects of CBD have been evaluated in several animal models of psychosis. In humans, a small clinical study in healthy adults shows that a single dose of CBD increases blood flow to the hippocampus, which could theoretically have an impact in schizophrenia. In another clinical study, improvement in psychotic symptoms with CBD was associated with higher levels of anandamide (an endogenous cannabinoid neurotransmitter present in the body). It has been proposed that anandamide opposes the activity of dopamine-2 receptors. Thus, administration of CBD could prevent overactivation of dopamine-2 receptors in psychotic disorders. - Neuroprotective In vivo and in vitro research suggests that CBD may have neuroprotective effects in neurodegenerative diseases such as Alzheimeru2019s disease and Huntingtonu2019s disease. Although the mechanism of these effects is not yet clear, it is thought to be related to anti-inflammatory and antioxidant effects. Other preliminary clinical research suggests that taking CBD reduces gamma-aminobutyric acid (GABA) levels and affects functional magnetic resonance imaging outcomes in patients with autism spectrum disorders.
Usages associés
Anxiolytic
Animal studies show that CBD has anxiolytic activity in animal models of generalized anxiety disorder, panic disorder, post-traumatic stress disorder, and obsessive-compulsive disorder. According to some animal research, the anxiolytic effects of CBD may follow an inverted U-shaped curve, with very high doses (over 20 mg/kg in rats) being ineffective. Brain imaging studies show that CBD influences brain activity in areas related to emotional processes. In vivo research suggests the following mechanisms may explain the anxiolytic effects of CBD: - Activation of 5-HT1A receptors - Facilitation of the endocannabinoid system - Enhancement of hippocampal neurogenesis, and/or activation of TRP channels. However, a small study in healthy volunteers found that consuming hemp oil without cannabidiol while being informed that it contained cannabidiol appears to reduce anticipated stress, but does not reduce other measures of stress and anxiety, which also suggests a placebo effect.
Usages associés
Analgesic
Formal reviews report that there is conclusive evidence that cannabis or cannabinoids are effective for the treatment of chronic pain in adults. Pain relief appears to be due to multiple mechanisms that include direct analgesia, anti-inflammatory activity, and modulation of neurotransmitters and endogenous opioids.
Antidepressant
Animal models of depression show that CBD has some antidepressant effects. These effects may be explained by CBD facilitating endocannabinoid activity, facilitating the activity of 5HT1A receptors (a receptor for the neurotransmitter serotonin), and/or facilitating hippocampal neurogenesis.
Anti-inflammatory
CBD has been shown to modulate tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 and interferon (IFN)-gamma and to suppress chemokine production. In a mouse model of rheumatoid arthritis, CBD improved arthritis symptoms and blocked disease progression. CBD may act indirectly by affecting CB1 and CB2 receptors. Activation of CB2 leads to a decrease in ROS and TNF-α levels, which reduces oxidative stress and inflammation. However, clinical research conducted in adults with type 2 diabetes shows that daily CBD intake for 13 weeks does not alter plasma levels of C-reactive protein (CRP), TNF-alpha, or IL-6. Another clinical study conducted in adults with Crohn's disease shows that daily CBD intake for 8 weeks does not alter plasma CRP levels and does not reduce disease activity.
Anticancer
Cannabis is frequently used by cancer patients, both to alleviate symptoms associated with the disease, such as loss of appetite, chemotherapy-induced nausea, depression, insomnia and pain, and to try to reduce tumor growth. rnrnThe anti-tumor effects of CBD have been studied in vitro and in vivo on the breast cancer, colon cancer, glioma, leukemia, lung cancer, lymphoma and thyroid cancer. In vitro and in vivo research shows that CBD inhibits breast cancer cell proliferation, interferes with breast cancer cell invasion and metastasis, and decreases tumor mass. Furthermore, concentration-dependent breast cancer cell death has been demonstrated with CBD in vitro. The presumed mechanisms of CBD-induced autophagy and apoptosis in breast cancer cells include induction of endoplasmic reticulum stress, inhibition of Akt, mTOR and 4EBP1 signaling, production of reactive oxygen species (ROS), and reduction of mitochondrial membrane potential, ultimately leading to activation of the intrinsic apoptotic pathway. rnrnAn animal model of colon cancer shows that CBD reduces polyps and tumor formation in vivo. In vitro studies show that CBD inhibits glioma cell proliferation, invasion and migration, and in vivo studies show that CBD reduces glioma tumor growth. rnrnSome in vitro and in vivo evidence also shows that CBD induces apoptosis and inhibits proliferation of leukemia and lymphoma cell lines, likely via ROS production and CB2 receptor activity, as well as thyroid cancer cells. rnrn
Safe dosage
Adults 18 years and older: 200 mg
Doses of cannabidiol up to 200 mg per day have been used with apparent safety for up to 13 weeks, while higher doses of 700 mg per day for up to 6 weeks and 1200 mg per day for up to 4 weeks have been used with apparent safety. A prescription cannabidiol oil (Epidiolex) has been used safely at doses of 10-25 mg/kg per day, adjusted according to response and tolerance.
Children 1 year and older: 2 mg/kg - 25 mg/kg
It has been used as an orally administered prescription cannabidiol oil (Epidiolex). This cannabidiol-based product has been used safely in clinical research at doses of 2 to 50 mg/kg per day in children aged 1 year and older. However, the maximum recommended dose of this product is 12.5 mg/kg twice daily (25 mg/kg/day); higher doses appear to carry a higher risk of adverse effects. Epidiolex is titrated according to response and tolerance. There is not enough reliable information available on the safety of other forms of cannabidiol in children.
Interactions
Médicaments
Citalopram: moderate interaction
A small open-label study conducted in young adults stabilized on citalopram or escitalopram shows that taking cannabidiol at 200-800 mg per day for 12 weeks increases plasma concentrations of citalopram.
Clobazam: moderate interaction
In clinical studies, the concomitant administration of cannabidiol and clobazam is associated with up to a 60% increase in serum levels of N-desmethylclobazam, the primary active metabolite of clobazam.
Everolimus: moderate interaction
Everolimus is a substrate of the CYP3A4 enzyme. Cannabidiol has been shown to inhibit CYP3A4.
Anticonvulsants: moderate interaction
- Two clinical pharmacokinetic studies in patients stabilized on stiripentol show that adding cannabidiol at 750 mg twice daily for 3 to 10 days or up to 20 mg/kg per day for 24 days increases the mean maximum concentration of stiripentol by 17% to 28%. - In clinical research, concomitant administration of cannabidiol and rufinamide is associated with a slight increase in rufinamide plasma levels. The mechanism of this interaction is unknown. - Brivaracetam is a substrate of CYP2C19. Clinical research shows that cannabidiol inhibits CYP2C19. - In clinical research, concomitant administration of cannabidiol and topiramate, a substrate of CYP2C9 and CYP2C19, is associated with a slight increase in topiramate plasma levels. - In clinical research, concomitant administration of valproic acid and cannabidiol is associated with an elevation of hepatic transaminases and rare cases of thrombocytopenia. - In clinical research, concomitant administration of cannabidiol and zonisamide, a substrate of cytochrome P450 3A4 (CYP3A4), is associated with a slight increase in zonisamide plasma levels.
Immunosuppressant: moderate interaction
Sirolimus and tacrolimus are substrates of cytochrome P450 3A4 (CYP3A4). Cannabidiol has been shown to inhibit CYP3A4 enzymes.
Plantes ou autres actifs
CBD: moderate interaction
A pharmacokinetic study in healthy adults shows that oral cannabidiol, starting at 250 mg once daily and titrated up to 750 mg twice daily for 24 days, increases the peak serum concentration of caffeine by 15%.
Precautions
Parkinson's disease: avoid
In theory, cannabidiol may worsen the symptoms of Parkinson's disease in some patients. A case series of 5 patients with Parkinson's disease found that taking 300 mg or more of cannabidiol per day worsened hypokinesia and resting tremor in 2 patients.
Liver disorders: avoid
In patients with moderate and severe hepatic impairment, a lower initial dose of cannabidiol and slower titration are necessary. A clinical study in patients with mild to severe hepatic impairment shows that taking a 200 mg dose of a specific cannabidiol oil solution (Epidiolex) results in higher blood levels of cannabidiol compared with patients with normal liver function.
Contraindications
Pregnancy: contraindicated
Cannabidiol-based products may contain tetrahydrocannabinol (THC) or other contaminants that can be harmful to the baby. In addition, animal research shows that high levels of cannabidiol can damage the reproductive system of male infants.
Breastfeeding: contraindicated
Cannabidiol-containing products may contain tetrahydrocannabinol (THC) or other contaminants that can be harmful to the baby. In addition, animal studies show that high levels of cannabidiol can damage the reproductive system of male infants.rnrn
