CBD: Benefits, Dosage, Contraindications
Scientific name(s)
cannabidiol
Family or group:
Phytosubstances
Indications
Rating methodology
EFSA approval.
Epilepsy ✪✪✪✪✪
Research on the use of cannabidiol for the treatment of epilepsy has mainly been conducted with a specific oil-based solution, Epidiolex. This product is FDA approved for the treatment of seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, or tuberous sclerosis complex in patients aged one year and older. Prescription cannabidiol is generally used as an adjunctive treatment to conventional antiepileptic drugs such as clobazam, valproic acid, lamotrigine, levetiracetam, and rufinamide.
Posologie
Oral administration
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 randomised, 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 individuals with alcohol use disorder revealed that smoking 1 to 3 g of cannabis flower containing about 24% cannabidiol (CBD) and 1% tetrahydrocannabinol (THC) for 5 days is associated with a reduction in alcohol consumption compared to smoking cannabis containing equal parts of CBD (10%) and THC (9%) or a THC concentration (24%) higher than that of CBD (1%). A small clinical study conducted in patients with a moderate cannabis use disorder shows that taking synthetic cannabidiol oil at doses of 400 mg or 800 mg in two doses per day for 4 weeks seems to reduce overall cannabis use, measured by urinary 11-nor-9-carboxy-tetrahydrocannabinol (THC-COOH) levels, compared to placebo. A small clinical trial conducted in drug-abstinent adults with heroin use disorder shows that taking a specific cannabidiol oil solution at 400 or 800 mg per day for 3 days reduces cravings and anxiety 7 days after the last cannabidiol dose compared to placebo. A small clinical study conducted in cigarette smokers wishing to quit suggests that inhaling a cannabidiol spray at 400 mcg during a cigarette craving reduces the number of cigarettes smoked during one week by 40% compared to the initial quantity.
Posologie
Oral administration
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, randomised, 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 to 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 to adding a placebo to standard treatment.
Posologie
Oral administration
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 disorders showed that taking 300 mg of CBD per day for 4 weeks improves anxiety compared to placebo. Other small clinical studies demonstrate that taking 300-600 mg of CBD in a single dose tends to reduce overall anxiety, but for some people, the reduction in anxiety was observed only before or after, and not during public speaking. These differences may be due to the small size of the studies, differences in baseline anxiety, and the use of non-standardized products. Furthermore, cannabidiol does not seem to reduce speech-related anxiety in patients at high risk of psychiatric complications.
Posologie
Oral administration
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 conducted in adults with eczema revealed that applying a gel containing 1% CBD with dimethicone and polysilicone-11 for 14 days modestly reduces general symptoms and the severity of itching compared to baseline.
Posologie
Topical application
gel, oil
Diabetic Neuropathy ✪✪✪✪✪
A small clinical study conducted in adults with peripheral neuropathy of various etiologies shows that applying an oil-based product containing cannabidiol, camphor, and eucalyptus leaf oil on symptomatic areas for 4 weeks modestly improves intense pain, acute pain, and sensations of cold and itching compared to a placebo oil. It is possible that any benefit of this product is 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 application
oil
Synergies
Properties
Neurological
Clinical research suggests that CBD has effects: - Antiepileptics 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 the levels of the antiepileptic treatment "clobazam", affects gamma-aminobutyric acid (GABA)-A receptors, and potentially impacts complementary anticonvulsive pathways. - Antipsychotics The exact mechanism of CBD's antipsychotic effects is not clear. The antipsychotic effects of CBD have been evaluated in several animal models of psychosis. In humans, a small clinical study conducted in healthy adults shows that a single dose of CBD increases blood flow in the hippocampus, which could theoretically impact 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 dopamine-2 receptor activity. Thus, CBD administration could prevent dopamine-2 receptor overactivation in psychotic disorders. - Neuroprotectors In vivo and in vitro research suggests that CBD may have neuroprotective effects in neurodegenerative diseases such as Alzheimer's disease and Huntington's disease. Although the mechanism of these effects is not yet clear, it is believed to be related to anti-inflammatory and antioxidant effects. Further 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 certain 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 processing. In vivo research suggests that the following mechanisms may explain the anxiolytic effects of CBD: - 5HT1A receptor activation - Facilitation of the endocannabinoid system - Enhancement of hippocampal neurogenesis, and/or activation of TRP channels. However, a small study on healthy volunteers showed that consuming hemp oil without cannabidiol while being informed it contains cannabidiol seems to reduce anticipated stress but does not reduce other measures of stress and anxiety, also suggesting 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, including direct analgesia, anti-inflammatory activity, and modulation of neurotransmitters and endogenous opioids.
Antidepressant
Animal models of depression show that CBD has certain antidepressant effects. These effects may be explained by the facilitation of endocannabinoid activity by CBD, facilitation of 5HT1A receptor activity (a serotonin neurotransmitter receptor), and/or facilitation of hippocampal neurogenesis.
Anti-inflammatory
It has been shown that CBD modulates tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and interferon (IFN)-gamma and suppresses the production of chemokines. 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-B1 levels, reducing oxidative stress and inflammation. However, clinical research conducted on adults with type 2 diabetes shows that daily CBD intake over 13 weeks does not alter plasma levels of C-reactive protein (CRP), TNF-alpha, or IL-6. Another clinical study conducted on adults with Crohn's disease shows that daily CBD intake over 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, as well as to try to reduce tumor growth. The anti-tumor effects of CBD have been studied in vitro and in vivo for breast cancer, colon cancer, glioma, leukemia, lung cancer, lymphoma, and thyroid cancer. In vitro and in vivo research shows that CBD inhibits the proliferation of breast cancer cells, interferes with breast cancer cell invasion and metastases, and decreases tumor mass. Moreover, breast cancer cell death as a function of concentration has been demonstrated with CBD in vitro. Presumed mechanisms of CBD-induced autophagy and apoptosis of breast cancer cells include endoplasmic reticulum stress induction, inhibition of Akt signaling, mTOR and 4EBP1, reactive oxygen species (ROS) production, and reduction of mitochondrial membrane potential, ultimately leading to intrinsic apoptotic pathway activation. An animal model of colon cancer shows that CBD reduces polyp and tumor formation in vivo. In vitro research shows that CBD inhibits the proliferation, invasion, and migration of glioma cells, and in vivo research shows that CBD reduces glioma tumor growth. Some in vitro and in vivo evidence also shows that CBD induces apoptosis and inhibits the proliferation of leukemia and lymphoma cell lines, probably via ROS production and CB2 receptor activity, as well as thyroid cancer cells.
Safety dosage
Adults from 18 years: 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. Prescription cannabidiol oil (Epidiolex) has been used safely at doses of 10-25 mg/kg per day, adjusted based on response and tolerance.
Children from 1 year: 2 mg/kg - 25 mg/kg
Has been used in the form of prescription cannabidiol oil (Epidiolex) orally. 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 recommended maximum dose of this product is 12.5 mg/kg twice daily (25 mg/kg/day); higher doses appear to pose a higher risk of adverse effects. Epidiolex is titrated based on 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 main active metabolite of clobazam.
EVEROLIMUS: moderate interaction
Everolimus is a substrate of the CYP3A4 enzymes. It has been demonstrated that cannabidiol inhibits CYP3A4.
Anticonvulsants: moderate interaction
- Two clinical pharmacokinetic studies in patients stabilized on Stiripentol show that adding cannabidiol at 750 mg twice a day 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, the concomitant administration of cannabidiol and rufinamide is associated with a slight increase in plasma levels of rufinamide. The mechanism of this interaction is unknown. - Brivaracetam is a substrate of CYP2C19. Clinical research shows that cannabidiol inhibits CYP2C19. - In clinical research, the concomitant administration of cannabidiol and topiramate, a substrate of CYP2C9 and CYP2C19, is associated with a slight increase in plasma levels of topiramate. - In clinical research, the concomitant administration of valproic acid and cannabidiol is associated with elevated liver 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 plasma levels of zonisamide.
Immunosuppressant: moderate interaction
Sirolimus and tacrolimus are substrates of the cytochrome P450 3A4 (CYP3A4) enzymes. It has been demonstrated that cannabidiol inhibits CYP3A4 enzymes.
Plantes ou autres actifs
CBD: moderate interaction
A pharmacokinetic study in healthy adults shows that oral administration of cannabidiol, starting at 250 mg once daily and titrating up to 750 mg twice daily for 24 days, increases the serum peak of caffeine by 15%.
Precautions
Parkinson's Disease: avoid
Theoretically, cannabidiol may exacerbate symptoms of Parkinson's disease in some patients. A case series involving 5 patients with Parkinson's disease revealed that taking 300 mg or more of cannabidiol per day exacerbated 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 conducted in patients with mild to severe hepatic impairment shows that taking a specific oil-based cannabidiol solution (Epidiolex) 200 mg results in higher blood levels of cannabidiol compared to patients with normal liver function.
Contraindications
Pregnant women: prohibited
Cannabidiol-based products may contain tetrahydrocannabinol (THC) or other contaminants that can be dangerous to the baby. Furthermore, animal research shows that high levels of cannabidiol can damage the reproductive system of male babies.
Breastfeeding women: prohibited
Cannabidiol-based products may contain tetrahydrocannabinol (THC) or other contaminants that can be dangerous to the baby. Furthermore, animal research shows that high levels of cannabidiol can damage the reproductive system of male babies.
