CBD has been shown to be well tolerated at very high doses (up to 5000 mg). 23 CBD is a potent inhibitor of various cytochrome P450 enzymes. 24,25 Higher doses may increase plasma concentrations of anticonvulsant drugs such as clobazam and topiramate. 26 Children with epilepsy who are on concomitant anticonvulsant drugs may be vulnerable to related adverse effects such as sedation, gastrointestinal upset and elevated liver transaminase levels. 11,27 In clinical trials outside of childhood epilepsy the only significant side effect with CBD was diarrhoea. 27 Interactions of CBD with drugs such as benzodiazepines, antidepressants and opioids appear unlikely to be clinically significant in adult clinical populations, but more research is required. Given this uncertainty, upwards dose titration is a valid precautionary practice in patients given CBD-containing products, particularly if they are also taking other medicines.
No cannabis products currently have a subsidy on the Pharmaceutical Benefits Scheme and costs can be considerable. These are typically around $5–$15 a day, 16 but substantially more for patients with conditions such as epilepsy that require very high doses of CBD. It is important for prescribers to have an open conversation with their patients around likely ongoing costs. Patients receiving disability pensions, aged pensions or other Centrelink benefits may be unable to afford medicinal cannabis.
Useful Australian websites on medicinal cannabis are listed in the Box.
Letter of support from specialist
Most approvals under SAS-B are for the treatment of chronic non-cancer pain (Fig. 2). This includes conditions such as arthritis, lower back pain, neck pain and various forms of neuropathic pain. These are typically treated with oral solutions that contain THC and sometimes additional CBD. Other common conditions among SAS-B approvals include anxiety, cancer-related symptoms (e.g. pain, nausea, anorexia), epilepsy, insomnia, and spasticity in multiple sclerosis (Fig. 2). CBD-only products are being used in all of these conditions, but there is a greater use of them in patients with epilepsy and anxiety. The anxiolytic effects of CBD are described in the literature. 13,17,18
TGA Therapeutic Goods Administration
Liver disease: People with liver disease may need to use lower doses of cannabidiol compared to healthy patients.
The passage of the 2018 Farm Bill made it legal to sell hemp and hemp products in the U.S. But that doesn’t mean that all hemp-derived cannabidiol products are legal. Since cannabidiol has been studied as a new drug, it can’t be legally included in foods or dietary supplements. Also, cannabidiol can’t be included in products marketed with therapeutic claims. Cannabidiol can only be included in “cosmetic” products and only if it contains less than 0.3% THC. But there are still products labeled as dietary supplements on the market that contain cannabidiol. The amount of cannabidiol contained in these products is not always reported accurately on the product label.
Insufficient evidence to rate effectiveness for.
Cannabidiol is a chemical in the Cannabis sativa plant, also known as marijuana or hemp. Over 80 chemicals, known as cannabinoids, have been identified in the Cannabis sativa plant. While delta-9-tetrahydrocannabinol (THC) is the major active ingredient in marijuana, cannabidiol is also obtained from hemp, which contains only very small amounts of THC.
Cannabidiol has effects on the brain. The exact cause for these effects is not clear. However, cannabidiol seems to prevent the breakdown of a chemical in the brain that affects pain, mood, and mental function. Preventing the breakdown of this chemical and increasing its levels in the blood seems to reduce psychotic symptoms associated with conditions such as schizophrenia. Cannabidiol might also block some of the psychoactive effects of delta-9-tetrahydrocannabinol (THC). Also, cannabidiol seems to reduce pain and anxiety.
Some medications changed by the liver include chlorzoxazone (Lorzone) and theophylline (Theo-Dur, others). Medications changed by the liver (Cytochrome P450 1A2 (CYP1A2) substrates) Some medications are changed and broken down by the liver. Cannabidiol might decrease how quickly the liver breaks down some medications. In theory, using cannabidiol along with some medications that are broken down by the liver might increase the effects and side effects of some medications. Before using cannabidiol, talk to your healthcare provider if you take any medications that are changed by the liver.
Psychiatric symptoms such as anxiety, illusions, changes in mood, and paranoid ideas have been reported during treatment with Sativex. These are likely to be the result of transient CNS effects and are generally mild to moderate in severity and well tolerated. They can be expected to remit on reduction or interruption of Sativex medication.
During the double-blind phase the mean NRS scores for patients receiving Sativex generally remained stable (mean change from randomisation in NRS score -0.19), while the mean NRS scores for patients switched to placebo increased (mean change in NRS score was +0.64 and median change was +0.29). The difference* between treatment groups was 0.84 (95% CI -1.29, -0.40).
Women of childbearing potential
There is insufficient experience in humans regarding the effects of Sativex on reproduction. Although no effect has been seen on fertility, independent research in animals found that cannabinoids affected spermatogenesis (section 5.3).
Therefore men and women of child bearing potential should take reliable contraceptive precautions for the duration of therapy and for three months after discontinuation of therapy.