Table 1
Recommended post-marketing studies to obtain a complete safety profile of cannabidiol (CBD)
| Non-clinical toxicity studies |
|---|
| Toxicity studies with CBD metabolite 7-COOH-cannabidiol in rat: |
| - embryo-foetal developmental study |
| - pre- and postnatal developmental study |
| - juvenile animal toxicity study |
| - 2-year carcinogenicity study with gavage |
| Toxicity studies with CBD |
| - 2-year carcinogenicity study in mouse |
| - 2-year carcinogenicity study in rat with gavage |
| Clinical studies |
| - Potential for chronic liver injury |
| - Effect on glomerular filtration rate |
| - Pregnancy outcome study |
| - QT interval prolongation trial at the maximum tolerable dose |
| Drug-drug interaction trials in healthy volunteers |
| CBD effect on the pharmacokinetics of: |
| - caffeine |
| - sensitive CYP2B6* and CYP2C9 substrate |
| - sensitive UGP1A9** and UGTB7 substrate |
| Strong CYP3A inhibitor effects on pharmacokinetics of CBD |
| Strong 2C9 inhibitor effects on pharmacokinetics of CBD |
| Rifampin effects on pharmacokinetics of CBD |
Table 2
Cannabidiol (CBD) abuse potential
| TYPE OF STUDY | RESULTS |
|---|---|
| Receptor binding studies | |
| - cannabinoid receptors | no significant affinity |
| - opioid receptors | no significant affinity |
| Non-clinical studies evaluating general behaviour (similarity to THC) | |
| - tetrad test | no meaningful abuse related signal |
| - drug discrimination study | no meaningful abuse related signal |
| - self-administration study | no meaningful abuse related signal |
| Clinical studies evaluating efficacy and safety in patients with LGS* or DS** | |
| - Phase I clinical study | no euphoria or other abuse-related signals |
| - Phase II/III studies | could not be evaluated*** |
| Phase I human abuse potential (HAP) study (N=40, with 35 completers) | |
| randomized, double blind, placebo-controlled trial | |
| subjects: healthy recreational poly-drug users | |
| positive control: THC (10, 30 mg), alprazolam (2 mg) | |
| negative control: placebo | |
| mean DRUG LIKING SCORE | |
| lower therapeutic dose: 750 mg/day | not significantly different |
| higher therapeutic dose: 1500 mg/day | significantly different (very small increase) |
| supra-therapeutic dose: 4500 mg/day | significantly different (very small increase) |
| Human physical dependence study following chronic administration | |
| 3 days after discontinuation | no withdrawal signs and symptoms |