Evaluating the pharmacokinetics, efficacy and safety of low-dose cannabidiol

Use of non-prescription cannabidiol (CBD) has increased in recent years, with dose recommendations ranging from ~10 to 70 mg/day. To investigate this trend, many studies have utilized low-dose CBD paradigms in healthy volunteers and patient populations. Here, we review the pharmacokinetics (PK), pharmacodynamics (PDs), and safety of low-dose CBD (≤2.5 mg/kg or ≤175 mg/day). PK studies using low-dose, oral CBD (all included PK studies ≤150 mg) showed that peak (C_max) and total exposure (area under the curve [AUC]) were 5- to 100-fold lower than a typical 20 mg/kg dose of Epidiolex. PD studies showed very little evidence of physical or neurological effects of low-dose CBD in healthy volunteers. Drug-drug interactions (DDIs) with Δ9-tetrahydrocannabinol, amitriptyline, and hydromorphone were observed at low doses (10, 30, 50, 60, 100 mg), which may have implications for patients who are co-administering non-prescription CBD with other medications. In randomized controlled trials, there was no evidence that low-dose CBD ameliorated any of the endpoints measured in patients with Parkinson's, Crohn's, pain, fibromyalgia, stress, ocular hypertension or psoriasis. In sleep disorders (sleep duration, 160 mg), alcohol use disorder (alcohol craving and impaired control, 150 mg/day CBD + 0.41 mg/day THC) and multiple sclerosis (timed walk test and pain, 80 mg/day), CBD improved a small selection of endpoints, but consistent changes were not observed across related endpoints and trials. No studies reported serious adverse events associated with low-dose CBD, which was well tolerated. In conclusion, low doses of CBD show very little evidence of any biological effect or therapeutic value.