3 Matching Annotations
  1. Feb 2023
    1. In this study, an at least 30-fold margin between hERG’s half maximal inhibitory concentration (IC50; indicates the quantity of substance needed to inhibit a given biological process in vitro by 50%) and the maximal concentration after 1 dose of cannabidiol (Cmax) has been proposed to be an acceptable degree of safety from arrhythmogenesis.5 There are human pharmacokinetic data showing that the Cmax values for CBD can reach 0.35–0.58 μM after smoking (19.2 mg) and oral intake (400 mg), respectively.6 Based on Orvos and colleagues,5 who showed that CBD had an inhibitory effect on hERG channel activity with an IC50 value of 2.07 μM, the ingestion of 400 mg of CBD results in a ratio of 3.57 (<30), thus suggesting the potential of proarrhythmic side effects in humans, especially in case of interactions with the metabolism of CBD.6 In vitro, CBD inhibits CYP isozymes (mainly CYP3A4 and CYP2C19),7 but it is unclear whether this occurs at concentrations achieved with doses used clinically.

      see here for an example calculation (confirm later)

      The study reporting on Cmax states:

      Cmax and AUC following oral administration also appears to be dose dependent. A dose of 10 mg CBD resulted in mean Cmax of 2.47 ng/mL at 1.27 h, and a dose of 400 or 800 mg co-administered with i.v. fentanyl (a highly potent opioid) to examine its safety resulted in a mean Cmax of 181 ng/mL (at 3.0 h) and 114 ng/mL (at 1.5 h) for 400 mg, and 221 ng/mL (at 3.0 h) and 157 ng/mL (at 4.0 h) for 800 mg, in 2 sessions, respectively (Guy and Robson, 2004b; Manini et al., 2015). A dose of 800 mg oral CBD in a study involving 8 male and female cannabis smokers, reported a mean Cmax of 77.9 ng/mL and mean Tmax of 3.0 h (Haney et al., 2016). Although, an increase in dose corresponds with an increase in Cmax, the Cmax between the higher doses of CBD does not greatly differ, suggesting a saturation effect (e.g., between 400 and 800 mg). One hour after oral capsule administration containing 5.4 mg CBD in males and females, mean Cmax was reported as 0.93 ng/mL (higher for female participants than male) (Nadulski et al., 2005a). A subset (n = 12) consumed a standard breakfast meal 1 h after the capsules, which slightly increased mean Cmax to 1.13 ng/mL. CBD remained detectable for 3–4 h after administration (Nadulski et al., 2005b). Cherniakov et al. examined the pharmacokinetic differences between an oromucosal spray and an oral capsule with piperine pro-nanolipospheres (PNL) (both 10 mg CBD) in 9 men. The piperine-PNL oral formulation had a 4-fold increase in Cmax (2.1 ng/mL vs. 0.5 ng/mL), and a 2.2-fold increase in AUC0−t (6.9 vs. 3.1 h × ng/mL), while Tmax was decreased (1.0 vs. 3.0 h) compared to the oromucosal spray (Cherniakov et al., 2017a). This group further developed self-emulsifying formulations and reported again an increased bioavailability and increased Cmax within a shorter time compared to a reference spray (Atsmon et al., 2017a,b).

  2. Aug 2019

      Sure. We at CBD-Reviwed.com are passionate about CBD.

  3. Nov 2014
    1. Marijuana kills cancer cells in proportion to its dose and duration of treatment, researchers found, and whole plant cannabis rich in THC was more efficacious than pure, lab-grade THC alone.

      We clearly have a lot to learn about cannabinoids and terpenes. There are maybe medical breakthroughs to be made here, breakthroughs that have been delayed for decades by reactionary, draconian drug laws.