INTRODUCTION/OBJECTIVE: In several EU and some US states, medical marijuana is an option for people suffering from various ailments and seeking relief. As cannabis is now sold as an oil extract, it has become a conceivable option for dogs too. There is anecdotal evidence of cannabis benefiting dogs with a range of clinical signs and diseases including seizures, nausea and other gastrointestinal signs, stress and anxiety, arthritis and cancer pain, but no information on its pharmacokinetics is available in dogs. MATERIALS AND METHODS: Six healthy intact female adult (5–7 years) Labrador dogs were used. Animals were randomly divided into 2 groups (n = 3). Group I was administered with Bedrocan (olive oil containing 20% tetrahydrocannabinol (THC) and 0.5% cannabidiol (CBD)) at 1.5 mg kg−1 THC after 12 h of fasting, while group II was administered with the same dose 15 minutes after being fed. Blood collections were performed at pre‐assigned time. Samples were analysed for THC and CBD content by LC/MS using an intra‐laboratory validated method. Briefly, to 100 μl of blood THC‐d3 and CBD‐d3 were added as internal standards (5 ng ml−1), followed by precipitation with 200 μl of acetonitrile. After shaking and centrifugation (3000 × g, 5 min), the supernatant was diluted 1:1 with the HPLC mobile phase and transferred into a LC vial. 25 μl of the sample were directly injected onto the LC‐HRMS system (a Q Exactive Orbitrap mass spectrometer coupled to a Dionex UltiMate 3000 with TurboFlow technology). Pharmacokinetic analyses were performed according to a non‐compartmental model. RESULTS AND CONCLUSIONS: No sign of excitation/sedation or visible adverse effects were detected in the dogs following the treatment. THC was quantified over the time period 45 min to 10 h and 15 min to 10 h after Bedrocan administration in the fasting and fed group, respectively. No detectable concentrations of CDB were found at any time. Fed dogs showed faster absorption Tmax (0.62 ± 0.17 h fed versus 2.33 ± 1.52 h fasted) and a higher maximal blood concentration (49.2 ± 25.5 ng ml−1 fed versus 19.1 ±8.7 ng ml−1 fasted). In contrast, feeding did not significantly affected the half‐life (2.3 ± 1.0 fasted versus 1.5 ± 0.5 h fed) or the AUC (73.8 ± 15.8 fasted versus 63.3 ± 9.2 fed ng×h ml−1) values. Although this is the first phase of a 2 × 2 cross‐over study and the power of the study is not yet adequate, after oral administration of Bedrocan, THC appears to be absorbed to the same extent reported in humans.
Pharmacokinetics of Bedrocan (marijuana extract oil) in fasted and fed dogs: a pilot study
Giorgi M.;Stefanelli F.;Chericoni S.
2018-01-01
Abstract
INTRODUCTION/OBJECTIVE: In several EU and some US states, medical marijuana is an option for people suffering from various ailments and seeking relief. As cannabis is now sold as an oil extract, it has become a conceivable option for dogs too. There is anecdotal evidence of cannabis benefiting dogs with a range of clinical signs and diseases including seizures, nausea and other gastrointestinal signs, stress and anxiety, arthritis and cancer pain, but no information on its pharmacokinetics is available in dogs. MATERIALS AND METHODS: Six healthy intact female adult (5–7 years) Labrador dogs were used. Animals were randomly divided into 2 groups (n = 3). Group I was administered with Bedrocan (olive oil containing 20% tetrahydrocannabinol (THC) and 0.5% cannabidiol (CBD)) at 1.5 mg kg−1 THC after 12 h of fasting, while group II was administered with the same dose 15 minutes after being fed. Blood collections were performed at pre‐assigned time. Samples were analysed for THC and CBD content by LC/MS using an intra‐laboratory validated method. Briefly, to 100 μl of blood THC‐d3 and CBD‐d3 were added as internal standards (5 ng ml−1), followed by precipitation with 200 μl of acetonitrile. After shaking and centrifugation (3000 × g, 5 min), the supernatant was diluted 1:1 with the HPLC mobile phase and transferred into a LC vial. 25 μl of the sample were directly injected onto the LC‐HRMS system (a Q Exactive Orbitrap mass spectrometer coupled to a Dionex UltiMate 3000 with TurboFlow technology). Pharmacokinetic analyses were performed according to a non‐compartmental model. RESULTS AND CONCLUSIONS: No sign of excitation/sedation or visible adverse effects were detected in the dogs following the treatment. THC was quantified over the time period 45 min to 10 h and 15 min to 10 h after Bedrocan administration in the fasting and fed group, respectively. No detectable concentrations of CDB were found at any time. Fed dogs showed faster absorption Tmax (0.62 ± 0.17 h fed versus 2.33 ± 1.52 h fasted) and a higher maximal blood concentration (49.2 ± 25.5 ng ml−1 fed versus 19.1 ±8.7 ng ml−1 fasted). In contrast, feeding did not significantly affected the half‐life (2.3 ± 1.0 fasted versus 1.5 ± 0.5 h fed) or the AUC (73.8 ± 15.8 fasted versus 63.3 ± 9.2 fed ng×h ml−1) values. Although this is the first phase of a 2 × 2 cross‐over study and the power of the study is not yet adequate, after oral administration of Bedrocan, THC appears to be absorbed to the same extent reported in humans.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
