Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Medical Marijuana Extracts and Cannabinoid Compounds
2.2. Reference Solutions and Extract Preparation
2.3. LC-ToF-MS Analysis of Medical Marijuana Extracts
2.4. Animals
2.5. Administration of Cannabinoid Formulations
2.6. Spared Nerve Injury (SNI) Model
2.7. Tissue Collection and Sample Preparation
2.8. LC-MS/MS Quantification of Δ9-THC, OH-THC, COOH-THC and CBD in Tissue Samples
2.9. Analysis of Quantitative Mass Spectrometry Data
2.10. Von Frey Test for Mechanical Thresholds
2.11. Data Analysis
3. Results
3.1. Quantification of Bioactive Cannabinoids and Flavonoids in Medical Marijuana Extracts
3.2. Pharmacokinetic Profile of Δ9-THC Bioavailability in Nervous Tissue and Plasma after Application of Medical Marijuana Extracts and Pure Compound
3.3. Pharmacokinetic Profile of Δ9-THC Metabolites in Nervous Tissue and Plasma after Application of Medical Marijuana Extracts and Pure Compound
3.4. Pharmacokinetic Profile of CBD Bioavailability in Nervous Tissue and Plasma after Application of Medical Marijuana Extracts and Pure Compound
3.5. Analgesic Potency of Medical Marijuana Extracts and Pure Cannabinoid Compounds
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
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Substance | MRM-Transition 1 | Dwell Time | DP 2 | CE 3 | CXP 4 | EP 5 |
---|---|---|---|---|---|---|
Δ9-THC and CBD (Quantifier) | 315.0 → 193.1 | 30 msec | 60 | 30 | 10 | 10 |
Δ9-THC and CBD (Qualifier) | 315.0 → 259.0 | 10 msec | 60 | 30 | 10 | 10 |
D3-THC (Quantifier) | 318.2 → 196.1 | 30 msec | 60 | 30 | 10 | 10 |
D3-THC (Qualifier) | 318.2 → 123.0 | 10 msec | 60 | 30 | 10 | 10 |
OH-THC (Quantifier) | 331.2 → 313.1 | 30 msec | 60 | 30 | 10 | 10 |
OH-THC (Qualifier) | 331.2 → 193.1 | 10 msec | 60 | 30 | 10 | 10 |
COOH-THC (Quantifier) | 345.2 → 299.2 | 30 msec | 60 | 30 | 10 | 10 |
COOH-THC (Qualifier) | 345.2 → 193.1 | 10 msec | 60 | 30 | 10 | 10 |
Analyte | C 1 Per Sample [ng/mL] | Mean C [ng/mL] 2 | SEM | C of Analysed Extract [μg/mL] | ng Analyte/ μg Extract | % [m/m] |
---|---|---|---|---|---|---|
CBC | 247.5 | 247.40 | 3.44 | 40 | 6.19 | 0.62 |
241.4 | ||||||
253.3 | ||||||
CBD | 63.30 | 63.08 | 1.04 | 40 | 1.58 | 0.16 |
64.77 | ||||||
61.18 | ||||||
CBDA | <LLOQ | <LLOQ 3 | N/A 4 | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
CBDV | 38.35 | 37.46 | 2.49 | 400 | 0.09 | 0.01 |
32.77 | ||||||
41.26 | ||||||
CBG | 297.2 | 300.37 | 2.16 | 40 | 7.51 | 0.75 |
304.5 | ||||||
299.4 | ||||||
CBN | 2343 | 2677.00 | 175.60 | 40 | 66.93 | 6.69 |
2750 | ||||||
2938 | ||||||
THCV | 110.4 | 90.95 | 12.39 | 40 | 2.27 | 0.23 |
94.52 | ||||||
67.92 | ||||||
THCA-A | 170 | 161.33 | 6.55 | 400 | 0.4 | 0.04 |
165.5 | ||||||
148.5 | ||||||
Δ9-THC | 1890 | 2043.33 | 79.90 | 4 | 510.83 | 51.08 |
2081 | ||||||
2159 | ||||||
API | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
LUT | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ |
Analyte | C 1 Per Sample [ng/mL] | Mean C [ng/mL] 2 | SEM | C of Analysed Extract [μg/mL] | ng Analyte/ μg Extract | % [m/m] |
---|---|---|---|---|---|---|
CBC | <LLOQ | <LLOQ 3 | N/A 4 | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
CBD | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
CBDA | 16.19 | 16.16 | 0.04 | 400 | 0.04 | 0.004 |
16.20 | ||||||
16.09 | ||||||
CBDV | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
CBG | 62.56 | 57.25 | 2.68 | 400 | 0.14 | 0.014 |
55.19 | ||||||
54.01 | ||||||
CBN | 30.61 | 29.66 | 0.55 | 40 | 0.74 | 0.07 |
29.66 | ||||||
28.72 | ||||||
THCV | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
THCA-A | 216.8 | 213.33 | 2.89 | 40 | 5.33 | 0.53 |
215.6 | ||||||
207.6 | ||||||
Δ9-THC | 502.6 | 504.97 | 1.89 | 400 | 1.26 | 0.13 |
508.7 | ||||||
503.6 | ||||||
API | <LLOQ | <LLOQ | N/A | N/A | N/A | N/A |
<LLOQ | ||||||
<LLOQ | ||||||
LUT | 17.38 | 18.41 | 0.70 | 400 | 0.05 | 0.005 |
19.74 | ||||||
18.11 |
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Dumbraveanu, C.; Strommer, K.; Wonnemann, M.; Choconta, J.L.; Neumann, A.; Kress, M.; Kalpachidou, T.; Kummer, K.K. Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment. Pharmaceutics 2023, 15, 853. https://doi.org/10.3390/pharmaceutics15030853
Dumbraveanu C, Strommer K, Wonnemann M, Choconta JL, Neumann A, Kress M, Kalpachidou T, Kummer KK. Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment. Pharmaceutics. 2023; 15(3):853. https://doi.org/10.3390/pharmaceutics15030853
Chicago/Turabian StyleDumbraveanu, Cristiana, Katharina Strommer, Meinolf Wonnemann, Jeiny Luna Choconta, Astrid Neumann, Michaela Kress, Theodora Kalpachidou, and Kai K. Kummer. 2023. "Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment" Pharmaceutics 15, no. 3: 853. https://doi.org/10.3390/pharmaceutics15030853
APA StyleDumbraveanu, C., Strommer, K., Wonnemann, M., Choconta, J. L., Neumann, A., Kress, M., Kalpachidou, T., & Kummer, K. K. (2023). Pharmacokinetics of Orally Applied Cannabinoids and Medical Marijuana Extracts in Mouse Nervous Tissue and Plasma: Relevance for Pain Treatment. Pharmaceutics, 15(3), 853. https://doi.org/10.3390/pharmaceutics15030853