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Common medical cannabis administration methods

Common medical cannabis administration methods
Method of use Bioavailability Peak or onset Duration of effect Advantages Disadvantages
Combusted flower Varies between 10 to 35% due to differences in number of breaths, duration of puff, breath holding, inhalation volume[1]. Onset: 3 to 10 minutes ≤2 hours[1]
  • Quick onset of action
  • Ease of dose titration
 Potential for short- and long-term adverse effects:
  • Intoxication[2]
  • Chronic bronchitis[3]

If unregulated, potential for contamination with other drugs, heavy metals, pesticides.
Inhaled oil or flower Varies between 2 to 56% due to difference in inhalation dynamics (number of puffs, spacing of puffs, hold time, inhalation time, etc)[1]. Peak: 9 minutes[1] ≤2 hours[1]
  • Quick onset of action
  • Ease of dose titration
 Potential for short- and long-term adverse effects:
  • Intoxication[2]
  • Chronic bronchitis[3]

If unregulated, potential for contamination with vitamin E acetate; can cause vaping lung injury.
Ingested 4 to 25% depending upon the study.[4-8] Variable due to drug degradation in the stomach, variable absorption in the stomach, and first-pass metabolism[9]. Peak: 1 to 5 hours[9] ≤25 hours[9]
  • Slow onset of action, low bioavailability
  • Avoids adverse effects of inhalation
  • Long duration of effect could be advantageous in certain clinical situations
  • Risk of dose stacking (ie, repeating doses before an effect is felt). Usually attributable to a long period before onset of effect. Results in unanticipated intoxication and adverse effects.[2,10]
  • Absorption and onset and duration of effect can vary based on individual patient factors (eg, fat content of meals, patient weight).
  • Difficult to titrate.
Sublingual/oral mucosal 87.5 to 90%[11] Onset: As early as 10 minutes[11,12] ≤10 hours[11]
  • Fast onset of action
  • Avoids adverse effects of inhalation
  • Advantageous for patients with swallowing difficulties
  • Taste.
  • Potential for user error because patients can swallow the product rather than wait for absorption through oral membranes.
Suppository 14 to 67%[13,14] Onset: 1 to 2 hours[15] ≤8 hours[15]
  • Avoids first-pass metabolism[15]
  • Avoids adverse effects of inhalation
  • Inconvenient dosing method
  • Very little supporting data for the use of suppositories
Topical Depends on formulation; data are extrapolated from animal models. There may be wide variability in effect onset based on formulation, heat application, and amount of fat in tissue where applied.[16] Onset: 2 hours[17] ≤48 hours[17]
  • Avoids adverse effects of inhalation
  • Helpful for patients unable to adhere to other formulations (terminal illness, etc)
  • Variability of bioavailability depending on formulation[17]
Dabs/waxes Unknown Peak: almost immediate 2 to 3 hours
  • Quick onset of action
  • Potential for lung injury[18]
  • Exposure to solvents (especially unregulated)[19]
  • Risk of psychosis due to very high doses of THC[20]
References:
  1. Huestis MA, Sampson AH, Holicky BJ, et al. Characterization of the absorption phase of marijuana smoking. Clin Pharmacol Ther 1992; 52:31.
  2. Monte AA, Shelton SK, Mills E, et al. Acute illness associated with cannabis use, by route of exposure: An observational study. Ann Intern Med 2019; 170:531.
  3. Joshi M, Joshi A, Bartter T. Marijuana and lung diseases. Curr Opin Pulm Med 2014; 20:173.
  4. Perez-Reyes M, Lipton MA, Timmons MC, et al. Pharmacology of orally administered 9 -tetrahydrocannabinol. Clin Pharmacol Ther 1973; 14:48.
  5. Wall ME, Sadler BM, Brine D, et al. Metabolism, disposition, and kinetics of delta-9-tetrahydrocannabinol in men and women. Clin Pharmacol Ther 1983; 34:352.
  6. Ohlsson A, Lindgren JE, Wahlen A, et al. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther 1980; 28:409.
  7. Goodwin RS, Gustafson RA, Barnes A, et al. Delta(9)-tetrahydrocannabinol, 11-hydroxy-delta(9)-tetrahydrocannabinol and 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in human plasma after controlled oral administration of cannabinoids. Ther Drug Monit 2006; 28:545.
  8. Gustafson RA, Moolchan ET, Barnes A, et al. Validated method for the simultaneous determination of Delta 9-tetrahydrocannabinol (THC), 11-hydroxy-THC and 11-nor-9-carboxy-THC in human plasma using solid phase extraction and gas chromatography-mass spectrometry with positive chemical ionization. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 798:145.
  9. Perez-Reyes M, Lipton MA, Timmons MC, et al. Pharmacology of orally administered 9-tetrahydrocannabinol. Clin Pharmacol Ther 1973; 14:48.
  10. Monte AA, Zane RD, Heard KJ. The implications of marijuana legalization in Colorado. JAMA 2015; 313:241.
  11. Karschner EL, Darwin WD, Goodwin RS, et al. Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. Clin Chem 2011; 57:66.
  12. Guy GW, Robson PJ. A Phase I, open label, four-way crossover study to compare the pharmacokinetic profiles of a single dose of 20 mg of a cannabis based medicine extract (CBME) administered on 3 different areas of the buccal mucosa and to investigate the pharmacokinetics of CBME per oral in healthy male and female volunteers (GWPK0112). J Cannabis Ther 2004; 3:79.
  13. Elsohly MA, Little TL Jr, Hikal A, et al. Rectal bioavailability of delta-9-tetrahydrocannabinol from various esters. Pharmacol Biochem Behav 1991; 40:497.
  14. ElSohly MA, Stanford DF, Harland EC, et al. Rectal bioavailability of delta-9-tetrahydrocannabinol from the hemisuccinate ester in monkeys. J Pharm Sci 1991; 80:942.
  15. Mattes RD, Shaw LM, Edling-Owens J, et al. Bypassing the first-pass effect for the therapeutic use of cannabinoids. Pharmacol Biochem Behav 1993; 44:745.
  16. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers 2007; 4:1770.
  17. Valiveti S, Hammell DC, Earles DC, Stinchcomb AL. In vitro/in vivo correlation studies for transdermal delta 8-THC development. J Pharm Sci 2004; 93:1154.
  18. Stephens D, Patel JK, Angelo D, Frunzi J. Cannabis butane hash oil dabbing induced lung injury mimicking atypical pneumonia. Cureus 2020; 12:e7033.
  19. Raber JC, Elzinga S, Kaplan C. Understanding dabs: contamination concerns of cannabis concentrates and cannabinoid transfer during the act of dabbing. J Toxicol Sci 2015; 40:797.
  20. Stogner JM, Miller BL. Assessing the dangers of "Dabbing": Mere marijuana or harmful new trend? Pediatrics 2015; 136:1.

Adapted from: Slawek DE, Curtis SA, Arnsten JH, Cunningham CO. Clinical approaches to cannabis: a narrative review. Med Clin North Am 2022; 106:131.

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