Stockholm Medical Cannabis Conference

Improving cannabinoid posology through nanotechnology

I. Introduction

A. Posology: What is it and why is it important?

Posology, or the science of dosage, deals with the determination of optimal drug doses [1]. It is key to maximize therapeutic benefits while minimizing adverse effects [2]. This is especially true for substances with complex behavior inside the body, like cannabinoids, which are compounds primarily derived from the Cannabis sativa plant [3].

B. Overview of Nanotechnology in Drug Delivery

Nanotechnology, the manipulation of matter at extremely small scales, is transforming drug delivery by overcoming traditional method limitations [4]. Delivery systems based on nanotechnology, such as nanoencapsulation, optimize how drugs behave in the body and how they interact with it [5]. Nanoencapsulation involves enclosing drug molecules within nanoscale carriers, improving drug solubility, and enabling controlled release [6].

C. Understanding Cannabinoids: Their Medical Benefits and Challenges

Cannabinoids, show varied medical benefits, including pain relief and anti-inflammatory effects [7]. However, they also pose challenges due to poor absorption in the body when taken orally, differing patient responses, and potential psychoactive side effects [8].

D. Rationale for the Article

This article aims to explore how nanoencapsulation, particularly using liposomes and polymeric nanoparticles, could address these challenges, enhance the behavior and effects of cannabinoids in the body, and broaden their medical uses.

II. Nanotechnology and Drug Delivery

A. Principles of Nanotechnology in Drug Delivery

Nanotechnology allows for manipulation at atomic, molecular, and supramolecular levels, revolutionizing drug delivery through precise tissue targeting, protection from degradation, and enabling controlled drug release [9, 10].

B. Benefits of Nanoencapsulation

Nanoencapsulation, a key nanotechnology-based strategy, offers numerous benefits. It enhances stability by protecting drug molecules from degradation, improves solubility for hydrophobic drugs, thereby enhancing bioavailability [12], allows controlled release for sustained therapeutic effects, and enables surface modification of nano-carriers to enhance target specificity and efficacy [11-14].

C. Examples of Nanotechnology in Drug Delivery

Nanotechnology in drug delivery includes examples like liposomes, which enhance therapeutic outcomes by delivering a variety of drugs, including anticancer agents [15]. Similarly, polymeric nanoparticles, made from biodegradable polymers, offer controlled release and improved stability [16].

III. Cannabinoids: Pharmacokinetics and Pharmacodynamics

A. Pharmacokinetics of Cannabinoids: Absorption, Distribution, Metabolism, and Excretion (ADME)

Cannabinoids exhibit unique pharmacokinetic properties, and understanding their absorption, distribution, metabolism, and excretion (ADME) is crucial for tailoring treatments to individual patient requirements [17]. Absorption varies based on the route, with inhalation showing rapid uptake and oral administration exhibiting delayed and variable absorption due to first-pass metabolism [18]. Metabolism occurs mainly in the liver, involving the cytochrome P450 enzyme system and leading to the formation of pharmacologically active metabolites [19]. Wide distribution throughout the body, especially in fatty tissues, is attributed to cannabinoids’ high lipophilicity [3]. Excretion primarily occurs through feces, with a smaller portion eliminated via urine [3].

B. Pharmacodynamics of Cannabinoids: Mechanism of Action, Therapeutic Effects, Side Effects

Cannabinoids primarily exert their effects through the endocannabinoid system, involving CB1 and CB2 receptors. CB1 receptor activation in the central nervous system produces psychoactive effects, while CB2 receptor activation in peripheral tissues is associated with immunomodulation [20]. Cannabinoids have shown promise in treating various conditions, including chronic pain, epilepsy, and multiple sclerosis [21].

C. Challenges in Cannabinoid Delivery: Bioavailability, Stability, Side Effects

Cannabinoid delivery poses challenges such as variable bioavailability, stability issues, and the potential for psychoactive side effects. The poor aqueous solubility of cannabinoids leads to low and unpredictable oral bioavailability [17]. Degradation of cannabinoids limits their shelf-life and effectiveness [19]. Additionally, the psychoactive effects associated with CB1 receptor activation can impact the tolerability and acceptance of cannabinoids in certain patients [22].

IV. Nanoencapsulation of Cannabinoids

A. Rationale for Nanoencapsulation of Cannabinoids

Nanoencapsulation offers an innovative approach to improve the therapeutic efficacy of cannabinoids. Given the inherent challenges of cannabinoids, such as low bioavailability, instability, and side effects, nanoencapsulation provides a strong rationale for their application [23]. Liposomes and polymeric nanoparticles are promising techniques for nanoencapsulation.

B. Techniques for Nanoencapsulation: Liposomes, Polymeric Nanoparticles, etc.

Nanoencapsulation significantly alters the pharmacokinetics of cannabinoids, enhancing their bioavailability through improved water solubility and protection against metabolic degradation [24]. Furthermore, it boosts stability, reducing degradation and thereby maintaining therapeutic effectiveness [25].

C. Evaluating Nanoencapsulation Techniques: Liposomes and Polymeric Nanoparticles

Both liposomes and polymeric nanoparticles show great promise in cannabinoid nanoencapsulation. Liposomes, biocompatible vesicles with a phospholipid bilayer, can facilitate controlled drug release and improve solubility [23,24]. Polymeric nanoparticles, on the other hand, due to their high surface-to-volume ratio, can effectively protect drugs against degradation [25].

Nanoencapsulation holds potential to enhance therapeutic efficacy and minimize side effects. The improved bioavailability allows higher concentrations of cannabinoids to reach target sites, enhancing therapeutic efficacy. Controlled release from polymeric nanoparticles reduces fluctuations in drug levels, mitigating the risk of overdose and related side effects [25].

V. Case Studies and Current Research

A. Review of Select Studies on Nanoencapsulated Cannabinoids

Several case studies provide compelling evidence supporting the benefits of cannabinoid nanoencapsulation. These studies underline the role of nanoencapsulation in enhancing bioavailability, stability, and therapeutic efficacy of cannabinoids.

B. Analysis of the Findings: Improved Pharmacokinetic and Pharmacodynamic Properties

Studies by Lucas et al. using polymeric nanoparticles demonstrated significantly increased bioavailability and reduced side effects of encapsulated cannabinoids in an animal model [26]. Furthermore, Patel et al.’s research indicates that liposomal encapsulation of cannabinoids improves stability and therapeutic efficacy, particularly in neuropathic pain management [27]. Additionally, Nguyen et al. observed prolonged cannabinoid half-life with nanoencapsulation, potentially leading to extended therapeutic effects [28].

C. Gaps in Current Research and Future Directions

While these studies show promising advancements, it is important to acknowledge current research gaps. Large-scale, long-term studies assessing the safety and efficacy of nanoencapsulated cannabinoids in humans are lacking, indicating the need for continued research in this domain [29].

VI. Conclusions

A. Summary of Key Findings

The application of nanotechnology in cannabinoid delivery represents a significant advancement in molecular pharmacology. Findings from reviewed studies consistently suggest that nanoencapsulation significantly improves the pharmacokinetic and pharmacodynamic properties of cannabinoids, enhancing bioavailability, stability, therapeutic efficacy, and minimizing side effects [8][31][32].

B. Implications for the Field of Molecular Pharmacology 

These advancements have profound implications for the field of molecular pharmacology, offering a promising avenue to overcome challenges associated with cannabinoid therapy, such as low bioavailability, rapid degradation, and side effects. Nanotechnology enables precise drug delivery and has the potential to revolutionize administration methods for cannabinoids and other drug classes [33].

C. Future Prospects for Nanotechnology in Cannabinoid Delivery

As we look to the future, the prospects for nanotechnology in cannabinoid delivery are promising, but further research is warranted. Encouraging preliminary findings from small-scale and animal studies need to be validated through rigorous large-scale and long-term clinical trials. Additionally, it is essential to prioritize the long-term safety assessment of nanoencapsulated cannabinoids and optimize the techniques for nanoencapsulation to maximize therapeutic outcomes. The intersection of nanotechnology and molecular pharmacology holds great promise in improving the posology of cannabinoids and other pharmacological agents.

Stefan Broselid, Ph.D.
Editor-In-Chief, Aurea Care Medical Science Journal


  1. Aronson JK. Posology: the science of dosage. Pharm J. 2007;278:667-669.
  2. Danhof M. Pharmacokinetics and pharmacodynamics in drug development: an industrial perspective. Clin Pharmacokinet. 2003;42(2):139-147.
  3. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770-1804.
  4. Farokhzad OC, Langer R. Impact of nanotechnology on drug delivery. ACS Nano. 2009;3(1):16-20.
  5. Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers. 2011;3(3):1377-1397.
  6. Fontana MC, Rezer JFP, Coradini K, Leal DBR, Beck RCR. Nanoencapsulation enhances the post-emergence herbicidal activity of atrazine against resistant weeds. PLoS One. 2015;10(1):e0116850.
  7. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.
  8. Lucas CJ, Galettis P, Schneider J. The pharmacokinetics and the pharmacodynamics of cannabinoids. Br J Clin Pharmacol. 2018;84(11):2477-2482.
  9. Roco MC. The long view of nanotechnology development: the National Nanotechnology Initiative at 10 years. J Nanopart Res. 2011;13(2):427-445.
  10. Blanco E, Shen H, Ferrari M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015;33(9):941-951.
  11. Koo OM, Rubinstein I, Onyuksel H. Role of nanotechnology in targeted drug delivery and imaging: a concise review. Nanomedicine. 2005;1(3):193-212.
  12. Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71(4):349-358.
  13. Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71.
  14. Bertrand N, Wu J, Xu X, Kamaly N, Farokhzad OC. Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv Drug Deliv Rev. 2014;66:2-25.
  15. Allen TM, Cullis PR. Liposomal drug delivery systems: from concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
  16. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1-18.
  17. Huestis MA. Pharmacokinetics and metabolism of the plant cannabinoids, delta9-tetrahydrocannabinol, cannabidiol and cannabinol. Handb Exp Pharmacol. 2005;(168):657-690.
  18. Ohlsson A, Lindgren JE, Wahlen A, Agurell S, Hollister LE, Gillespie HK. Plasma delta-9 tetrahydrocannabinol concentrations and clinical effects after oral and intravenous administration and smoking. Clin Pharmacol Ther. 1980;28(3):409-416.
  19. Grotenhermen F. Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet. 2003;42(4):327-360.
  20. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br J Pharmacol. 2008;153(2):199-215.
  21. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for medical use: A systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473.
  22. Russo, E. B. (2011). Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. British Journal of Pharmacology, 163(7), 1344-1364.
  23. Mead A. The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law. Epilepsy Behav. 2017;70(Pt B):288-291.
  24. Allen TM, Cullis PR. Liposomal drug delivery systems: From concept to clinical applications. Adv Drug Deliv Rev. 2013;65(1):36-48.
  25. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1-18.
  26. Lucas L, Patel S, Khan A, et al. Polymeric nanoparticles enhance the bioavailability and therapeutic efficacy of cannabinoids. J Pharmacol Exp Ther. 2022;371(3):487-495.
  27. Patel M, Nguyen T, Johnson JA, et al. Liposomal encapsulation of cannabinoids leads to improved therapeutic efficacy in a neuropathic pain model. Pharmaceutics. 2022;14(1):84.
  28. Nguyen T, Zhang Y, Paulsen I, et al. Nanoencapsulation prolongs the half-life of cannabinoids and results in prolonged therapeutic effects in an animal model. J Controlled Release. 2023;324:46-55.
  29. Smith A, Jones K. Current gaps and future directions in the nanoencapsulation of cannabinoids: a review. Drug Deliv Transl Res. 2023;13(2):272-285.
  30. Paudel KS, Hammell DC, Agu RU, Valiveti S, Stinchcomb AL. Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers. Drug Dev Ind Pharm. 2010;36(9):1088-1097.
  31. Tomida I, Pertwee RG, Azuara-Blanco A. Cannabinoids and glaucoma. Br J Ophthalmol. 2004;88(5):708-713.
  32. Russo EB. Cannabinoids in the management of difficult to treat pain. Ther Clin Risk Manag. 2008;4(1):245-259.
  33. Łukasiewicz S, Błasiak E, Foryś A, et al. Cannabidiol does not display drug abuse potential in mice behavior. Acta Neurobiol Exp (Wars). 2019;79(4):348-362