Nanotechnology for the Efficacious Delivery of Medicinal Cannabis and Pharmaceutical Medicines

Nanotechnology is creating new possibilities for the delivery of medicinal cannabis and pharmaceutical medicines. This 2025 narrative review examines how nanoscale delivery systems may help overcome common problems such as poor solubility, inconsistent absorption, low bioavailability, gastrointestinal degradation, and first-pass metabolism.

These challenges are especially relevant to cannabinoids such as THC and CBD because they are highly lipophilic compounds. The review discusses how nanoparticle systems may improve cannabinoid stability, targeting, controlled release, selectivity, and overall delivery while exploring alternative routes including oro-buccal, nasal, ocular, and transdermal administration.

The paper directly discusses THC, CBD, dronabinol, nabilone, nabiximols, high-THC cannabis, and NanoCelle™ formulations designed to deliver THC and CBD through the oral mucosa. The authors emphasize that nanotechnology may allow cannabinoid medicines to be delivered more precisely, with improved absorption and reduced loss through first-pass metabolism.

“The application of nanoparticles as nanomedicines, particularly for the targeted and efficacious delivery of drugs is an expanding platform in the field of cannabinoid and pharmaceutical drug delivery. By refocusing the route of drug administration beyond the oral gut pathway, this technology provides significant advancements that are especially relevant for cancer treatments. Orally administered drugs face significant challenges as they traverse the gastrointestinal tract (GIT) and are subject to first-pass GIT metabolism. Physiological conditions encountered in the GIT such as food effects, hormones, gastric pH, emptying time, and intestinal transit time vary widely across individuals. Fluid composition and enzymatic activity in the small intestine and large bowel also influence drug dissolution and absorption. These factors in conjunction with the intestinal cohort of bacteria can metabolize drugs before absorption, contributing to poor and variable drug bioavailability, which can be exacerbated by gut dysbiosis. Drug delivery that bypasses the oral-GIT route and hence first-pass metabolism offers a plausible solution for enhanced safety and drug efficacy.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC12472836

Exploring the Potential of Cannabinoid Nanodelivery Systems for CNS Disorders

Cannabinoids such as THC and CBD have shown therapeutic potential in neurological disorders, but poor water solubility and low bioavailability can limit their effectiveness. This review explores how nanotechnology may overcome these barriers by improving cannabinoid stability, controlled release and targeted delivery to the central nervous system, including strategies designed to enhance passage across the blood-brain barrier.

“Cannabinoids have a major therapeutic value in a variety of disorders. The concepts of cannabinoids are difficult to develop, but they can be used and are advantageous for a number of diseases that are not sufficiently managed by existing treatments. Nanoconjugation and encapsulation techniques have been shown to be effective in improving the delivery and the therapeutic effectiveness of drugs that are poorly soluble in water. Because the bioavailability of cannabinoids is low, the challenge is to explore different administration methods to improve their effectiveness. Because cannabinoids cross the blood-brain-barrier (BBB), they modify the negative effects of inflammatory processes on the BBB and may be a key factor in the improvement of BBB function after ischemic disease or other conditions. This review discusses various types of cannabinoid administration, as well as nanotechnologies used to improve the bioavailability of these compounds in CNS diseases.”

“The growing acceptance of Cannabis and cannabinoids has led to an increasing number of clinical trials testing various nanoproducts. CNS disorders are key therapeutic targets for cannabinoids, and nanoformulation platforms for cannabinoid nanoconjugates provide efficient transport across the BBB. Selected examples of cannabinoid nanoconjugates have shown enhanced bioavailability and improved bio-efficacy with promising outcomes in biomedical applications. We expect to see many results from clinical trials in the near future to evaluate the adverse effects and effectiveness of this treatment. However, precise delivery of these nanoformulations to pathological sites inside the brain remains a challenge.”

https://pmc.ncbi.nlm.nih.gov/articles/PMC9863859/

Prospects in the Use of Cannabis sativa Extracts in Nanoemulsions

Cannabis sativa contains a wide range of biologically active compounds with medicinal potential, including cannabinoids, terpenes, flavonoids and other plant chemicals. This review examined extraction methods and nanoemulsion technologies that could improve the stability, delivery, bioavailability and preservation of these compounds while expanding the potential use of whole-plant cannabis extracts.

The authors highlight antioxidant, antimicrobial and immunomodulatory activity associated with Cannabis sativa extracts and argue that nanoformulations could help move this research toward broader pharmaceutical development. They specifically call for greater industry participation to advance new delivery methods, scale up cannabis nanoemulsion production and support the progression from animal research toward eventual human applications.

“Cannabis sativa plants have been widely investigated for their specific compounds with medicinal properties. These bioactive compounds exert preventive and curative effects on non-communicable and infectious diseases.

However, C. sativa extracts have barely been investigated, although they constitute an affordable option to treat human diseases.

Nonetheless, antioxidant, antimicrobial, and immunogenicity effects have been associated with C. sativa extracts.

Furthermore, innovative extraction methods in combination with nanoformulations have been proposed to increase desirable compounds’ availability, distribution, and conservation, which can be aided by modern computational tools in a transdisciplinary approach.

This review aims to describe available extraction and nanoformulation methods for C. sativa, as well as its known antioxidant, antimicrobial, and immunogenic activities. Critical points on the use of C. sativa extracts in nanoformulations are identified and some prospects are envisaged.”

https://pubmed.ncbi.nlm.nih.gov/39727490

“Given all this, the pharmaceutical industry’s active participation is needed to advance and exploit other forms of distribution in animals and, finally, application in humans.”

“The industry could participate in innovation in harnessing Cannabis and scaling up the production of nanoemulsions.” 

https://www.mdpi.com/2673-6284/13/4/53


Analgesic effect of delta-9-tetrahydrocannabinol

A preliminary double-blind clinical trial found that oral delta-9-tetrahydrocannabinol (THC) produced significant pain relief in patients with cancer pain. In the 10-patient study, THC doses of 15 and 20 mg provided significantly greater analgesic effects than placebo.

The study’s main clinical takeaway is that THC showed a measurable analgesic effect at higher oral doses, but the benefit was accompanied by dose-limiting central nervous system side effects. In practical terms, the findings suggest a potential role for THC in cancer pain management while also underscoring the importance of balancing pain relief against sedation, cognitive impairment, and overall tolerability.

“A preliminary trial of oral delta-9-tetrahydrocannabinol (THC) demonstrated an analgesic effect of the drug in patients experiencing cancer pain. Placebo and 5, 10, 15, and 20 mg THC were administered double blind to ten patients. Pain relief significantly superior to placebo was demonstrated at high dose levels (15 and 20 mg). At these levels, substantial sedation and mental clouding were reported.”

https://pubmed.ncbi.nlm.nih.gov/1091664

https://accp1.onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1975.tb02348.x

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Antiemetic effect of delta-9-tetrahydrocannabinol in patients receiving cancer chemotherapy

Oral delta-9-tetrahydrocannabinol (THC) was tested in a randomized, double-blind, placebo-controlled study involving cancer patients receiving chemotherapy known to cause nausea and vomiting. Among 20 evaluable patients, an antiemetic effect was seen in 14 of 20 THC treatment courses and in none of 22 placebo courses. In patients who completed the study, THC produced a response in 12 of 15 courses compared with 0 of 14 placebo courses. The researchers concluded that oral THC had significant antiemetic effects and was better than placebo at reducing chemotherapy-induced vomiting.

“Anecdotal accounts suggested that smoking marihuana decreases the nausea and vomiting associated with cancer chemotherapeutic agents.

Oral delta-9-tetrahydrocannabinol was compared with placebo in a controlled, randomized, “double-blind” experiment.

All patients were receiving chemotherapeutic drugs known to cause nausea and vomiting of central origin. Each patient was to serve as his own control to determine whether tetrahydrocannabinol had an antiemetic effect. Twenty-two patients entered the study, 20 of whom were evaluable.

For all patients an antiemetic effect was observed in 14 of 20 tetrahydrocannabinol courses and in none of 22 placebo courses. For patients completing the study, response occurred in 12 of 15 courses of tetrahydrocannabinol and in none of 14 courses of placebo (P less than 0.001).

No patient vomited while experiencing a subjective “high”.

Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducting vomiting caused by chemotherapeutic agents.”

https://pubmed.ncbi.nlm.nih.gov/1099449

https://www.nejm.org/doi/abs/10.1056/NEJM197510162931603

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Δ9-Tetrahydrocannabinol (Δ9-THC) Improves Ischemia/Reperfusion Heart Dysfunction and Might Serve as a Cardioprotective Agent in the Future Treatment

Researchers examined whether Δ9-THC could protect heart tissue from ischemia/reperfusion injury—the damage that can occur when blood flow returns after a period of oxygen deprivation. Using isolated rat hearts and human cardiac cells, the study found that THC improved recovery of heart function, reduced cellular injury and death, supported antioxidant defenses, and helped restore normal cardiac mechanical function.

“Background: Ischemia/reperfusion (I/R) is a pivotal mechanism of organ injury during clinical stetting for example for cardiopulmonary bypasses. The generation of reactive oxygen species (ROS) during I/R induces oxidative stress that promotes endothelial dysfunction, DNA dissociation and local inflammation. In turn, those processes induce cytokine release, resulting in damage to cellular structures and cell death. One of the major psychoactive compounds of Cannabis is delta-9-tetrahydrocannabinol (Δ9-THC), which is known as an anti-inflammatory mediator. Our research aimed to test if Δ9-THC may be protective in the treatment of cardiovascular system dysfunction arising from I/R heart injury.

Methods: Two experimental models were used: isolated rat hearts perfused with the Langendorff method and human cardiac myocytes (HCM) culture. Rat hearts and HCM underwent ex vivo/chemical in vitro I/R protocol with/without Δ9-THC treatment. The following parameters were measured: cell metabolic activity, morphology changes, cell damage as lactate dehydrogenase (LDH) activity, ceramide kinase (CERK) activity, ROS level, total antioxidant capacity (TAC) and heart hemodynamic parameters.

Results: Δ9-THC protected the heart, as evidenced by the improved recovery of cardiac function (p < 0.05, N = 3-6). Cells subjected to I/R showed lower cytoplasmic LDH activity, and 10 μM Δ9-THC treatment reduced cell injury and increased LDH content (p = 0.019, N = 6-9). Morphology changes of HCM-spherical shape, vacuolisation of cytoplasm and swollen mitochondria-were inhibited due to Δ9-THC treatment. I/R condition affected cell viability, but 10 μM Δ9-THC decreased the number of dead cells (p = 0.005, N = 6-9). The total level of CERK was lower in the I/R group, reflecting oxidative/nitrosative stress changes. The administration of Δ9-THC effectively increased the production of CERK to the level of aerobic control (p = 0.028, N = 6-9). ROS level was significantly decreased in I/R cells (p = 0.007, N = 6-8), confirming oxidative stress, while administration of 10 μM Δ9-THC enhanced TAC in cardiomyocytes subjected to I/R (p = 0.010, N = 6-8).

Conclusions: Δ9-THC promotes the viability of cardiomyocytes, improves their metabolic activity, decreases cell damage and restores heart mechanical function, serving as a cardioprotective. We proposed the use of Δ9-THC as a cardioprotective drug to be, administered before onset of I/R protocol.”

https://pubmed.ncbi.nlm.nih.gov/35468673/

“In conclusion, in this study we found that Δ9-THC promotes the viability and improves the metabolic activity of cardiomyocytes, as well as decreasing cell damage and restoring heart mechanical function, proving that it has a cardioprotective function at the pre-treatment level.

We propose the use of THC as a potentially cardioprotective compound to be, administered before ischemia and during the first minutes of reperfusion.

We hope that this cannabis product may be included in future clinical investigations using similar models of ischemia-reperfusion injury. We also recommend the presented data to be considered alongside clinical observations of patient outcomes with history of cannabis use.”

https://www.imrpress.com/journal/FBL/27/4/10.31083/j.fbl2704114

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Transient CB2R modulation durably restricts breast cancer plasticity by stabilizing a luminal like cell identity

New breast cancer research suggests that brief modulation of cannabinoid receptor 2 (CB2R), including with THC, may have lasting effects on tumor cell behavior. Researchers found reduced self-renewal, invasiveness, and tumor-initiating capacity, along with greater tamoxifen sensitivity and a durable shift toward a more stable luminal-like cell identity.

“Cancer cell plasticity enables therapy resistance and metastasis by allowing transitions between stem-like and differentiated states. Differentiation-based strategies aim to stabilize tumor cell identity, yet pharmacological approaches that induce durable lineage restriction remain limited.

Here, we show that transient modulation of cannabinoid receptor 2 (CB2R) durably restricts breast cancer cell plasticity by stabilizing a luminal-like cell state. Using patient-derived and murine tumor organoids, we demonstrate that brief, low-dose CB2R modulation reduces self-renewal, invasiveness and tumor-initiating capacity, while enhancing tamoxifen sensitivity and limiting the emergence of resistant phenotypes.

These effects persist under pro-dedifferentiation conditions, including TGFβ exposure, stromal co-culture, immune signaling and mechanical stress, and are maintained in vivo following orthotopic transplantation. RNA sequencing reveals a progressive transition from an early plastic state toward a stabilized luminal-like identity, supported by CUT&Tag profiling that uncovers chromatin remodeling associated with this stabilization.

Together, our findings redefine CB2R as a regulator of tumor cell state and establish transient CB2R modulation as a strategy to durably constrain breast cancer plasticity through differentiation-based therapy.”

https://www.nature.com/articles/s42003-026-10837-1

“Low-dose THC keeps breast cancer cells in tumor models from reverting to an aggressive state”

https://medicalxpress.com/news/2026-09-dose-thc-breast-cancer-cells.html

Benefits of cannabis in treating lower urinary tract symptoms: A scoping review

Cannabis-based therapies may offer another approach to managing lower urinary tract symptoms such as urinary urgency, frequency, and incontinence. A 2026 scoping review found encouraging evidence that THC, CBD, and combined cannabinoid formulations can improve several urinary symptoms and quality-of-life measures, with the most consistent evidence found among patients with multiple sclerosis.

“Introduction: Anticholinergics and β3-agonists remain the mainstay for bladder dysfunction but are limited by side effects and poor adherence. Cannabinoids are a potential alternative given receptor distribution in bladder control pathways. Early studies suggested that cannabis may demonstrate benefits in overactive bladder (OAB) and lower urinary tract symptoms (LUTS), but findings are limited by small sample sizes and cross-sectionality. This review investigates the therapeutic utility of cannabis and its impact on LUTS.

Methods: This scoping review was conducted following Cochrane and PRISMA guidelines. Eligible studies included adults with OAB symptoms due to neurogenic disease, benign prostatic hyperplasia (BPH), or cystitis, treated with cannabis vs. placebo, no treatment, or active therapies. Outcomes included urinary function and quality of life. Databases searched included MEDLINE, EMBASE, and CENTRAL. Non-English studies were excluded.

Results: From 998 abstracts, 31 full-text articles were reviewed and 12 were included. Studies showed consistent evidence on the effectiveness of cannabis-based therapies for managing LUTS, particularly in patients with multiple sclerosis (MS). Cannabis interventions, including THC, CBD, and combined formulations, showed some improvements in incontinence episodes, frequency, and quality-of-life measures. Mild adverse effects, including dizziness and dry mouth, were common (2-18%) and sometimes led to treatment discontinuation. Nine of 12 studies were done on MS populations, and only three studies were randomized controlled trials.

Conclusions: Evidence for the benefits of cannabis in treating LUTS is limited and largely observational. While preliminary findings are encouraging, randomized trials focusing on patient-centered outcomes are needed to clarify its role in clinical practice.”

https://pubmed.ncbi.nlm.nih.gov/42678682

https://cuaj.ca/index.php/journal/article/view/9478

Effects of delta-9 tetrahydrocannabinol and cannabidiol on cognitive outcomes following acute use of cannabis for chronic pain

In a study of 183 adults using edible cannabis for chronic low back pain, researchers found no significant acute changes in executive function, episodic memory, or processing speed after cannabis use. Participants using CBD-dominant products performed better on working memory than those using CBD + THC one hour after use, while the CBD group also showed more stable verbal-learning scores than participants using THC or mixed CBD/THC products. The findings add useful evidence to the discussion of how different cannabinoid profiles may affect cognition when cannabis is used for chronic pain.

“Rationale: An estimated two-thirds of medical cannabis users in the United States are motivated by chronic pain, but clinical guidance remains guarded as to whether the potential benefit of cannabinoids for pain outweighs potential risks, such as effects on cognition.

Objectives: In a study where participants experienced benefits of cannabinoids for pain and tension, we evaluated cannabis effects on executive function, processing speed, memory, and verbal learning following acute use for chronic, non-specific low back pain.

Methods: Participants were in one of three self-selected edible cannabis groups: a) CBD-dominant, b) THC-dominant, or c) a mixed ratio of CBD to THC and completed a battery of cognitive tasks at pre-use, 1 h post-use use, and 2 h post-use.

Results: Among 183 participants (56.8% female; Mage = 45.6), those in the group using CBD outperformed participants using CBD + THC 1 h post use in working memory and produced more stable scores in verbal learning after use than participants using THC or CBD + THC. Additionally, while older age was associated with better working memory in the CBD group before use, that relationship was progressively attenuated over the subsequent timepoints. There were no significant effects of cannabis use on cognition in the domains of executive function, episodic memory, or processing speed.

Conclusions: Given the ubiquity of cannabis use for chronic pain and the ongoing call for more data, this study is relevant for informing clinical guidance on whether, and how, cannabis could be used in this context. In particular, understanding the acute impact on cognition from cannabis is critical, as cognitive functioning directly affects patients’ daily lives and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/42678518

“In summary, these findings support CBD’s potential to preserve cognitive performance in the context of chronic pain, contrasting with the more variable effects of THC across cognitive domains. The observed influence of age, particularly among those using CBD, suggests that both cannabinoid composition and individual factors shape cognitive outcomes following acute cannabinoid use.”

https://link.springer.com/article/10.1007/s00213-026-07157-x

Cannabinoid efficacy for pain: dose, chronicity and route

Cannabinoid pain relief depends on more than whether THC or CBD is used. Dose, route of administration, treatment duration and the type of pain can all influence whether a cannabis-based therapy provides meaningful analgesia or produces unwanted effects. This review examines those variables across preclinical and clinical research, while also considering the independent and combined roles of cannabis-derived terpenes.

“Cannabis-based therapies are widely used for chronic pain, yet their mechanisms and therapeutic windows remain incompletely defined. This review synthesizes preclinical and clinical evidence on how dose, route of administration, treatment duration, and chemical composition shape analgesic efficacy and adverse-effect liability for Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and select cannabis-derived terpenes.

Across rodent pain models, acute THC reliably produces antinociception, but its therapeutic window is narrow because analgesic doses overlap with CB1 receptor-mediated side effects such as sedation, hypothermia, hyperphagia, and motor impairment. Repeated THC exposure leads to tolerance and dependence.

In contrast, CBD shows limited acute efficacy in naïve and inflammatory models but demonstrates more consistent benefit with repeated dosing in neuropathic and chemotherapy-induced pain, often without cannabimimetic adverse effects.

Terpenes such as linalool, β-caryophyllene, myrcene, limonene, α-terpineol, and α-bisabolol exhibit independent antinociceptive and anti-inflammatory properties and are thought to pharmacologically interact with cannabinoids in a dose-, ratio-, and route-dependent “entourage” effect that either enhance or constrain therapeutic benefit.

This review also focuses on integrating machine learning-based behavioral phenotyping of rodents to refine cannabinoid analgesia preclinical research. Computer vision pose-estimation and unsupervised clustering approaches enable high-resolution quantification of spontaneous and evoked natural behaviors, allowing the analytical dissociation of true analgesia from sedation, ataxia, or reduced exploration. By coupling these behavioral pipelines with pharmacokinetic and circuit-level analyses, emerging frameworks will define therapeutic windows with greater precision and improve the translational relevance of cannabinoid-based pain therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/42661783

“Cannabinoid-based therapeutics are among the most widely used treatments for pain indications, with nearly one-third of adults with chronic pain using Cannabis for pain management.”

“Taken together, the studies reviewed here demonstrate that the analgesic efficacy of THC, CBD, and Cannabis-derived terepenes is dependent on dose, route of administration, treatment chronicity, and chemical composition.”

https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2026.1888863/full