This latter category is broader and more complex than many of us give it credit for. Inside the mouth, it includes both buccal (between the gums and cheek, as with a lozenge) and sublingual (under the tongue, as with a tincture) modes of absorption.
Everywhere else, it includes two additional routes that work in very different ways: topically, via cannabinoid receptors and secondary targets including TRP (“trip”) channels, PPARs (nuclear receptors), and serotonin receptors that are expressed widely in skin cells and superficial tissues; and transdermally, by entering the bloodstream through the skin.
Advantages and disadvantages
Traditional topicals – including water-based lotions and creams and oil-based balms and salves – offer a quick onset time, no psychoactivity, and the potential to treat not only aches, pains, and inflammation, but also skin conditions like psoriasis and eczema. On the other hand, they’re short-acting, relatively low in bioavailability, and limited to the area to which they’re applied.
Transdermal or “skin-crossing” formulations, meanwhile, are systemic. They act on the entire body (and thus may produce mild psychoactivity if THC is involved); they also last longer, and take effect more slowly. Such products rely on chemical enhancers (called “excipients”) like ethanol, propylene glycol, oleic acid, and even terpenes to help cannabinoids sneak past the skin barrier and into the bloodstream. They also employ special delivery systems like adhesive patches, hydrogels, and nano-emulsions.
Of course, what matters most to patients and clinicians is whether topical and transdermal cannabinoids really work. Much of the research to date has focused on testing cannabidiol or CBD’s ability to treat various forms of pain through a variety of molecular mechanisms – either locally, as with arthritis, muscle soreness, or inflammatory skin conditions; or systemically, for chronic ailments requiring a more controlled and sustained release.
So what do the studies say?
Clinical benefits?
A May 2024 article in the International Journal of Molecular Sciences assesses efforts thus far using CBD to treat inflammatory pain (such as in arthritis) via transdermal delivery systems. It reviews about half a dozen such studies, plus another ten looking at transdermal CBD for other conditions, including drug addiction, neurodegeneration, skin cancer, wound healing, and epilepsy.
Though the Canada-based authors conclude that transdermal delivery of CBD “shows great promise” and represents “a potential novel treatment for chronic inflammatory pain,” they also acknowledge that the jury is still out on its ability to achieve that key benchmark of offering “tangible clinical benefits.”
“A lot of work remains to be done,” they write.
About nine months earlier, another review by a team of Thai researchers appeared in the journal Cannabis and Cannabinoid Research . In this case, the focus was on both topical (local) and transdermal (systemic) formulations. The authors identified a total of just eight studies that met their criteria. Ultimately, they concluded that the available data on pain and other outcomes was unreliable, with a high risk of bias. “New clinical trials are urgently needed,” they repeat in a familiar refrain.
Literature review
In our own literature review, Project CBD identified four newer studies that were not included in the abovementioned reviews. Three address strictly topical/local formulations and one addresses a transdermal formulation. The findings are mixed.
A July 2024 article in Cannabis and Cannabinoid Research evaluates a topical CBD cream’s ability to relieve muscle soreness after exercise. Researchers with the University of Kentucky randomized 28 men and women (n=15 and 13, respectively) in their early and mid-20s to perform a series of lower-body resistance exercises, then do one of the following: a) apply a CBD-containing cream (~100mg) to their quadriceps; b) apply a placebo cream; or c) apply neither and just sit and rest.
Next the researchers administered questionnaires and a few exercise tests to ascertain muscle soreness and physical performance. Their findings after three days of repeating the protocol? Placebo recipients reported the most recovery and relief, while the CBD cream appeared to have no significant effects.
A 2022 paper in The Journal of Arthroplasty evaluating the ability of topical CBD to reduce acute localized pain after knee replacement surgery comes to a similar conclusion. In this double-blinded, placebo-controlled trial, 80 patients were randomly assigned to apply either topical CBD, essential oil, CBD and essential oil, or a placebo three times daily for two weeks following the operation.
On postoperative days 0, 1, 2, 7, 14, and 42, researchers with Thomas Jefferson University in Philadelphia collected data on patient pain, sleep, and opioid use. But upon analyzing the data, they found no significant relationship between CBD use and any of these outcomes.
A killer app for pain?
However, other studies from the last few years have come to opposite conclusions. For example, a phase-two double-blinded, randomized, controlled trial of topical CBD for the treatment of arthritis of the thumb, written up in the Journal of Hand Surgery in July 2022 underscores CBD’s analgesic potential.
University of Virginia researchers randomized 18 participants to receive a twice-daily treatment of either shea butter alone or shea butter with CBD. After a one-week washout period, participants switched groups. This time the results indicated that treatment with topical CBD led to significant improvements in a variety of self-reported measures including pain and disability.
Finally, a May 2024 article in Scientific Reports details the findings of an open-label feasibility trial – meaning it lacked a placebo control but may point the way toward a more rigorous clinical trial – where 15 patients with hand osteoarthritis applied a transdermal CBD gel three times a day for four weeks.
Self-reported pain ratings significantly declined over time. Self-reported fatigue, stiffness, and anxiety all improved. And grip strength as measured by a Bluetooth-connected squeeze ball increased. During a subsequent one-week washout phase, pain and grip strength reverted back towards baseline.
“Transdermal CBD gel may have a beneficial effect on pain and grip strength in participants with symptomatic hand osteoarthritis, but requires further exploration,” the authors conclude. “[Future] research should incorporate a double-blind, randomized study design with greater participant numbers and more comprehensive pharmacokinetic and biomarker analysis.”
Nate Seltenrich, Project CBD contributing writer, is the author of the column Bridging the Gap. An independent science journalist based in the San Francisco Bay Area, he covers a wide range of subjects, including environmental health, neuroscience, and pharmacology.
Project CBD feedback request: Have you used a CBD-rich topical product? What’s been your experience? Let us know
References:
1. Lefebvre, È.; Tawil, N.; Yahia, L. Transdermal Delivery of Cannabidiol for the Management of Acute Inflammatory Pain: A Comprehensive Review of the Literature. Int. J. Mol. Sci. 2024, 25, 5858. https://doi.org/10.3390/ijms25115858
2. Scholfield, CN; Waranuch, N; Kongkaew, C. Systematic Review on Transdermal/Topical Cannabidiol Trials: A Reconsidered Way Forward Cannabis and Cannabinoid Research 2023 8:4, 589-602
3. Pastina JT, Abel, MG, Bollinger, LM, Best, SA. Topical Cannabidiol Application May Not Attenuate Muscle Soreness or Improve Performance: A Randomized, Double-Blinded, Placebo-Controlled Pilot Study. Cannabis and Cannabinoid Research 9 July 2024, https://doi.org/10.1089/can.2024.001
4. Haffar, Amer et al., Topical Cannabidiol (CBD) After Total Knee Arthroplasty Does Not Decrease Pain or Opioid Use: A Prospective Randomized Double-Blinded Placebo-Controlled Trial, Journal of Arthroplasty, Volume 37, Issue 9, 1763 – 1770
5. Heineman, John T. et al. A Randomized Controlled Trial of Topical Cannabidiol for the Treatment of Thumb Basal Joint Arthritis. Journal of Hand Surgery, Volume 47, Issue 7, 611 – 620
6. Bawa, Z., Lewis, D., Gavin, P.D. et al. An open-label feasibility trial of transdermal cannabidiol for hand osteoarthritis. Sci Rep 14, 11792 (2024). https://doi.org/10.1038/s41598-024-62428-x
Acknowledgement: This article was made possible by a grant from OP6 CBD. Project CBD is able to exist due to the organizations and brands who support our work financially. Our contributing journalists and researchers operate independently of any influence from our supporting partners.
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