Chronic Pain: Transdermal Cannabinoid v Opioid Therapy


Pain control is the most common use for medical cannabis in the United States. While cannabis isn’t strong enough for severe pain, e.g. post-surgical pain or a broken bone, it is quite effective for the chronic pain that plagues millions of Americans, especially the elderly. Cannabis has been used for thousands of years as treatment for chronic pain yet the tradition of Western medicine healthcare providers to base their treatment decisions on the gold standard of FDA, opioids remain the leading Western medicine choice. Cannabis is classified as a Schedule 1 drug and as such, acceptable studies are extremely limited. There are advantages to using cannabinoid formulations over opioids for chronic pain treatment, particularly via transdermal delivery. There are a few disadvantages to cannabinoid formulations yet overall compared to opioids, the use of cannabis for local chronic pain management treatment compared to opioids disadvantages outweigh the risks and dangers of opioids.

The National Academies of Science published in its landmark report on cannabis and cannabinoids Conclusion 4-1 in 2017, “There is substantial evidence that cannabis is effective treatment for chronic pain in adults.”  Whiting, et al published a review of a few studies researching the efficacy of cannabis on chronic pain. [1]Using both THC and CBD together each with its recognized benefits as studied with pharmacologic and pharmacokinetic properties as part full-spectrum of the cannabis plant with specific terpenes, is the best for treating pain. [2] THC is beneficial for treating the psychologic effects of pain at the CB1 receptor, enhancing mood. CB2 receptors have been shown to modulate acute pain, chronic inflammatory pain, post-surgical pain, cancer pain and pain associated with nerve injury.  As an agonist at CB2, THC also treating inflammation in the body.

Benefits of Transdermal Delivery

Transdermal cannabinoid therapy delivers the formulation through the skin. This route of administration has several benefits:

  1. Improved patient compliance.
  2. There is no first-pass metabolism effect.
  3. It is non-invasive.
  4. Allows for a steady infusion of the drug.
  5. Can be quickly terminated with removal of the device from the skin surface.
  6. It is ideal to treat localized symptoms from dermatologic conditions, arthritis as well as peripheral neuropathic pain.

If an opioid therapy is delivered similarly by transdermal application, there is no first-pass metabolism effect, e.g., transdermal fentanyl (TF). Fentanyl is considered effective and well tolerated for the treatment of chronic pain yet patients can develop unpleasant and dangerous opioid-related adverse effects (i.e, sedation, dizziness, nausea, vomiting, constipation, physical dependence and respiratory depression) especially hypoventilation.[1] Opioid withdrawal syndrome (WS) has been reported in patients in the first 24 hours of switching to morphine to TF. Frequent symptoms include flu-like symptoms, tachycardia, abdominal cramps and diarrhea, nausea, profuse sweating and agitation. [2]When used in conjunction with opioid treatment, cannabinoids may provide the opportunity for lower opioid dosing. [3]

The Challenges

There are disadvantages to using transdermal cannabinoid therapy. The skin contains numerous receptors for drugs which irritate or sensitize the skin. These receptors can induce an itch response. This can range from a slight irritant to a significant issue. This disadvantage applies to both transdermal cannabinoid and opioid therapy.

The skin has differences in it barrier function between sites as well as between individuals. The extreme hydrophobicity of cannabinoids make crossing the aqueous layer of the skin challenging. A permeation enhancer is necessary to ensure that a transdermal therapy is successful. There can also be a variation in adhesive effectiveness in different individuals.

Zero Risk of Death

According to data released in 2018 by the CDC, 128 people die every day in the US because of opioid overdose. This is a significant advantage of using transdermal cannabinoid formulations (and all other delivery methods) instead of opioids. Opioids bind to opioid receptors in the cardio-respiratory and pulmonary systems in the brain stem and activates them which produces respiratory-depressing effects because of a lack of oxygen. There are no cannabinoid receptors in the brain regions which control these systems, so there is zero risk of a fatal overdose using cannabinoid therapy.

A zero risk of fatal overdose versus the launch of an epidemic is a powerful endorsement for the use of cannabis for local chronic pain management over opioids.

Jacquie Cohen Roth, MS is Founder/CEO of CannabizMD and Tea Pad. She is a member of the 2021 cohort of MS in Medical Cannabis Science and Therapeutics at the University of Maryland, School of Baltimore.


[1] National Academies of Sciences. The Health Effects of Cannabis and Cannabinoids. Washington, DC. 2017:87-90.

[2] Wedman-St. Louis B. Cannabis: A Clinician’s Guide. Boca Raton: Taylor & Francis Group, LLC; 2018:43.

[3] Natascia Bruni, Carlo Della Pepa, Simonetta Oliaro-Bosso, Enrica Pessione, Daniela Gastaldi, Franco Dosio. Molecules. 2018 Oct; 23(10): 2478. Published online 2018 Sep 27. doi: 10.3390/molecules23102478. Accessed May 3, 2020.

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