Marijuana (Cannabis)

Topical Use of Marijuana

Medications designed to be applied topically to the skin for therapeutic purposes are generally referred to as “topicals.” Technically, however, topically applied medications may be either  “transdermal” or “topical.” The distinction is quite important and determines the therapeutic effectiveness of the product.

 

Transdermal vs Topical

Transdermal medications are designed to penetrate the skin barrier in order to provide systemic (whole body) benefits. By penetrating through the epidermis, the topmost layers of the skin, and into the underlying dermis layer where the blood vessels are, transdermal products are transported through the blood to the organs and especially the central nervous system including the spinal cord and brain where cannabinoids provide therapeutic benefits.

Topical formulations, on the other hand, refers to creams, lotions, ointments, and other products designed to be massaged into the epidermis only. These products target the skin itself to provide benefits only locally to the area of application. They don’t carry cannabinoids into the blood vessels of the derma below and therefore are not meant to enter systemic circulation.

 

Links to other Pertinent Educational Pages:

Links to ALL Marijuana Educational Pages

LA Marijuana Products – Topicals

 

 

See also:

Cannabidiol (CBD)

Terpenes – An Overview

Terpenes – β-Caryophyllene

Terpenes – Linalool

 

The medical information on this site is provided as a resource for information only, and is not to be used or relied upon for any diagnostic or treatment purposes and is not intended to create any patient-physician relationship.  Readers are advised to seek professional guidance regarding the diagnosis and treatment of their medical concerns.

 

Key to Links:

Grey text – handout

Red text – another page on this website

Blue text – Journal publication

 

This page is incomplete and continues to be developed…

 

 

Marijuana Products – Topically Applied

There are multiple ways to use cannabis medically. Most attention has been directed at the three most common methods of use: inhalation via smoking, inhalation via vaporization (vaping), and ingestion of edible products. Each method can impact the onset, intensity, and duration of its effects, including psychoactive effects, effects on organ systems, and the addictive potential and side effects associated with use. However, there is growing interest and knowledge regarding the topical use of cannabis-based products and their therapeutic benefits.

 

Unfortunately, as with so much of our knowledge regarding medicinal use of marijuana and its constituents, there is little research to guide us with respect to using topically applied cannabis-based products.

 

Popularity

In the past several years, there has been a large surge in the availability and demand of topical marijuana products, mostly cannabidiol (CBD)-based for medical uses, including for pain, itching (pruritus), and general skincare. While over-the-counter (OTC) CBD-based products are the most commonly used due to greater availability and less expense, there is growing use of topical products that also include significant amounts of THC which require special physician recomendations. In LA, there are currently four topical formulations containing THC.

See: LA Marijuana Products – Topicals

 

Topical Applications – Safety

In general, the use of topical cannabis-based products is safe, although caveats apply. A common obstacle to the use of commercially available over-the-counter (OTC) products, especially CBD, is the lack of oversight FDA regulation. There are no standardization processes to ensure that commercially available CBD/hemp oil products are appropriately sourced or prepared.

 

Studies assessing commercial OTC CBD products, including oral and topical products, have revealed that the labels are more often than not inaccurate, usually identifying significantly less presence of CBD, but sometimes more. The use of “trusted brands” is encouraged and more importantly, “certificates of analysis (COA)” should be reviewed to confirm accuracy of labeling. These COAs should be available from the website or manufacturer. Some have recommended purchasing quality CBD/hemp oil products imported from Europe over those made in the United States due to stricter regulations. However , a recent study also evaluated European OTC CBD products and found the poor quality control.

 

Topically Applied CBD Safety

Although rigorous safety studies for transdermal CBD are lacking, data on adverse effects can be inferred from studies evaluating oral CBD treatment..These studies demonstrate CBD at doses exceeding 300 mg daily can be used safely for for at least six months.

 

Cannabinoid Allergies

Cannabinoids do not appear to be highly allergenic or likely to create a contact allergy.  In fact, they might actually be helpful in reducing allergic contact dermatitis. However, the final products may contain contact allergens
or irritants in the other ingrediets and potentially aggravate dermatitis, reinforcing the need for appropriate labeling of these products.

 

THC in CBD Products

Of particular importance for patients using topical CBD products is possible contamination with THC. Due to the laws and mandated drug testing by individual organizations, a positive drug screen from an OTC product labeled “THC Free” could be disastrous and, unfortunately, this has happened. As OTC products remain unregulated and widely available, it is difficult to definitively answer for the safety of testing for THC across commercial CBD products, especially orally ingested or vaped products. Caution is advised when purchasing any OTC product and product labels should not be relied upon.

Fortunately, CBD has low cross-reactivity (<0.1%) in most THC drug testing, although no studies are available to pinpoint individual product testing. Unlike oral ingestion of CBD products, topical CBD products are highly unlikely to contribute to a positive drug screen for THC due to poor systemic absorption o topically applied THD.

 

Transdermal Use – Cannabinoids

Cannabinoids are lipophilic, meaning they absorb well into fat but not water and as a result, they doesn’t mix well with the skin due to the high levels of water in the skin. Therefore they will not penetrate to the dermis without modification or inclusion of absorption enhancers. Different enhancers include liposomal, polymeric and nano-particle delivery systems, many variations of which are being explored by researchers. Of particular interest is that a number of terpenes have also been identified that can act as skin penetration enhancers for both CBD and THC.

 

Transdermal THC

Transdermal THC patches are now hitting the market, although not legal yet in LA., and are infused with THC and applied to the body. Small amounts of THC are released from the patch and penetrate through skin and into the small blood vessels in the deeper layers of skin.

 

Because of the limited, slow absorption over a number of hours rather than all at once, it is purported that there are fewer side effects without the intense psychoactive high one gets with smoking or vaping. There may be less paranoia as can be seen with other forms of THC administration and less appetite spiking “munchies.” THC patches can be worn all-day or all-night to provide relief to those suffering from chronic issues like pain and anxiety.

 

A major advantage to the use of transdermal THC patches is that the THC is absorbed directly into the blood and transported to the brain and throughout the body. This method of delivery bypasses the lungs, liver, and stomach, thus avoiding metabolic breakdown before reaching the brain. When THC is taken orally it is metabolized in the gut then the liver where a large proportion of it is metabolized into 11-hydoxy THC, which has a different and possibly more powerful psychoactive effect compared with THC. Furthermore, 11-hydoxy THC may not provide the same therapeutic benefits such as pain relief as does THC.

See: THC Pharmacokinetics & Marijuana (Cannabis) – Oral Use (Edibles)

 

The patches may be designed as a matrix patch, where the THC is infused into the matrix of the patch along with absorption enhancers and when applied to the skin, the THC penetrates to the deep layers of  the skin. Another alternative is a reservoir patch that contains a reservoir within the patch which holds the THC in solution or gel and releases it through a rate-controlling membrane between the reservoir, the adhesive, and your skin.

Current Topically applied, THC-Based Products in LA
Currently, topically applied Ilera brand topical products available with THC from the LA pharmacies do NOT contain enhancers and therefore are believed not to be  transdermal or systemically effective. The topically applied Wellcana brand (Good Day Farm) products may contain enhancers but their effectiveness has not been confirmed.

 

Transdermal CBD

Transdermal CBD with enhancing agents offers a promising delivery route for CBD, but simply standardizing the amount of CBD in a topical product might not be a valid indicator of the final bioavailability which depends on the product and enhancer employed. Furthermore, the over-the-counter commercial market is not regulated with any production oversight. Studies have found that when tested, current oral formulations on the open market, the product labeling has been found to be significantly inaccurate as to how much CBD is actually present, with more than half of tested products containing markedly less than advertised. This same problem is likely to occur with transdermal preparations as well.

See: CBD Pharmacokinetics

 

 

Topical Use – Cannabinoids

Benefits and Effectiveness

Neuropathic Pain

Both THC and CBD have evidence of benefit for neuropathic (nerve) pain when taken orally or inhaled. Therefore topical application of these cannabinoids would appear likely to offer benefit. However, there remains a lack of research at this time to confirm this expectation.

 

Chemotherapy-Induced Peripheral Neuropathy (CIPN)

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose- and age-dependent side effect associated with the main antitumor drug classes. CIPN prevalence averages 68% in the first month after finishing chemotherapy and 60% at 3 months and 30% after 6 months or more. Symptoms described by CIPN patients are generally described as burning and tingling pain in the hands and feet along with hyperalgesia (hypersensitivity to painful stimuli) and allodynia (experiencing pain with stimuli that are not normally painful.

CIPN is challenging to treat since most neuropathic pain medications such as tricyclic antidepressants (Elavil/amitriptylene), anticonvulsants (Neurontin/gabapentin and Lyrica/pregabalin), or serotonin-norepinephrine reuptake inhibitors (SNRIs, primarily Cymbalta/duloxetine) provide only limited benefit for most patients and they may have significant side effects.

The mechanism of CIPN injury largely involves the production of nerve toxicity and inflammation. These chemotherapy agents cause damage to peripheral sensory, motor and autonomic neurons, via  DNA damage, altered ion channel activity, myelin sheath damage, oxidative stress and mitochondrial damage. In addition, this damage leads to increased activation of the immune system which contributes to cell damage and death in peripheral nerves and peripheral sensitization. While both the mechanisms and their ultimate damage to nerves is different from other peripheral neuropathies such as diabetic neuropathy and CRPS, there may be enough overlap to suggest possible extrapolation to the treatment of these other peripheral neuropathies.

In an informal study published in 2021, cancer patients with CIPN were interviewed regarding their use of topical cannabis-based products. Patients were specifically asked by about the type of products, duration of response, and any side effects. In some cases, creams contained only CBD and were derived from hemp, with 0.3% or less of THC. The other creams mostly contained between 120-600 mg CBD per unit (tube or jar)  and 6-600 mg THC per unit. Additionally, some of the creams contained other ingredients reported to increase skin absorption, such as essential oils. Unfortunately, information was lacking regarding their use of transdermal vs topical formulations, specific dosing, presence or absence of terpenes etc. That being said, it is likely the majority of the preparations were topical, not transermal.

 

Examples of some individual’s responses include:

  • A 49 y/o male who had been using oral cannabis for years for arthritis pains/sleep, but it had no effect on his CIPN. He started using a CBD cream (250 mg/jar) 1 to 2 times per day and reported significant improvement in his neuropathic pain. His cream contained essential oils and ingredients that may have enhanced skin penetration. He rated his baseline pain at 7 to 10 which diminished to 4-5/10 within 5 minutes of applying the cream. He reported that the benefit lasted all night with no side effects except a slight feeling of heat upon applying the cream.
  • A 65-year-old male who developed CIPN after chemotherapy who’s baseline neuropathy was rated as 6/10 in his feet and hands. He reported using a cream containing approximately 600 mg CBD and 600 mg THC per jar with essential oils to aid in absorption.  His symptoms improved to 4/10 after application within a few days and benefits lasted most of the day with no adverse effects.
  • A 71-year-old female who developed painful CIPN after chemotherapy, rated at 7/10. She reported using a CBD cream (250mg/jar) containing essential oils that reduced pain to 3/10 within minutes, and lasted about 12 hours with no side effects.. This cream contains essential oils and other ingredients to enhance skin absorption. She uses the cream daily with no side effects.
  • A 59-year-old male with severe CIPN in his feet and hands who rated his pain at 10/10 baseline. He used a cream with 200 mg CBD/jar  only and reported improvement  after about 30 minutes which lasted about 3 hours, without any side effects.

    Most of the patients reported benefit described as a partial decrease in painful CIPN symptoms with onset of  benefit in about 10 to 15 minutes and lasted a few hours up to 24 hours. A minority of patients using topical products did not find any benefit while only 1 patient reported a side effect of transient worsening of neuropathic pain that returned to baseline after discontinuing the topical cream.

     

Topical Use – Terpenes

Terpenes may serve two functions when applied topically: they may provide an enhanced carrier function to other constituents with which they are applied, including CBD. Additionally, some terpenes offer their own therapeutic benefits, particularly β-caryophyllene.

 

 Topical β-caryophyllene

 Topical Myrcene

Topical Linalool

 

 

 

 

 

Resources:

National Academy of Sciences

The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research

 

www.Healer.com

This website appears to be good resource for exploring medical marijuana.

 

References:

Medical Marijuana – Prescribing Guidelines

  1. Simplified guideline for prescribing medical cannabinoids in primary care – Canadian Family Physician – 2018
  2. Physician Recommendation of Medical Cannabis Guidelines Calif Medical Assoc – 2011
  3. Prescribing smoked cannabis for chronic noncancer pain. Preliminary recommendationsCanadian Family Physician – 2014

 

Medical Marijuana – Topical Use

  1. Safety and Sourcing of Topical Cannabinoids – Many Questions, Few Answers – 2021
  2. Tolerability profile of topical cannabidiol and palmitoylethanolamide a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin – PubMed – 2021
  3. Cannabinoid Signaling in the Skin – Therapeutic Potential of the “C(ut)annabinoid” System – 2019 
  4. Topical Cannabinoids for Treating Chemotherapy-Induced Neuropathy – A Case Series – 2021

 

Topical Cannabinoids

CBD – Topical Use

  1. Tolerability profile of topical cannabidiol and palmitoylethanolamide a compilation of single-centre randomized evaluator-blinded clinical and in vitro studies in normal skin – PubMed – 2021

 

CBD – Quality Control

  1. Safety and Sourcing of Topical Cannabinoids – Many Questions, Few Answers – 2021
  2. Quality Traits of “Cannabidiol Oils” – Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations – 2018
  3. Analysis of Cannabidiol, Δ9-Tetrahydrocannabinol, and Their Acids in CBD Oil:Hemp Oil Products – 2020

 

Topical Terpenes

Terpenes – Routes of Use:

  1. The Effects of Essential Oils and Terpenes in Relation to Their Routes of Intake and Application – 2020
  2. Antiviral effect of phytochemicals from medicinal plants – Applications and drug delivery strategies – 2020
  3. Cannabinoid Delivery Systems for Pain and Inflammation Treatment – 2018

 

Terpenes – CB2 Receptor

  1. Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain – an updated review – 2021
  2. β-Caryophyllene, a CB2 receptor agonist produces multiple behavioral changes relevant to anxiety and depression in mice – 2014
  3. The CB2 receptor and its role as a regulator of inflammation – 2016
  4. Cannabinoid CB2 Receptors Regulate Central Sensitization and Pain Responses Associated with Osteoarthritis of the Knee Joint

 

Topical Terpenes – Wound Healing:

  1. Beta-caryophyllene enhances wound healing through multiple routes – 2019

 

Topical Terpenes – Individual Terpenes

Topical β-Caryophyllene

  1. Beta-caryophyllene enhances wound healing through multiple routes – 2019

 

 

 

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