Accurate Education - Marijuana (Cannabis): Topical Use of Marijuana

Marijuana (Cannabis)

Topical Use of Marijuana-Based Products (Cannabinoids & Terpenes)

The use of marijuana derivatives topically on the skin is being explored commercially and by the research community. While the research is lacking for definitive answers regarding their effectiveness, the cannabinoids CBD and THC are thought to potentially offer benefits for multiple conditions. Additionally, other compounds found in marijuana including terpenes are also gaining attention for their benefit (See: Terpenes).

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.

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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, addictive potential and side effects associated with use. However, there is growing interest 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.

Cannabis-Based Topicals

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 pain, itching (pruritus), and general skin care. 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 recommendations. In LA, there are currently four topical formulations containing THC.

See: LA Marijuana Products – Topicals

Topical Cannabis 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 ingredients 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 of topically applied THD.

Transdermal Use – Cannabinoids

Cannabinoids are lipophilic, meaning they absorb well into fat but not water and as a result, they don’t mix well with the skin due to the high levels of water in the skin. Therefore they will not penetrate to the deeper dermis level 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 including less intense psychoactive effects than what one gets with smoking or vaping. There also 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.

Topical CBD

CBD has the ability to modulate the skin inflammatory response which provides benefit in the treatment of several dermatological conditions, including psoriasis, atopic dermatitis, acne.and scar formation. A recent study found that more than 70% of dermatologists consider recommending topical CBD in their practice.

Topical CBD has shown benefit in symptomatic arthritis, peripheral neuropathy of the lower extremities and following total knee arthroplasty (replacement), but with some mixed results.

Arthritis

Topical application of CBD products for management of arthritis swelling and pain has been shown to be beneficial. Animal studies have identified the reduction of pro-inflammatory markers, ]joint swelling, and immune infiltration in a rat model of arthritis. Despite the growing prevalence of using CBD for joint pain, there is scant, well-vetted research on its tolerability and efficacy in humans.

Thumb Joint Arthritis

A 2022 study monitored 18 participants with symptomatic thumb basal joint arthritis treated for 2 weeks of twice-daily treatment with Cannabidiol (CBD, 6.2 mg/ml with shea butter) or shea butter alone as a control.The study concluded that topical CBD treatment demonstrated significant improvements in thumb basal joint arthritis-related pain and disability without adverse events.

Hip and Knee Joint Arthritis (Osteoarthritis – OA)

A 2021 study evaluating 200 patients with hip and knee joint arthritis (80 hip OA, 108 knee OA, and 12 both), 66% were female, and average age was 67 years (range 36 to 89 years). Of these patients, 24% (48/200) of endorsed use of CBD products. Sixty percent of these patients learned about CBD through friends, and 67% purchased CBD directly from a dispensary. Oral tinctures (43%) and topical applications (36%) were the most commonly used forms. While there was a 24% incidence of CBD use among these patients with hip or knee OA, no significant perceived benefit of CBD use seemed to exist compared with its nonuse, as patients who used CBD reported significantly worse pain scores than nonusers. While at a glance this study suggest a lack if benefit withe the use of CBD for hip or knee arthritis, this findings also suggests that the patients taking CBD may have had more symptomatic OA or they were more prone to self-medicating.

Neuropathic Pain

A 2020 four-week, randomized and placebo controlled crossover study evaluated the effectiveness of a topical CBD oil in the management of neuropathic pain. A total of 29 patients including 62.1% males and 37.9% females with a mean age of 68 years with symptomatic peripheral neuropathy were treated with a product containing 250 mg CBD/3 fl. oz. There was a statistically significant reduction in intense pain, sharp pain, cold and itchy sensations in the CBD group when compared to the placebo group. No adverse events were reported in this study.

Chronic Lower Extremity Pain in Athletes

A 2023 study evaluated 20 former professional athletes (football, track and field, and basketball) with careers ranging from 4 to 10 years who suffered with chronic lower extremity pain resulting from lower extremity injuries. Participants received topical CBD (10 mg twice daily and were assessed for pain, pain-related disability, and activities of daily living over a 6-week study period.

50% of the study participants reported no adverse effects and 50% reported minor adverse effects. The mostly commonly reported adverse effects were skin dryness (43%) and skin rash (21%), which rapidly resolved without the need for hospitalization or other medical care.

There was a significant improvement in self-reported pain levels and pain-related disability, including family and home responsibilities, life support activities, occupational activities, recreational activities, self-care, sexual function, and social activities. Unfortunately the study did not report any specifics regarding the pain diagnoses but one can assume the conditions were largely muscle and joint pain

CBD Synergy

CBD has been shown to interact with other compounds including other cannabinoids, terpenes and certain antibiotics resulting in benefits that are greater than the simple sum of their individual benefits, something called “synergy.” This has been demonstrated with THC, BCP (beta-caryophylline) and PEA (palmitoylethanolamide) in the management of pain.

See: Topical Medications for Pains: Synergy and Synergy between CBD and PEA

Topical CBD has also been shown to act synergistically with bacitracin against Staphylococcus aureus and other Gram-positive bacteria, suggesting potential for treatment of skin infections.

CBD Enhancers

The effectiveness of a topically applied agent will depend largely on the ability of the agent to permeate the skin and its subsequent retention in the skin. A recent study evaluating the use of agents to enhance skin permeability and retention concluded that the use of a hydrophilic gel consisting of propylene glycol (79%, w/w), may be the optimal choice for the topical administration of CBD.

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 Uses of Mixed 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 generally described by CIPN patients are 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 traditional neuropathic pain medications (including 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 is largely due to 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. Specific concentrations were not available. 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.

Dermatology and Topical Cannabinoids

Dermatologic Effects of CBD

With the caveat that these effects require additional study to confirm, the following beneficial effects have been proposed:

Acne & seborrhea
Hypopigmentation
Epidermolysis bullosa
Allergic inflammation
Certain hair growth disorders

Skin and the Endocannabinoid System (ECS)

Impact of Activating the CB1 Receptor

Activation of the CB1 receptor can be done by direct or indirect action on the receptor. Direct stimulation of the CB1 receptor appears to be mostly limited to THC, whereas CBD may indirectly impact the CB1 receptor (for example, by slowing the breakdown of c0mpounds that activate CB1 including endocannabinoids). As one can see below, proposed benefits often have opposite effects identified. The nature of the ECS is that the receptors can often engage opposing effects because their effects are dependent on the context of the activity which is modified by many other variables that cannot be accurately determined at this time.

The following impacts on the skin from the CB1 receptor include:

Beneficial Effects:

- Anti-fibrotic effects
- Desired hair growth ↑
- Unwanted hair growth ↓
- Alleviation of sunburn
- Anti-tumor effects (?)
- Pigmentation ↑/↓ (?) Pigmentation ↑/↓ (?)
- Delayed barrier recovery Unwanted hair growth ↑
- Anti-pruritic effects (Itch)
- Anti-inflammatory effects
- Anti-tumor effects
- Barrier recovery ↑

Detrimental Effects:

- Pigmentation ↑/↓ (?)
- Delayed barrier recovery
- Unwanted hair growth ↑
- Unwanted hair loss ↑
- Itch ↑
- Fibrosis

Impact of Activating the CB2 Receptor

As with the CB1 receptor, activation of the CB2 receptor can be done by direct or indirect action on the receptor. THC and beta-caryophylline (BCP) act directly on the CB2 receptor to stimulate its activity, while other compounds such as NSAIDs and palmitoylethanolamide (PEA) may indirectly affect CB2 activity again by suppressing the breakdown of compounds that stimulate the CB2 rcceptor.

The following impacts on the skin from the CB2 receptor include:

Beneficial Effects:

- Anti-acne/Anti-seborrhea
- Accelerated barrier recovery
- Alleviation of sunburn
- Anti-pruritic (itch) effects (?)
- Skin dryness↓
- Anti-fibrotic Anti-inflammatory
- Anti-tumor effects

Detrimental Effects:

- Unknown

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.

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

Medical Marijuana – Topical Use

Topical Cannabinoids

CBD – Topical Use

Topical Medications – Formulations

Topical Analgesics – Critical Issues Related to Formulation and Concentration – 2016

Topical Medications – Analgesics

CBD – Quality Control

Topical Terpenes

Terpenes – Routes of Use:

Terpenes – CB2 Receptor

Topical Terpenes – Wound Healing:

Beta-caryophyllene enhances wound healing through multiple routes – 2019

Topical Terpenes – Individual Terpenes

Topical β-Caryophyllene

Beta-caryophyllene enhances wound healing through multiple routes – 2019

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Accurate Education – Marijuana (Cannabis): Topical Use of Marijuana