The cannabis plant contains a wide spectrum of fascinating medicinal compounds, with cannabinoids being the most notable. Another class of compounds, the terpenoids, have also attracted substantial attention in recent years. Unlike cannabinoids, which are almost exclusively associated with cannabis, terpenoids are found in thousands of other plants and contribute to their smells, colors, and tastes. Substantial research has revealed medical benefits associated with terpenoids, including the ability to heal wounds and protect against wound infections. With the rising incidence of antibiotic-resistant bacteria, new tools from the plant world will almost certainly be needed to combat them. It is important to note that terpenoids include simple terpenes, composed of just hydrogen and carbon, as well as modified terpenes that include additional functional groups (usually containing oxygen) in their chemical structures.
The Wound Healing Benefits of Beta-Caryophyllene
Beta-caryophyllene is one of the most prominent terpenes in cannabis and is also a prominent constituent of black pepper. It is notable for being able to activate the CB2 receptors and deliver anti-inflammatory effects. A 2019 study tested topical application of beta-caryophyllene on the skin wounds of mice, finding that the terpene enhanced re-epithelization. During this process, epithelial cells (which line surface of the body, including the skin) migrate towards the wound to repair it. There was also increased cell proliferation and upregulated gene expression for specific stem cells that facilitate wound healing.
The Wound Healing Benefits of Limonene
Limonene is an uplifting terpene that has a wide variety of medical benefits. In cannabis, it is one of the key terpenes that can help enhance energy and fight depression. It is also found in high quantities in lemons and may contribute to the classic lemon odor. Both limonene and another minor cannabis terpene, fenchone, were studied in a 2017 article for their wound healing properties. Researchers created excision wounds on rats and compared how the wounds healed when treated with limonene and/or fenchone versus a control group. By Day 6, contraction of wounds was greater in the limonene group than control group, and by Day 10, further wound contraction and re-epithelization was observed in both fenchone and limonene groups. The authors concluded, “The anti-inflammatory and antimicrobial activities of fenchone and limonene oil increased collagen synthesis and decreased the number of inflammatory cells during wound healing and may be useful for treating skin wounds.”
The Wound Healing Benefits of Linalool
Linalool is an exceptionally calming terpene found in cannabis as well as lavender. It is primarily associated with helping people relax and fall asleep, but emerging evidence suggests it can assist with wound healing as well. A 2017 study that incorporated linalool into a special wound dressing found that the terpene helped accelerate wound healing and enhance the formation of new connective tissue and blood vessels known as granulation tissue. Prevention of inflammation and scar formation was observed as well, along with strong antibacterial properties. While the nature of the study was not clear, it likely involved mice or rats, and clearly demonstrated the potential of linalool as a wound healing accelerant.
Another study published in 2020 examined linalool by itself and in its whole-plant form of lavender essential oil, finding that both possessed anti-psoriatic properties and could reduce inflammation. The authors noted that lavender oil has been traditionally used for wound healing as well. Specifically, linalool was found to reduce epidermal hyperplasia, where there is an overdevelopment of cells in the outer layer of skin; this effect likely contributes at least partially to linalool’s benefits.
The Wound Healing Benefits of Alpha-Bisabolol
Alpha-bisabolol is a terpene found predominantly in German chamomile and in reasonable quantities in many types of cannabis. It may possess anticancer properties and has been shown in two studies to assist with wound healing. A short article in 2001 pointed to alpha-bisabolol having wound healing properties, but a 2019 study which integrated the terpene into a complex delivery mechanism expanded on the mechanisms more deeply. Alpha-bisabolol treatment was associated with accelerated migration and proliferation of fibroblasts, which synthesize new supportive tissue, and enhanced wound closure compared to controls. Normal keratinization was also observed, which is the process by which the cytoplasm of certain epidermal cells is replaced by the structural protein keratin.
The effect of alpha-bisabolol combined with an oil enriched with ozone (which can have healing properties on its own) was tested in a 2015 clinical trial against chronic venous leg ulcers in 29 patients. The ozonated oil/alpha-bisabolol topical combination resulted in 25% of patients achieving complete ulcer healing, compared to 0% in the control group that used a cream containing vitamin A, vitamin E, talc, and zinc oxide. Wound healing continued to increase over time, with measurements at 7 days, 14 days, and 30 days showing progressive improvements. It appears that several patients without complete resolution still experienced significant healing, pointing to the efficacy of this treatment.
The Wound Healing Benefits of Geraniol
Geraniol is a terpenoid associated with rose oil and citronella oil; it is also an alcohol. A study conducted in 2018 discovered that geraniol was exceptionally potent in healing gastric ulcers induced by ethanol or acetic acid in mice. Geraniol functioned with ever greater potency than lemongrass essential oil. The effects were measured by contraction of the gastric ulcer and enhancement of mucin, a key component of mucus that protects against bacterial and fungal infections.
The Wound Healing Benefits of Nerolidol
Sedative strains of cannabis are often high in nerolidol, which is reported to have relaxing effects. It is found in a wide variety of other plants and flowers. A 2016 study combined nerolidol with chitosan, a polysaccharide with antibacterial properties derived from the shells of shrimp and other crustaceans, and examined antibacterial and wound healing effects. Direct contact tests revealed total inhibition of Staphylococcus aureus growth, and healing tests in an animal model showed enhanced re-epithelization and collagen reorganization. Since preventing bacterial infections is an important part of healing, this combination may be especially powerful.
The Wound Healing Benefits of Whole-Plants Rich in Cannabis-Associated Terpenes
Several studies have examined the wound healing benefits of whole-plant extracts with substantial concentrations of terpenes. Aspilia Africana is a flowering plant native to Africa that has traditionally been used for wound healing and even stopping substantial bleeding. It contains a wide variety of compounds, including the terpenes alpha-pinene, germacrene, carene, and beta-caryophyllene. A 2019 review study that summarized several rat studies found that A. Africana’s healing effects were connected to its abilities to speed wound contraction, reduce bleeding, increase the concentrations of growth factors, and stimulate both red and white blood cells. While it is impossible to attribute all of these effects to the terpenes, it is likely they played some role in these effects.
In Turkish folk medicine, the plant Pinus pinaster has been used for pain and wound healing. The essential oil from their pine cones, which is mainly comprised of alpha-pinene, has been shown in experimental studies to possess powerful anti-inflammatory and wound healing activities.
Another plant with alpha-pinene as the main constituent, Pistacia atlantica, was demonstrated in a 2013 study to improve development of blood vessels and growth factors associated with acceleration of burn wound healing in rats, although there was no significant difference between wound sizes in the control and treatment groups. There was a non-statistically-significant improvement, though, especially in groups treated with 5% and 10% extract concentration, with the 20% concentration actually being less effective. This demonstrates the importance of dosing when using plant extracts for medicinal purposes. The researchers suggested using different doses and longer treatment times in further studies.
Cymbopogon nardus is a plant whose leaves are used in Ayurvedic medicine for pain, inflammation, and microbial infections. Major terpene constituents associated with cannabis include geraniol and citronellol. To investigate objective efficacy on these measures, researchers tested the essential oil of C. nardus (EO-CN) on diabetic wounds of mice that were infected with the fungus Candida albicans. The treatment was effective in reducing the amount of C. albicans present in the wound, reducing inflammation, and accelerating wound healing. Researchers concluded, “This study suggests that through significant anti-Candida and anti-inflammatory activity, EO-CN attenuates the growth of the fungus on diabetic wounds and simultaneously reduces the inflammation which leads to acceleration of the wound healing process.”
The Effects of Non-Cannabis-Associated Terpenoids on Wound Healing
Other terpenoids not found in cannabis, or found in very low quantities, still have incredible benefits and may even possess some cannabinoid-like activity. For example, ursolic acid is a triterpenoid found in high levels in apples, which reportedly can bind to the CB1 receptor. Both ursolic acid and another triterpenoid, oleanolic acid (found in olive oil), have been shown to reduce the formation of advanced glycation end products (AGEs), which are implicated in impaired wound healing.
