Cannabis Allergies:

Why terpenes may be the cause

Contact allergy is a condition that can be caused by many different chemicals following skin exposure. Repeated contact with a chemical can lead to the clinical manifestation known as allergic contact dermatitis (ACD). To develop ACD, skin sensitizers, which are generally reactive chemicals, modify proteins in the skin, thereby rendering them immunogenic. To cause sensitization, a chemical needs to bind the macromolecules in the skin and change them, such that our immune system suddenly perceives them as foreign and dangerous. [1]

However, some known allergens do not exhibit this effect. They are innocuous on their own, and after exposure, don’t seem to be reactive at all. Instead of directly modifying the skin, they seem to require some external factor to become activated—only then entering a reactive state where they exert their allergenic effect. These compounds are called prohaptens—or skin sensitizers that must be chemically modified before they become allergic. And they can become activated in the skin by host enzyme activity, or even before skin contact by chemical reactions in the air. [2]

Cannabis allergies (CA) are becoming an increasingly common occurrence as the industry grows and more people begin to have regular, long-term exposure to the cannabis plant. The majority of research into CA has focused on specific plant proteins which our bodies can become sensitized to. [3] However, this does not fully explain why similar symptoms can develop during the use of extracts and concentrates which don’t contain those implicated proteins. An important source of allergens that should therefore be explored is cannabis-derived terpenes.

In the world of clinical immunology, fragrance terpenes belong in the category of prohaptens. Cosmetics research has identified over a hundred individual ingredients in substances and extracts which “must be considered contact allergens, and the presence of which should be declared in cosmetics.” [4]

One major cause of haptenization is the oxidation of the terpene in air. [5] Linalool is a major constituent of cannabis and can be a very weak allergen, if an allergic reaction occurs at all. However, linalool autoxidizes on air exposure, and the oxidation products can cause contact allergy. If a person who develops an allergy to these byproducts inhales linalool via concentrates, a strong anaphylaxis, or systemic allergic reaction which includes the familiar symptoms of hyperventilation, hives, and itchiness, can likewise occur. [6]

It’s becoming increasingly clear that people who are exhibiting symptoms of dermatitis or ACD as a result of cannabis use should get tested for an allergy to terpenes. This is important because studies have shown very little cross-reactivity between terpene allergies. [7] That may mean, generally speaking, that an allergy can come down to a specific sensitization to a single terpene.

If you can figure out the one terpene you are sensitive to, and cut it out of your “diet”, then you may be able to resume the habit that is causing you so much grief now!

References

Karlberg, A.T., et al. “Allergic contact dermatitis–formation, structural requirements, and reactivity of skin sensitizers”. Chem Res Toxicol. 2008; 21(1): 53-69 [Times cited = 231, Journal impact factor = 3.278].
Natsch, Andreas and Haupt, Tina. “Utility of Rat Liver S9 Fractions to Study Skin-Sensitizing Prohaptens in a Modified KeratinoSens Assay”. Tox Sci. 2013; 135(2): 356–368 [Times cited = 27, Journal impact factor = 4.081].
Decuyper, Ine I., et al. “Exploring the Diagnosis and Profile of Cannabis Allergy”. J Allergy Clin Immunol Pract. 2019; 7(3): 983-989.e5. [Times cited = 2, Journal impact factor = 6.966].
Uter, W. “Contact allergy to fragrances: current clinical and regulatory trends”. Allergol Select. 2017 Aug 4;1(2):190-199 [Times cited = 2, Journal impact factor = N/A].
Hagvall, L., et al. “Fragrance compound geraniol forms contact allergens on air exposure. Identification and quantification of oxidation products and effect on skin sensitization”. Chem Res Toxicol. 2007; 20(5): 807-14 [Times cited = 117, Journal impact factor = 3.278].
Christensson, J.B., et al. “Linalool–a significant contact sensitizer after air exposure”. Contact Dermatitis. 2010 Jan;62(1):32-41 [Times cited = 75, Journal impact factor = 4.275.
Christensson, J.B., et al. “Oxidized limonene and oxidized linalool – concomitant contact allergy to common fragrance terpenes”. Contact Dermatitis. 2016 May;74(5):273-80 [Times cited = 27, Journal impact factor = 4.275].