Cannabis allergy

Cannabis is a plant of the family Cannabaecae, originally from central Asia and cultivated in all regions of the world. Cannabis refers to preparations derived from Cannabis sativa indica (Indian hemp); marijuana corresponds to dried flowers of the female plant and contains up to 25% THC (tetrahydrocannabinol) and hashish is a preparation of resin from the plant with a THC content of from 10% to 30%.

Cannabis has been used for recreational purposes for many decades, and for a few years for its medicinal value. About 4% of the world population use cannabis. In 2020 it was estimated that about 25% of Canadians have consumed cannabis.

An allergy to cannabis has been known for many years, first described in 1971, and is increasing in frequency. Allergic reactions may occur from inhalation, ingestion, skin contact with the cannabis plant or through intravenous injection. They may also occur in the form of occupational allergy in cannabis workers.

A cofactor can increase the severity of the allergic reaction from any allergen (food, medication, insect venom) and there is no reason to think this would be different with cannabis: cofactors include alcohol, the use of NSAIDS, exercise in the hours preceding exposition, and the premenstrual period.

Reactions occur most commonly after direct exposure, but they have also been reported after passive exposure. More than 80% of patients allergic to cannabis have a sensitization to pollens, particularly to birch tree pollen, and to several fruits and vegetables.

 

 

An allergy to cannabis can present:

• as an immediate, IgE mediated reaction (the most common):
• repiratory: rhinoconjunctivitis and asthma
• cutaneous: contact urticaria, hives and angioedema
• gastrointestinal: oral allergy syndrome, nausea, vomiting, diarrhea
• systemic: anaphylaxis
• as a delayed reaction (rarely):
• contact dermatitis

 

Sensitization to cannabis usually occurs after direct contact (smoking, handling, or ingesting cannabis). Passive sensitization (breathing in the smoke of others) has also been described, recently in a 5 year-old child. The major allergen of cannabis es the nsLTP (non specific lipid transfert protein), and other principal allergens are profilin, OEEP2 (oxygen evolving enhancer protein 2) and PR10 (pathogenesis related protein 10) ; there are other allergenic molecules in cannabis that have been less well studied.

A cannabis allergy is often associated with other allergies through cross-reactions to the principal allergen, nsLTP that is found in several vegetables. European authors have coined the term to describe this cross reaction as the "cannabis-fruit and vegetable syndrome", which describes the observation that people allergic to cannabis often subsequently develop an allergy to fruits and vegetables. nsLTP, which is found in certain fruits, vegetables, legumes, other plants and grains, is responsible for sometimes severe food allergies. This type of allergy is more frequent in southern Europe. This protein of vegetable origin is a powerful allergen. It is resistant to heat and to digestive enzymes, which explains its toxicity. The principal fruits and vegetables associated with this cross reaction are: kiwi, bananas, peaches, apples, cherries, peanuts, certain nuts, potatoes, tomatoes and occasional citrus fruits, certain grains, certain alcoholic drinks (beer and wine) and latex. Additional cross reactions have also been seen with hemp (hemp seed) and tobacco.

Diagnostic tests

It is possible to perform percutaneous prick tests using a part of the plant (flower, stem, leaf or extracts): however these tests have not been standardized and false positive and false negatives are both possible. Tests for specific antibodies (specific IgE) are not yet commercially available. Tests incorporating basophil activation could be useful but are not available commercially. With the legalization of marijuana, it is conceivable that provocation tests or challenges become possible clinically.

Treatment

Primary prevention, that is to say, avoiding exposure to cannabis, will prevent sensitization.

Once allergic, all forms of exposure should be avoided, and an epinephrine autoinjector should be carried in case of a systemic reaction after accidental exposure. One should also avoid those foods to which one has become allergic through cross reactions.

Eventually, immunotherapy may become a valid treatment option for this allergy.

References

1. Liskow B, Liss JL, Parker CW. Allergy to marihuana. Ann Internal Med 1971;75(4):571–573.
2. Majmudar V, Azam NA, Finch T. Contact urticaria to Cannabis sativa. Contact Dermatitis 2006;54(2):127.
3. Dutau G, Rancé F. Historique et description des principales allergies croisées. Rev Fr Allergol 2009;49:180–188.
4. Anselme A, Metz-Favre C, de Blay F. Allergie aux stupéfiants. Rev Fr Allergol 2011;51(6):548–552.
5. Van Gasse AL, Sabato V, Bridts CH, Ebo DG. L’allergie au cannabis : bien plus qu’un voyage stupéfiant. Rev Fr Allergol 2014;54:144–147.
6. Decuyper II, Van Gasse AL, Faber MA, Hagendorens, MM, Sabato V, Bridts CH, et al. Syndrome cannabis-fruits et légumes : une mise au point. Rev Fr Allergol 2015;55:480-482.
7. Decuyper II, Rickebosch H, Van Gasse AL, Sabato V, Faber M, Bridts CH, et al. Cannabis allergy: what do we know anno 2015. Arch Immunol Ther Exp 2015;63:327-332.
8. Fontaine J-F. Les protéines de transfert lipidique : actualités et implications cliniques. Rev Fr Allergol 2015;55:176-177.
9. Omidi A, Sauvage C, Vandezande LM, Wallaert B. La LTP du cannabis : une voie de sensibilisation aux LTP alimentaires. Rev Fr Allergol 2015;55:501-505.
10. Decuyper II, Faber MA, Sabato V, Bridts CH, Hagendorens MM, Rihs H-P, et al. Where there’s smoke, there’s fire: cannabis allergy through passive exposure. J Allergy Clin Immunol Pract 2016;5(3):864-865.
11. Decuyper II, Van Gasse AL, Faber MA, Elst J, Mertens C, Rihs H-P, et al. Exploring the diagnosis and profile of cannabis allergy. J Allergy Clin Immunol Pract 2019;7(3):783-789.
12. Alkhammash S, Tsui H, Thomson DMP. Cannabis and hemp seed allergy. J Allergy Clin Immunol Pract 2019;7(7):2429-2430. e1.
13. Skypala IJ, Jeimy S, Brucker H, Nayak AP, Decuyper II, Bernstein JA, et al. Cannabis-related allergies: an international overview and consensus recommendations. Allergy 2022;77(7):2038-2052.
14. Toscano A, Ebo DG, Abbas K, Brucker H, Decuyper II, Naimi D, et al. A review of cannabis allergy in the early days of legislation. Ann Allergy Asthma Immunol 2023;130(3):288-295.

__________________________

André Caron, MD FRCPC, allergologue et immunologue
(translation: Andrew Moore, MD FRCPC)

Updated 10/2024