How Do You Diagnose and Treat Cannabis Allergies?

As medicinal and recreational cannabis become legal and more popular in more places, clinicians need to learn how to diagnose and manage cannabis allergies, an international overview and consensus document recommends.

Allergic reactions to cannabis include rhinitis, conjunctivitis, asthma, skin reactions, and anaphylaxis to hemp seed. Exposure can come from smoking, eating, inhaling cannabis pollen or smoke, and contact with skin, and includes occupational allergies.

"Cannabis can provoke both type 1 and type 4 allergic reactions. Officially recognized allergens include a pathogenesis-related class 10 allergen, profilin, and a nonspecific lipid transfer protein," lead author Isabel J. Skypala, PhD, RD, of Imperial College London, London, United Kingdom, and her colleagues write in Allergy.

"Cannabis is the most widely used recreational drug in the world. Cannabis sativa and Cannabis indica have been selectively bred to develop their psychoactive properties. The increasing use in many countries has been accelerated by the COVID-19 pandemic," they add.

Diagnosing Cannabis Allergy Is Difficult

Roughly 192 million people — 3.9% of the world's population — use medical or recreational Cannabis sativa (Can s), but its illegality has hampered research and posed diagnostic challenges.

Clinical history is the most important test for immunoglobulin E (IgE)-dependent cannabis allergy, but patients may not admit using cannabis illegally. The authors recommend creating a standardized intake form with cannabis-related questions.

No commercial extracts are available for clinical testing, so unstandardized prick-prick tests with cannabis buds, leaves, or seeds may be the only option, if available. But cross-reactivity in patients sensitive to pollen and plant foods may make positive prick-prick results clinically insignificant.

Although skin-prick tests using pre-prepared cannabis extracts can be better standardized and designed to concentrate known allergen components, they may not be available in clinics, and — as with prick-prick tests — patient sensitization may affect results. No commercial specific IgE (sIgE) antibody tests for Cannabis sativa or Cannabis indica are available for clinical use.

The authors recommend initial testing with skin-prick tests using a native extract and/or quantification of sIgE hemp, and, if needed, calculating the sIgE/total IgE ratio, molecular diagnostics and/or basophil activation test or passive mast cell activation test, if available. Negative results indicate that cannabis allergy is very unlikely.

They do not advise provocation challenge with inhaled cannabis, due to possible legal issues and the risk for inhaled cannabis fumes triggering nonspecific hyperresponsiveness while not confirming allergy. And the reliability of oral challenges to edible cannabis products or hemp seed and sensitization to other allergens including molds, pollens, and foods is unknown.

Continuing Education and Research Are Needed

Cannabis allergy may become a significant public health issue, the authors write. More real-world data are needed, testing and treatment protocols need to be developed, and providers need to learn how to communicate with their patients so they can provide optimal care.

The paper on cannabis allergy is an early step. To help educate healthcare professionals and foster future research about cannabis allergies, members of the American College of Asthma Allergy and Immunology (ACAAI), the European Academy of Allergy and Clinical Immunology (EAACI), and the Canadian Society of Allergy and Clinical Immunology (CSACI) have formed the Cannabis Allergy Interest Group (CAIG).

To collect more real-world data, the CAIG plans to establish a registry and biobank to collect samples from Europe, the United States, and Canada, and develop international guidelines on cannabis allergy diagnosis and management. The group is also conducting a survey from the membership of its three societies about knowledge, attitudes, and practices related to cannabis allergy.

Tailoring Treatment to Patient Goals

The only current treatment for cannabis allergy is avoidance, and when that's not possible, as with occupational exposure, the authors recommend treating the symptoms with antihistamines, intranasal and inhaled corticosteroids, ophthalmic antihistamine/mast cell stabilizers, or auto-injectable epinephrine.

Dr David Lo

David Lo, MD, PhD, senior associate dean for research and distinguished professor in the Division of Biomedical Sciences at the University of California, Riverside School of Medicine, told Medscape Medical News that allergies can occur to nearly any organic materials, including those that are plant-based, as in the case of food allergies.

"Most people do not develop allergies to these things, but when they do, it is usually to some protein or fragment in the material," he said in an email.

"Allergies to plant extracts from plants such as cannabis can be avoided, if the main goal is to deliver an active ingredient such as THC or related compounds," Lo, who was not involved in developing the consensus document, explained. "In that case, a more highly purified — or even better, a synthetic version — would be used, so the protein that is the target of the allergy would be absent."

"On the other hand, if the goal is to deliver an extract where the active component is known to be a protein or fragment of protein, then the problem is more difficult, and it might be necessary to synthesize a recombinant protein that does not have the allergen in it," he added.

Extreme purification from crude plant material is possible but often difficult to accomplish, Lo said.

"That's why you see so many food labels saying the food was prepared in a factory where nuts or peanuts are processed. Allergens can be detected by the immune system, and potentially trigger anaphylaxis, at extremely low concentrations.

"However, in the case of cannabis, it is unlikely that the desired active ingredient is a protein; it is most likely compounds such as THC or related chemicals," he noted. "So synthetic versions are the ideal solution for those with known allergies, but they are probably very expensive."

Raising Awareness and Ongoing Challenges

Tiffany Owens, MD, assistant professor of allergy and immunology at The Ohio State University Wexner Medical Center in Columbus, called the consensus document an important, thorough review of the available literature that summarizes up-to-date information about cannabis allergy.

Dr Tiffany Owens

"Many non-allergists may not be aware that allergy to cannabis is a possible problem," she said in an email. "I hope this report will help expand differential diagnoses to include cannabis allergy when appropriate and help patients receive appropriate advice and treatment.

"It remains difficult for some clinicians and patients to discuss cannabis allergy due to concerns about legalities of cannabis acquisition, possession, and use; lack of clinicians' knowledge about cannabis use; and patients' hesitancy to discuss their cannabis use," Owens, who also was not involved in the study, added.

"It will be important to continue to assist clinicians and patients with evidence-based information about cannabis risks and benefits," she said. "I will be interested to see what future allergy testing modalities become available."

Skypala and several coauthors report financial relationships with the pharmaceutical industry. Lo and Owens report no relevant financial relationships. The International Cannabis Allergy Collaboration from the American College of Allergy, Asthma and Immunology, the Canadian Society of Allergy and Clinical Immunology, and the European Academy of Allergy and Clinical Immunology provided financial support.

Allergy. Published online January 31, 2022. Full text.

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