Should cannabis be a higher priority for allergists? A history and look down the pipe

According to the United Nations, there are more than 200 million cannabis users globally, and unlike most other plant-based drugs, cannabis is produced in almost all countries worldwide.¹

The medicinal history of Cannabis, a genus that includes multiple psychoactive species and is also known as hemp or marijuana (the designation differing by the content of delta-9-tetrahydrocannabinol [Δ⁹-THC]), is long, arguably dating to BC 2800: Emperor Shen Nung described using flowers from the female plant in his pharmacopoeia as safe and useful for treatment of numerous conditions, including rheumatic pain and digestive disorders. The topical application of cannabis for inflammation is mentioned as early as BC 1500 in the Egyptian Ebers papyrus, and further medical use was also well-documented throughout the Roman Empire, including by Pliny the Elder, Dioscorides, and Galen, and by the Greeks, Assyrians, and Indian Hindus.²

Europe rediscovered the medicinal and psychoactive properties of cannabis through the translation of Arabic books and manuscripts by scholars, followed by the scientific observations of physicians in the age of European colonial expansion, such as those documented by Irishman William Brooke O’Shaughnessy in his publication “On the Preparations of the Indian Hemp, or Gunjah (Cannabis indica), Their Effects on the Animal System in Health, and Their Utility in the Treatment of Tetanus and Other Convulsive Diseases.”²

By the late 19th century, cannabis was increasingly used by Western physicians, with notable patients, including Queen Victoria of the United Kingdom, who took cannabis for painful menses, and Empress Elisabeth (Sissi) of Austria, who used it for treatment of respiratory ailments.³

Since 1940, more than 100 phytocannabinoids have been isolated from Cannabis sativa—the primary species of Cannabis—with the 2 most pharmacologically significant compounds being cannabidiol and Δ⁹-THC.²

These molecules act on specific cannabinoid receptors within the human endocannabinoid system (ECS) which modulates many physiological processes, including neuronal development, brain plasticity, learning and memory, regulation of appetite, stress and emotions, proliferation, differentiation, cell survival, metabolism, and immunity. ECS alterations are associated with numerous diseases, including inflammatory and immune-mediated disorders. Research investigating relationships between cannabis, the ECS, and food allergy has mostly surrounded modulation. For example, data reveal that the messenger RNA levels of CB1 are significantly higher in peripheral blood mononuclear cells from children with peanut allergy compared with healthy controls.⁴

Another important, underdeveloped body of research, one that which Zeiger et al.⁵ advance in the present study, surrounds the immunogenicity of cannabis, its demonstrated capacity to illicit a dangerous, immunoglobulin E-mediated allergic reaction, and whether health care providers are equipped to manage or counsel patients who use and/or who have a suspected cannabis allergy.

Part of the existing research gap can be explained by restrictions imposed on cannabis throughout much of the 20th century, catalyzed by the 1936 release of the highly influential movie Reefer Madness, which demonized cannabis users as violent delusional addicts. The 1937 passage of Marijuana Tax Act followed, which drastically curtailed the recreational US market for cannabis and effectively halted research into its medical benefits.⁶ Although Zeiger et al⁵ describe how a shift toward liberalization of marijuana laws in many countries has led to dramatic expansion of access to legally prescribed (and recreational) cannabis, in the United States, there remains a federal prohibition on cannabis cultivation and sale, codified in the 1970 Controlled Substances Act, which states that cannabis has “no accepted medical use and a high potential for abuse.” However, even with the longstanding federal ban, 18 states (in addition to the federal District of Columbia) have legalized cannabis for recreational use among US adults, 31 states have decriminalized it, 37 states have comprehensive medical cannabis laws, and an additional 12 states recognize the value of at least some medical cannabis preparations (as of May 2022).⁷

Furthermore, laws seem to only cover certain components of marijuana (THC) and not other pharmacologically effective components. Similarly disparate laws exist among European Union member states, with full cannabis legalization in Malta contrasting with French laws that impose fines and imprisonment for possessing small quantities of cannabis.⁸

This highlights the dynamic nature of drug policy and suggests an important role for clinicians and health services researchers to ensure alignment with evidence and principles of health justice.

This is a paradoxical landscape for patients and physicians alike, making the present study by Zeiger et al⁵ especially timely and enlightening. In this international survey of active members of the American College of Allergy, Asthma and Immunology, Canadian Society of Allergy and Clinical Immunology, and the European Academy of Allergy and Clinical Immunology, the authors assessed whether allergist knowledge and attitudes regarding cannabis influenced their allergy practice. This is particularly important given evidence of rapidly shifting patient attitudes toward more favorable perceptions of cannabis—particularly among young people, with 33% of high school seniors and 43% of college-aged youth reporting use in the past year.⁹

Furthermore, a growing number of cannabis products, including topical, sublingual, and edible preparations, are marketed as providing relief for common allergic symptoms, including skin and airway inflammation, with some—albeit limited—mechanistic support for their effectiveness.¹⁰

However, although clearly warranted, research into the safety and efficacy of many cannabis-derived therapeutics remains challenging given the asymmetries between federal- and state-level regulatory regimes in many countries and residual social stigma around “illegal drug” use, rendering federal monies and other key supports (eg, standardized cannabis extracts for skin prick testing) inaccessible to many clinician-researchers, which, in turn, hinders our collective ability to serve those patients in need.

Given the many scientific, regulatory, and clinical uncertainties around cannabis and its use by patients with allergy, it is perhaps unsurprising that the authors observed substantial heterogeneity regarding allergist knowledge and attitudes toward cannabis, which in turn was associated with varying levels of comfort communicating with patients about cannabis across the surveyed members of major North American and European allergy societies. This highlights the need for more cannabis education of clinical allergy care providers so that they are better equipped to provide informed, useful guidance to their patients—many of whom are already using or considering using cannabis—regarding its potential risks and therapeutic benefits.