Cannabis is a complex genus of dioecious, annual, wind-pollinated herbs that diverged from Humulus—a small genus that includes H. lupulus, whose bitter female flowers form the hops used to flavor beer—approximately 27.8 million years ago [2]. Cannabis is among humanity’s oldest crops with records of its use for food, fiber, medicine, and inebriation dating back over 6000 years. Despite its long history of use, its taxonomy remains disputed, with some suggesting a monotypic classification with several subspecies of C. sativa [2], and others suggesting three distinct species (C. sativa, C. indica, and C. ruderalis) [3, 4]. The biochemistry of Cannabis is similarly complex, with at least 118 cannabinoids and 489 described constituents, the most well know and psychoactive of which being tetrahydrocannabinol (THC) and cannabidiol (CBD) [5]. “Indica” varieties of Cannabis tend to have a higher THC content, and higher THC to CBD ratio than “sativa” varieties [2]. “Indica” varieties are known for a more mellow high and a terpenoid profile with an acrid, skunk smell, whereas “sativa” varieties are known for a more exciting high and a sweet, herbal aroma [2]. However, these strains are heterogeneous with genome-wide variability that is not limited solely to the genes involved in THC and CBD production [4].

Study of specific culprit Cannabis allergens is still in its infancy. A handful of IgE immunoblot experiments, summarized in Table 1, have identified several potential allergens. Of these, the Cannabis non-specific lipid transfer protein (nsLTP), Can s 3, was the first identified and is the best studied [6]. Thaumatin-like protein (TLP), ribulose-1,5-bisphosphate carboxylase oxygenase (RuBisCO), and oxygen evolving enhancer protein 2 have also been recognized as potential sensitizing allergens in Cannabis allergy [7, 8].

Cannabis sensitivity spans the spectrum of allergic response. As an aeroallergen, Cannabis pollen has been implicated in allergic rhinitis, allergic keratoconjunctivitis, hypersensitivity pneumonitis, and exacerbations of asthma symptoms [9] (Fig. 1a). Additionally, patients may experience cutaneous reactions in the form of generalized pruritus, contact urticaria, and angioedema. A case of occupational contact urticaria was reported in a forensic sciences technician who had regular occupational contact with Cannabis for a period of 2 years. She was neither a recreational user, nor an atopic or dermatographic individual, suggesting sensitization specifically from repeated handling [10]. Erythema multiforme (in one case report) has also been associated with recreational consumption [11]. This individual experienced the eruption of vesicobullous, scaled, and targetoid rash on his distal extremities which progressed proximally to his trunk within a two-week period, waxing and waning synchronously with his use of Cannabis [11]. Anaphylaxis to C. sativa with hempseed ingestion, smoking, and injection have also been reported [12–14].

Cannabis has reasonably common, expected, but undesirable physiologic effects (conjunctival injection, sinus tachycardia, orthostatic hypotension, anxiety or panic reactions, dysphoria). It is important to not ignore or mis-attribute similar symptoms when the index of suspicion for a serious reaction or anaphylaxis is high [9].

Cannabis consumption also carries a risk to immunosuppressed patients in the form of microbiological contaminants, particularly when inhaled. Aspergillus has been isolated repeatedly from Cannabis samples [15, 16]. In one observational study, a majority of Cannabis users had antibody evidence of Aspergillus exposure compared to a minority of abstinent controls [17]. Furthermore, cases of pulmonary aspergillosis have been linked to contaminated Cannabis use in immunosuppressed populations [16, 17]. Fungal spores resist destruction from smoking and vaporization [18]. Thus, hypersensitivity and immunosuppression are clinically relevant states with regard to Cannabis consumption.