"Cannabis sativa is a weed and it causes reactions just like any other pollen allergy," said William Silvers, MD, from the University of Colorado School of Medicine in Aurora.

Silvers' clinic began to see people with allergic reactions to the plant after the increase in direct exposure that accompanied the legalization of recreational marijuana in Colorado. For people with allergic tendencies, first- and second-hand exposure to C.sativa will increase "classic responses," such as allergic rhinitis, sneezing, wheezing, itching, and asthma, he told Medscape Medical News.

Smoking the weed, direct exposure to the plant, contact with others who have touched plants, and breathing air in a grow operation "can all cause reactions," he said. "And the more exposure they had, the greater the reaction, especially those who have allergic tendency," he said.

The type of exposure to C.sativa is also a factor. Smoking the plant can induce typical allergic responses, the ingestion of hemp seed has been known to induce anaphylaxis, and "working with the plant can lead to dermatitis or contact urticaria," he explained.

The health risks and benefits associated with C.sativa will be discussed at the upcoming American Academy of Allergy, Asthma and Immunology (AAAAI) 2020 Meeting in Philadelphia. The new AAAAI cannabis working group will also meet during the event to discuss the next steps for patient care.

Edibles made with C.sativa have led to overdoses because dosing is difficult to determine. "It takes an hour or so to have an effect, so you don't have as much control as inhaling it," Silvers explained.

A 2018 case report describes a 24-year-old daily marijuana smoker who experienced anaphylaxis after ingesting hemp seed. He had a history of allergies to stoned fruits, nuts, crustaceans, and aeroallergens. It was his first known exposure to hemp seed.

The patient developed urticaria on his arms after contact with C.sativa leaves and flowers, but had no reaction when smoking marijuana. This case indicates how important mode of exposure is.

"There are only a few cases of anaphylaxis known from ingestion of hemp seed," Silvers said, "but the 'stoned fruit, stoned patients' cross-reactivity looks to be a real thing."

People allergic to ragweed and sage are more likely than others to have a reaction to cantaloupe and other fruits in the melon family, he explained. There is a common antigen in the C.sativa pollen and in certain foods with cross-reacting proteins, such as tomato, peach, and hazelnut. "We see a pollen and food cross-reactivity via nonspecific lipid transfer proteins."

A 2017 review of C.sativa allergy points out that few reports of IgE-dependent allergic reactions have been published because of the illegal status of cannabis. However, it is becoming more prevalent as a potential allergen. For example, in Nebraska, C.sativa pollen accounts for 36% of the total pollen count.

People with IgE-mediated cannabis allergy can have a sensitization to the nonspecific lipid transfer protein of C.sativa, Cans3, which might explain the secondary plant-derived food allergies seen in European patients with a cannabis allergy, according to the review. Cans3 cross-reacts with various plant homologues.

"This is the sort of information that allergists need to have," Silvers said.

The fact that federal law prohibits cannabis use in the United States has made research difficult.

A strain distributed by the University of Mississippi can be used for research, "but it's potency is very low, at 5% or 7%," Silvers explained. At medical marijuana dispensaries, the potency of the flower can be as high as 25%, and in other forms, the THC content can be above 80%.

The legal status makes cannabis allergy difficult to diagnose and impossible to treat. Immunotherapy is out of the question. "With federal illegality, we need to stay out of trouble in that regard," said Silvers, adding that, currently, avoidance is advised.

But research is emerging from Canada, where medicinal and recreational marijuana use is legal. Results from a survey showing the prevalence of response in marijuana-exposed allergic patients will be reported at the meeting by Ryan Lo, MD, from the University of Toronto.

The impact of cannabis exposure on human respiratory health will be addressed by several speakers, including Angela Lemons, from the National Institute for Occupational Safety and Health in the United States.

Stigma around cannabis is still high. "Nobody wants to be seen as a 'pot doctor'," said Silvers. But after it became legal in Colorado in 2015, he was asked to give a talk and decided to speak up.

"I have never written a medical prescription for marijuana," he said, explaining that he is involved with the Center for Bioethics and Humanities at the University of Colorado. "I try to take a societal as well as a medical perspective, looking at the value and concerns for abuse and misuse."

"As it becomes more available, more legalized, patients are having more reactions," he said. "Allergists need to get in the game."

Attitudes need to change. Physicians and allergists need to understand what's happening in the population "and be open-minded about it so they know what to do," he added.

Users of medical marijuana can become dependent, said Ellen Burnham, MD, also from the University of Colorado.

"Patients want a blessing from care providers that it's okay to use," she told Medscape Medical News. "We're in a state where people are really interested in holistic approaches to health, and cannabis is a natural product, but it may exacerbate allergies."

Some components of cannabis might have bronchodilator properties but there are so many unknowns at this time. "I don't think allergists should be recommending or condoning cannabis as part of a patient's therapy," she said. "It's not okay for everybody."

As business flourishes for operators in the cannabis industry and for the legal profession, Burnham said she worries that there isn't enough protection for workers. "Do workers exposed to plant material on a daily basis have adequate workplace protection," such as masks and gowns? "There's a downstream effect that impacts people that nobody has really thought about," she pointed out.

If the cannabis industry becomes driven by money, with a lobby like the tobacco industry, there will be no way to keep people who are vulnerable from using cannabis.

Is an occasional joint, much like an occasional glass of wine, okay? "We don't know," said Burnham. "We just don't have enough information about it."

Research is needed to develop medicinal strains of cannabidiol, cannabigerol, and cannabinol, which offer "medicinal and anti-inflammatory relief without the psychologic affects," Silvers added.

American Academy of Allergy, Asthma and Immunology (AAAAI) 2020 Meeting.

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Marijuana Allergies on the Rise - Medscape