NB: I'm not going to comment on TAAR1 activity in the neuroimmune system.
The immunological effects of TAAR1 activation in white blood cells (see
https://en.wikipedia.org/wiki/TAAR1#Immune_system, specifically the 2nd paragraph) explain why some people experience an exacerbation of their allergies following amphetamine use. In a nutshell, some white blood cells express both TAAR1 and TAAR2, and it is strongly suspected that TAAR1-TAAR2 hetero-oligomers (probably heterodimers of those receptors) form in those cells; upon activation of TAAR1 by TAAR1/TAAR2 co-expressing T-cells,
interleukin 4 is secreted. This doesn't occur in TAAR1⁺/TAAR2⁻ T-cells, which is why it's likely mediated by TAAR1-TAAR2 heterodimers. Also, TAAR1 agonists cause
immunoglobulin E (IgE) secretion from
B cells that co-express TAAR1/TAAR2 (but not from TAAR1⁺/TAAR2⁻ B cells). Since IL-4 induces B-cell proliferation and since IgE (technically: IgE-allergen crosslinking at the FcεRI receptor) is the primary biomolecular mediator of all
true allergies (type-I hypersensitivity reactions), the induction of IL-4 and IgE expression in white blood cells by amphetamine binding at TAAR1 is the mechanism by which it exacerbates symptoms of allergic diseases (e.g., allergic rhinitis, asthma, hay fever, etc.) in some people. I
n the event you're familiar with the Th1/Th2 model of immunity, the effect of TAAR1 agonists on IL-4 and IgE expression exclusively promotes Th2-mediated - i.e., "allergic" - immune responses. Since this is a toxicogenomic effect, it's strongly dose-dependent. Even though amphetamine exacerbates allergic reactions via this mechanism, it also indirectly activates alpha-1 and beta-2 adrenergic receptors through the secretion of norepinephrine and epinephrine into peripheral blood plasma (NB: methylphenidate also does this), which has the opposite effect on allergy symptoms. This is the primary mechanism by which it alleviates the symptoms of allergic reactions in some people, as well as why it was prescribed for treating asthma and nasal congestion in the 1930s and 1940s.
In the event you're interested in references, the
IUPHAR page on TAAR1 covers what I mentioned about its expression pattern in the "Tissue distribution" section. The "Functional assays" section and the corresponding citation covers what I've mentioned about TAAR1/TAAR2 and IL-4/IgE secretion by white blood cells. For comparison, table 2 of
this paper shows serum Th1 and Th2 cytokine levels in healthy controls vs in amphetamine-dependent individuals (at baseline and at 1 month abstinence). Medication guides for several brands of amphetamine list allergic rhinitis as a statistically significant side effect with an incidence between 1-10% (e.g.,
https://dyanavelxrpro.com/side-effects lists 4% incidence vs 0% for placebo;
https://www.drugs.com/sfx/amphetamine-side-effects.html lists 1-10% incidence).