Low threshold responders are individuals who experience a type of drug hypersensitivity that causes amplified or abnormal effects from medications and psychoactive substances which are caused by biological and genetic sensitivities. These individuals have abnormal responses to antidepressants, antipsychotics, stimulants, sedatives, and recreational substances like caffeine, alcohol, cannabis, and psychedelics. Unlike general adverse drug reactions which can be sudden and unexpected, low threshold responders have a predictable pattern of intolerance to multiple substances due to neurotransmitter imbalances, slowed metabolism, or receptor sensitivity.

The biggest cause of this is due to mutations in specific genes that regulate dopamine, serotonin, or other neurotransmitter responses, especially when given anything that changes the levels of neurotransmitters in the brain. These individuals are often mislabeled as treatment resistant as they may develop an intolerance to substances that impact neurotransmission or may have a heightened response to these substances.