Panic attacks may also be caused by substances. Discontinuation or marked reduction in the dose of a substance such as a drug (drug withdrawal), for example an antidepressant (antidepressant discontinuation syndrome), can cause a panic attack. According to the Harvard Mental Health Letter, "the most commonly reported side effects of smoking marijuana are anxiety and panic attacks. Studies report that about 20% to 30% of recreational users experience such problems after smoking marijuana."
Genetics and family history (e.g., parental anxiety) may predispose an individual for an increased risk of an anxiety disorder, but generally external stimuli will trigger its onset or exacerbation. Genetic differences account for about 43% of variance in panic disorder and 28% in generalized anxiety disorder. Although single genes are neither necessary nor sufficient for anxiety by themselves, several gene polymorphisms have been found to correlate with anxiety: PLXNA2, SERT, CRH, COMT and BDNF. Several of these genes influence neurotransmitters (such as serotonin and norepinephrine) and hormones (such as cortisol) which are implicated in anxiety. The epigenetic signature of at least one of these genes BDNF has also been associated with anxiety and specific patterns of neural activity.