Psycholeptics, psychoanaleptics, and cardiovascular drugs alter individual tolerance to extreme heat. To explore the influence of heat waves on their toxicity in acute overdose, we retrospectively analyzed all human exposures to psycholeptics and psychoanaleptics (PLAexp) as well as cardiovascular drugs (CVDexp) registered by the Poisons Information Center (PIC) Erfurt between June to September of the years 2003 to 2018 for frequency, age groups, sex, circumstances of exposure, and symptom severity. The results of the non-heat years (NHY) 2004-2005 and 2007-2014 (average air temperature June-September 16.2 °C) were compared to the results of the heat years (HY) 2003, 2006 and 2015-2018 (average air temperature June-September 17.5 °C). In total, 13,191 cases (HY 5,117; NHY 8,074) of PLAexp and 2,960 cases (HY 1,168; NHY 1,792) of CVDexp were registered. During HY, accidental PLAexp (11.2% versus 9.7%) and CVDexp (40.6% versus 36.8%) were more often seen. Severe symptoms were less frequent in PLAexp (4.4% versus 6.3%) and CVDexp (3.3% versus 4.9%). Although in HY, no higher rates of moderate or severe PLAexp and CVDexp were detected than in NHY, patients with these medications should be observed carefully during heat waves because of affected body's usual cooling mechanisms.