An important exception to making a diagnosis of DSM-5 substance use disorder with two criteria pertains to the supervised use of psychoactive substances for medical purposes, including stimulants, cocaine, opioids, nitrous oxide, sedative-hypnotic/anxiolytic drugs, and cannabis in some jurisdictions (96, 97). These substances can produce tolerance and withdrawal as normal physiological adaptations when used appropriately for supervised medical purposes. With a threshold of two or more criteria, these criteria could lead to invalid substance use disorder diagnoses even with no other criteria met. Under these conditions, tolerance and withdrawal in the absence of other criteria do not indicate substance use disorders and should not be diagnosed as such.