The primary health concerns about LSD use are related to psychological health rather than risk of physical damage to the body or brain. As senior LSD researcher Dr. David Nichols, Distinguished Chair of Pharmacology at Purdue University and head of one of the world's top LSD research labs, stated in his 2004 review article on hallucinogens, "There is no evidence that any of the hallucinogens, even the very powerful semisynthetic LSD, causes damage to any human body organ. [...] Hallucinogens do not cause life-threatening changes in cardiovascular, renal, or hepatic function because they have little or no affinity for the biological receptors and targets that mediate vital vegetative functions."1 Deaths resulting from the pharmacological effects of LSD are rare to non-existent.

However, like all psychoactive drugs, LSD can induce cognitive and emotional alterations that can greatly affect behavior. With psychedelics such as LSD, there can be powerful and unexpected changes in thinking and perception. While under the influence of these drugs, an individual can exhibit poor judgement and delusional behavior, leading to accidents or dangerous situations. In those individuals predisposed toward certain psychiatric conditions, hallucinogens may precipitate psychotic responses or depression. In some individuals, long-lasting anxiety and/or depression may result from the unpleasant experiences and frightening visions that occurred during the psychedelic experience.

Experienced users often caution new users of psychedelics about the dangers of inebriated behavior and a common fear while inebriated that the effects of the drug will be permanent. One bit of popular trip wisdom highlights some risks of LSD use: "Cars are real. Cliffs are real. Cops are real. You cannot fly. It's never a good time to die. And don't forget: you will eventually come down." Sober sitters or psychotherapeutic guides are often suggested as a means of substantially reducing the risk related to adverse mental and physical events that may be associated with LSD use. Individuals have also been encouraged to prepare themselves psychologically for the experience, by being ready to accept whatever emerges out of their psyche ("I love this, too... even the snarling spider about to eat me who looks like my mother.").

LSD is reported to have some beneficial effects on health, including improvements in mental health; increased connection to spirituality; insights into self and world; the treatment of cluster headaches; use in combating addiction to other drugs and behaviors; and reducing use of pain medications and anxiety levels in people facing terminal illnesses. Although small-scale clinical studies by legitimate scientific laboratories have suggested these claims may be worthy of further investigation, large-scale clinical studies have yet to be conducted to validate this pilot work.