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Ask the Mental Health Expert Archives 2001-2004

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LSD as an Antidepressant

Q. I've recently become interested in alternative treatments of depression. After doing some research there was at one point, in the 1960s, where LSD was used as a treatment for the disorder. Is this still used today? How successful was it in its time?

A. LSD is not used today as a treatment for depression, though a few fringe therapists may advocate the use of other psychedelic drugs (such as Ecstasy/MDMA) as adjunctive agents in psychotherapy. To my knowledge, there are no well-designed, randomized, controlled studies from the 1960s-80s showing that LSD is effective for what we would now call major depression.

That said, there is an older literature claiming that LSD and perhaps other hallucinogens may be useful in the psychotherapeutic process; e.g., see Grieco & Bloom, "Psychotherapy with hallucinogenic adjuncts from a learning perspective," in Int J Addict 1981 Jul;16(5):801-27; and also Yensen R, "LSD and psychotherapy," in J Psychoactive Drugs 1985 Oct-Dec;17(4):267-77.

There is also a case report of LSD's use in a suicidal patient (Van Ree F, Ned Tijdschr Geneeskd 1969 Aug 23;113(34):1470-2). It's very hard to judge, from this older literature, the effectiveness of LSD for any psychiatric condition, including depression, since the modern criteria for major depression, and for measuring mood improvement, were not applied in these studies. From a theoretical perspective, however, LSD is an interesting agent. It interacts with binding sites (receptors) for the brain chemical (neurotransmitter) serotonin, which--as you may know--is almost certainly involved in depression.

There have been some intriguing reports of our modern SSRI (selective serotonin reuptake inhibitor) medications, such as Prozac or Zoloft, re-activating LSD flashbacks in some heavy LSD users, even after many years of abstinence. The hypothesis is that the similarity in receptor physiology for both LSD and serotonin may underlie this phenomenon (see Markel et al, "LSD flashback syndrome exacerbated by selective serotonin reuptake inhibitor antidepressants in adolescents," J Pediatr 1994 Nov;125(5 Pt 1):817-9). But-this hardly qualifies as an endorsement for LSD therapy!

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April 2002

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