To the Editor: Several recent studies have documented an association of a serotonin 5-HT2A receptor promoter polymorphism, -1438G/A, with anorexia nervosa (1). Now the same genetic association has been extended to obsessive-compulsive disorder (OCD) (2), the symptoms of which have been shown to share considerable commonality with anorexia (3). Since such functional promoter variants usually alter transcription frequency and thereby affect receptor population, drugs that selectively induce down-regulation of 5-HT2A receptors might alleviate the symptoms of anorexia and OCD.
It is known that the classic psychedelic drugs-LSD, psilocybin (the active agent in Psilocybe mushrooms), and mescaline (the alkaloid in peyote cacti)-act as agonists at 5-HT2A receptors, inducing a rapid and robust tolerance and cross-tolerance to their hallucinogenic effects by means of down-regulation of the 5-HT2A receptor system (4).
Anecdotal evidence indicates that the symptoms of OCD are mitigated by hallucinogens, and the newly recognized 5-HT2A receptor promoter polymorphism provides the likely mechanism for this effect. Three reports have surfaced in the literature of individuals with long-standing OCD who experienced significant alleviation of their disorder after what was initially a 'recreational' use of LSD, peyote, or Psilocybe mushrooms. The most recent of these (5) relates that a 34-year-old man who had suffered from OCD since the age of 6 found that both peyote and Psilocybe mushrooms moderated his symptoms (which included incapacitating and compulsive counting, showering, and ritualistic washing of his clothes, hands, and body). He began a 4-year course of daily Psilocybe mushroom ingestion, which resulted in improvement of his OCD symptoms, unaccompanied by any hallucinogenic effects because of his acquired tolerance. During a subsequent 2-year period, his OCD remained in control without the need for him to ingest Psilocybe, but then the symptoms gradually returned to their initial levels.
Some beginnings have been made in studying the effects of psychedelic drugs for alleviating OCD. The potential benefits of these drugs in anorexia nervosa, a devastating and not infrequently life-threatening disorder with few or no fully successful treatment options, should likewise be studied.
1.Sorbi S, Nacmias B, Tedde A, Ricca V, Mezzani B, Rotella CM:5-HT2A promoter polymorphism in anorexia nervosa (letter). Lancet 1998; 351:1785
2.Enoch M-A, Kaye WH, Rotondo A, Greenberg BD, Murphy DL, Goldman D:5-HT2A promoter polymorphism -1438G/A, anorexia nervosa, and obsessive-compulsive disorder (letter). Lancet 1998; 351:1785-1786
3.Pigott TA, Altemus M, Rubenstein CS, Hill JL, Bihari K, L'Heureux F, Bernstein S, Murphy DL: Symptoms of eating disorders in patients with obsessive-compulsive disorder. Am J Psychiatry 1991; 148:1552-1557
4.Buckholtz NS, Zhou DF, Freedman DX, Potter WZ: Lysergic acid diethylamide (LSD) administration selectively downregulates serotonin2 receptors in rat brain. Neuropsychopharmacology 1990; 3:137-148
5.Moreno FA, Delgado PL: Hallucinogen-induced relief of obsessions and compulsions (letter). Am J Psychiatry 1997; 154:1037-1038