Hallucinogens, serotonin and obsessive-compulsive disorder

The serotonin (5-HT) neurotransmitter system has been implicated in the pathophysiology of several neuropsychiatric disorders, especially obsessive-compulsive disorder (OCD). Blockade of 5-HT reuptake appears to be an important initial neurobiological event in the therapeutic mechanism of action of antiobsessional drugs. However, for reasons that continue to be poorly understood, clinical improvement following initiation of treatment with 5-HT reuptake inhibitors can take up to eight to 12 weeks, and most patients do not fully improve. Recent data suggest that activation of 5HT(2A) and/or 5-HT2C receptors may be important for the improvement of OCD symptoms. Most psychedelic drugs are potent agonists at 5-HT2A and 5-HT2C receptors and their binding potency to these receptors is strongly correlated with their human potency as hallucinogens. This article will briefly review the relevant clinical and preclinical studies relating to the effects of hallucinogens on OCD. These data suggest that activation of 5-HT2 receptors by hallucinogens may lead to acute reduction of, as well as possible longer-lasting beneficial effects on, the symptoms of OCD. Evidence for and against involvement of 5-HT2A and/or 5-HT2C receptors in the therapeutic effects of drug therapies for OCD are reviewed. Issues related to the pharmacological properties and safety of psychedelic drugs, when considered as potential treatments for patients with OCD, are summarized. The authors suggest that controlled trials of potent 5-HT2 agonists in people suffering from OCD are warranted.