Originally appeared at: http://www.medscape.com/viewarticle/727438 August 25, 2010 — Low doses of psychedelic drugs, including lysergic acid diethylamide (LSD), ketamine, and psilocybin, may reduce clinical symptoms in patients with depression, anxiety, obsession-compulsive disorders (OCDs), and chronic pain, without inducing depersonalization or hallucinations, according to a new Perspectives article published online August 18 in Nature Reviews Neuroscience. The study authors note that this may be due to the drugs’ effect on patients’ altered brain circuits and neurotransmitter systems, including serotonin and glutamate systems, according to recent neuroimaging data. “These findings raise the possibility that research into psychedelics might identify novel therapeutic mechanisms and approaches that are based on glutamate-driven neuroplasticity,” write Franz X. Vollenweider, MD, director of the Neuropsychopharmacology and Brain Imaging Research Unit at the University Hospital of Psychiatry in Zurich, Switzerland, and colleagues. “These are serious, debilitating, life-shortening illnesses, and as the currently available treatments have high failure rates, psychedelics might offer alternative treatment strategies that could improve the well-being of patients and the associated economic burden on [them] and society,” they add. Recent Research Although research on psychedelics has been restricted for almost 40 years because of the drugs’ negative connotations, “recent advances in our understanding of the neurobiology of psychedelics” have led to renewed interest, write the study authors. Recent study findings have included the following: •The N-methyl-D-aspartate antagonist ketamine can significantly reduce symptoms of depression within 24 hours, with a sustained effect for at least 72 hours. “In particular, patients with depression who are suicidal might benefit from such a rapid and marked effect,” the study authors write. However, many patients have relapsed within 2 weeks of their single treatment. Currently ketamine is also being tested as a treatment for bipolar disorder, and it has the “potential as a treatment for addiction.” •A recent review of studies conducted in the 1960s found that psilocybin and LSD are effective treatments for OCD, and a current study showed that psilocybin significantly reduced symptoms of OCD in treatment-resistant patients within an average of 2 hours and lasted up to 24 hours. •Several studies are currently looking at psilocybin and LSD as treatments for anxiety and depression in patients with terminal cancer, with 1 recently completed trial finding that psilocybin improved mood and reduced anxiety and lasted between 2 weeks and 6 months. •A recent study found that both psilocybin and LSD “aborted attacks, terminated the cluster period, or extended the remission period in people suffering from cluster headaches. “Taken together, these findings support early observations in the 1960s that classical hallucinogens have antinociceptive potential and may not only reduce symptoms but also induce long-lasting adaptive processes,” the study authors report. In addition, they note that because the dissociative effects of psychedelic drugs resemble some of the symptoms of psychosis, the drugs could also potentially be used to study the brain basis of psychotic disorders such as schizophrenia. “This Perspective proposes that classical psychedelics, such as psilocybin, and dissociative anesthetics, such as ketamine, alter glutamatergic neurotransmission in prefrontal-limbic circuitries and that this leads to neuroplastic adaptations, presumably through enhancement of AMPA [α-amino-3-hydroxy-5-methyl-4-isoxazole] receptor function,” the study authors write. They add that more studies are needed to further validate this hypothesis. They also note that understanding the molecular mechanism of action and “further evaluations of the dose-response relationship” may help minimize the adverse effects of these drugs. A discussion about the recent article published in Nature Reviews Neuroscience which indicates that several psychedelic drugs such as ketamine, LSD and psilocybin may be effective for treating depression, anxiety, OCD and chronic pain.