Given those earlier findings, the fMRI data reported by Dr. Nutt’s group are somewhat surprising. Methodological issues (such as route of administration, dose, and the spectrum and extent of psilocybin-induced symptoms) may be at least partially responsible for these differences, since the processes being measured are not identical. It is also important to consider that the 5-HT2A receptor is not the only type of serotonin receptor that is activated by psilocybin. Dr. Vollenweider’s experiments have confirmed that the increase in metabolic activity detected by PET is mediated by the 5-HT2A receptor (the serotonin receptor responsible for the psychedelic effects of psilocybin). Because Dr. Nutt’s group did not conduct a similar test to verify that the effects they observed are mediated by the 5-HT2A receptor, this would be a logical next step.
Hopefully, follow-up studies will provide an explanation for these discrepant findings, and will settle the debate over whether hallucinogens act by increasing or reducing brain activity. Clinical trials are currently being conducted to investigate whether hallucinogens can be used to relieve stress and anxiety in terminal cancer patients, to attenuate the symptoms of obsessive-compulsive disorder, and to reduce the frequency of cluster headaches, so it is important to determine the mechanism for the therapeutic effects of hallucinogens. Additionally, there appears to be some overlap between the effects of hallucinogens and the symptoms of psychosis, so understanding how hallucinogens work could potentially provide insight into the causes of schizophrenia and facilitate the development of more effective treatments. In any event, it is important to note that studies have consistently identified the mPFC and ACC as playing key roles in mediating the effects of hallucinogens. In light of what is known about the core functions of these brain regions, it is not unreasonable that they would be involved in mediating the effects of hallucinogenic drugs. Therefore, although it is not yet clear whether hallucinogens act on the mind through the mechanism proposed by Huxley, it appears that we have succeeded in identifying some of the key brain regions targeted by these powerful agents.
Adam Halberstadt is a postdoctoral fellow in the Department of Psychiatry at the University of California San Diego. He studies the serotonin system and its involvement in psychiatric disorders. Mark Geyer is a Distinguished Professor of Psychiatry and Neurosciences at the University of California San Diego. His laboratory uses animal models to study human drug effects and schizophrenia. He is also a co-founder of the Heffter Research Institute, an organization that promotes scientific research with hallucinogens.
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