Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Psilocybin and other 5-hydroxytryptamine2A agonist classic psychedelics have been used for centuries as sacraments within indigenous cultures. In the mid-twentieth century they were a focus within psychiatry as both probes of brain function and experimental therapeutics. By the late 1960s and early 1970s these scientific inquires fell out of favor because classic psychedelics were being used outside of medical research and in association with the emerging counter culture. ⋯ Safety data from these various trials, which involve careful screening, preparation, monitoring, and follow-up, indicate the absence of severe drug-related adverse reactions. Modest drug-related adverse effects at the time of medication administration are readily managed. US federal funding has yet to support therapeutic psilocybin research, although such support will be important to thoroughly investigate efficacy, safety, and therapeutic mechanisms.
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Adult hippocampal neurogenesis (AHN) occurs in humans and every other mammalian species examined. Evidence that AHN is stimulated by a variety of treatments and behaviors with anxiolytic properties has sparked interest in harnessing AHN to treat anxiety disorders. However, relatively little is known about the mechanisms through which AHN modulates fear and anxiety. ⋯ Based on studies of the role of AHN in Pavlovian fear conditioning, we conclude that AHN modulates the consequences of aversive experience by influencing 1) the efficiency of hippocampus-dependent memory acquisition; 2) generalization of hippocampal fear memories; 3) long-term retention of hippocampal aversive memories; and 4) the nonassociative effects of acute aversive experience. The preclinical literature suggests that stimulation of AHN is likely to have therapeutically relevant consequences, including reduced generalization and long-term retention of aversive memories. However, the literature also identifies four caveats that must be addressed if AHN-based therapies are to achieve therapeutic benefits without significant side effects.