Psilocybin, a serotonin 2A receptor agonist, facilitates extinction of conditioned fear responses in mice, with low doses producing faster extinction than high doses or saline. The drug also reduces hippocampal neurogenesis in a dose-dependent manner, but the low doses that enhanced extinction did not decrease neurogenesis and instead showed a trend toward increase. This suggests that psilocybin's effect on fear extinction may involve brain regions other than the hippocampus, such as the amygdala, which processes fear perception. Psilocybin and similar agents warrant exploration as potential treatments for post-traumatic stress disorder and related conditions.
Ibogaine, an indole alkaloid from the rain forest shrub Tabernanthe iboga, has been used by indigenous peoples in equatorial Africa to combat fatigue and hunger and as a religious sacrament. Anecdotal reports from addict self-help groups claim a single dose eliminates withdrawal symptoms and reduces drug cravings for extended periods, but these purported antiaddictive properties require rigorous validation. A rising tolerance study with single administration has been initiated to assess ibogaine's safety for treating cocaine dependency, with primary objectives to determine safety, pharmacokinetics, dose effects, and relevant efficacy parameters. Pharmacokinetic and pharmacodynamic characteristics are assessed via concentration-time data from the Phase I trial and in vitro experiments on metabolism.