Diseases displaying hypofrontality (e.g. depression, addiction) are among the most common. Both sleep and psychedelics are being explored to treat these diseases. We hypothesized they are working through serotonin 5-HT2A receptors that promote neuroplasticity and dendritic growth in the prefrontal cortex. We reviewed the literature to determine if support exists for this potential mechanism, because understanding it may improve treatments without the negative side effects like hallucinations or sleep deprivation.