A narrative review examined the neurobiological mechanisms that may explain the rapid antidepressant effects of serotonergic psychedelics such as psilocybin, LSD, and ayahuasca. The drugs act as agonists or partial agonists at serotonin 5HT2A receptors, and their rapid effects may involve downregulation of these receptors. They also influence brain-derived neurotrophic factor and immune responses. Neuroimaging studies suggest that psychedelics may disrupt the default mode network, a brain system involved in self-referential thinking that is overactive in major depressive disorder. The review concludes that multiple competing theories are being investigated and more research is needed to identify the most robust evidence.
A critical appraisal of clinical trials on serotonergic psychedelics for major depressive disorder and end-of-life distress finds that current evidence is low-level due to methodological limitations. Small randomized trials of psilocybin combined with psychotherapy showed superiority to waitlist controls and comparable efficacy to an active comparator, with similar preliminary positive effects for single-dose ayahuasca in treatment-resistant depression and lysergic acid diethylamide for end-of-life distress. Adverse events were mild and transient. However, small homogenous samples, expectancy bias, functional unblinding, and lack of standardized psychotherapy limit all studies. Psychedelics should remain experimental interventions used within clinical trials.
Hallucinations and delusions are common in borderline personality disorder (BPD) and often resemble those in schizophrenia spectrum disorders. In a study of 89 adults, 81% of those with BPD reported visual and tactile hallucinations, 75% reported olfactory hallucinations, and 94% experienced delusions. Comparing BPD with and without voices showed no significant differences in nonpsychotic psychopathology. Hallucinations in BPD were similar to those in schizophrenia, though the BPD group had higher rates of paranoia and delusions of guilt. Multisensory hallucinations and delusions in BPD warrant clinical attention.