Psychedelic medicines for mood disorders: current evidence and clinical considerations.

PURPOSE OF REVIEW: Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions. RECENT FINDINGS: Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood. SUMMARY: Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.

Psychotherapeutic and neurobiological processes associated with ayahuasca: A proposed model and implications for therapeutic use.

Ayahuasca is a psychoactive Amazonian plant brew. It is usually made from the Banisteriopsis caapi vine (Spruce ex Griseb. Morton, Malpighiaceae), which contains three primary harmala alkaloids, along with the leaves of Psychotria viridis (Ruiz et Pavon, Rubiaceae) in which the potent psychedelic dimethyltryptamine (DMT) is found. DMT-harmaloid concoctions have gained popularity in recent years, due to growing anecdotal and scientific reports of therapeutic benefits associated with their consumption. Ayahuasca is now ingested in a variety of different settings across the globe, from traditional ethnobotanical to so called "neo-shamanic" ceremonies. Furthermore, related preparations involving alternative sources of DMT and harmala alkaloids are becoming increasingly common as knowledge of ayahuasca continues to spread internationally. This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers, to propose a model of psychotherapeutic processes associated with the consumption of ayahuasca. We assert that it is these processes, facilitated by a range of neurobiological effects, that lead to beneficial mental health and wellbeing outcomes. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.