Psilocybin and esketamine show a similar safety and efficacy for treatment of depression

The resurgence in psychedelic medicine may be due in part to its applications to a number of mental health conditions, including depression, anxiety, PTSD, eating disorders, and substance use disorders, all of which appear to be growing in scale and suffering. In 2023, Oregon became the first state to legalize psilocybin for use in state-certified service centers.1 Psilocybin and other naturally occurring psychedelic substances have been used for millennia for healing and ceremony across many continents and cultures. Some speculate that psychedelic mushrooms may even have played a role in human evolution.2,3 But it is over the past 30 years that the psychedelic renaissance has occurred, driven by a revived interest in the therapeutic potential of these substances, especially for mental health care.4 This paper will examine 2 psychedelic medicines (psilocybin and ketamine) used as a part of an evidence-based treatment strategy. In addition to reviewing the literature, I will report on a current study in which I serve as both external researcher and participant-observer. The paper concludes by examining the interaction between psychedelics, nature, and healing.

Psilocybin, a naturally occurring, tryptamine alkaloid prodrug, is currently being investigated for the treatment of a range of psychiatric disorders. Preclinical reports suggest that the biological effects of psilocybin-containing mushroom extract or “full spectrum” (psychedelic) mushroom extract (PME), may differ from those of chemically synthesized psilocybin (PSIL).

Direct observation of therapeutic human connection is feasible, sensitive to changes in states of consciousness and requires evaluation of audible and visual data.

This article highlights the potential spiritual effects of a popular anesthetic, ketamine, and how these spiritual effects can be used to help promote the reconciliation of spiritual and physical health. Ketamine, like the prominent psychedelic, psilocybin, has reportedly caused feelings of spiritual revelation and “out of body experiences” that many physicians may not feel qualified to discuss with their patients. This reluctance to address ketamine-induced spiritual experiences may affect the health outcomes of the patient. The primary goal of this project is to bring academic validity to considerations of the spiritual health of patients. This paper (1) investigates the extent that ketamine-induced, non-ordinary experiences can help bring awareness to the compatibility of spiritual and physical health and (2) compares the mechanisms of ketamine and psilocybin, as well as their value to the medical community due to the spiritual experiences that they catalyze. Thus, this research seeks to demonstrate that understanding the spiritual value of ketamine may encourage better communication between the physician and patient and promote more holistic healthcare approaches.

Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

Psychedelic compounds, including psilocybin, LSD, DMT, and 5-MeO-DMT all of which are serotonin (5-HT) 2A receptor agonists are being investigated as potential treatments. This review aims to summarize the current clinical research on these four compounds and mescaline to guide future research. Their mechanism/s of action, pharmacokinetics, pharmacodynamics, efficacy, and safety were reviewed. While evidence for therapeutic indications, with the exception of psilocybin for depression, is still relatively scarce, we noted no differences in psychedelic effects beyond effect duration. It remains therefore unclear whether different receptor profiles contribute to the therapeutic potential of these compounds. More research is needed to differentiate these compounds in order to inform which compounds might be best for different therapeutic uses.