Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes.

Great apes reach momentary altered mental states by spinning

Among animals, humans stand out in their consummate propensity to self-induce altered states of mind. Archaeology, history and ethnography show these activities have taken place since the beginnings of civilization, yet their role in the emergence and evolution of the human mind itself remains debatable. The means through which modern humans actively alter their experience of self and reality frequently depend on psychoactive substances, but it is uncertain whether psychedelics or other drugs were part of the ecology or culture of pre-human ancestors. Moreover, (nonhuman) great apes in captivity are currently being retired from medical research, rendering comparative approaches thus far impracticable. Here, we circumvent this limitation by harnessing the breadth of publicly available YouTube data to show that apes engage in rope spinning during solitary play. When spinning, the apes achieved speeds sufficient to alter self-perception and situational awareness that were comparable to those tapped for transcendent experiences in humans (e.g. Sufi whirling), and the number of revolutions spun predicted behavioural evidence for dizziness. Thus, spinning serves as a self-sufficient means of changing body-mind responsiveness in hominids. A proclivity for such experiences is shared between humans and great apes, and provides an entry point for the comparative study of the mechanisms, functions, and adaptive value of altered states of mind in human evolution.

Psychedelics and the Default Mode Network

Modern neuroscience has demonstrated that psychedelics such as LSD, psilocybin, the active ingredient in magic mushrooms, as well as ayahuasca operate to significantly reduce activity in the brain’s default mode network (DMN). This reduction in DMN activity functions as a kind of ‘rebooting’ of the brain, and is thought to be linked to one of the most enduring therapeutic effects of psychedelic substances.

Bicycle Day and other Psychedelic Essays by Alan Piper

“What are the roots of psychedelic culture? Why are psychedelics seen as transgressive? How was Albert Hofmann’s discovery of LSD’s effects entwined with a world at war? In Bicycle Day and other Psychedelic Essays, Alan Piper explores the often forgotten or ignored early histories of psychoactive drugs that helped shape psychedelia.

Falling between the eighteenth century, the Club des Hashischins and the psychedelic sixties, the less explored interwar period has a surprisingly rich culture of drug-induced mind states, which are intimately connected with the birth of modernism. From the literature of Hope Mirrlees, David Lindsay and Ernst Jünger, to Harvard peyote experiments, Hofmann’s occultic network and the relationship of Sandoz pharmaceuticals with Nazi Germany, Alan Piper’s collection is a rich tapestry of literary and social drug history.”

The costs and benefits of psychedelics on cognition and mood

Anecdotal evidence has indicated that psychedelic substances may acutely enhance creative task performance, although empirical support for this claim is mixed at best. Clinical research has shown that psychedelics might have enduring effects on mood and well-being. However, there is no neurocognitive framework that ties acute changes in cognition to long-term effects in mood. In this review, we operationalize creativity within an emerging cognitive control framework and assess the current empirical evidence of the effects of psychedelics on creativity. Next, we leverage insights about the mechanisms and computations by which other psychoactive drugs act to enhance versus impair cognition, in particular to those that act on catecholamines, the neurophysiological consequences of which are relatively well understood. Finally, we use the same framework to link the suggested psychedelic-induced improvements in creativity with enduring psychedelic-induced improvements in mood.

The need for establishing best practices and gold standards in psychedelic medicine

Psychedelic substances are under investigation in several drug development programs. Controlled clinical trials are providing evidence for safe and effective use of psychedelic therapies for treating mental health conditions. With the anticipated FDA approval of MDMA-assisted therapy for posttraumatic stress disorder in 2023 and psilocybin therapy for depression disorders soon after, now is the time for the medical community to become informed on best practices and to actively participate in developing standards of care for these new treatments. Given the emergence of numerous drug sponsors and other companies developing therapeutic modalities for combination with psychedelic medications, it is essential that the medical professional field is at the forefront of communicating unbiased information related to safety and effectiveness. Gold standards have long been a part of medicine and serve to distinguish treatments and assessments as the highest quality by which all others can be compared to. For a treatment to be established as a gold standard, several factors are considered including the quantity and quality of the supporting data, the rigor of trials, and the safety and efficacy compared to other treatments. In this article, we review the origins of psychedelic-assisted therapy (PAT), minimum requirements for safe use of psychedelics, criteria for gold standards in mental health, and the nuances regarding how to establish gold standards in psychedelic medicine and guide clinical decision making.

Low dose ketamine infusion for comorbid posttraumatic stress disorder and chronic pain: a randomized double-blind clinical trial

Objective: To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions.

Methods: We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion.Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale-Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale-Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion.

Results: Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only.

Conclusions: This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

Studying Harms Is Key to Improving Psychedelic-Assisted Therapy—Participants Call for Changes to Research Landscape

Although psychedelic drugs generally have good safety profiles, a recent systematic review concluded that adverse events in psychedelic trials are poorly defined, not systematically assessed, and likely underreported. In the past year there have been multiple reports of serious adverse events (SAEs), and long-lasting harms to participants in clinical trials of psychedelic-assisted therapy (PAT) have emerged. We draw attention to a unique and overlooked category of risk in PAT stemming from the interactions between therapists and patients receiving high doses of psychedelics. In our view, the understudied therapeutic component of PAT presents the most serious risks. Addressing it requires interdisciplinary approaches by researchers free from conflicts of interests.