In a recent episode of Last Week Tonight, John Oliver turned his sardonic attention to patents in the for-profit psychedelic business world. He referenced a Compass Pathways patent application that included claims describing the basic setting of psychedelic therapy, saying, “It’d be like me patenting the concept of wearing a suit while sitting at a desk.”
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.
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.
Background: A resurgence of neurobiological and clinical research is currently under-way into the therapeutic potential of serotonergic or ‘classical’ psychedelics, such as the prototypical psychedelic drug lysergic acid diethylamide (LSD), psilocybin (4-phosphoryloxy-N,N-dimethyltryptamine), and ayahuasca – a betacarboline- and dimethyltryptamine (DMT)-containing Amazonian beverage. The aim of this review is to introduce readers to the similarities and dissimilarities between psychedelic states and night dreams, and to draw conclusions related to therapeutic applications of psychedelics in psychiatry. Methods: Research literature related to psychedelics and dreaming is reviewed, and these two states of consciousness are systematically compared. Relevant conclusions with regard to psychedelic-assisted therapy will be provided. Results: Common features between psychedelic states and night dreams include perception, mental imagery, emotion activation, fear memory extinction, and sense of self and body. Differences between these two states are related to differential perceptual input from the environment, clarity of consciousness and meta-cognitive abilities. Therefore, psychedelic states are closest to lucid dreaming which is characterized by a mixed state of dreaming and waking consciousness. Conclusion: The broad overlap between dreaming and psychedelic states supports the notion that psychedelics acutely induce dreamlike subjective experiences which may have long-term beneficial effects on psychosocial functioning and well-being. Future clinical studies should examine howtherapeutic outcome is related to the acute dreamlike effects of psychedelics.
The neural correlates of the psychedelic experience are increasingly being investigated with noninvasive functional neuroimaging methods. This research has now provided a preliminary understanding of the neural substrates of various stages and contents of psychedelic experience, elucidating how various stages differ from one another, and also relate to kindred “altered” states of consciousness such as dreaming and creative thinking. Several conclusions can be gleaned from this review. First, psychedelic experiences involving strong visual hallucinatory components activate the same brain areas as “natural” altered states involving high rates of visual imagery, most notably daydreaming and nighttime dreaming. Second, peak psychedelic experiences involving loss of the sense of the self or “ego-dissolution” involve deactivation or disintegration of brain networks, most notably the default mode network, that are widely thought to maintain and subserve an internal stream of thoughts and a coherent sense of self.
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.
Salvia divinorum L. (Lamiaceae) has been used for centuries by the Mazatecan culture and has gained popularity as a recreational drug in recent years. Its potent hallucinogenic effects seen in case reports has triggered research and led to the discovery of the first highly selective non-nitrogenous κ opioid receptor agonist salvinorin A. This review critically evaluates the reported pharmacological and toxicological properties of S. divinorum and one of its major compounds salvinorin A, its pharmacokinetic profile, and the analytical methods developed so far for its detection and quantification. Recent research puts a strong emphasis on salvinorin A, which has been shown to be a selective opioid antagonist and is believed to have further beneficial properties, rather than the leaf extract of S. divinorum. Currently animal studies show a rapid onset of action and short distribution and elimination half-lives as well as a lack of evidence of short- or long-term toxicity. Salvinorin A seems to be the most promising approach to new treatment options for a variety of CNS illnesses. However, many further investigations are necessary to fully understand and elucidate the various medicinal properties of the plant itself and to provide the legislative authorities with enough information to cast judgement on S. divinorum.
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.
A increasing number of studies points toward beneficial effects of psychedelic experiences if administered in the right setting. A smaller number of studies present explanations for why psychedelics have these therapeutic effects. Of these most argue that psychedelic experiences increase neuroplasticity, allowing subjects to let go of unhelpful entrenched beliefs. I argue that (1) psychedelics are likely therapeutic because they help subjects align their beliefs with their respective contexts; (2) relaxation of entrenched beliefs need not occur at higher cognitive levels concerned with the self or ego to be therapeutic; and (3) the proneness toward having supernatural entity experiences can be explained using this contextual approach. I conclude that therapeutic effects of psychedelics are not necessarily tied to beliefs about the self.
Johns Hopkins Medicine was awarded a grant from the National Institutes of Health (NIH) to explore the potential impacts of psilocybin on tobacco addiction. This is the first NIH grant awarded in over a half century to directly investigate the therapeutic effects of a classic psychedelic, consistent with a recent study published online that searched NIH funding and found zero grants were awarded between 2006 and 2020. Johns Hopkins Medicine will lead the multisite, three-year study in collaboration with University of Alabama at Birmingham and New York University. The study will be conducted simultaneously at the three institutions to diversify the pool of participants and increase confidence that results apply to a wide range of people who smoke. The grant, totaling nearly $4 million, is funded by NIH’s National Institute on Drug Abuse.