Browsing by Subject "Psychedelics"

Individuals suffering from anorexia nervosa (AN) have one of the highest mortality rates of all psychiatric disorders, as a consequence of health complications that follows severe malnutrition. The impairments in cognitive flexibility, including an extreme focus on restricting food despite a rapid decline in body weight in AN, also plays an important role in the development of the disorder and has been suggested as a hallmark of AN. This cognitive inflexibility, common among many psychiatric disorders such as depression and obsessive-compulsive disorder, is linked to alterations in serotonin (5-HT) signaling in the medial prefrontal cortex (mPFC). Reduced 5-HT2A receptor activity and potentially increased 5-HT1A receptor activity are evident in the mPFC in individuals with AN and may be linked to impaired cognitive flexibility, however, the mechanisms through which 5-HT and inflexibility interact in AN are not fully understood. A better understanding of this link could pave the way toward more effective pharmacological treatments for AN. Psilocybin, a psychedelic compound produced by so-called “magic” mushrooms, has a high affinity for several 5-HT receptor subtypes including 5-HT1A and 5-HT2A receptors, and has now been empirically demonstrated to increase cognitive flexibility in individuals with major depressive disorder (MDD). In this study, we sought to understand how the development of pathological weight loss and/or psilocybin administration influenced the expression of RNA molecules of 5-HT2A and 5-HT1A receptors expression in the mPFC of rats. To this end, we used the activity-based anorexia (ABA) model, the only experimental model known to elicit voluntary reductions in food intake and voluntary hyperactivity that leads to rapid body weight loss in the majority of animals exposed to ABA conditions. Outcomes were compared against an age-matched control group that were not exposed to the ABA paradigm. Animals were administered psilocybin (1.5 mg/kg) or saline (control) and 4-10 days later brain tissue was collected for processing. Receptor expression was detected using a novel multiplex RNA fluorescent in situ hybridization (FISH) technology, RNAscope®. The main aim of this study was to examine changes in the expression of RNA molecules of 5-HT2A and 5-HT1A receptors in the mPFC elicited by ABA conditions and determine whether these were ameliorated by the administration of psilocybin. We found that animals exposed to ABA demonstrated a significant reduction of 5-HT2A receptors’ RNA levels in the mPFC, and that this was not influenced by psilocybin treatment. There have been reports from clinical trials that individuals with AN experience “less than expected” subjective effects from psilocybin, which may be explained by reduced expression of RNA molecules of 5-HT2A receptors in the mPFC, and is supported by our results in rats. Taken together, these results highlight a specific serotonergic mechanism that could underly the development of pathological weight loss and offers insight into possible issues with the therapeutic application of psilocybin for AN. Future studies will need to examine the effects of psilocybin during a more acute period following treatment to define these effects. Moreover, whether or not the reduced 5- HT2A receptors’ RNA level expression induced by ABA is restored with body weight recovery should be determined.

Scientific and scholarly attention to psychedelics has recently faced a resurgence. Recent studies suggest that psychedelic experiences can change values and behavioral dispositions, for example increase appreciation of nature and increase prosocial behavior. For this reason psychedelics have been identified as a promising option for moral neuroenhancement. However, we still struggle to understand these changes in the valuations psychedelics induce, or why exactly they are morally enhancing. In this thesis I construct a philosophical framework to understand these changes. I combine Iris Murdoch and Abraham Maslow’s thinking with empirical studies on psychedelics and experiences of self-transcendence. Psychedelics induce experiences of self-transcendence which involve evaluative changes. I argue that these changes are not random but result from an intelligible process. I first claim that psychedelics in some cases induce unselfing, that is, perspectival and evaluative changes resulting from reduction of salience attributed to oneself. By reducing egoic centering, unselfing opens our attention to the world and can cause perspectival widening from egocentric into more allocentric (other-directed) or cosmocentric (universal) perspective. The second main claim is that the process of unselfing is often connected to sharpened perception of values. The increased attention to the world and reduced egocentric attributions of salience, resulting from unselfing, can widen our evaluative context and make it possible to perceive or grasp intrinsic values better, thus ‘tuning the moral compass’ away from instrumental egocentric mode of evaluation. This thesis makes an original contribution to current discussions on moral neuroenhancement by presenting a well-elaborated connection between the experiences of self-transcendence and the evaluative changes. At least some changes in values associated with psychedelic experiences are related to unselfing. Further the framework provided is relevant not only for understanding value changes in psychedelic experiences, but it can be used to understand and to conceptually and theoretically integrate various phenomena which involve unselfing and techniques that aim at spiritual, moral and existential changes. Another original contribution of this thesis is that psychedelic experiences and moral neuroenhancement are discussed with the conceptual means of Murdoch’s and Maslow’s thought.