Tiwanaku Iconography in South Central Andean Snuffing ParaphernaliaThis work presents an analysis of Tiwanaku iconography depicted on snuffing equipment, referring to other media when appropriate. This hallucinogenic equipment facilitates a basic study of Tiwanaku's iconographic configuration because of its specific function, duration and widespread distribution. The snuffing kit consists of a distinct set of implements: a small rectangular tray, a snuffing tube, a small spoon, and leather pouches that functioned as snuff powder containers. I have documented 84 snuff trays and 23 snuffing tubes with Tiwanaku iconography. Their geographical distribution is noted and the major themes represented are discussed. This is followed by an analysis of the components of the iconographic system, a discussion of the different structural schemes and variations in thematic emphasis. / En este trabajo se presenta un análisis de la iconografía tiwanaku en los equipos de inhalar polvos psicoactivos, con referencia a la escultura lítica, textiles y cerámica. Estos equipos permiten un estudio inicial de la configuración iconográfica tiwanaku debido a su función específica y a su amplia distribución geográfica y temporal. El ajuar inhalatorio consiste de una tableta rectangular, un tubo, una cucharilla y una bolsa de cuero como recipiente para los polvos. El autor ha documentado 84 tabletas y 23 tubos con este tipo de iconografía. Se discuten los temas representados, sus variaciones y componentes, y distribución geográfica.

This thesis investigates the possibility of utilizing data from multiple modalities to enable an automated recycling system to separate ferrous from non-ferrous debris. The two methods sensor fusion and hallucinogenic sensor fusion were implemented in a four-step approach of deep CNNs. Sensor fusion implies that multiple modalities are run simultaneously during the operation of the system.The individual outputs are further fused, and the joint performance expects to be superior to having only one of the sensors. In hallucinogenic sensor fusion, the goal is to achieve the benefits of sensor fusion in respect to cost and complexity even when one of the modalities is reduced from the system. This is achieved by leveraging data from a more complex modality onto a simpler one in a student/teacher approach. As a result, the teacher modality will train the student sensor to hallucinate features beyond its visual spectra. Based on the results of a performed prestudy involving multiple types of modalities, a hyperspectral sensor was deployed as the teacher to complement a simple RGB camera. Three studies involving differently composed datasets were further conducted to evaluate the effectiveness of the methods. The results show that the joint performance of a hyperspectral sensor and an RGB camera is superior to both individual dispatches. It can also be concluded that training a network with hyperspectral images can improve the classification accuracy when operating with only RGB data. However, the addition of a hyperspectral sensor might be considered as superfluous as this report shows that the standardized shapes of industrial debris enable a single RGB to achieve an accuracy above 90%. The material used in this thesis can also be concluded to be suboptimal for hyperspectral analysis. Compared to the vegetation scenes, only a limited amount of additional data could be obtained by including wavelengths besides the ones representing red, green and blue.

In this study, I investigate how serotonergic modulation of the medial prefrontal cortex (mPFC) affects neuronal activity and impacts cognitive flexibility, anxiety, and fear extinction (Figure 1). I begin in Chapter 1 with general information on the PFC with a focus on the mPFC, then discuss the role and complexity of serotonin and how manipulation of serotonin affects behavior. I, finally, introduce what is understood about how serotonin modulates the mPFC, the significance of which has implications for cognitive and emotional behaviors. In Chapter 2, I studied the role of serotonin in cognitive flexibility. Specifically, I used retrograde tracing to determine the origin of mPFC and assessed how terminal release of 5-HT affects mPFC pyramidal neuron activity using whole-cell electrophysiology in acute brain slices. Furthermore, through in vivo fiber photometry, I evaluated the activity of 5-HTergic neurons projecting to the mPFC during cognitive flexibility behavior. Lastly, by selectively increasing or decreasing mPFC 5-HTergic terminal release through in vivo optogenetics, I assessed the modulatory role of 5-HTergic input into the mPFC on intradimensional rule reversal and extradimensional rule shift performance in the cognitive flexibility task. Furthermore, I evaluated the activity of 5-HTergic neurons projecting to the mPFC during an open field task using in vivo fiber photometry and, in Chapter 3, used in vivo optogenetics to determine the role 5-HT in the mPFC plays in modulating fear-related behavior. In Chapter 4, I examined a pharmacological screen of a psychedelic drug in the cognitive flexibility task outlined in Chapter 2. I conclude in Chapter 5 with a discussion of the study implications and future directions.

Serotonin 2A receptor (5-HT2aR) agonists and κ-opioid receptor (KOR) agonists have been demonstrated to be effective treatments for several central nervous system (CNS) disorders including depression, anxiety, addiction, and pain. In a recent clinical study, psilocybin (a classical hallucinogen) was shown to significantly decrease the symptoms of Major Depressive Disorder (MDD) and Treatment Resistance Depression (TRD) in humans for up to six weeks after a single dose. Several KOR agonists have been shown to be effective treatments of chronic pain without the physical dependence risks of µ-opioid receptor agonists. Also, due to KOR’s involvement in a biological anti-reward system, agonists for this receptor possess anti-addiction properties as demonstrated by their ability to decrease the self-administration of drugs of abuse in multiple different animal species. Despite the great therapeutic potential for both these classes of molecules, their hallucinogenic and disassociate effects have been a major roadblock in the approval new pharmaceuticals.This dissertation describes the synthesis and behavioral evaluation of known and novel 5-HT2aR and KOR agonists. In the first half, the synthesis of several molecules related to the structure of ibogaine are described and the novel “oxa-iboga” class is introduced. One of the molecules in this class, oxa-noribogaine, has been evaluated in a variety of in vivo mouse tests including tail-flick, open field, and forced swim test. The results demonstrate that oxa-noribogaine is a potent KOR agonist and analgesic but has a lower side-effect profile compared to other KOR agonists such as noribogaine, epi-oxa-noribogaine, and U50,488H. In the second half, two emerging classes of antidepressants, NMDAR antagonists and 5-HT2aR agonists, are described. Molecules from both these classes cause rapid acting antidepressant effects that can be induced after a single dose. This is a sharp contrast to traditional antidepressants such as SSRIs which require 4-6 weeks of consistent use before therapeutic effects are achieved. In our lab, a set of substituted phenethylamines which act as 5-HT2aR agonists were evaluated in vivo in the head twitch assay, forced swim test, sucrose preference test, and fear extinction assays. Their hallucinogenic and antidepressant-like effects are reported. One molecule, 4-CT, was designed and synthesized based on the structure of Ariadne, a 5-HT2aR agonist with low or no psychedelics effects. 4-CT produced a decreased number of head twitches compared to DOI (a hallucinogenic research control) and showed possible antidepressant-like effects in the forced swim test.

The intent of this study was to compare life value differences using the Life Values Inventory. Differences among non-psychedelic users and psychedelic users were examined. Participants, ranging from age 18 to 48 from the University of Central Florida (UCF), a large state university, were recruited on a voluntarily basis. This was primarily done through online message board, the Sona System, and classroom announcements. The study was presented through the Sona System provided by UCF. In addition, all participants were students of the university. Results indicated significant differences among three out of 14 life values measured. The three life values that were shown to be significantly different among the non-psychedelic users and psychedelic users were: 1) concern for others, 2) loyalty to family or group, and 3) responsibility. In addition, the life value of spirituality was only found to be marginally significant.

Over the course of three studies, this dissertation quantitatively examines the relationship between mystical experience and mental health, first in general, and then in the context of naturalistic psychedelic use. The first study of the dissertation proposes a model for understanding the within-population variability of this relationship, and identifies a “relational triad” of three factors which help to explain it: belongingness/social connectedness, mindfulness, and spirituality. The dissertation’s second and third studies draw upon longitudinal data collected from individuals planning to take a psychedelic substance in a naturalistic context, and apply the “relational triad” model to help predict the quality of individuals’ psychedelic experience (Study 2), as well as individuals’ mental health trajectories in the aftermath of a psychedelic experience (Study 3). Baseline mood, as well as the three “relational triad” factors identified in Study 1, were found to be implicated in individuals’ psychedelic experiences and their post-experience mental health trajectories. Finally, clinically-oriented recommendations are offered based on this set of empirically-derived findings, and a screening/predictive measure is proposed.

Le récepteur de la sérotonine (5-hydroxytryptamine, 5-HT) 2A a été identifié comme la cible principale des hallucinogènes psychédéliques comme le diéthylamide de l'acide lysergique (LSD). Ces agonistes sont connus pour reproduire quelques uns des principaux symptômes de la schizophrénie. Un paradoxe non résolu est que seuls certains agonistes des récepteurs 5-HT2A présentent une activité hallucinogène, alors que des composés de structure apparentée avec une affinité comparable au niveau du récepteur n'ont pas des propriétés psychoactives. En utilisant une approche quantitative phosphoproteomic combinant un marquage isotopique stable en acides aminés dans la culture cellulaire (SILAC), un double enrichissement en phosphopeptides par chromatographie d'interaction hydrophile (HILIC) / chromatographie d'affinité (IMAC) et la spectrométrie de masse haute résolution, nous avons comparé les phosphoprotéome dans des cellules HEK-293 cellules exprimant de manière transitoire le récepteur 5-HT2A sous trois conditions: cellules non stimulées, cellules exposées aux hallucinogènes [2,5-diméthoxy-4-iodophényl]-2-aminopropane (DOI) et LSD les cellules exposées aux agonistes non- hallucinogènes Lisuride et Ergotamine. Parmi les 5996 phosphopeptides identifiés, 454 sont spécifiquement régulés par les hallucinogènes. Il s'agit notamment d'un résidu sérine du récepteur 5-HT2A éventuellement impliqués dans la régulation de la désensibilisation des récepteurs qui a été spécifiquement phosphorylée lors de l'exposition aux deux hallucinogènes. La phosphorylation différentielle des récepteurs 5-HT2A dans les cellules exposées aux agonistes hallucinogènes (DOI et le LSD) vs non hallucinogènes (lisuride et l'ergotamine) a été confirmé par l'analyse par spectrométrie de masse du récepteur purifié. Parallèlement, l'exposition des cellules aux agonistes hallucinogènes induit une internalisation et une désensibilisation des récepteurs moins prononcée qu'après exposition à la non-agonistes hallucinogènes. En conclusion, les résultats de cette thèse révèlent que la stimulation du récepteur 5-HT2A par les hallucinogènes et les agonistes non hallucinogènes induit deux modèles différents de phosphorylation qui pourraient être impliqués directement dans leurs réponses comportementales distinctes. ils fournissent également l'une des premières manifestations de la phosphorylation différentielle d'un récepteur couplé aux protéines G lors de la stimulation du récepteur par des agonistes biaisée. / The serotonin (5-hydroxytryptamine, 5-HT)2A receptor has been identified as the primary target of psychedelic hallucinogens such as lysergic acid diethylamide (LSD), which reproduce some of the core symptoms of schizophrenia. A non-resolved paradox is that only some 5-HT2A receptor agonists exhibit hallucinogenic activity, whereas structurally related compounds with comparable affinity and agonist activity lack psychoactive properties. Using a quantitative phosphoproteomic approach combining stable isotope labelling by amino acids in cell culture (SILAC), phosphopeptide enrichment by hydrophilic interaction chromatography (HILIC) / immobilized metal affinity chromatography (IMAC) and high resolution mass spectrometry, we compared the phosphoproteome in HEK-293 cells transiently expressing the 5-HT2A receptor under three conditions: non-stimulated cells, cells exposed to the phenethylamine hallucinogen 1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) and cells exposed to the non-hallucinogenic 5-HT2A agonist lisuride. Among the 5,996 identified phosphopeptides, 454 were specifically regulated by DOI but not by lisuride. These include a serine residue of 5-HT2A receptor possibly involved in regulation of receptor desensitization which was specifically phosphorylated upon DOI exposure. Differential phosphorylation of 5-HT2A receptor in cells exposed to hallucinogenic (DOI and LSD) vs. non-hallucinogenic (lisuride and ergotamine) agonists was further confirmed by mass spectrometry analysis of purified receptor. Correspondingly, cell exposure to hallucinogenic agonists induced a less pronounced receptor desensitization and internalization than exposure to non-hallucinogenic agonists. In conclusion, our phosphoproteomic analysis revealed that 5-HT2A receptor stimulation by hallucinogenic and non hallucinogenic agonists induces different phosphorylation patterns that might underlie their distinct behavioural responses. It also provides one of the first demonstrations of differential phosphorylation of a G protein-coupled receptor upon stimulation by biased agonists.

Unlike their European predecessors in the experimentation with hallucinogens and aesthetics who undertook it as an exotic tradition brought from afar, many Latin American and North American authors turned to visionary practices and substances (cannabis, peyote, psilocybin mushrooms and ayahuasca, among others) as a main element of their own cultural heritage and territory. Though commonly restricted to the specific category of "psychedelia," the narratives in this corpus from the 20th century only acquire their true depth once included within a much vaster realm, that of visionary traditions, mostly originated in non-Western sources --with exceptions among divinators, witches and sorcerers in Europe -- both in the Old World of the Orient and Africa, but particularly in the New World, in America. Problematically blurring use and exchange value, the 20th century seized these substances as sources of forbidden pleasures which alienated laborers, while their prohibition generated immense fortunes that destabilized democracies throughout the continent, motivated violence, and funded mafias, guerrillas and paramilitary groups. Yet, visionary plants and practices spread with a transcultural power that even today allows for the survival of ethnic groups and traditional knowledge long hidden, while also feeding urban consumptions that generate innumerable subcultures, time and again misunderstood as a sign of decadence. In this dissertation these "underworld" practices are also manifestations of something prior and parallel to the birth of a culture of mass consumers: they mark an encounter between Indigenous, Afro, rural and mestizo influences in the voices of authors who contributed to culture from the margins of very hierarchical and racist societies, and assumed a leading role in their intellectual debate, capturing its mixtures, dark humor, conflicts and transculturations via writing and films. Initially marginalized in the low worlds of taverns, destitute neighborhoods, crime, prisons and prostitution venues, hallucination and hallucinogens--simultaneously a colonial anathema and a sacred pre-Columbian ritual of transcendence--survive and thrive, passing on to the urban minorities of artists and thinkers I will examine in this dissertation, now even including synthetics like Lysergic Acid Diethylamide (LSD). Late Avant-gardes between the 1950s and 1990s--beatniks, counterculture, yippies and Chicanos in the US, the Onda generation and the "jipitecas'' in Mexico, and the "nadaístas'' and the Cali group in Colombia--partially rescued this knowledge, but, above all, its consumptions, preserving some of them as an original heritage within their metaphysics, politics and aesthetics, and as a core part of many of their ideological and secular inquiries. Banned and misconstrued by the viceregal, republican, national and transnational elites, both in the colonial past, and in the contemporary moment of an hemispheric circuit -- within the geopolitics of Nixon‘s War on Drugs -- visionary and hallucinogenic uses continue shaping much of the cultural panorama of America today. The variety of films and texts observed in this project gives a measure of the true heterogeneity of Latin American and US authors of the 20th century: In their works we reconnect a fracture that divides not only two, but many worlds, while it makes possible, for once, to conceive the simultaneous reality of them all.