UC Berkeley

In this dissertation, I used theories of serotonin to understand the effects of serotonergic hallucinogens on visual perception and attention. I began by studying hallucinatory syndromes in drug users in Chapter 1. Despite long-standing reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder (HPPD) and related visual abnormalities in hallucinogen users. I used an online questionnaire to document the prevalence, symptoms, and relationship to drug use of persisting unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet, and 2,679 were included in the study. Most participants (61.7%) reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 3.9 % of the sample) found them distressing or impairing enough to consider seeking treatment. In Chapters 2 and 3, I used three pharmacological agents to alter serotonergic functioning: 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenedioxymethamphetamine (MDMA, `Ecstasy'); and the selective serotonin reuptake inhibitor (SSRI) antidepressant citalopram. Chapter 2 focuses on mechanisms of hallucinations, which I investigated by measuring the perceptual effects of the hallucinogenic 5-HT2AR agonist and 5-HT releaser 3,4-methylenedioxyamphetamine (MDA) in a double-blind placebo-controlled study. I found that MDA produced a significant increase in closed-eye visuals (CEVs), with considerable individual variation. Magnitude of CEVs after MDA was associated with lower performance on measures of contour integration and object recognition, supporting a hypothesized link between hallucinations and impairments in sensory or perceptual processing. Chapter 3 concerned the effects of the aforementioned serotonergic drugs on attention to threat-related stimuli. The serotonergic system appears important for evaluation of social stimuli and may modulate amygdala sensitivity to threat-related stimuli. Hallucinogens and related serotonergic drugs vary in their ability to release 5-HT, but no studies have measured how these drugs affect attentional biases for emotional stimuli. In this chapter, I describe two double-blind placebo-controlled experiments on the effects of the serotonergic drugs 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) on attention to emotional stimuli. Using a dot-probe task, I found preliminary evidence that MDA and MDMA may modify processing of threat-related stimuli. These effects appear unrelated to state anxiety. In contrast, I did not detect significant effects of the selective serotonin reuptake inhibitor (SSRI) citalopram. Further research with these understudied drugs may clarify the role of serotonin in the brain.