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Abstract

Recently, there has been a resurgence in research exploring how certain psychoactive drugs might be used in the treatment of mental disorders associated with emotional episodic memory disturbances, such as posttraumatic stress disorder (PTSD). However, the effects of these drugs on particular stages of emotional episodic memory (i.e., encoding, consolidation, and retrieval) have not been properly isolated. The goal of this dissertation is to better understand the effects of these and other drugs of abuse on different stages of emotional and neutral memory, knowledge that is needed to maximize any benefits while minimizing the harms. In Chapter 1, I comprehensively review the scientific literature on the effects of the most commonly used and abused psychoactive drugs on the encoding, consolidation, and retrieval of emotional episodic memories. This review highlights the emotional selectivity of drug effects on memory, methodological considerations, and current gaps in the literature. This review also incorporates key findings from my own recent work, aimed at addressing some of these gaps, including three drug studies that are more fully described in Chapters 2, 3, and 4. In these subsequent chapters, I studied drugs that are commonly associated with PTSD because of their potential to impact emotional memories. In Chapter 2, I tested the effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on the retrieval of emotional memories. It is known that THC attenuates the encoding of emotional memories more selectively than neutral memories, but its effects during the retrieval of emotional memories had never been tested. I show that THC robustly increases false memories with no evidence of memory suppression, which has implications for the use of cannabis in medicine. In Chapter 3, I provide the first test of ±3,4-methylenedioxymethamphetamine (MDMA) on the encoding and retrieval of emotional episodic memories. I demonstrate that MDMA has specific amnestic effects on emotional memory encoding and to a lesser extent, emotional memory retrieval. Furthermore, I show that these effects only become apparent when using methods aimed at dissociating two fundamental episodic memory processes: recollection and familiarity. This finding is relevant to the use of MDMA-assisted psychotherapy in patients with PTSD. In Chapter 4, using the process dissociation procedures from Chapter 3, I reanalyzed a dataset in which the effects of alcohol were tested on the encoding and consolidation of emotional memories. This earlier study found that alcohol at encoding had emotionally selective amnestic effects, similar to THC and MDMA. In my reanalysis of this study, I found that alcohol impairs encoding and enhances consolidation of both recollection and familiarity. These findings are bolstered by my reanalysis of several previous studies that tested the effects of other GABAA positive allosteric modulators (PAMs) on encoding. Although the emotionally selective amnestic effects of alcohol and other GABAA PAMs may resemble those of THC and MDMA, the impact of these drugs on different episodic memory processes implicate distinct roles for each drug in medicine. Finally, I conclude with a discussion of the importance of dissociating component processes of episodic memory in pharmacology studies aiming to target aspects of memory that are dysfunctional in mental disorders. This discussion ends with clinical implications for PTSD, as well as addiction, and future directions that incorporate both behavioral manipulations and neuroimaging.

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