Date of Award
Doctor of Philosophy
Dr. Lisa Baker
Dr. Anthony DeFulio
Dr. Cynthia Pietras
Dr. John Spitsbergen
Low dose lysergic acid diethylamide, delay discounting
The resurgence of Lysergic Acid Diethylamide (LSD) as a therapeutic tool requires a revival in research, both basic and clinical, to bridge gaps in knowledge left from a previous generation of work. Currently, no study has been published with the intent of establishing optimal microdose concentrations of LSD in an animal model. In the present study, rats were administered a range of LSD doses to quantify potential augmentations in choice behavior in a rodent model of delay discounting. In the first experiment, rats were administered LSD (20 or 40 μg/kg, i.p.) or saline at the start of terminal baseline training to determine the drug’s influence on choice responding for a large, delayed reward when a novel, impactful set of delays is introduced. For the second experiment, a within-subject design (n= 8) was utilized to quantify the effects of LSD (20, 40, 80, & 160 μg/kg, i.p.) on choice behavior in an ascending dose pattern across four weeks.
Results from Experiment I indicate once weekly administration of low dose LSD during exposure to a novel set of delays does not produce significant changes in choice responding for the larger reward. In Experiment II, rats receiving 40 or 160 μg/kg LSD displayed increases in response selection for the immediate smaller reward during the first two delay conditions (0 and 10 seconds) when compared to saline or non-injection sessions. In Experiment I, response latencies among rats administered 20 μg/kg were significantly reduced at the 0 and 10 second delay conditions when compared to training-control and saline-treated rats, although no differences in overall response latency were observed among treatment groups. In Experiment II, 40 and 160 μg/kg LSD produced the slowest overall responding when compared to 20 or 80 μg/kg. Considered together, these results are consistent with recent reports that repeated dosing with low dose LSD does not produce cognitive impairments in humans. However, further research is necessary to determine the extent of LSD’s effect on behavior at doses lower than those typically administered. Moreover, given the increase in discounting displayed by rats receiving the highest dose of LSD, and the fact that therapeutic doses are typically higher than those administered in the present study, further research is warranted to elucidate any potential negative impairments associated with higher doses typically administered in therapeutic settings.
Kohler, Robert J., "The Effects of Low Dose Lysergic Acid Diethylamide Administration in a Rodent Model of Delay Discounting" (2020). Dissertations. 3565.