Optimized infusion rates for N,N-dimethyltryptamine to achieve a target psychedelic intensity based on a modeling and...

Area of Science:

• Pharmacology
• Psychiatry
• Computational modeling

Background:

• N,N-dimethyltryptamine (DMT) is a psychedelic compound with therapeutic potential for psychiatric disorders.
• Its short half-life necessitates continuous infusion strategies to prolong effects.
• Population pharmacokinetic/pharmacodynamic (PopPK/PD) modeling is key to optimizing DMT infusion protocols.

Purpose of the Study:

• To design a DMT infusion protocol based on desired psychedelic intensity using PopPK/PD modeling.
• To compare continuous variable and bounded integer PopPK/PD models for protocol design.
• To evaluate the impact of model choice on dose recommendations.

Main Methods:

• Utilized a previously published continuous variable model and two new bounded integer models.
• Performed simulations to determine optimal DMT bolus dose and infusion rates.
• Assessed model performance in achieving target psychedelic intensity ratings (7-9 on a 0-10 scale).

Main Results:

• Optimal doses varied between models: 16mg bolus + 1.4mg/min infusion (continuous model) vs. 14mg bolus + 1.2mg/min infusion (integer models).
• Proportion of simulations within the target intensity range was low (<53%) for all models.
• Bounded integer models predicted lower target achievement and higher overshoot compared to the continuous model, especially at scale boundaries.

Conclusions:

• Individual dose adjustments are necessary for DMT infusion protocols due to model variability.
• Model choice (continuous vs. bounded integer) influences DMT dose recommendations and predicted outcomes.
• Further refinement of PopPK/PD models is needed for precise DMT therapeutic administration.