Interactions between fentanyl and 2,5-dimethoxy-4-methylamphetamine: Ventilatory effects in nonhuman primates

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Growing interest in psychedelic therapeutics necessitates understanding potential drug interactions.
• Opioid use, particularly with fentanyl, carries significant risks, including respiratory depression.
• Psychedelics are increasingly available, raising concerns about concurrent use with other substances.

Purpose of the Study:

• To investigate the interaction between 2,5-dimethoxy-4-methylamphetamine (DOM) and fentanyl.
• To determine if DOM affects fentanyl-induced respiratory depression in a preclinical model.

Main Methods:

• Rhesus monkeys (n=6) were administered fentanyl and DOM alone and in combination.
• Head plethysmography was used to measure ventilatory function (tidal volume).
• Dose-response relationships were assessed for each drug and their mixtures.

Main Results:

• Fentanyl alone caused a dose-dependent decrease in tidal volume.
• DOM alone did not significantly affect ventilation.
• Combining DOM with fentanyl resulted in greater ventilatory depression than fentanyl alone in most subjects.

Conclusions:

• 2,5-dimethoxy-4-methylamphetamine (DOM) may exacerbate opioid-induced respiratory depression.
• This interaction could increase the risk of overdose when psychedelics and opioids are co-administered.
• Further research is needed to determine if these findings apply to other opioid and psychedelic combinations.