Abuse liability profile of three substituted tryptamines

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Synthetic hallucinogens like DIPT, 5-MeO-DET, and 5-MeO-AMT are structurally related to compounds with known psychoactive effects.
• Abused hallucinogens primarily target 5-hydroxytryptamine (5-HT) receptors (5-HT1A and 5-HT2A), while psychostimulants affect monoamine transporters.

Purpose of the Study:

• To evaluate the abuse liability of DIPT, 5-MeO-DET, and 5-MeO-AMT in a rat discrimination model.
• To investigate the binding and functional activities of these compounds at 5-HT receptors and monoamine transporters.

Main Methods:

• Rats were trained to discriminate between hallucinogenic and psychostimulant drugs.
• Behavioral substitution tests were conducted with DIPT, 5-MeO-DET, and 5-MeO-AMT.
• In vitro assays assessed receptor binding and functional activity at 5-HT1A, 5-HT2A receptors, and monoamine transporters.

Main Results:

• DIPT and 5-MeO-DET fully substituted for dimethyltryptamine (DMT) and DOM, indicating hallucinogenic-like effects.
• 5-MeO-AMT showed partial substitution for lysergic acid diethylamide (LSD) and did not substitute for psychostimulants.
• All three compounds interacted with 5-HT receptors and serotonin transporters; 5-MeO-AMT also affected dopamine transporters.

Conclusions:

• DIPT, 5-MeO-DET, and 5-MeO-AMT exhibit abuse liability profiles consistent with hallucinogens, not psychostimulants.
• DIPT and 5-MeO-DET may possess abuse potential comparable to established hallucinogens.
• The observed activities and potential lethality at high doses suggest these compounds may pose significant health risks.