AMT HCI

Pharmacological Actions

AMT exhibits a range of pharmacological effects, primarily through its interaction with monoamine systems. It acts as a releasing agent for serotonin, norepinephrine, and dopamine, with specific EC50 values indicating potency: serotonin release ranges from 22 to 68 nM, dopamine from 79 to 112 nM, and norepinephrine from 79 to 180 nM. Additionally, AMT is a non-selective serotonin receptor agonist, with notable activity at the 5-HT2A receptor, showing an EC50 of 23 nM and an Emax of 103%, suggesting strong agonist properties. It also functions as a reversible inhibitor of monoamine oxidase A (MAO-A), with an IC50 of 380 nM, and its potency in rats is comparable to harmaline at 7 μM/kg (1.5 mg/kg harmaline, 1.2 mg/kg AMT). These actions contribute to its stimulant, entactogenic, and psychedelic effects, mediated by increased neurotransmitter availability and receptor activation.
Metabolites identified in male Wistar rats include 2-Oxo-αMT, 6-hydroxy-αMT, 7-hydroxy-αMT, and 1′-hydroxy-αMT, indicating metabolic pathways involving hydroxylation and conjugation, consistent with tryptamine metabolism.

Pharmacokinetics

The pharmacokinetics of AMT are not fully elucidated in the literature. The onset of action is typically 3-4 hours, with effects lasting 12-24 hours, suggesting a prolonged duration that may indicate a long half-life. However, specific half-life data is not available, though the alpha substitution is noted to make AMT a poor substrate for MAO-A, potentially prolonging its presence in the system. Bioavailability, particularly for the oral route, is not quantitatively documented, but its effectiveness when taken orally implies sufficient absorption, supported by predicted high human intestinal absorption (probability 1.0) and blood-brain barrier penetration (probability 0.9856) from ADMET models.
Metabolic studies in human hepatocytes show slow metabolism, with a 25% decrease in signal intensity after 3 hours, which may explain the prolonged psychedelic effects. Postmortem concentrations in overdose cases range from 2.0 µg/mL to 4.7 µg/mL in blood, with higher levels in urine and bile, but these do not directly translate to pharmacokinetic parameters like half-life or bioavailability.

Pharmacokinetics

Dosage recommendations vary based on intended effects and user reports. For antidepressant purposes, under the brand name Indopan, doses of 5-10 mg were prescribed. Recreational use for psychedelic effects typically starts at 20-30 mg, with strong effects at 40-60 mg and heavy effects at 60-80 mg. Erowid reports include individuals taking doses as high as 400 mg, though with severe effects, and recommends starting at threshold or light levels (5-25 mg) to avoid dangerously strong reactions, especially for new users or with new batches. The minimum effective dose for psychedelic effects is around 20 mg, while doses above 60 mg are associated with increased risks, including hospitalization, based on unverifiable reports.

Safety and Toxicity

Safety concerns are significant, particularly at higher doses. Doses exceeding 60 mg have been linked to hospitalization, and there were 22 deaths associated with AMT in England and Wales from 2012 to 2015, though exact doses are not specified. Case reports, such as a fatality in Miami in 2003, involved a 22-year-old college student with postmortem blood concentrations of 2.0 mg/L, but ingested dose is unclear. Another case reported a plasma concentration of 440 µg/L with severe serotoninergic syndrome, indicating potential toxicity at high exposures.
Animal toxicity data from the European Chemicals Agency (ECHA) lists an oral LD50 of less than 5 mg/kg, dermal LD50 less than 50 mg/kg, and inhalation LD50 less than 0.5 mg/L/4h, classifying it as Acute Tox. 2, indicating high acute toxicity. However, this animal data seems inconsistent with human use, where doses up to 80 mg (approximately 1.14 mg/kg for a 70 kg person) are reported without immediate fatality, though with significant adverse effects. This discrepancy highlights the need for caution, as individual sensitivity varies widely, and AMT's MAO-A inhibition may increase risks of interactions with tyramine-rich foods or other drugs, potentially leading to hypertensive crises or serotonin syndrome.
The maximum safe dose without high risks is difficult to determine, but based on reports, it seems likely that doses above 60-80 mg are increasingly dangerous, with potential for severe adverse effects like anxiety, tachycardia, vomiting, and in extreme cases, fatality. The evidence leans toward starting with low doses and having a trusted companion present, given the variability in response.

Time Influence and Risk Assessment

The influence of AMT's pharmacological actions over time is reflected in its long duration (12-24 hours), which may be due to slow metabolism and prolonged neurotransmitter effects. The onset, taking 3-4 hours, can lead to redosing errors, increasing overdose risk, as effects may take time to fully develop. Risks increase significantly at higher doses, with reports of severe reactions at 40 mg and above, and fatalities associated with use, particularly in polydrug contexts.

Conclusion

AMT's pharmacological profile includes monoamine release, serotonin receptor agonism, and MAO-A inhibition, with effects lasting 12-24 hours and significant safety concerns at doses above 60 mg. While exact half-life and bioavailability data are lacking, its oral effectiveness is clear. Dosage should start low, with careful monitoring for adverse effects, given the potential for severe toxicity and fatalities at higher exposures. Further research is needed to clarify pharmacokinetics and establish precise LD50 values in humans, given the controversy around animal data and human use patterns.