5-MeO-AMT

5-MeO-AMT
Clinical data
Other names5-MeO-AMT; 5-Methoxy-α-methyltryptamine; α,O-Dimethylserotonin; α,O-DMS; Alpha-O
Routes of
administration		Oral[1]
Drug classSerotonin receptor agonist; Serotonin 5-HT2A receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code
  • None
Legal status
Legal status
  • AU: S9 (Prohibited substance)
  • BR: Class F2 (Prohibited psychotropics)[3]
  • CA: Unscheduled
  • DE: NpSG (Industrial and scientific use only)
  • UK: Class A
  • US: The DEA considers 5-MeO-AMT a controlled substance analogue.[2]
  • Illegal in Sweden and Florida
Pharmacokinetic data
Duration of action12–18 hours[1]
Identifiers
  • 1-(5-methoxy-1H-indol-3-yl)propan-2-amine
CAS Number
PubChem CID
ChemSpider
UNII
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC12H16N2O
Molar mass204.273 g·mol−1
3D model (JSmol)
Melting point216 to 218 °C (421 to 424 °F)
  • N[C@@H](C)CC1=CNC(C=C2)=C1C=C2OC
  • InChI=1S/C12H16N2O/c1-8(13)5-9-7-14-12-4-3-10(15-2)6-11(9)12/h3-4,6-8,14H,5,13H2,1-2H3 checkY
  • Key:OGNJZVNNKBZFRM-UHFFFAOYSA-N checkY
  (verify)

5-MeO-αMT, also known as 5-methoxy-α-methyltryptamine or as α,O-dimethylserotonin (α,O-DMS or Alpha-O), is a serotonergic psychedelic of the tryptamine, α-alkyltryptamine, and 5-methoxytryptamine families.[1] It is a derivative of α-methyltryptamine (αMT) and an analogue of 5-MeO-DMT.[1] The drug is said to be the most potent psychedelic of the simple indolealkylamines (i.e., tryptamines).[4] It is active at oral doses of 2 to 4 mg.[4][1]

Use

5-MeO-AMT blotters.

The dosage range of 5-MeO-AMT listed in TiHKAL is 2.5 to 4.5 mg and its duration is listed as 12 to 18 hours.[1] However, a wider recreational dosage range of 0.5 to 15 mg has also been reported.[5][6]

5-MeO-AMT has supposedly been sold as 4 mg tablets by the street name Alpha-O and taken as a recreational drug. Since the DEA arrests of the makers of a huge percentage of the United States' LSD in 2000, 5-MeO-AMT may have occasionally been sold under the guise of LSD in liquid, sugar cube, or blotter form, though this may be due to DEA reports of finding it on sugar cubes and blotters like LSD.[7][8]

The most common route of administration for 5-MeO-AMT is orally. Anecdotal reports, however, have described snorting or smoking the substance. Intravenous (IV) and intramuscular (IM) routes are rarely, if ever, used outside research settings due to the high potency, powerful effects and quicker onset.

Effects

Tabs of gelatin containing 5-MeO-AMT.

Erowid lists the following effects:[9]

Positive

  • Increased energy
  • Improved mood heading into euphoria at higher doses
  • Increased sociability, gregariousness
  • Increased giggling and laughter
  • Increased sense of creative thinking
  • Increased pleasure from sense of touch
  • Intensification of sex for some users

Neutral

  • Lightheadedness
  • Brightening of colors
  • Visuals including motion, waves, breathing walls, etc. (usually at higher doses, over 4–5 mg)
  • Increased attention to detail
  • Auditory distortions and/or hallucinations (usually at higher doses)

Negative

  • Headache
  • Body fatigue
  • Chills from elevated body temperature (potential dehydration)
  • Stress and extreme fatigue from long duration of effects.
  • Nausea, diarrhea
  • Vomiting
  • Difficulty sleeping or resting for 12–24 hours after ingestion.
  • Paranoia, irritability, anxiety (increasing with dose).
  • Delusional, aggressive, or dissociated behaviour at very high doses (20+ mg)
  • Risk of death

Dangers

If misrepresented as LSD, 5-MeO-AMT can be extremely dangerous; users may take a number of "hits" of 5-MeO-AMT, assuming that it is LSD. Unlike LSD, which is very safe in overdose, 5-MeO-AMT can be very harmful or fatal. Particularly sensitive individuals can experience symptoms of overdose at dosages in the normal (for most users) range — as low as 20 mg. This has led to at least a few hospitalizations and possibly more than one death.[10][11] It is likely that the overdose potential of the compound is due to its sympathomimetic effects, as the side effects noted in overdose cases include cardiac arrhythmia and seizure. It also seems that oral consumption is safer than insufflation.

Gloria Discerni, 18, died after overdosing on a drug initially believed to be LSD. Authorities learned months later that the drug wasn't LSD but a "designer drug" identified as 5-MeO-AMT.[12]

Interactions

See also: Psychedelic drug § Interactions, and Trip killer § Serotonergic psychedelic antidotes

Pharmacology

Pharmacodynamics

5-MeO-AMT activities
Target Affinity (Ki, nM)
5-HT1A 46–194 (Ki)
680 (EC50Tooltip Half-maximal effective concentration)
101% (EmaxTooltip maximal efficacy)
5-HT1B 417 (rat)
5-HT2A 3.1–34 (Ki)
2–8.4 (EC50)
84% (Emax)
5-HT2B 4 (EC50)
5-HT2C 90
α1A >12,000
α2A 11,000
D1 >25,000
D2 >25,000
D3 >25,000
H1 >25,000
TAAR1 1,100 (Ki) (rat)
4,800 (Ki) (mouse)
>10,000 (EC50) (human)
SERTTooltip Serotonin transporter 8,270–12,000 (Ki)
1,980–17,000 (IC50Tooltip half-maximal inhibitory concentration)
460 (EC50)
NETTooltip Norepinephrine transporter >22,000 (Ki)
37,000–78,000 (IC50)
8,900 (EC50)
DATTooltip Dopamine transporter >26,000 (Ki)
2,690–43,000 (IC50)
1,500 (EC50)
MAO-ATooltip Monoamine oxidase A 31,000 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [13][14][15][16][17][18][19]

5-MeO-AMT acts as a non-selective serotonin receptor agonist, including of the serotonin 5-HT1A, 5-HT2A, and 5-HT2B receptors, among others.[15][14] Its EC50Tooltip half-maximal effective concentration at the serotonin 5-HT2A receptor has been found to be 2 to 8.4 nM.[15][14] In relation to this, it is an extremely potent agonist of the serotonin 5-HT2A receptor in vitro, showing the highest potency of any other tryptamine assessed in one study.[14] Its potency in activating the serotonin 5-HT2A receptor was 38-fold higher than that of dimethyltryptamine (DMT) and 361-fold higher than that of psilocin in the same study.[14] It is also a highly potent agonist of the serotonin 5-HT2B receptor, with an EC50 of 4 nM.[14]

Whereas tryptamine, serotonin (5-hydroxytryptamine), and αMT show potent activity as monoamine releasing agents, including of serotonin, norepinephrine, and/or dopamine, the monoamine-releasing activity of 5-methoxylated tryptamine derivatives, like 5-methoxytryptamine, 5-MeO-NMT, and 5-MeO-DMT among others, is dramatically reduced or abolished.[20][21][22][16][15] Accordingly, whereas the EC50 values of αMT for induction of monoamine release are 22 to 68 nM for serotonin, 79 to 112 nM for norepinephrine, and 79 to 180 nM for dopamine, the EC50 values in the case of 5-MeO-AMT are 460 nM for serotonin, 8,900 nM for norepinephrine, and 1,500 nM for dopamine.[16][21][14] Similarly, it is of very low potency as a monoamine reuptake inhibitor (IC50Tooltip half-maximal inhibitory concentration values >1,000 nM).[16][14] Considering the very high potency of 5-MeO-AMT in activating the serotonin 5-HT2A receptor, its weak activities as a monoamine releasing agent and reuptake inhibitor are of questionable significance.[16][21][14][15]

5-MeO-AMT is a weak monoamine oxidase A (MAO-A) inhibitor, with an IC50 of 31,000 nM.[23][18] For comparison, the IC50 of AMT for MAO-A inhibition was 380 nM (~82-fold more potent than 5-MeO-AMT)[23][18] and the IC50 values of amphetamine (and its enantiomers) for MAO-A inhibition have been reported to be 11,000 to 70,000 nM.[23]

5-MeO-AMT produces the head-twitch response, a behavioral proxy of psychedelic effects, in rodents, and this is reversed by the serotonin 5-HT2A receptor antagonist ketanserin.[24][6][25] It substitutes for other psychedelics such as DOM and LSD in animal drug discrimination tests, but does not substitute for entactogens like MDMA or psychostimulants like dextromethamphetamine or cocaine.[26][15] In contrast to other psychedelics, 5-MeO-AMT has been found to not fully substitute for other psychedelics including DOM, LSD, and dimethyltryptamine (DMT), but did partially generalize to LSD (67% responding).[15] This is analogous to findings with 5-MeO-DMT, which has a major serotonin 5-HT2A receptor-mediated component to its discriminative stimulus properties.[27][28][29] 5-MeO-AMT does not produce locomotor hyperactivity, behavioral sensitization, conditioned place preference, or self-administration, further indicating a lack of psychostimulant-like effects as well as misuse potential.[15][24] Instead, 5-MeO-AMT produces hypolocomotion.[15] 5-MeO-AMT is known to produce sympathomimetic effects, but these effects likely depend on serotonin 5-HT2A receptor activation rather than on monoamine release or reuptake inhibition.[14] Other serotonergic psychedelics are also well known to produce sympathomimetic effects.[30][31][32]

Chemistry

5-MeO-AMT, also known as 5-methoxy-α-methyltryptamine, is a substituted tryptamine derivative. It is a derivative of tryptamine (T), 5-methoxytryptamine (5-MeO-T or 5-MT), and α-methyltryptamine (AMT or αMT) and is an analogue of other tryptamines like α-methylserotonin (5-HO-AMT) and 5-MeO-DMT. Some derivatives of 5-MeO-AMT include α,N-dimethyl-5-methoxytryptamine (5-MeO-α-Me-NMT or α,N,O-TMS) and α,N,N-trimethyl-5-methoxytryptamine (5-MeO-α-Me-DMT or α,N,N,O-TMS). As noted by Alexander Shulgin, the α-methylated tryptamines can be seen at as the tryptamine homologues of the amphetamines (α-methylated phenethylamines).

5-MeO-AMT is soluble in water and ethanol but not in ether.[33]

History

5-MeO-AMT was first synthesized and described in the scientific literature in 1958.[34][33][35] Its psychedelic effects in humans were first observed in 1976 and were described by Alexander Shulgin and David E. Nichols and colleagues by 1978.[34][33][36]

Society and culture

Australia

5-MeO-AMT is considered a Schedule 9 prohibited substance in Australia under the Poisons Standard (October 2015).[37] A Schedule 9 substance is a substance which may be abused or misused, the manufacture, possession, sale or use of which should be prohibited by law except when required for medical or scientific research, or for analytical, teaching or training purposes with approval of Commonwealth and/or State or Territory Health Authorities.[37]

Finland

5-MeO-AMT is scheduled in the "government decree on psychoactive substances banned from the consumer market".[38]

Sweden

Sveriges riksdags health ministry Statens folkhälsoinstitut classified 5-MeO-αMT as "health hazard" under the act Lagen om förbud mot vissa hälsofarliga varor (translated Act on the Prohibition of Certain Goods Dangerous to Health) as of Oct 1, 2004, in their regulation SFS 2004:696 listed as 5-metoxi-alfametyltryptamin (5-MeO-AMT), making it illegal to sell or possess.[39]

United Kingdom

5-MeO-αMT was made illegal in the United Kingdom as of 7 January 2015, along with 5-MeO-DALT. This was following the events of 10 June 2014 when the Advisory Council on the Misuse of Drugs recommended that 5-MeO-αMT be scheduled as a class A drug by updating the blanket ban clause on tryptamines.

United States

5-MeO-AMT is unscheduled at the federal level in the United States.[40] However, the DEA considers the chemical a controlled substance analogue.[2] The agency's opinion on this matter may change at any time.

Florida

5-MeO-AMT is a Schedule I controlled substance in the state of Florida, making it illegal to buy, sell, or possess.[41]

See also

References

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