4-HO-MET

4-HO-MET, also known as 4-hydroxy-N-methyl-N-ethyltryptamine or as metocin, is a lesser-known psychedelic drug of the tryptamine family related to psilocin.^[1] It is a close structural and functional analogue of psilocin (4-HO-DMT) and is the 4-hydroxyl analogue of methylethyltryptamine (MET).^[1] The drug has been encountered as a novel recreational and designer drug.^[4]

4-HO-MET

Clinical data
Other names	4-Hydroxy-N-methyl-N-ethyltryptamine; 4-OH-MET; Metocin; Methylcybin
Routes of administration	Oral[1]
Drug class	Serotonin receptor agonist; Serotonergic psychedelic; Hallucinogen
ATC code	None
Legal status
Legal status	US: Unscheduled Schedule I controlled substance in Virginia[2]
Pharmacokinetic data
Duration of action	4–6 hours[1][3]
Identifiers
IUPAC name 3-{2-[Ethyl(methyl)amino]ethyl}-1H-indol-4-ol
CAS Number	77872-41-4
PubChem CID	21786582
ChemSpider	10513072
UNII	6RN01B78NY
CompTox Dashboard (EPA)	DTXSID70228491
Chemical and physical data
Formula	C13H18N2O
Molar mass	218.300 g·mol−1
3D model (JSmol)	Interactive image
SMILES CCN(C)CCc2c[nH]c1cccc(O)c12
InChI InChI=1S/C13H18N2O/c1-3-15(2)8-7-10-9-14-11-5-4-6-12(16)13(10)11/h4-6,9,14,16H,3,7-8H2,1-2H3 Key:ORWQBKPSGDRPPA-UHFFFAOYSA-N

Effects

4-HO-MET was first synthesized by Alexander Shulgin.^[5][1] In his book TiHKAL (Tryptamines I Have Known and Loved), the dosage is listed as 10 to 20 mg orally and its duration as 4 to 6 hours.^[1][6][3] However, a wider recreational dosage range of 2 to 45 mg or more, with a dose estimate of 15 mg, has also been reported.^[7]

The effects of 4-HO-MET have been reported to include mydriasis, euphoria, tingling sensations, perceptual changes, closed- and open-eye visuals, synesthesia, time dilation, intensified perceptions, thoughts, and feelings, and a general change in thought processes.^[3][8][1]

4-HO-MET is said to produce qualitative effects very similar to those of psilocin.^[1][8][3] However, it has also been described as being a relatively or very light and more clear-headed and functional psychedelic with less head space.^[8] On the other hand, it is said to still produce strong visuals.^[8] This has been described as being analogous to the case of 2C-B.^[8]

Interactions

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

Pharmacology

Pharmacodynamics

4-HO-MET activities

Target	Affinity (Ki, nM)
5-HT1A	135–950 (Ki) 1,390 (EC50Tooltip half-maximal effective concentration) 90% (EmaxTooltip maximal efficacy)
5-HT1B	331
5-HT1D	197
5-HT1E	161
5-HT1F	ND
5-HT2A	4.0–177 (Ki) 18–97 (EC50Tooltip half-maximal effective concentration) 54–95% (EmaxTooltip maximal efficacy)
5-HT2B	12 (Ki) 2.64–>20,000 (EC50) 44–71% (Emax)
5-HT2C	141–164 (Ki) 30–113 (EC50) 87–101% (Emax)
5-HT3	ND
5-HT4	ND
5-HT5A	304
5-HT6	70
5-HT7	60
α1A	9,700
α1B, α1D	ND
α2A	1,666–2,400
α2B, α2C	IA
β1–β3	ND
β2	ND
D1	25,000
D2	4,000
D3	6,700
D4, D5	IA
H1	483–820
H2	IA
H3, H4	ND
M1–M3, M5	ND
M2	IA
I1	ND
σ1, σ2	IA
TAAR1Tooltip Trace amine-associated receptor 1	12,000 (Ki) (mouse) 3,100 (Ki) (rat) 2,500 (EC50) (mouse) 2,100 (EC50) (rat) >10,000 (EC50) (human) 78% (Emax) (mouse) 71% (Emax) (rat)
SERTTooltip Serotonin transporter	200–2,310 (Ki) 830–9,000 (IC50Tooltip half-maximal inhibitory concentration) IA (EC50)
NETTooltip Norepinephrine transporter	13,000 (Ki) 11,000 (IC50) IA (EC50)
DATTooltip Dopamine transporter	>26,000 (Ki) >100,000 (IC50) IA (EC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [9][10][11][12][13]

4-HO-MET binds to various serotonin receptors and is known to act as an agonist of the serotonin 5-HT_2A, 5-HT_2B, 5-HT_2C, and 5-HT_1A receptors.^{[9][10][11][12]} It is thought that the hallucinogenic effects of serotonergic psychedelics like 4-HO-MET are mediated by serotonin 5-HT_2A receptor activation.^[14]

Pharmacokinetics

The metabolism of 4-HO-MET has been studied.^[15]

History

4-HO-MET was first synthesized and discovered by Alexander Shulgin in the 1970s.^[8][5][1] It was first described in the scientific literature by David Repke and colleagues by 1981.^[16] Subsequently, 4-HO-MET was described by Shulgin in his book TiHKAL (Tryptamines I Have Known and Loved) in 1997.^[1] It was encountered as a novel recreational and designer drug in Europe by 2008.^[4]

Legal status

Finland

Scheduled in the "government decree on psychoactive substances banned from the consumer market".^[17]

Germany

4-HO-MET is ruled under the Neue-psychoaktive-Stoffe-Gesetz (NpSG) since July 18, 2019. Production and Import with intent to distribute is punishable. Possession is forbidden but not punishable, although ordering it in small quantities can still be seen as an intent to distribute it and be punished.^{[citation needed]}

Sweden

The Swedish Riksdag added 4-HO-MET to Schedule I ("substances, plant materials and fungi which normally do not have medical use") as narcotics in Sweden as of May 1, 2012, published by Medical Products Agency in their regulation LVFS 2012:6.^[18]

United Kingdom

4-HO-MET is a class A drug in the UK, as a result of the tryptamine catch-all clause.^{[citation needed]}

United States

4-HO-MET is not scheduled at the federal level in the United States, but it is possible that it could be considered an analogue of psilocin, in which case purchase, sale, or possession could be prosecuted under the Federal Analogue Act.^[19]

It is a schedule I substance in some states, such as South Dakota^[20] and West Virginia.^[21]

See also

• 4-HO-DET
• Borax combo