6-Methoxyharmalan

Pharmaceutical compound From Wikipedia, the free encyclopedia

6-Methoxyharmalan, or 6-methoxyharmalane, also known as 6-methoxy-1-methyl-3,4-dihydro-β-carboline, is a naturally occurring serotonin receptor modulator, monoamine oxidase inhibitor, and hallucinogen of the β-carboline family related to harmaline (7-methoxyharmalan).^[2]^[3]^[4] It is a cyclized tryptamine and analogue of 5-MeO-DMT and melatonin (N-acetyl-5-methoxytryptamine).^[3]^[5] The compound has been isolated from Virola species.^[6]^[7]

Other names6-Methoxyharmalane; 6-Methoxy-1-methyl-3,4-dihydro-β-carboline; 10-Methoxyharmalan; 6-MeO-harmalan; 6-OMe-harmalan; 6-Methoxy-3,4-dihydroharman; 6-MeO-DHH

Routes of
administrationOral, intravenous injection^[1]

Drug classHallucinogen; Oneirogen; Monoamine oxidase inhibitor; Reversible inhibitor of MAO-A; Serotonin receptor modulator

ATC code

None

Quick facts Clinical data, Other names ...

6-Methoxyharmalan
Clinical data


Other names	6-Methoxyharmalane; 6-Methoxy-1-methyl-3,4-dihydro-β-carboline; 10-Methoxyharmalan; 6-MeO-harmalan; 6-OMe-harmalan; 6-Methoxy-3,4-dihydroharman; 6-MeO-DHH
Routes of administration	Oral, intravenous injection^[1]
Drug class	Hallucinogen; Oneirogen; Monoamine oxidase inhibitor; Reversible inhibitor of MAO-A; Serotonin receptor modulator
ATC code	None
Pharmacokinetic data
Onset of action	Oral: 1 hour^[1] IVTooltip Intravenous injection: almost immediate^[1]
Identifiers
IUPAC name 6-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole
CAS Number	3589-73-9
PubChem CID	417052
ChemSpider	10522291
UNII	43F45VJV8C
ChEBI	CHEBI:92962
ChEMBL	ChEMBL338115
CompTox Dashboard (EPA)	DTXSID80957306
Chemical and physical data
Formula	C₁₃H₁₄N₂O
Molar mass	214.268 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES CC1=NCCC2=C1NC3=C2C=C(C=C3)OC
InChI InChI=1S/C13H14N2O/c1-8-13-10(5-6-14-8)11-7-9(16-2)3-4-12(11)15-13/h3-4,7,15H,5-6H2,1-2H3 Key:HMBHRMFLDKKSCT-UHFFFAOYSA-N

Use and effects

6-Methoxyharmalan has been reported to be hallucinogenic in humans at a dose of 1.5 mg/kg (~100 mg) orally, with slightly (1.5-fold) greater potency than harmaline.^[8]^[1]^[9]^[3]^[4] Its onset of action via oral administration is about 1 hour.^[1] The drug also produces hallucinogenic effects at a dose of 1 mg/kg intravenously and with a near-immediate onset by this route.^[1] Its hallucinogenic effects are described as similar to those of harmaline.^[10] The hallucinogenic effects of β-carbolines like harmaline and 6-methoxyharmalan have been described as qualitatively distinct from those of serotonergic psychedelics like mescaline.^[1]^[4] On the other hand, they have been said to be similar to those of ibogaine.^[11]^[10]

Pharmacology

Pharmacodynamics

More information Target, Affinity (Ki, nM) ...

6-Methoxyharmalan activities
Target	Affinity (K_i, nM)
5-HT_1A	>10,000
5-HT_1B	>10,000
5-HT_1D	>10,000
5-HT_1E	ND
5-HT_1F	ND
5-HT_2A	4,220–5,600 (K_i) (rat) >10,000 (EC₅₀Tooltip half-maximal effective concentration) >10,000 (IC₅₀Tooltip half-maximal inhibitory concentration)
5-HT_2B	ND
5-HT_2C	924 (rat)
5-HT₃	>10,000
5-HT₄	ND
5-HT_5A	>10,000
5-HT₆	1,930
5-HT₇	2,960
α_1A–α_1D	ND
α_2A–α_2C	ND
β₁, β₃	ND
D₁–D₅	>10,000 (human/rat)
H₁–H₄	ND
M₁–M₅	>10,000
I₁, I₂	ND
σ₁, σ₂	ND
TAAR1Tooltip Trace amine-associated receptor 1	ND
BDZ	>10,000 (rat)
PCP	>10,000 (rat)
SERTTooltip Serotonin transporter	>10,000 (K_i)
NETTooltip Norepinephrine transporter	4,100 (K_i)
DATTooltip Dopamine transporter	>10,000 (K_i) (bovine)
MAO-ATooltip Monoamine oxidase A	ND (IC₅₀)
MAO-BTooltip Monoamine oxidase B	ND (IC₅₀)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: ^[12]^[13]^[14]^[3]^[15]

6-Methoxyharmalan shows modest affinity for the serotonin 5-HT_2A receptor (K_i = 4,220–5,600 nM) and for the serotonin 5-HT_2C receptor (K_i = 924 nM).^[14]^[3] Its affinity for the serotonin 5-HT_2A receptor is similar to that of harmaline.^[14]^[3] Despite their appreciable affinities for the serotonin 5-HT_2A receptor, neither 6-methoxyharmalan nor harmaline showed any agonist or antagonist activity at the receptor at a concentration of 10,000 nM (and also at 20,000 nM in the case of harmaline).^[14] On the other hand, 6-methoxyharmalan has been reported to be a potent serotonin antagonist in other in-vitro systems, such as the isolated rat uterus and isolated guinea pig ileum.^[16] 6-Methoxyharmalan does not bind to the serotonin 5-HT_1A receptor or the dopamine D₂ receptor.^[14] However, it does also bind to the serotonin 5-HT₆ and 5-HT₇ receptors (K_i = 1,930 nM and 2,960 nM, respectively), but not to various other serotonin receptors, the serotonin transporter (SERT), or a variety of other targets.^[13] The compound has also been reported to be a very weak glycine receptor antagonist (IC₅₀Tooltip half-maximal inhibitory concentration = 82,000–101,000 nM).^[17]^[18] Besides receptor and transporter interactions, 6-methoxyharmalan has been reported to be a potent monoamine oxidase inhibitor (MAOI).^[19]^[20]

Similarly to harmaline, but in contrast to harman and harmine, 6-methoxyharmalan substitutes for the serotonergic psychedelic DOM in rodent drug discrimination tests.^[2] In addition, 6-methoxyharmalan fully substitutes for the atypical hallucinogen ibogaine in drug discrimination tests, whereas harmaline partially to fully substitutes for ibogaine in these tests.^[11]^[21]

It is unclear whether the serotonin 5-HT_2A receptor mediates the hallucinogenic effects of 6-methoxyharmalan and other β-carbolines or not.^[13]^[14] While 6-methoxyharmalan and harmaline showed no serotonin 5-HT_2A receptor agonistic activity in vitro, there could be limitations of the assay or they might have active metabolites that activate the receptor instead, among other possibilities.^[14] Alternatively, the hallucinogenic effects of these compounds may not be mediated by serotonin 5-HT_2A receptor activation.^[13]^[14] This would be in accordance with their hallucinogenic effects being described as distinct from those of psychedelics like mescaline^[1]^[4] but similar to those of the structurally related ibogaine.^[22]^[23] Moreover, the relatively selective serotonin 5-HT_2A receptor antagonist pirenperone did not affect harmaline's substitution of ibogaine in rodent drug discrimination tests.^[22]^[23]

History

6-Methoxyharmalan was first described by at least the early 1960s.^[19]^[16] Its hallucinogenic effects were first described by Claudio Naranjo in 1967.^[3]^[4] Melatonin can easily undergo cyclization into 6-methoxyharmalan under physiological conditions in vitro^[5] and 6-methoxyharmalan has been hypothesized to be a minor metabolite of melatonin in vivo.^[19]^[1] It was once suggested, by William McIsaac and colleagues in the early 1960s, that excessive production of 6-methoxyharmalan from melatonin might be involved in the pathophysiology of psychiatric disorders.^[19]^[16]^[24]^[25] However, all attempts to find 6-methoxyharmalan in living organisms were unsuccessful.^[26]

Society and culture

Legal status

Canada

6-Methoxyharmalan is not a controlled substance in Canada as of 2025.^[27]

References

[1]
Brimblecombe RW, Pinder RM (1975). "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. OL 4850660M. 6-Methoxyharmalan (4.32) produces marked subjective changes in man at oral doses of 1.5 mg./kg., being about 1.5 times as active as the isomeric harmaline (4.30). Intravenous doses of 1 mg./kg. are effective almost immediately but subjective changes appear about one hour following oral administration. 6-Methoxytetrahydroharman (4.34) was also psychoactive, eliciting mild subjective changes at 1.5 mg./kg. (p.o.), but being only three times as potent as harmaline. 1,2,3,4-Tetrahydroharmaline (4.31) was tested in only one subject, where it appeared to be about one-third as potent as harmaline in doses of 300 mg. (p.o.). Some of the responses to harmala alkaloids reported by Naranjo are nausea, dizziness, and general malaise, together with pareaesthesias of the hands, feet, and face, followed by numbness. Distortions of body image and of objects in the environment, so common with LSD or mescaline were not present and there was no enhancement of colour. However, there was abundant closed-eye imagery, hypersensitive hearing, and the superposition of imaginary scenes simultaneously with an undistorted perception of surrounding objects. [...] It is possible also that 6-methoxyharmalan could be derived from melatonin by dehydrative cyclization, and the compound has been tentatively proposed as a melatonin metabolite (Mcisaac and others, 1961). Both β-carbolines are hallucinogenic in man (Naranjo, 1967), [...]
[2]
Glennon RA, Young R, Jacyno JM, Slusher M, Rosecrans JA (January 1983). "DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines". European Journal of Pharmacology. 86 (3–4): 453–459. doi:10.1016/0014-2999(83)90196-6. PMID 6572591.
[3]
Grella B, Dukat M, Young R, Teitler M, Herrick-Davis K, Gauthier CB, et al. (April 1998). "Investigation of hallucinogenic and related beta-carbolines". Drug and Alcohol Dependence. 50 (2): 99–107. doi:10.1016/s0376-8716(97)00163-4. PMID 9649961. 6-Methoxyharmalan is reportedly hallucinogenic at oral doses of 1.5 mg/kg, and 6-methoxytetrahydroharman elicited mild psychoactive effects at 1.5 mg/kg and is said to be about one-third as potent as 6-methoxyharmalan (Naranjo, 1967); however, details were not provided and only scant information is available about these latter agents. [...] The DOM stimulus also generalizes to harmaline and 6-methoxyharmalan (Glennon et al., 1983). [...] We have also demonstrated that the DOM stimulus generalizes to harmaline (ED50= 6.19 mg/kg) and 6-methoxyharmalan (ED50=5.13 mg/kg; Glennon et al., 1983).
[4]
Claudio Naranjo (1967). "Psychotropic Properties of the Harmala Alkaloids" (PDF). In Efron DH, Holmstedt B, Kline NS (eds.). Ethnopharmacologic Search for Psychoactive Drugs, Proceedings of a Symposium held in San Francisco, California, January 28–30, 1967. Raven Press. pp. 385–391. ISBN 978-0-89004-047-8.
[5]
Shulgin AT (1980). "Hallucinogens". In Burger A, Wolf ME (eds.). Burger's Medicinal Chemistry. Vol. 3 (4 ed.). New York: Wiley. pp. 1109–1137. ISBN 978-0-471-01572-7. OCLC 219960627. Finally, the hormone melatonin (60.15), associated with the pineal gland, can undergo facile cyclization to 60.16 in vitro under physiological conditions (47), and there is a single report (48) that it has central activity in man. However, attempts to identify it in body fluids or tissue extracts have failed.
[6]
González-Rodríguez M, Ruiz-Fernández C, Francisco V, Ait Eldjoudi D, Farrag AbdElHafez YR, Cordero-Barreal A, et al. (February 2021). "Pharmacological Extracts and Molecules from Virola Species: Traditional Uses, Phytochemistry, and Biological Activity". Molecules. 26 (4). Basel, Switzerland: 792. doi:10.3390/molecules26040792. PMC 7913652. PMID 33546469. The β-carbolines 6-methoxyharmalan and 6-methoxyharman, which have been suggested to possess some psychoactive effects, have also been isolated from V. elongata [19].
[7]
Cassady JM, Blair GE, Raffauf RF, Tyler VE (March 1971). "The isolation of 6-methoxyharmalan and 6-methoxyharman from Virola cuspidata". Lloydia. 34 (1): 161–162. PMID 5140263.
[8]
Nichols DE, Glennon RA (1984). "Medicinal Chemistry and Structure-Activity Relationships of Hallucinogens". In Jacobs BL (ed.). Hallucinogens: Neurochemical, Behavioral, and Clinical Perspectives. New York: Raven Press. pp. 95–142. ISBN 978-0-89004-990-7. OCLC 10324237. Harmaline (80) appears to be about twice as active as its fully saturated counterpart harmine (152). Naranjo (151,152) determined that harmaline was effective at intravenous doses of 1 mg/kg and at total oral doses of 300 to 400 mg. In a limited study, tetrahydroharmine (81) was found to be approximately one-third as active as harmaline, with an oral dose of 300 mg producing an effect similar to that of 100 mg harmaline (152). Repositioning of the 7-methoxy group of harmaline to the 6-position gives 6-methoxyharmalan (85). This compound was active at oral doses of approximately 100 mg (1.5 mg/kg). Reduction to the tetrahydro counterpart, 6-methoxytetrahydroharman (86), resulted in a compound with about one-third the potency of the parent 6-methoxyharmalan (152).
[9]
Shulgin AT (1976). "Psychotomimetic Agents". In Gordon M (ed.). Psychopharmacological Agents: Use, Misuse and Abuse. Medicinal Chemistry: A Series of Monographs. Vol. 4. Academic Press. pp. 59–146. doi:10.1016/b978-0-12-290559-9.50011-9. ISBN 978-0-12-290559-9. In the analogous 6-methoxyharman series, Naranjo has reported the analog of harmaline, 6-methoxyharmalan (XL VI) to be orally active with threshold effects noted at oral levels of 1.5 mg/kg. The same levels of the tetrahydro counterpart, 6-methoxytetrahydroharman (XL VII) led to "mild effects." It is uncertain if the totally aromatic analog, 6-methoxyharman, was evaluated. The psychic changes associated with the most thoroughly studied member of this series, harmaline, have been discussed at length (Naranjo, 1969) and compared with several other pharmacologically related psychotomimetic drugs (Naranjo, 1973).
[10]
Naranjo C (1969). "Psycotherapeutic Possibilities of New Fantasy-Enhancing Drugs". Clinical Toxicology. 2 (2): 209–224. doi:10.3109/15563656908990930. ISSN 0009-9309. Retrieved 27 May 2025. I intend to speak here of two drugs, harmaline and ibogaine, which bear some resemblance to one another in chemical constitution and may be grouped together in terms of their effects. [...] I have reported elsewhere [3] that a study carried out at the University of Chile demonstrated that 10-methoxyharmalan, when administered to humans, elicited subjective effects quite similar to those of harmaline. [...]
[11]
Helsley S, Rabin RA, Winter JC (2001). "Drug discrimination studies with ibogaine". The Alkaloids. Chemistry and Biology. 56: 63–77. doi:10.1016/s0099-9598(01)56008-3. PMID 11705117. One group of hallucinogens that has received little attention is the betacarboline (or Harmala) alkaloids group. Interestingly, these agents bear a strong structural resemblance to ibogaine. Anecdotal reports suggest that the tremorigenic and subjective effects of agents, such as harmaline and harmine, are not unlike those of ibogaine (13). Several of these alkaloids were tested in ibogaine-trained rats (10). The results are shown in Figure 3. Full generalization was observed with 6-methoxyharmalan and harmaline, while partial generalization was seen with harmine, harmane, harmalol, and THBC (tetrahydro-beta-carboline). No generalization was seen to 6,7-dimethoxy-4- ethyl-β-carboline-3-carboxylate (DMCM) or norharmane. Unfortunately, the mechanism of action of the harmala alkaloids remains unknown. [...]
[12]
Liu T. "BindingDB BDBM50132104 6-Methoxy-1-methyl-4,9-dihydro-3H-beta-carboline::6-methoxy-harmalan::CHEMBL338115". BindingDB. Retrieved 18 June 2025.
[13]
Grella B, Teitler M, Smith C, Herrick-Davis K, Glennon RA (December 2003). "Binding of beta-carbolines at 5-HT(2) serotonin receptors". Bioorganic & Medicinal Chemistry Letters. 13 (24): 4421–4425. doi:10.1016/j.bmcl.2003.09.027. PMID 14643338. [...] several β-carbolines, including harmaline (1) and its positional isomer 6-methoxyharmalan (4) substituted for the hallucinogenic (5-HT2A agonist) phenylalkylamine [DOM] in a drug discrimination task with rats trained to discriminate DOM from saline vehicle.10 However, neither harmaline (1; Ki=7790 nM) nor 6-methoxyharmalan (4; Ki=5600 nM) binds with high affinity at 5-HT2A receptors, and both were found to lack action as 5-HT2A agonists in a phosphoinositol (PI) hydrolysis assay.5,9 [...] At this time, it is not known if the actions of 1 and 4 in the PI hydrolysis assay reflect their low affinity, low efficacy, or whether the actions of the β-carbolines (in drug discrimination and/or other assays) is attributable to, or compromised by, their actions at other populations of receptors—particularly 5-HT receptors—or by possible interactions with the serotonin transporter.
[14]
Glennon RA, Dukat M, Grella B, Hong S, Costantino L, Teitler M, et al. (August 2000). "Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors" (PDF). Drug and Alcohol Dependence. 60 (2): 121–132. doi:10.1016/s0376-8716(99)00148-9. hdl:11380/17721. PMID 10940539.
[15]
Beato A, Gori A, Boucherle B, Peuchmaur M, Haudecoeur R (February 2021). "β-Carboline as a Privileged Scaffold for Multitarget Strategies in Alzheimer's Disease Therapy". J Med Chem. 64 (3): 1392–1422. doi:10.1021/acs.jmedchem.0c01887. PMID 33528252.
[16]
Hoffer A, Osmond H (1967). "Indole Hallucinogens Derived from Tryptophan". The Hallucinogens. Elsevier. pp. 443–516 (468). doi:10.1016/b978-1-4832-3296-6.50008-2. ISBN 978-1-4832-3296-6. LCCN 66030086. OCLC 332437. OL 35255701M. Melatonin is converted to 10-methoxyharmalan by the loss of one molecule of water (Mclsaac et al., 1961). The sequence of change (Mclsaac, 1961a,b) was from melatonin to 10-methoxyharmalan which is similar to harmine or harmaline. Mclsaac suggested that due to a peculiarity in metabolism, some serotonin could be converted to 5-methoxytryptamine and to a harminelike alkaloid or from serotonin to acetyl serotonin, melatonin, and then a harminelike toxic substance. Once produced, this would block monoamine oxidase, decrease the destruction of serotonin by a common pathway, and so increase the production of more psychotogen. This chemical reverberating system would perpetuate the illness (Mclsaac, 1961a,b). [...] Woolley and Shaw (1957) reported harmaline was a serotonin antagonist. Using the isolated estrus rat uterus (Mclsaac et al., 1961) found that 0.2 µg of serotonin was completely blocked by 0.5 µg of LSD and 50 µg of harmine or harmaline added 5 minutes before. At higher levels they caused muscle contractions and later antagonism to serotonin was reduced. Methoxyharmalan was 25 times as active and 2 µg was as effective as 0.5 µg of LSD. Similar results were obtained on isolated guinea pig ileum. It seemed likely 10-methoxyharmalan and serotonin were competitive. The methoxyharmalan also antagonized the pressor effect of serotonin.
[17]
Hamill J, Hallak J, Dursun SM, Baker G (2019). "Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness". Current Neuropharmacology. 17 (2): 108–128. doi:10.2174/1570159X16666180125095902. PMC 6343205. PMID 29366418. Another study showed that 4 beta-carbolines (1,2,3,4-tetrahydronorharmane, norharmane, harmane, and 6-methoxyharmalan) act as competitive antagonists at the glycine receptor ligand binding site, leading to inhibition at the glycine receptor [111].
[18]
Chen X, Cromer BA, Lynch JW (September 2009). "Molecular determinants of beta-carboline inhibition of the glycine receptor". J Neurochem. 110 (5): 1685–1694. doi:10.1111/j.1471-4159.2009.06273.x. PMID 19619142.
[19]
Szmuszkovicz J, Heinzelman RV (2013) [1963]. "Recent Studies in the Field of Indole Compounds". Progress in Drug Research / Fortschritte der Arzneimittelforschung / Progrès des recherches pharmaceutiques. Vol. 5. Basel: Birkhäuser Basel. pp. 75–150. doi:10.1007/978-3-0348-7050-4_2. ISBN 978-3-0348-7052-8. PMID 14287134. Retrieved 27 May 2025. Melatonin is formed from serotonin by N-acetylation followed by O-methylation [137, 204, 14, 15]. Its major metabolic pathway involves 6-hydroxylation to (X), followed by conjugation [119, 122]. A minor non-indolic metabolite is also produced, possibly by cyclodehydration of melatonin to form 3,4-dihydro-6-methoxy-l-methyl-9H-pyrido-[3,4-bJindole (XI) [122]. Depending on the numbering system used, this compound has been variously named '10-methoxyharmalan' [122], '6-methoxyharmalan' and '7-methoxyharmalan'. An interesting hypothesis concerning the cause of mental disease has been proposed by McIsAAC [134] who suggests that in certain cases of mental disease the normal metabolism of serotonin is blocked, causing formation of abnormally large amounts of melatonin and, hence, of its hypothetical metabolite (XI). The latter, a powerful monoamine oxidase inhibitor, would further inhibit the normal metabolism of serotonin and, by a chemical feedback mechanism, ultimately cause its own accumulation. Furthermore, (XI) was shown to be both a potent serotonin antagonist and a 'psychotomimetic agent', as evidenced by its effect on avoidance escape behavior in rats [136, 134]. {{cite book}}: |journal= ignored (help)
[20]
McKenna DJ (1984). Monoamine oxidase inhibitors in Amazonian hallucinogenic plants : ethnobotanical, phytochemical, and pharmacological investigations (Ph.D. thesis). University Of British Columbia. doi:10.14288/1.0096656. Archived from the original on 21 February 2020.
[21]
Helsley S, Rabin RA, Winter JC (March 1998). "The effects of beta-carbolines in rats trained with ibogaine as a discriminative stimulus". European Journal of Pharmacology. 345 (2): 139–143. doi:10.1016/s0014-2999(98)00002-8. PMID 9600629.
[22]
Alper KR (2001). Alper KR, Glick SD (eds.). "Ibogaine: A Review" (PDF). The Alkaloids. Chemistry and Biology. 56. San Diego: Academic: 1–38. doi:10.1016/S0099-9598(01)56005-8. ISBN 978-0-12-469556-6. ISSN 1099-4831. OCLC 119074989. PMID 11705103. Archived from the original (PDF) on 27 September 2007. A high degree of stimulus generalization is reported between ibogaine and some of the Harmala alkaloids, a group of hallucinogenic beta-carbolines that are structurally related to ibogaine (101,102). While the discriminative stimulus for both the Harmala alkaloids and ibogaine apparently involves the 5-HT2 receptor (84,85,103), it does not appear essential to generalization between ibogaine and harmaline, as generalization to the harmaline stimulus was unaffected by the addition of a 5-HT2 antagonist in ibogaine-trained animals (84).
[23]
Helsley S, Fiorella D, Rabin RA, Winter JC (February 1998). "Behavioral and biochemical evidence for a nonessential 5-HT2A component of the ibogaine-induced discriminative stimulus". Pharmacology, Biochemistry, and Behavior. 59 (2): 419–425. doi:10.1016/s0091-3057(97)00451-6. PMID 9476990.
[24]
McIsaac WM (August 1961). "A biochemical concept of mental disease". Postgraduate Medicine. 30 (2): 111–118. doi:10.1080/00325481.1961.11694351. PMID 13774015.
[25]
McIsaac WM, Khairallah PA, Page IH (September 1961). "10-Methoxyharmalan, a potent serotonin antagonist which affects conditioned behavior". Science. 134 (3480). New York, N.Y.: 674–675. Bibcode:1961Sci...134..674M. doi:10.1126/science.134.3480.674. PMID 13774014.
[26]
Shulgin AT (1969). "Psychotomimetic Agents Related to the Catecholamines". Journal of Psychedelic Drugs. 2 (2): 14–19. doi:10.1080/02791072.1969.10524409. ISSN 0022-393X. More intriguing are the isomers of marmaline wherein the methoxyl group is relocated to the position entirely analogous to serotonin. This material is 6-methoxyharmalan (Vib; Figure 4), and its dehydro- and dihydro- counterparts (6-methoxyharman and 6-methoxytetrahydroharman) are all several times more potent than the 7-methoxy compounds. They have yet to be found in nature. They have, nonetheless, been generated in vitro by the cyclization of melatonin, and although such reactions are most appealing in the hypothesis of the in situ generation of an active psychotogen from a known pineal metabolite, all searches for this product in the intact living system have failed.
[27]
"Controlled Drugs and Substances Act". Department of Justice Canada. Retrieved 19 January 2026.