Asubstituted β-carboline, also known as asubstituted 9H-pyrido[3,4-b]indole, is achemical compound featuring aβ-carbolinemoiety with one or moresubstitutions. β-Carbolines include more than one hundredalkaloids and synthetic compounds. The effects of these substances depend on their respectivesubstituent. Natural β-carbolines primarily influencebrain functions but can also exhibitantioxidant[1] effects. Synthetically designed β-carbolinederivatives have recently been shown to haveneuroprotective,[2]cognitive enhancing and anti-cancer properties.[3]
β-Carbolines areindole alkaloids featuring a fusedpyridine andindole ring structure similar totryptamine, forming a three-ringed system with variable saturation in the third ring. β-Carbolinealkaloids naturally occur widely inprokaryotes,plants,animals, certain marinetunicates, and foods likecoffee and smokedmeats, and are also responsible for the fluorescence ofscorpion cuticles underultraviolet light. β-Carbolines occurring naturally inPeganum harmala (Syrian rue) are known asharmala alkaloids.[4]
Some β-carbolines, likeharmaline, arehallucinogenic.[5][6][7] According toAlexander Shulgin, harmaline is the only β-carboline that has been extensively studied and well-established as a hallucinogen.[5][6][7] β-Carbolines are known to act asmonoamine oxidase inhibitors (MAOIs), among possessing otheractivities.[4][8] They are an essential component ofayahuasca, by inhibiting themetabolism of thepsychedelicdimethyltryptamine (DMT).[8][4]
β-Carbolines arecyclized tryptamines related toserotonergic psychedelics likedimethyltryptamine (DMT) and5-MeO-DMT.[5][6][7][9] Some simple β-carbolines have been reported to behallucinogenic and have been referred to asoneirogens.[5][6][7][9][10] These includeharmine,harmaline,tetrahydroharmine,6-methoxyharmalan, and6-methoxytetrahydroharman (6-MeO-THH).[5][6][7][9] According toAlexander Shulgin however, harmaline is the only β-carboline that has been extensively studied and well-established as a hallucinogen.[5][6][7] β-Carbolines are active bothorally andparenterally, with doses, depending on the compound, in the area of 100 to 300 mg or more orally and 1 to 1.5 mg/kg (~70–100 mg for a 70-kg person)intravenously.[9][11][12] Althoughstructurally related to psychedelic tryptamines, the hallucinogenic effects of β-carbolines are said to be qualitatively distinct from those of serotonergic psychedelics.[11][13] Instead, they are described as being similar to those ofibogaine, which is also a cyclized tryptamine and structurally related atypical hallucinogen.[14][10]
Various β-carbolines arepotentmonoamine oxidase inhibitors (MAOIs), more specificallyreversible inhibitors of MAO-A (RIMAs).[12] They are used inayahuasca toinhibit themonoamine oxidase (MAO)-mediatedmetabolism of theserotonergic psychedelicdimethyltryptamine (DMT) to allow it to beorally active and to have a much longerduration than it would otherwise.[12][15][4][16] They can also used in a similar fashion with5-MeO-DMT.[12]
| Compound | Chemical name | Dose (hallucinogen) | Potency | Dose (MAOI) | Duration |
|---|---|---|---|---|---|
| Harman | 1-Methyl-β-carboline | >250 mg | Unknown | >250 mg | Unknown |
| Harmine | 7-Methoxyharman | >300 mg | ≤50% | 140–250 mg | 6–8 hours |
| Harmaline | 7-Methoxy-3,4-dihydroharman | 150–400 mg | 100% | 70–150 mg | 5–8 hours |
| Tetrahydroharmine | 7-Methoxy-1,2,3,4-tetrahydroharman | ≥300 mg | ~33% | Unknown | Unknown |
| 6-Methoxyharmalan | 6-Methoxy-3,4-dihydroharman | ~100 mg | ~150% | Unknown | Unknown |
| 6-MeO-THH | 6-Methoxy-1,2,3,4-tetrahydroharman | ≥100 mg | ~50% | Unknown | Unknown |
| P. harmala seeds | – | ≥5–28 ga | – | 3–5 ga | Unknown |
| Footnotes:a =P. harmala seeds in ground form. They contain 2–7%harmala alkaloids, with 1 teaspoon ≈ 3 g ≈ 60–180 mg alkaloids; 1 tablespoon ≈ 9 g ≈ 200–600 mg alkaloids; and 1 large (OO) gelatin capsule ≈ 0.7 g ≈ 15–45 mg alkaloids. For comparison,B. caapi contains 0.05–1.95% (average 0.45%) harmala alkaloids.Note:Harmine and otherβ-carbolines have also been tested by non-oralroutes such assublingual,subcutaneous injection,intramuscular injection, andintravenous injection.Refs: See template page. | |||||
The pharmacological effects of specific β-carbolines are dependent on theirsubstituents. For example, the natural β-carbolineharmine has substituents on position 7 and 1. Thereby, it acts as a selectiveinhibitor of theDYRK1Aprotein kinase, a protein necessary forneurodevelopment.[17][18] It also exhibits variousantidepressant-like effects in rats by interacting withserotonin receptor 2A.[19][20] Furthermore, it increases levels of thebrain-derived neurotrophic factor (BDNF) in rathippocampus.[20][21] A decreased BDNF level has been associated with majordepression in humans. The antidepressant effect of harmine might also be due to its function as aMAO-A inhibitor by reducing the breakdown ofserotonin andnoradrenaline.[21][22]
A syntheticderivative,9-methyl-β-carboline, has shownneuroprotective effects including increasedexpression ofneurotrophic factors and enhancedrespiratory chain activity.[23][24] This derivative has also been shown to enhancecognitive function,[25] increasedopaminergic neuron count and facilitatesynaptic anddendritic proliferation.[26][27] It also exhibited therapeutic effects in animal models forParkinson's disease and otherneurodegenerative processes.[24]
However, β-carbolines with substituents in position 3 reduce the effect ofbenzodiazepine onGABA-A receptors and can therefore haveconvulsive,anxiogenic and memory enhancing effects.[28] Moreover, 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect offlurazepam in rodents and – by itself – can decrease sleep in a dose-dependent manner.[29] Another derivative, methyl-β-carboline-3-carboxylate, stimulates learning and memory at lowdoses but can promote anxiety and convulsions at high doses.[28] With modification in position 9 similar positive effects have been observed for learning and memory without promotion of anxiety or convulsion.[25]
β-carboline derivatives also enhance the production of theantibiotic reveromycin A in soil-dwellingStreptomyces species.[30][31] Specifically, expression ofbiosyntheticgenes is facilitated by binding of the β-carboline to a largeATP-binding regulator of theLuxR family.
AlsoLactobacillus spp. secretes a β-carboline (1-acetyl-β-carboline) preventing the pathogenic fungusCandida albicans to change to a morevirulent growth form (yeast-to-filament transition). Thereby, β-carboline reverses imbalances in themicrobiome composition causingpathologies ranging fromvaginal candidiasis to fungal sepsis.[32]
Since β-carbolines also interact with variouscancer-related molecules such asDNA,enzymes (GPX4,kinases, etc.) andproteins (ABCG2/BRCP1, etc.), they are also discussed as potential anticancer agents.[3]
The hallucinogenic effects of β-carbolines are said to be qualitatively distinct from those ofserotonergic psychedelics likemescaline but similar to those ofibogaine.[11][13][14][10] Along these lines, β-carbolines and ibogaine fully substitute for each other in rodentdrug discrimination tests.[14][33][34] Themechanism of action of hallucinogens of the β-carboline and ibogaine type is unclear.[35][14][33][34][36][37][19] Findings are conflicting on whetherserotonin5-HT2A receptoractivation may be involved or not.[35][19][34][36] β-Carbolines and ibogaine do have lowaffinity for the serotonin 5-HT2A receptor, but β-carbolines failed to activate the receptor even at high concentrations.[34][37][19] β-Carbolines and ibogaine show stimulus generalization with serotonergic psychedelics likeDOM andLSD in rodentdrug discrimination tests and this generalization can be blocked by serotonin5-HT2 receptorantagonists.[35][34][14][36] On the other hand, a fairlyselective serotonin 5-HT2A receptor antagonist did not affect harmaline's substitution of ibogaine in rodent drug discrimination tests.[34][36] Moreover, unlike psychedelics, ibogaine does not produce thehead-twitch response in rodents.[38][39]
The extract of thelianaBanisteriopsis caapi has been used by the tribes of theAmazon as anentheogen and was described as ahallucinogen in the middle of the 19th century.[40] In early 20th century, European pharmacists identifiedharmine as the active substance.[41] This discovery stimulated the interest to further investigate its potential as a medicine. For example,Louis Lewin, a prominent pharmacologist, demonstrated a dramatic benefit in neurological impairments after injections ofB. caapi in patients withpostencephalitic Parkinsonism.[40] By 1930, it was generally agreed thathypokinesia,drooling, mood, and sometimes rigidity improved by treatment with harmine. Altogether, 25 studies had been published in the 1920s and 1930s about patients withParkinson's disease and postencephalitic Parkinsonism. The pharmacological effects of harmine have been attributed mainly to its centralmonoamine oxidase (MAO) inhibitory properties.In-vivo and rodent studies have shown that extracts ofBanisteriopsis caapi and alsoPeganum harmala lead tostriataldopamine release.[42][43][44] Furthermore, harmine supports the survival of dopaminergic neurons inMPTP-treated mice.[45] Since harmine alsoantagonizesN-methyl-d-aspartate(NMDA) receptors,[46] some researchers speculatively attributed the rapid improvement in patients with Parkinson's disease to these antiglutamatergic effects.[40] However, the advent of syntheticanticholinergic drugs at that time led to the total abandonment of harmine.[40]
β-Carbolines belong to the group ofindole alkaloids and consist ofa pyridine ring that is fused to anindole skeleton.[47] The structure of β-carboline is similar to that oftryptamine, with theethylamine chain re-connected to theindole ring via an extracarbon atom, to produce a three-ringed structure. The biosynthesis of β-carbolines is believed to follow this route from analogous tryptamines.[48] Different levels ofsaturation are possible in the third ring which is indicated here in thestructural formula by coloring the optionally double bonds red and blue:
| Indole sub. | Aromatic (H0) | Dihydro (H2) | Tetrahydro (H4) | Tryptamine counterpart[a] |
|---|---|---|---|---|
| with a 1-methyl substituent | ||||
| Ar-H | Harman | Harmalan | Tetrahydroharman | Tryptamine |
| Ar-5-OH | 5-Harmol | 5-Harmalol | 5-Tetrahydroharmol | 4-Hydroxytryptamine |
| Ar-5-OMe | 5-Methoxyharman | 5-Methoxyharmalan | 5-MeO-THH | 4-Methoxytryptamine |
| Ar-6-OH | 6-Harmol | 6-Harmalol | 6-Tetrahydroharmol | Serotonin (5-HT) |
| Ar-6-OMe | 6-Methoxyharman | 6-Methoxyharmalan | 6-MeO-THH | 5-Methoxytryptamine |
| Ar-7-OH | Harmol | Harminol | Tetrahydroharmol | 6-Hydroxytryptamine |
| Ar-7-OMe | Harmine | Harmaline | Tetrahydroharmine | 6-Methoxytryptamine |
| with a 1-hydrogen substituent | ||||
| Ar-H | βC (norharman) | DHβC | Tryptoline (THβC) | Tryptamine |
| Ar-5-OH | 5-HO-βC | 5-HO-DHβC | 5-HO-THβC | 4-Hydroxytryptamine |
| Ar-5-OMe | 5-MeO-βC | 5-MeO-DHβC | 5-MeO-THβC | 4-Methoxytryptamine |
| Ar-6-OH | 6-HO-βC | 6-HO-DHβC | 6-HO-THβC | Serotonin (5-HT) |
| Ar-6-OMe | 6-MeO-βC | 6-MeO-DHβC | Pinoline (6-MeO-THβC) | 5-Methoxytryptamine |
| Ar-7-OH | 7-HO-βC | 7-HO-DHβC | 7-HO-THβC | 6-Hydroxytryptamine |
| Ar-7-OMe | 7-MeO-βC | 7-MeO-DHβC | 7-MeO-THβC | 6-Methoxytryptamine |
| Refs:[49][50][19] | ||||
A list of simple β-carbolines is tabulated by structure below. Their structures may contain the aforementioned bonds marked by red or blue.
| Short name | R1 | R5 | R6 | R7 | R8 | R9 | Structure | Tryptamine counterpart[a] |
|---|---|---|---|---|---|---|---|---|
| β-Carboline (norharman; βC) | H | H | H | H | H | H | | Tryptamine |
| Tryptoline (THβC) | H | H | H | H | H | H |  | Tryptamine |
| Harmane | CH3 | H | H | H | H | H |  | Tryptamine |
| Tetrahydroharman | CH3 | H | H | H | H | H |  | Tryptamine |
| Harmine | CH3 | H | H | OCH3 | H | H |  | 6-Methoxytryptamine |
| Harmaline | CH3 | H | H | OCH3 | H | H |  | 6-Methoxytryptamine |
| 6-Methoxyharman | CH3 | H | OCH3 | H | H | H |  | 5-Methoxytryptamine |
| 6-Methoxyharmalan | CH3 | H | OCH3 | H | H | H |  | 5-Methoxytryptamine |
| 6-HO-THβC | H | H | OH | H | H | H |  | 5-Hydroxytryptamine |
| Pinoline (6-MeO-THβC) | H | H | OCH3 | H | H | H |  | 5-Methoxytryptamine |
| 6-MeO-THH | CH3 | H | OCH3 | H | H | H |  | 5-Methoxytryptamine |
| Harmol | CH3 | H | H | OH | H | H |  | 6-Hydroxytryptamine |
| Tetrahydroharmol | CH3 | H | H | OH | H | H |  | 6-Hydroxytryptamine |
| Harmalol | CH3 | H | H | OH | H | H |  | 6-Hydroxytryptamine |
| Tetrahydroharmine (THH) | CH3 | H | H | OCH3 | H | H |  | 6-Methoxytryptamine |
| Norharmine | H | H | H | OCH3 | H | H |  | 6-Methoxytryptamine |
| 5-Methoxyharmalan | CH3 | OCH3 | H | H | H | H |  | 4-Methoxytryptamine |
| 9-Methyl-β-carboline | H | H | H | H | H | CH3 |  | 1-Methyltryptamine |
| 3-Carboxy-THβC | H / CH3 / COOH | H | H | H | H | H |  | – |
.jpg)
β-Carbolinealkaloids are widespread inprokaryotes,plants andanimals. Some β-carbolines, notably tetrahydro-β-carbolines, may be formed naturally in plants and the human body withtryptophan,serotonin andtryptamine asprecursors.
Recent studies tested i.v. DMT with different administration regimens. Such protocols entailed 0–19.2 mg bolus 0.5–0.8 mg/min constant infusion of DMT freebase (as hemifumarate) for up to 90 min (Basel) [7], 11.2 mg bolus 1.2 mg/min infusion of DMT freebase (as fumarate) for up to 30 min (London) [8], and constant infusion totaling 13.4 mg DMT freebase (as fumarate) over 10 min (London) [110]). [...] The various β-carbolines in B. caapi, especially harmine and harmaline, enable the attainment of sufficient plasma DMT concentrations to evoke psychedelic effects lasting 4–6 h [5, 61].
Close biosynthetic relatives of harmaline (harmine and tetrahydroharmine) are known components of plants of several other genera which have medical use but no reputation as hallucinogens [...] The effective dose range of harmaline in man is 70-100 mg i.v., or 300-400 mg orally. The initial effects are noted about one hour following oral administration and persist for about 6 hours [...] The indicators of physical toxicity are common and often severe. Paresthesias of hands, feet, or face are almost always present with the onset of effects, and are usually followed by the sensation of numbness. There can be isolated symptoms such as pressure in the head or chest, nausea and distressful vomiting, dizziness, and general malaise. Mydriasis and pressor effects are never seen. The anxiety and general discomfort encourages a withdrawal from social contact, and a quiet dark environment is preferred by most subjects. The modality most consistently affected by harmaline is the visual sense. There can be vivid images generated, often in the form of meaningful dream-like sequences, and frequently containing subject matter such as wild animals or jungle scenes. Other reported visual syntheses are limited to the generation of geometric patterns which are entertaining but not felt to be of any intrinsic significance.
An additional family of compounds should be mentioned here, the β-carbolines. [...] In nature, they usually are found in one of three degrees of hydrogenation: harmine, harmaline, and tetrahydroharmine. [...] Only harmaline, one of the principal components of Ayahuasca, has a reputation for being intrinsically an active hallucinogen. The aromatic analog, harmine, has little if any psychotropic activity.
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).
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. [...] At the dosage level of 4–5 mg/kg" both harmaline and ibogaine elicit subjective reactions such as will be described in the following pages, which last for approximately 6 hr. [...] Soon after the intravenous injection of 100 mg of harmaline, the subject reported a feeling of elation associated with the sensation of being suspended in empty space. [...] The fragment reported here constitutes about 75% of the total session after the intake of 300 mg of harmaline by mouth and consists of my notes of his continuous monolog from a time shortly after the onset of the drug's effect.
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.
I have indeed found harmaline to be hallucinogenic at dosage levels above 1 mg./kg. i.v. or 4 mg./kg. by mouth, which is about one half the threshold level for harmine. It may be interesting to note at this point that the onset of effects of harmaline or other derivatives is about one hour after ingestion by mouth, but almost instantaneous after intravenous injection, if circulation time from elbow to brain is taken into account. [...] Tetrahydroharmine, the reduction product of harmaline, is another substance studied by Gunn and shown to be similar to its more saturated homologs, but three times less active than harmaline. Racemic tetrahydroharmine, up to the amount of 300 mg. by mouth, was administered by us to one volunteer, who reported that at this dosage level there were subjective effects similar to those he experienced with 100 mg. of harmaline. More trials would be required to assess the mean effective dosage of tetrahydroharmine as a hallucinogen, but this single experiment suggests that racemic tetrahydroharmine is about one-third as active as harmaline, corresponding to Gunn's estimation on the basis of lethal dosage. 6-Methoxyharmalan was indeed shown to be hallucinogenic, as was anticipated, subjective effects becoming apparent with approximate oral dosages of 1.5 mg./kg. The ratio between threshold doses of harmaline and its 6-methoxy analog is 3:2, 6-methoxyharmalan being the more active. 6-Methoxytetrahydroharman [...] was also shown to be psychoactive, eliciting mild effects at a dosage level of 1.5 mg./kg. The relative activities of the two 6-methoxyharmans are approximately 1:3, the harmalan being more active than its unsaturated homolog, [...]
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. [...]
Doses for vaporized or inhaled free-base DMT are typically 40–50 mg, although larger doses have been reported (100 mg; Shulgin and Shulgin 1997). Pallavicini et al. (2021) have reported that vaporization of approximately 40 mg of DMT, administered in a natural setting, produced potential electroencephalographic markers of mystical-type experiences in 35 volunteers. The onset of effects for inhaled DMT is rapid, similar to that of IV administration, but lasts less than 30 min (Riba et al. 2015; Davis et al. 2020). [...] For administration of pharmahuasca, 50 mg DMT:100 mg harmaline is usually the recommended dosage. However, combinations of 50 mg harmaline:50 mg harmine and 50 mg DMT have been tested with success. The harmalas and DMT are typically put into separate gelatin capsules, with the harmaline/harmine being taken first and the DMT being taken 15 to 20 min later. The use of moclobemide, a reversible inhibitor of MAO-A, has also been reported in DMT "pharmahuasca" studies (Kaasik et al. 2020; Ruffell et al. 2020).
Since the β-carbolines per se could not explain the legendary psychoptic (visionary) activity of the jungle ambrosia, this had to be due to its DMT content, which amounted to an average of 29 mg/dose in the 16 potions analyzed (range: 25-36 mg/dose). [...] TABLE 1 Human Pharmacology of Psychoptic Tryptamines [...]
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).
[...] 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.
Harmine was examined in 28 subjects in total doses ranging from 20 to 960 mg; routes of administration included oral, subcutaneous and intravenous (Pennes and Hoch, 1957). (+)LSD and mescaline were used for comparison. Harmine was inactive after oral (up to 960 mg) and subcutaneous (up to 70 mg) administration. However, harmine produced some subjective effects at 35–45 mg (Slotkin et al., 1970) and hallucinogenic effects at 150–200 mg i.v.; doses of greater than 300 mg could not be investigated [...] (Pennes and Hoch, 1957). Anecdotal reports of harmine intoxication are available (Stafford, 1977). In an investigation employing 30 subjects, harmaline produced subjective effects in humans at about half the dose required for harmine. That is, harmaline was found to be hallucinogenic at doses greater than 1 mg/kg i.v., and was also orally active at a dose of 4 mg/kg (Naranjo, 1967). Detailed accounts of the intoxication produced by harmaline, administered at doses of 100 mg i.v. and 300 mg p.o., have been published (Naranjo, 1969, 1973). Racemic tetrahydroharmine has been examined only in a single subject and subjective effects, similar to those seen with harmaline, were reported at 300 mg p.o. (Naranjo, 1967). 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. Although there is an obvious need for additional human studies before strict potency comparisons can be made, there is adequate documentation that certain b-carbolines (in particular harmine and harmaline) are hallucinogenic in humans. [...] As mentioned in the Introduction, there currently exists too little information on the human potencies of b-carbolines to make any quantitative comparisons. However, harmine, harmaline, and a few related agents appear to be active in the 100–300 mg dose range; that is, they are hallucinogens of modest potency.
{{citation}}: CS1 maint: work parameter with ISBN (link)