Harmaline

Harmaline, also known as 7-methoxyharmalan or as 3,4-dihydro-7-methoxy-1-methyl-β-carboline, is a fluorescent indole alkaloid from the group of harmala alkaloids and β-carbolines. It is the partly hydrogenated form of harmine. It is a reversible monoamine oxidase inhibitor (RIMA). It produces vivid dream-like visual effects and physical discomfort at oral doses of 300 to 400Template:Nbspmg, often leading users to seek solitude in a quiet, dark environment.

Plants containing harmaline are combined in ayahuasca to inhibit monoamine oxidase, allowing orally ingested DMT to remain active in the brain and produce psychoactive effects. Harmala alkaloids, including harmaline, are psychoactive on their own in humans, with harmaline being particularly hallucinogenic, although other compounds such as harmine and tetrahydroharmine have also been reported to produce hallucinogenic effects as well.

Harmaline exhibits weak affinity for 5-HT_2A and 5-HT_2C receptors, partially substitutes for the psychedelic DOM in rodents, inhibits acetylcholinesterase and histamine N-methyltransferase, and stimulates dopamine release at high doses.

Harmaline is present in Peganum harmala (Syrian rue). Syrian rue seeds contain about 3% harmala alkaloids by dry weight. Harmaline was first isolated from plants in 1841, its chemical structure identified in 1919, and it was first synthesized in 1927.

Use

Harmaline-containing plants and tryptamine-containing plants are used in ayahuasca brews. The inhibitory effects on monoamine oxidase allows dimethyltryptamine (DMT), the psychoactively prominent chemical in the mixture, to bypass the extensive first-pass metabolism it undergoes upon ingestion, allowing a psychologically active quantity of the chemical to exist in the brain for a perceivable period of time.

Effects

The harmala alkaloids are psychoactive in humans. According to Alexander Shulgin, harmaline is the only harmala alkaloid that has a reputation of being hallucinogenic. However, other harmala alkaloids and β-carbolines, like harmine, tetrahydroharmine (THH), 6-methoxyharmalan, and 6-methoxytetrahydroharman, have also been reported to be hallucinogenic.

Interactions

Harmaline is a reversible inhibitor of MAO-A (RIMA)". This means that the risk of a hypertensive crisis, a dangerous high blood pressure crisis from eating tyramine-rich foods such as cheese, is likely lower with harmaline than with irreversible MAOIs such as phenelzine. Since harmaline is a RIMA, it could, in theory, induce both serotonin syndrome and hypertensive crises in combination with tyramine, serotonergics, catecholaminergics drugs or prodrugs.

Pharmacology

Harmaline activities

Target	Affinity (Ki, nM)
5-HT1A	>10,000 (rat/human)
5-HT1B	>10,000
5-HT1D	>10,000
5-HT1E	ND
5-HT1F	ND
5-HT2A	5,010–7,790 (Ki) (rat) >20,000 (Template:Abbrlink) >10,000 (Template:Abbrlink)
5-HT2B	ND
5-HT2C	9,430 (rat)
5-HT3	>10,000
5-HT4	ND
5-HT5A	>10,000
5-HT6	1,480
5-HT7	5,500
α1A	>10,000
α1B	>10,000
α1D	ND
α2A	2,540
α2B	1,130
α2C	810
β1, β2	>10,000
β3	ND
D1–D5	>10,000 (human/rat)
H1–H4	ND
M1–M5	>10,000
I1	13,800
I2	22
σ1, σ2	ND
Template:Abbrlink	ND
BDZ	>10,000 (rat)
PCP	>10,000 (rat)
Template:Abbrlink	>10,000 (Ki)
Template:Abbrlink	3,260 (Ki)
Template:Abbrlink	>10,000 (Ki) (bovine)
Template:Abbrlink	2.5–33 (IC50)
Template:Abbrlink	100,000 (IC50)
Template:Abbrlink	4,600 (IC50)
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs:

Harmaline shows weak but significant affinity for the serotonin 5-HT_2A and 5-HT_2C receptors (in the low micromolar range). Harmaline and the psychedelic DOM partially substitute for each other in rodent drug discrimination tests. Harmaline was much more effective in substituting for DOM than harman and harmine, which did not achieve significant generalization and produced behavioral disruption at higher doses. On the other hand, harmaline and 6-methoxyharman were comparable in terms of DOM substitution. Harmaline shows high affinity for the imidazoline I₂ receptor (K_i = 22Template:NbspnM).

Chemistry

File:Harmaline Harmine.jpg

Harmaline and harmine fluoresce under ultraviolet light. These three extractions indicate that the middle one has a higher concentration of the two compounds.

Harmaline, also known as 7-methoxyharmalan or 3,4-dihydro-7-methoxy-1-methyl-β-carboline, is a β-carboline and a cyclized tryptamine analogue of 6-methoxy-DMT.

It is fluorescent under ultraviolet light.

Natural occurrence

Various plants contain harmaline including Peganum harmala (Syrian rue) as well as the hallucinogenic beverage ayahuasca, which is traditionally brewed using Banisteriopsis caapi. Present at 3% by dry weight, the harmala alkaloids may be extracted from the Syrian rue seeds.

History

Harmaline was first isolated from plants in 1841. The chemical structure of harmaline was not correctly identified until 1919. Harmaline was first synthesized in 1927.

Society and culture

Legal status

Australia

Harmala alkaloids are considered Schedule 9 prohibited substances under the Poisons Standard (October 2015). 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.

Canada

Harmaline and Harmalol are considered Schedule III controlled substances by the Controlled Drugs and Substances Act. Every person found to be in possession of a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding three years; or for a first offence, guilty on summary conviction, to a fine not exceeding one thousand dollars or to imprisonment for a term not exceeding six months, or to both. Every person found to be trafficking a Schedule III drug is guilty of an indictable offence and liable to imprisonment for a term not exceeding ten years, or is guilty on summary conviction (first-time offenders) and liable to imprisonment for a term not exceeding eighteen months.

See also

• Substituted β-carboline
• 6-Methoxyharmalan
• 5-Methoxyharmalan
• Harmalol
• Tetrahydroharmine
• Ibogamine

External links

• Harmaline - Isomer Design
• Harmaline - TiHKAL - Erowid

Template:Psychedelics Template:Serotonin receptor modulators Template:Imidazoline receptor modulators Template:Acetylcholine metabolism and transport modulators Template:Monoamine metabolism modulators