Harmala alkaloid: Difference between revisions
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Harmala alkaloids are a | Harmala alkaloids are a group of naturally occurring alkaloids, found primarily within the seeds of '''Peganum Harmala''' (''Syrian Rue''), which exhibit psychoactive effects. | ||
==Chemistry== | ==Chemistry== | ||
Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. | Harmala alkaloids are based upon the molecule [[beta-Carbolines|''beta''-carboline]]s. The ''beta''-Carboline structure itself is comprised of an indole ring attached to a pyridine ring. | ||
==Pharmacology== | ==Pharmacology== | ||
Harmala alkaloids | Harmala alkaloids inhibit the activity of monoamine oxidase metabolic enzymes, of which two varieties exist; MOA-A and MOA-B. The alkaloids bind reversibly to the active site of the enzyme, inhibiting its endogenous function of destroying amine functions of neurotransmitters and externally administered centrally active drugs. This has the effect of potentiating and prolonging the central and peripheral activity of both neurotransmitters and a variety of drugs. | ||
Harmala alkaloids are selective for MOA-A at reasonable doses and binds to the enzyme temporarily so is classed as a '''reversible inhibitor of Monoamine-A''' (''RIMA''). At higher doses, they also begin to affect the MOA-B enzyme. Because of the reversible selectivity for MAO-A, Harmala alkaloids are considered to be less dangerous in combination with food which contains tyramine and other substances with monoamine moieties, which are reliant on monoamine oxidase for decomposition, as is traditionally a respected consideration when using non-selective MAOIs in a clinical setting. | |||
However, it is important to understand that this does not imply that Harmala alkaloids will not cause neurotoxicity. Harmala alkaloids temporarily disable the brain's primary mechanism for breaking down neurotransmitters and drugs, which can have negative consequences as material builds up in the synapses, leading to a huge range of downstream central and peripheral effects including; sedation, stimulation, anxiety, dysphoria, euphoria, headaches, eye strain, convulsions, etc. | |||
Since DMT is broken down by monoamine oxidase-A, inhibition of this enzyme allows for the oral activation of DMT, and prolongs the experience for the duration of the harmala alkaloids' effects. In combination, harmala alkaloids and DMT is known as [[Ayahuasca]]. this of course is a dirty hack, and a much safer route would be to introduce protective moieties to the DMT molecule itself. | |||
==Examples== | ==Examples== | ||
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Tetrahydroharmine does not inhibit monoamine oxidase A. Instead, it weakly inhibits [[serotonin]] reuptake. At dosages of 200mg, it has been reported to cause dream-like euphoria, pleasurable tingling sensations and a head space similar to that of [[LSD]]. | Tetrahydroharmine does not inhibit monoamine oxidase A. Instead, it weakly inhibits [[serotonin]] reuptake. At dosages of 200mg, it has been reported to cause dream-like euphoria, pleasurable tingling sensations and a head space similar to that of [[LSD]]. | ||
Note: all three of these dosages seem wildly exaggerated to me. 100 molecules of harmaline will inhibit 100 molecules of MAO-A, since it must bind with the enzyme. Effective inhibition dose could be calculated by determining the concentration of MOA in the body. Harmine is certainly active at <100mg, and the synergistic property of combined harmala alkaloids as found within Peganum Harmala likely increases their efficacy; two MAO-A inhibitors will be more effective with less side effects than a higher quantity of one alkaloid alone. | |||
==Toxicity and Harm Potential== | ==Toxicity and Harm Potential== | ||
===Drug Interactions=== | ===Drug Interactions=== | ||
While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup). | While safer than general [[MAOIs]], RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup, nicotine, caffeine, etc). Sedatives are likely easier tolerated, but potentiation should be expected. | ||
===Lethal Dosage=== | ===Lethal Dosage=== | ||
Revision as of 11:37, 30 March 2014
Harmala alkaloids are a group of naturally occurring alkaloids, found primarily within the seeds of Peganum Harmala (Syrian Rue), which exhibit psychoactive effects.
Chemistry
Harmala alkaloids are based upon the molecule beta-carbolines. The beta-Carboline structure itself is comprised of an indole ring attached to a pyridine ring.
Pharmacology
Harmala alkaloids inhibit the activity of monoamine oxidase metabolic enzymes, of which two varieties exist; MOA-A and MOA-B. The alkaloids bind reversibly to the active site of the enzyme, inhibiting its endogenous function of destroying amine functions of neurotransmitters and externally administered centrally active drugs. This has the effect of potentiating and prolonging the central and peripheral activity of both neurotransmitters and a variety of drugs.
Harmala alkaloids are selective for MOA-A at reasonable doses and binds to the enzyme temporarily so is classed as a reversible inhibitor of Monoamine-A (RIMA). At higher doses, they also begin to affect the MOA-B enzyme. Because of the reversible selectivity for MAO-A, Harmala alkaloids are considered to be less dangerous in combination with food which contains tyramine and other substances with monoamine moieties, which are reliant on monoamine oxidase for decomposition, as is traditionally a respected consideration when using non-selective MAOIs in a clinical setting.
However, it is important to understand that this does not imply that Harmala alkaloids will not cause neurotoxicity. Harmala alkaloids temporarily disable the brain's primary mechanism for breaking down neurotransmitters and drugs, which can have negative consequences as material builds up in the synapses, leading to a huge range of downstream central and peripheral effects including; sedation, stimulation, anxiety, dysphoria, euphoria, headaches, eye strain, convulsions, etc.
Since DMT is broken down by monoamine oxidase-A, inhibition of this enzyme allows for the oral activation of DMT, and prolongs the experience for the duration of the harmala alkaloids' effects. In combination, harmala alkaloids and DMT is known as Ayahuasca. this of course is a dirty hack, and a much safer route would be to introduce protective moieties to the DMT molecule itself.
Examples
Common Harmala alkaloids include:
Harmine
Harmine is a reversible inhibitor of MAO-A (RIMA) at dosages of 200mg.
Harmaline
Harmaline is a reversible inhibitor of MAO-A (RIMA) at dosages of 100mg.
Tetrahydroharmine
Tetrahydroharmine does not inhibit monoamine oxidase A. Instead, it weakly inhibits serotonin reuptake. At dosages of 200mg, it has been reported to cause dream-like euphoria, pleasurable tingling sensations and a head space similar to that of LSD.
Note: all three of these dosages seem wildly exaggerated to me. 100 molecules of harmaline will inhibit 100 molecules of MAO-A, since it must bind with the enzyme. Effective inhibition dose could be calculated by determining the concentration of MOA in the body. Harmine is certainly active at <100mg, and the synergistic property of combined harmala alkaloids as found within Peganum Harmala likely increases their efficacy; two MAO-A inhibitors will be more effective with less side effects than a higher quantity of one alkaloid alone.
Toxicity and Harm Potential
Drug Interactions
While safer than general MAOIs, RIMAs still have highly dangerous and sometimes fatal interactions with many common drugs. In particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost any antidepressant or stimulant, common migraine medications, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup, nicotine, caffeine, etc). Sedatives are likely easier tolerated, but potentiation should be expected.
Lethal Dosage
When intravenously injected into mice, the LD50 of harmine is 38mg/kg. There is no data for the other harmala alkaloids in humans or animals.
Tolerance and Addiction Potential
There is no tolerance built up with harmala alkaloid use. There are no real reports of addiction to harmala alkaloids.
Natural sources
Banisteriopsis caapi
Banisteriopsis caapi (also known as ayahuasca, caapi or yajé) is a South American jungle vine of the family Malpighiaceae. It contains harmine, harmaline, and tetrahydroharmine in the following proportions:
- Harmine, 0.31-8.43%
- Harmaline, 0.03-0.83%
- Tetrahydroharmine, 0.05-2.94%
Peganum harmala (Syrian Rue)
Peganum harmala, commonly called Syrian rue, is a plant native to the eastern Iranian region west to India. It has also spread invasively throughout Arizona, California, Montana, Nevada, Oregon, Texas and Washington. The plant itself produces seeds which contain harmala alkaloids and is freely available and legal to purchase online through the use of google. Powdered Syrian rue seeds act as a reversible inhibitor of MAO-A (RIMA) at dosages of 2 - 5g.
Syrian rue seeds contain several different harmala alkaloids at slightly varying percentages, only some of which are monoamine oxidase A inhibitors MAOI. In one study, total harmala alkaloids were at least 5.9% of dried weight.
- Harmane, 0.16%
- Harmine, 0.44% (The coatings of the seeds are said to contain large amounts of harmine.)
- Harmaline, 0.25%
- Harmalol, 0.6%
- Tetrahydroharmine, 0.1%
- Vasicine (peganine), 0.25%<
- Vasicinone, 0.0007%
Legal Issues
Harmala alkaloids and their natural sources are legal in most parts of the world.
- Australia: Harmala alkaloids are Schedule IX drugs.
- Canada: Harmala alkaloids are Schedule III drugs.
- France: Possession and sale of harmala alkaloids is illegal.