Ayahuasca
Mahendra Rai, Shandesh Bhattarai, Chistiane M. Feitosa in Wild Plants, 2020
These compounds are related by the structure they share of the tricyclic indole alkaloids, for which reason they are called “β-carbolines” or also “harmala alkaloids”, because they were first discovered in the Peganum harmala L. plant (Domínguez-Clavé et al. 2016). Their MAO inhibitory action defines the hallucinatory response and physiological effects of Ayahuasca, which may contain a varied range of β-carbolinic alkaloids, and this amount can vary substantially for the reasons already mentioned. In a quantitative evaluation of Ayahuasca samples from different times of the year, the range of harmine, harmaline, and THH concentrations was recorded, ranging from 294.5 to 2893.8 µg/mL, 27.5 to 181.3 µg/mL, and 849.5 to 2052 g/ml of Ayahuasca, respectively (Lanaro et al. 2015).
Phytochemistry of Harmal
Ephraim Shmaya Lansky, Shifra Lansky, Helena Maaria Paavilainen in Harmal, 2017
The β-carboline indole alkaloids within P. harmala seeds are derived from tryptamine, a derivative of the indolic amino acid tryptophan. The parent skeleton is indole itself, the key plant growth hormone. P. harmala β-carboline indole alkaloids are also commonly known as “harmala alkaloids” after the plant species in question (Figures 6.1 through 6.3). Harmine is further found in other plants besides P. harmala, including the South American “vine of the soul,” Banisteriopsis caapi, the “engine” of the hallucinogenic brew, ayahuasca (Shanon 2010), tobacco, Nicotinia tabacum, and passion flowers (Passiflora incarnata).
Traditional Use of Banisteriopsis caapi Alone and Its Application in a Context of Drug Addiction Therapy
Published in Journal of Psychoactive Drugs, 2021
Matteo Politi, Fabio Friso, Gary Saucedo, Jaime Torres
Psychotropic properties of harmala alkaloids which belong to the group of β-Carbolines derivatives have been a matter of discussion since the early investigations of psychedelic drugs (Naranjo 1967). Preliminary studies of these alkaloids in humans, in particular harmine, report their visual hallucination effects of varying degrees of complexity and organization (Pennes and Hoch 1957). Recently, there has been a particular rise in interest with regards to β-Carbolines and research for mental health (Dos Santos and Hallak 2017). For instance, harman and harmine are considered multi-target antidepressant compounds and may be useful in the treatment of depressive disorders (Ferraz et al. 2019). β-Carbolines are of great interest due to their diverse biological activities including the interaction with benzodiazepine receptors and 5-hydroxy serotonin receptors demonstrating sedative, anxiolytic, hypnotic, and anticonvulsant activities (Cao et al. 2007), as well as potential effects against neurodegenerative diseases such as Parkinson’s and Alzheimer’s (Piechowska, Zawirska-Wojtasiak, and Mildner-Szkudlarz 2019).
Ayahuasca, a potentially rapid acting antidepressant: focus on safety and tolerability
Published in Expert Opinion on Drug Safety, 2022
Giordano Novak Rossi, Isabella Caroline da Silva Dias, Glen Baker, José Carlos Bouso Saiz, Serdar M. Dursun, Jaime E. C. Hallak, Rafael G. Dos Santos
In this regard, classical hallucinogens (also known as serotoninergic hallucinogens or psychedelics) are currently being investigated as potential rapid-acting antidepressants, amongst other therapeutic applications [6,7]. These drugs include psilocybin (produced by psychoactive mushrooms), lysergic acid diethylamide (LSD, derived from the ergot fungus), mescaline (produced by psychoactive cactus such as peyote) and N,N-dimethyltryptamine (DMT). The last-mentioned of these compounds is proposed to be is the main psychoactive substance in ayahuasca, a botanical preparation usually made by the decoction of the stalks of the Banisteriopsis caapi vine together with the leaves of the bush Psychotria viridis [8]. Ayahuasca is traditionally used in the ritualistic context by indigenous tribes from the Amazon Basin and more recently (20th century onward) in religious rituals in South America and other countries [8]. Besides DMT, which comes from P. viridis, ayahuasca also contains a class of substances called beta-carbolines (or harmala alkaloids), most notably harmine, tetrahydroharmine (THH) and harmaline [9]. These compounds are found in B. caapi and are responsible for inhibiting the function of the enzyme monoamine oxidase type A (MAO-A) in the human body, allowing DMT to reach the central nervous system (CNS) [9]. DMT acts primarily as an agonist of serotoninergic 5-HT1A,2A,2C receptors, and it is thought that its interaction with 5-HT2A receptors is the main pharmacological mechanism by which DMT/ayahuasca (and other psychedelics) manifest their effects [8,10–12].
Chemical Composition of Traditional and Analog Ayahuasca
Published in Journal of Psychoactive Drugs, 2021
Helle Kaasik, Rita C. Z. Souza, Flávia S. Zandonadi, Luís Fernando Tófoli, Alessandra Sussulini
Potencies of harmine and harmaline as MAO-A inhibitors are different (Santillo et al. 2014). They also found nonlinear (antagonistic) interaction between harmine and harmaline at 50% MAO-A inhibition. The antagonism increased with decreasing levels of MAO-A inhibition, therefore, it may be even stronger at lower levels of MAO-A inhibition which correspond to lower doses of ayahuasca. Also, these compounds differ in other biochemical properties beyond MAO inhibition. These differences in biochemical properties of harmaline and harmine may cause differences in subjective and pharmacological effects of ayahuasca brews with different proportions of concentrations of these compounds. The differences of the subjective effects of brews containing P. harmala and B. caapi have been described, based on experiences shared in online forums: “substituting, say, Syrian rue for the ayahuasca vine, even though the rue contains the same harmala alkaloids, does apparently make an experiential difference. The experience with rue has been described as crystalline, cold, overwhelming, erratic, and uncaring, compared with that of the ayahuasca vine, which has been described as warm, organic, friendly, and purposeful.” (Beyer 2009, 253).
Related Knowledge Centers
- Alkaloid
- Harmaline
- Harmine
- Peganum Harmala
- Tobacco
- Dopamine
- Reward System
- Monoamine Oxidase Inhibitor
- Harmalol
- Β-Carboline