Anecdotally, ayahuasca has an enormous capacity to facilitate psychological and physical healing.
However, to date, little research has systematically explored its healing properties.
In a long-standing collaboration with Jordi Riba, the Beckley/Sant Pau Research Programme is investigating how ayahuasca modulates brain activity to elicit its therapeutic effects.
1. Ayahuasca and neurogenesis
Conducted in collaboration with researchers from the Spanish National Research Council (CSIC): Jose Morales-García, María Isabel Rodriguez-Franco, Ana Pérez-Castillo and Mario de la Fuente Revenga.
- For a long time, the dogma persisted that new neurons were not generated in the adult brain.
- However, since the late 1990’s, experimental evidence in rodents has challenged this dated paradigm. The birth of new neurons, known as neurogenesis, has been found to occur in two areas of the adult brain – one surrounding the lateral ventricles and another in a region of the hippocampus.
Figure 1. Neurogenesis, or the birth of new neurons, has been found to occur in two regions of the adult brain: the subventricular zone (SVZ) of the lateral ventricles and the dendate gyrus of the hippocampus.
- The hippocampus plays a key role in learning and memory, and with normal aging its functioning declines. However, in some neurodegenerative disorders such as Alzheimer’s and other dementias, this diminished functioning is even more severe, leading to a sharp decay in the quality of life for those afflicted.
- Therefore, stimulating the birth of new neurons may help counteract the decline of cognition in these neurodegenerative diseases.
- This study was the first to demonstrate that certain components of the psychedelic brew ayahuasca have potent neurogenic properties.
- β-carbolines are alkaloids found in high concentrations in ayahuasca that have monoamine oxidase-inhibiting properties, meaning that their action allows the DMT also contained in ayahuasca to be psychoactive when it ingested orally through the psychedelic brew.
- In this experiment, when we added these β-carbolines (harmine, tetrahydroharmine, harmaline, and harmol) to cell cultures containing neural stem cells, there were dramatic increases in the proliferation and migration of these cells, and in their differentiation into new adult neurons.
Blue staining = cell nucleus (marks all cells) Green staining = young neurons Red staining = mature neurons
Figure 2. β-carbolines found in ayahuasca actively stimulate the proliferation and growth of neuronal progenitor cells into new neurons. A: No effects are seen following treatment of progenitor cells with a saline control. B and C: following the addition of harmine and tetrahydroharmine (as well as harmaline and harmol, not pictured), there was a marked increase in the growth of new neurons.
- To build upon these spectacular findings, we plan to investigate these effects in animal models (in vivo); the replication of these findings in vivo would open a totally new avenue of research for ayahuasca and its active principles.
- Eventually, the knowledge gained from this research could lead to the development of novel treatments for neurodegenerative and psychiatric disorders and to redress brain damage due to stroke or trauma.
2. Ayahuasca and Glutamate
- Glutamate is a key neurotransmitter involved in memory, neurogenesis, and neuronal plasticity.
- We hypothesized that glutamate is involved in the psychedelic state, and that long-term users of ayahuasca would show structural changes in the brain due to glutamate-induced neurogenesis.
- We blocked glutamate receptors with an antagonist so that we could determine the extent to which glutamate neurotransmission plays a role in the subjective effects of DMT, the psychoactive constituent of ayahuasca.
- The study also investigated the psychological aspects of the ayahuasca experience and their potential therapeutic benefits, such as improved mindfulness.
- Using Magnetic Resonance Spectroscopy we found first evidence of the involvement of glutamate neurotransmission in the effects of psychedelics in humans: ayahuasca reduced glutamate levels in the posterior cingulate cortex, an important hub of the default mode network.
- fMRI data obtained before and 24 hours after ayahuasca intake showed a decreased anticorrelation between, or functional independence of, the posterior parietal cortex (i.e., the default mode network) and the anterior cingulate cortex, a key region of the Task-Positive Network (TPN). This means that after ayahuasca the activity of these networks became more aligned across time, whereas under normal conditions when one network is engaged the activity of the other is diminished.
- Interestingly, these neural changes correlated with an increased capacity of mindfulness in the 24 hours after intake and predicted a sustained elevation in this capacity 2 months later.
- These findings provide a neural basis for the beneficial effects of ayahuasca and strongly support its therapeutic potential, as it is the goal of mindfulness-based psychotherapeutic interventions to enhance the capacity to actively notice and modify one’s thought patterns.
3. Ayahuasca and ketanserin
- Ayahuasca, like other classical psychedelic drugs, is thought to produce its characteristic effects through interaction with the 2a subtype of serotonin receptors (5-HT2A).
- This study sought to test if the psychological and physiological effects of ayahuasca persist after the blockade of this receptor with ketanserin, a drug that selectively binds to the 5-HT2A
- In previous studies with psilocybin, pretreatment with ketanserin completely abolished the drug’s subjective effects; a similar effect was therefore expected to occur with ayahuasca.
- Usually ayahuasca induces very strong visual experiences. These phenomena are associated with a decrease in brain waves, called alpha oscillations, in the visual cortex and other areas implicated in sensory processing and memory.
- In this experiment, we found that ketanserin blocked these decreases, and markedly diminished the visual effects of ayahuasca, suggesting that despite its chemical complexity, 5-HT2A activation may be the main contributor to ayahuasca’s psychotropic effects.
- Unexpectedly, however, ketanserin did not completely block the subjective effects of ayahuasca, but merely reduced their intensity.
- It is possible that this could be due to DMT interacting with receptors besides 5-HT2A, as well as influencing the activity of cellular transporters which move neurotransmitters across the cell membrane of neurons.
- This study confirms the crucial role of 5-HT2A receptors in the effects of ayahuasca, but stresses the importance of investigating other mechanisms of action of this psychedelic substance.
1. Ayahuasca and well-being
Conducted in collaboration with the International Center for Ethnobotanical Education, Research & Service (ICEERS)
- We are currently working on a project at the Temple of the Way of Light in Peru, studying long-term effects of ayahuasca on personal development, spirituality, and health in Western users.
- This study is the largest of its kind, with a large sample size of around 580 participants each year.
- A documentary film will be produced about the war veterans who are participating in this study.
2. Ethnobotanical research programme
Conducted in collaboration with Pablo Friedlander
- A series of projects are planned for in-depth investigations of traditional healing/teaching plants that have been recognized as sacred for millennia:
(b) Trichocereus cactus of San Pedro
(d) Psilocybin mushrooms
(e) Other ethnobotanical medicines from diverse cultures
About Ayahuasca and DMT
Ayahuasca (from ‘aya’ = soul and ‘wasca’/‘huasca’ = vine or rope, hence ‘vine of the soul’) is the Quechua name for a tea used for ritual purposes by indigenous populations of the Amazon; its use dates back to at least 2000 BC. The ‘non-indigenous’ religious use of ayahuasca originated in Brazil, where traditions and rituals of the native tribes and African people were combined with Christian beliefs. Santo Daime, União do Vegetal (UDV), and Barquinha are the three major syncretic religious movements where ayahuasca is used as a sacrament.
Various plant combinations can be used in preparation of the drink, but the most common variation of the tea combines B. caapi with the leaves of the shrub Psychotria viridis. The drink’s psychoactive compound, N,N-Dimethyltryptamine (DMT), is structurally similar to the brain chemicals serotonin and melatonin. Its psychedelic effects, like LSD and psilocybin, are thought to result from its interaction with the serotonin system. Serotonin (abbreviated 5-HT for 5-hydroxytryptamine) is a naturally occurring brain chemical (‘neurotransmitter’) that binds to serotonin receptors. Numerous serotonin receptor subtypes have been discovered and are identified by number-letter combinations. DMT primarily binds to serotonin 2A (5-HT2A) receptors. However, it causes a different series of events to happen than serotonin does, which is why DMT has psychedelic effects and serotonin does not.
Related compounds: 5-MeO-DMT is a derivative of DMT and a naturally occurring psychedelic present in numerous plants (e.g. bark of Dictyoloma incanescens) and in the venom of Bufo alvarius (Colorado River toad). It is used in some traditional South American shamanic snuffs and sometimes in ayahuasca brews. 5-MeO-DMT was first synthesized in 1936, and in 1959 it was isolated as one of the psychoactive ingredients of Anadenanthera peregrina (yopo) seeds. Bufotenine is a naturally occurring psychedelic present in Anadenanthera colubrina (cebil), many other species of plants (e.g. mimosa, amanita mushrooms) and Colorado River toad skin glands. It is similar in chemical structure to the psychedelics psilocin (4-HO-DMT), 5-MeO-DMT, and DMT.
In the largest study of its kind to date, Bouso et al. (2012) showed that regular users of ayahuasca presented no signs of cognitive impairment or mental health problems; on the contrary, they performed better on neuropsychological tests, scored higher on spirituality questionnaires, and showed better psycho-social adaptation, as reflected by ratings of ‘purpose in life’ and ‘subjective well-being.’ However, very little is known about the neuroscience underlying these effects.