Is Ayahuasca The Future Of Psychoactive Medication?

Dr. Brandon Weiss discusses his new research on the medicinal properties of ayahuasca.

By Mark Travers, Ph.D. | December 29, 2021

A recent paper published in the academic journal Nature argues that the ceremonial use of ayahuasca (a hallucinogenic drink) may help quell the personality dimension that many psychologists view as the core of all mood and anxiety disorders: neuroticism or negative emotionality.

I recently spoke with Dr. Brandon Weiss, a psychologist at Imperial College London and lead author of the research, to discuss these findings in more detail. Here is a summary of our conversation.

What inspired you to investigate changes in personality following the ceremonial use of ayahuasca and what did you find?

Contemporary practices of ayahuasca shamanism appear to be at least 300 years old and involve a rich and unique anthropological context including distinct metaphysics and cosmology. The ceremony experience is also unique in containing somatic challenge as the body digests the decoction, emotional challenge as the mind explores its core beliefs and assumptions, experiences of unity and sacredness, engagement with an elder shaman, and communion with other ceremony partners.

Given that previous prospective work had observed personality changes in relation to psilocybin use, and previous cross-sectional work had alluded to personality changes in relation to ayahuasca, I felt that investigating possible changes in personality was well warranted.

Personality is incredibly useful because it encompasses so much of the manners in which people think, feel, and behave in the world as well as their different interests and motivations. In fact, there are even new systems of mental illness that seem to fit into the framework of the Five-Factor model of personality (Neuroticism/Negative Affectivity, Extraversion/Detachment, Openness/Psychoticism, Agreeableness/Antagonism, Conscientiousness/Disinhibition). Given this, personality is a useful tool for understanding how human beings psychologically and behaviorally change following psychedelic experiences.

We found substantial changes in the Five-Factor Model personality traits, particularly Negative Emotionality (or Neuroticism) and Openness following ayahuasca use. These changes persisted over 3 months and were corroborated by reports from participants' close significant others.

Participants showed even greater adaptive change who reported heightened mystical-type experiences and experiences involving Reappraisal, an acute experience that emerged from our qualitative data. Reappraisal involves an experience during the ceremony of profound changes to former beliefs and apprehensions including gratitude for lessons learned from previous hardship, trauma, and transgressions, acknowledgments of being too hard on oneself, and resolutions to change entrenched patterns of acting/feeling that are not helpful.

In addition, we also found evidence that participants who experienced themselves as purging out a negative part of themselves showed more adaptive change in most personality traits while controlling for all other acute experiences.

Can you provide some historical context on the use of ayahuasca in different cultures/civilizations?

Ayahuasca shamanism exists across the Amazonian basin in multiple modern-day South American countries including Peru, Brazil, and Columbia. Scholars differ on the precise time-course of ayahuasca shamanism's development, with some proposing that modern ceremonial practices (involving use of Banisteriopsis caapi vine and Psychotria or Diplopterys shrubs) emerged no more than 300 years ago in South America within a Spanish missionary context and propagated itself along a network of economic activity involving rubber camps. The basis for this assessment is multifaceted, but perhaps the most compelling evidence involves common terminology for ayahuasca and common musical structure to ayahuasca-related icaro prayers/songs across geographically distant groups, and ritualistic use of tobacco smoke in ways convergent with Catholic practices.

Other scholars however assert modern practices have been uninterrupted among indigenous South American groups for five thousand years. However, even if ayahuasca shamanism in its current ceremonial form may be relatively recent, there exists earlier archeological evidence of ritual use of similar plant combinations that pair mono-amine oxidase inhibiting properties with psychedelic properties.

Specifically, chemical traces of bufotenine, dimethyltryptamine, and harmine were recently observed to be contained in a "ritual bundle" dating back 1000 years in modern-day Bolivia, leading the authors to suggest that these were part of shamanic paraphernalia at that time.

How is ayahuasca similar to, and different from, other psychedelics?

Most other psychedelics involve the ingestion of one substance whose psychoactive elements can be broken down in the stomach and transferred through the blood to receptors in the brain. Ayahuasca involves the combination of two plant substances, which separately do not produce meaningful subjective psychedelic effects. The NN-DMT-containing Psychotria and Diplopterys shrubs are orally inactive without ingesting the ayahuasca vine (Banasteriopsis Caapi), which inhibits the mono-amine oxidase enzyme from neutralizing the NN-DMT. More than other substances, though not unique in this regard, Ayahuasca is also more associated with digestive discomfort and the act of purging (or vomiting) out the substance in the course of the ceremony. This purgative aspect is considered by shamans and facilitators to hold healing properties, and some qualified evidence has been found supporting this.

Ayahuasca is also different by virtue of the unique ceremonial elements accompanying its use. In the Shipibo tradition, for example, pasajeros sit in a round perimeter within a maloka ritual space and listen to a shaman sing icaros, prayers or songs, to them. Shipibo shamans believe that the icaros, not merely the ayahuasca, are instrumental in the ceremonial healing, and that these stem from previous experiences the shamans have over multiple years dieting other plant teachers.

Accompanying their relatively isolated engagement with these plant teachers, shamans develop understanding of the plants' spirits, alliances with them, and learn to sing icaros reportedly emanating from them. Ayahuasca is understood by the shamans as a sensory amplifier that enables them to observe diseased energies, and their icaros are understood as means of opening up portals to guide positive spirits (operating as muses or doctors) in to extract diseased energies. These ceremony aspects in addition to the shaman's passionate focus on cultivating health and connection to self, community, and the larger world make ayahuasca particularly unique within the context of other psychedelic substances and practices.

Ayahuasca can also be contrasted with conventional group-based psychotherapy in productive ways. The Ayahuasca ceremony appears to present individuals with states of psychological difficulty (both psychological and physical), and the group format baldly displays this process to other group members. Examples include audible displays of grief, moaning, and physical purging that command others' awareness. This experience of shared vulnerability and emotional processing may set in motion processes involving heightened feelings of compassion toward others/oneself that help one transform their relationship to their own and others' emotional pain.

What are the risks or downsides to using ayahuasca?

Our recent data showed that in a sample of 188 who were asked to report on possible negative side-effects from their ayahuasca experience at 3-month follow-up, 11 participants (6% of subsample) reported negative side-effects. These side-effects included difficulty relating to people (1 participant), "hypersensitivity" (1), flashbacks/recollections of adverse subjective experience during ceremony (2), distressing dreams (1), auditory hallucination/voices (1), worsening of Hallucinogen-Persisting Perception Disorder (1), speech impairment/mispronunciation of words (2), brain fog (1), and difficulty concentrating/focusing, e.g., on mathematical/financial information (3).

What happens in the brain for ayahuasca to have the effect it does?

Recent findings have shown that under ayahuasca, the higher-order frontal regions that normally exert executive control over the flow of information within the brain (e.g., have specific and predictable relations with sensory-related posterior regions) are no longer functionally connected to other major regions in the same way. Entropy in the brain is increased, indexing a breakdown to conventionally reliable patterns of connectivity between and within brain networks.

Scholars propose that higher-order frontal regions that formally constrain incoming signals (both external and internal) and regulate how information is interpreted experience diminished control, allowing information (both external internal) to reach higher levels in the hierarchy of brain function and to become conscious and perceptible.

Scholars have linked these dynamics to changes in consciousness and insight: "Mismatch signals or "discrepancies" with predictions will be sent upstream and a constant updating of these predictions will be necessary in the brain's attempt to "make sense" of the experience. The novelty and spontaneity of the thought associations occurring, the facilitation of insight, and the new perspective gained into a given matter are dramatic effects of psychedelics. These sensations of novelty and deep meaning are sometimes so compelling that they are experienced as revelations." (Citation)

Did you find any gender differences or other demographic differences?

We tested differences in response to ayahuasca based on individual characteristics including sex, age, education level, parental income, and previous experience with psychedelics/ayahuasca. We found that male participants showed a greater increase in Extraversion following ayahuasca ceremony, younger participants showed greater change in Negative Emotionality (lower), Extraversion (higher), Openness (higher), and Conscientiousness (higher) immediately following ayahuasca ceremony (but not at 3-month follow-up).

Lastly, ayahuasca-naïve participants showed a greater increase in Agreeableness following ayahuasca ceremony than participants with previous experience.

After conducting your research, are you more likely to view ayahuasca as a possible treatment for certain personality disorders or other psychological conditions?

Absolutely, I believe the strongest evidence was for therapeutic change to Negative Emotionality (or Neuroticism), which has been characterized by some scholars as the core of all mood and anxiety disorders and a good index of distress and emotional impairment.

The implications are fairly broad, therefore. In addition to suggesting ayahuasca's efficacy in treating mood and anxiety disorders, many other disorders may also be amenable to change including personality disorders with a strong negative emotional core such as Borderline Personality Disorder.

In addition, many other disorder spectra such as Antagonistic Externalizing (involving aggression, rule-breaking, abuse, and criminality) and Disinhibiting Externalizing (involving impulsivity and substance misuse) frequently also have an emotional component and in many cases an emotional origin. Certain individuals may externalize with behaviors like aggression and substance use to address strong emotional disturbances (anger, sadness, stress; this is referred to as negative urgency in the literature wherein individuals act on urges to escape from negative emotion). As such, I believe there is a good empirical basis for utilizing ayahuasca transdiagnostically in the future.

How does your research connect with, and inform, other research showing a link between psychedelics and personality change?

A relatively consistent finding across the literature on psychedelic-induced personality change has been change in Neuroticism (or Negative Emotionality). We found this recently in our online survey data (Weiss et al., 2021 Frontiers), and it also emerges when looking at changes in depressed individuals who undergo Psychedelic-Assisted Therapy (Erritzoe et al., 2018). Change in Neuroticism has not been observed in all studies, but this may be a consequence of investigating personality change among participants who are already lower in Neuroticism. It is also important not to underestimate the effect of set and setting on the changes that take place.

In the study reviewed here, we also found changes in Extraversion, Openness, Agreeableness, and Conscientiousness. However, these changes were only observed when we asked the participants themselves (and not their close significant others) (exception here was Openness). And most importantly, these changes are more inconsistently observed across existing studies. The variability with which these trait changes take place will be important to probe in future research. We believe that trait changes have a lot to do with the sample being examined (how much potential for change exists), and the context of their use and post-acute integration practices.

Do you have plans for follow-up research? Where would you like to see research on psychedelics go in the future?

I think my next step will be to look into the effects of ayahuasca (and other psychedelics) on new areas of mental illness such as stress stemming from perpetual engagement with traumatic experiences, commonly arising in the course of first-responding, policing, and firefighting, as well as Antagonistic Externalizing (i.e., aggression, abuse, criminality).

We have just collected data on ayahuasca-induced changes in post-traumatic stress symptoms in a cohort of special forces veterans. I was present in a research capacity during the cohort's time at an Ayahuasca healing center, and the profound changes in their outlook on themselves and life were incredibly moving. Collaborators are as we speak analyzing this cohort's heart rate during ceremony, gut microbiome related to ayahuasca, and videos containing facial affect (using AI facial affect analysis software), with an eye toward detecting relationships between these variables and therapeutic response.

I am also very much looking forward to a greater understanding of the connections between metaphysical and spiritual changes undergone during ayahuasca and mental health. Some understandings of self, others, and the world may be more hospitable to the at times confusing and stressful human condition. I also think that in addition to doing work that optimizes safety and treatment outcomes, research will also be important that tracks the longer developmental trajectory of individuals who have meaningful psychedelic experiences. In Western industrialized society, we generally do not pay much attention to developmental stages as adults. It would be interesting to explore how psychedelics may catalyze adult growth in ways possibly congruent with the work of Clare Graves, Ken Wilber, and Susan Cooke-Greuter.