University research

To gain more insight into the results of a psilohuasca or magic truffle ceremony, MindTravellers supports several universities in the Netherlands. Ayahuasca ceremonies can be booked in various locations in the Netherlands, and they are frequently used by people seeking meaning or stress reduction, as well as those struggling with severe depression. Why are more and more people seeking solace in plant medicines like ayahuasca, and what exactly does ayahuasca do?

In October 2019, the Amsterdam Court of Appeal ruled that ayahuasca, the hallucinogenic plant from South America, poses a threat to public health and subsequently banned its use. Until then, the Santo Daime Church, a Brazilian religious community with offices in Amsterdam and The Hague, had been permitted to offer ayahuasca as a sacrament in its church services.

What does science say about ayahuasca? After decades of criminalization, psychedelics appear to be making a comeback in psychiatry. There is even talk of a true "psychedelic revolution" (Sessa, 2018). Hundreds of publications have appeared on the use of substances such as MDMA, psilocybin, LSD, ketamine, and ayahuasca as treatments for post-traumatic stress disorder (PTSD), depression, and addiction (Aday et al., 2020; Andersen et al., 2021). Over the past five years, various clinical trials have investigated the potential of these substances. For example, MDMA has shown great success in treating PTSD (Mitchell et al., 2021), and psilocybin has the same effect on depression (Carhart-Harris et al., 2021). Because at least half of patients with depression and PTSD do not respond to conventional treatment, there is a need for new interventions. Initial results with psychedelics are promising, with good response, moderate relapse, and fewer sessions than standard treatment (Cavarra et al., 2022). Ayahuasca is another psychedelic gaining increasing scientific interest. This article explains what ayahuasca is, how it works in the brain, what research shows about its effects on stress, depression, and anxiety, and what the risks are.

What is ayahuasca and how is it used?

Ayahuasca has been used for decades by indigenous Amazonian tribes for healing purposes (Frecska, Bokor, & Winkelman, 2016). It is a mixture originally composed of two plants: the leaves of the Psychotria veridis plant and the bark of the Banisteriopsis caapi. Meanwhile, in the West, other, similar, and more easily accessible plants are also offered as ayahuasca or ana-huasca. The active ingredient, NN-dimethyltryptamine (DMT), is found in the leaves, while the bark contains a substance that allows DMT to be absorbed by the body. Once in the brain, DMT increases the circulation of serotonin, a neurotransmitter involved in depression, among other things (Cameron & Olson, 2018).

Ayahuasca is usually consumed in a group, sitting or lying on a mattress. A shaman guides the group, usually using rituals such as burning herbs and singing medicine songs (icaros). There are usually several guides to assist participants, for example, to the restroom. After about 30-45 minutes, changes in perception and consciousness occur. Audiovisual hallucinations, feelings of unity, spiritual insights, and bliss, as well as anxiety and physical sensations such as excessive sweating and palpitations, are reported. Most users also experience vomiting, also known as purging. This vomiting is often experienced by users as liberating and cleansing for both body and mind. It is therefore considered an essential part of the therapeutic application of ayahuasca (Fotiou & Gearin, 2019). An ayahuasca session lasts an average of 4-6 hours.

Can ayahuasca help with mental health issues?

Ayahuasca users often seek meaning and spiritual growth (Gonzalez et al., 2020). Research with healthy ayahuasca participants has shown that after the session, people experienced less depression, anxiety, and stress symptoms compared to before (Dos Santos et al., 2016; Uthaug et al., 2018; Van Oorsouw et al., 2021). Substance use also decreased (Jimenez-Garrido et al., 2020). Two of these studies followed healthy participants who primarily consumed ayahuasca to gain more self-awareness. In both studies, the researchers asked participants of an ayahuasca session in the Netherlands, Colombia, or the Czech Republic to indicate the effects of the session on self-reported depression, anxiety, stress, mindfulness, and quality of life both one day and one month after the session (see Uthaug et al., 2018 and Van Oorsouw et al., 2021). The first study found that one day after the session, participants experienced less depression and stress, reported a higher quality of life, and indicated they were more mindful. Depression and stress levels remained reduced for up to a month. The second study found no immediate decrease in depression, anxiety, or stress, but an increase in quality of life and mindfulness. One month later, there was a decrease in stress, and this time also a decrease in anxiety and an increase in mindfulness. Although there was no control group, these two studies suggest that ayahuasca can reduce depression, anxiety, and stress in healthy participants and increase mindfulness for up to one month after attending an ayahuasca session.

In addition, ayahuasca may also contribute to the treatment of serious psychological problems such as depression (Van Oorsouw, Toennes, & Ramaekers, 2022; Palhano-Fontes et al., 2018). Of the 280 million adults worldwide who suffer from depression, a third do not respond to conventional treatment with psychotherapy or medication (Conway, George, & Sackeim, 2017; WHO, 2021). It is not surprising that some people in this group are looking for an alternative. Increasingly, research is being conducted on the effects of psychedelics such as ayahuasca on depression. For example, Palhano-Fontes and colleagues (2018) showed that patients with (treatment-resistant) depression showed fewer symptoms up to 3 weeks after drinking ayahuasca. In the placebo group, this was significantly less (see also Sanches et al., 2016; Zeifman et al., 2019).

A recent study in a group of Dutch patients with depression investigated whether these effects could last longer than a few weeks (Van Oorsouw et al., 2022). Twenty patients diagnosed with "mild to severe depression" participated in the study. All had experienced depression for at least two years and were (or had been) receiving treatment from a therapist. The majority had previously used antidepressants. Participants voluntarily attended an ayahuasca session with the primary goal of curing their depression. Changes in depression, anxiety, stress, mindfulness, and quality of life were measured for up to one year after the ayahuasca session. Altered states of consciousness (mystical and unpleasant experiences) during the ayahuasca session were also examined. In addition, all participants were interviewed (semi-structured) after the last assessment to determine whether they had done anything else in the year prior that could have influenced their depression. The graph below shows a decrease in depression. Sixty percent of participants were no longer depressed one day after the ceremony. After one year, this figure was 71%. Besides depression, anxiety and stress also decreased, and mindfulness increased (Van Oorsouw et al., 2022). Besides the ayahuasca session, other factors influenced recovery rates. Almost 90% of participants changed their lifestyle after the ayahuasca session: they lived healthier, started meditating, or spent more time in nature. Nine participants used a second psychedelic (ayahuasca or something else) in the intervening year. Two participants resumed their therapy or were now able to utilize it more effectively in their recovery.

How does that work?

The acute effect of ayahuasca is attributed to increased communication between brain regions. Under the influence of ayahuasca, brain activity increases and new connections are formed, as shown in human brain scans (Bouso et al., 2015; Madrid et al., 2022; Riba et al., 2004; 2006). Research with mice also found that new brain cells grow under the influence of ayahuasca (Morales-Garcia et al., 2020). The increased brain activity leads to changes in consciousness. Examples include visual hallucinations (colored and moving geometric patterns), spiritual insights, bliss, and the feeling of becoming part of something "divine or universal." The ego (self) dissolves, and the person feels part of a larger whole, beyond their learned and acquired identity. These are called mystical experiences or “ego dissolution” (Frecska et al., 2016; Sarris et al., 2021). The more of these experiences people reported, the less they suffered from depressive feelings the day after drinking ayahuasca (Uthaug et al., 2018; Van Oorsouw et al., 2021). Several studies have shown that having mystical experiences is a strong predictor of positive health outcomes from psychedelics such as ayahuasca (Van Oorsouw et al., 2021; 2022), psilocybin (Roseman et al., 2018), 5-Meo-DMT (Uthaug et al., 2019) and enketamine (Aust et al., 2019). In contrast, having anxious experiences during an ayahuasca session appears to predict negative outcomes. People who experienced that the condition would never end, who felt like they were losing control, or who had unpleasant physical experiences, did not report less but more anxiety after the session (Van Oorsouw et al., 2021).

Extensive research has been conducted on the relationship between changes in brain activity and altered consciousness under the influence of psychedelics (Doss et al., 2022). Simply put, the part of the brain normally responsible for "control" over how we perceive ourselves and the world around us becomes less active under ayahuasca. Conversely, brain areas linked to senses and emotions become more active, transmitting new signals to the former "control area." Recent research suggests that this shift in brain activity could explain why people develop new beliefs about themselves and thus recover from their depression in the long term (Carhart-Harris et al., 2019; Doss et al., 2022) and become more mindful of life (Sampedro et al., 2017).

What is the role of set and setting in ayahuasca use?

While the studies described above represent a first step toward learning more about the effects of ayahuasca on mental health, no firm conclusions can yet be drawn. Placebo-controlled clinical trials with an ayahuasca product approved for medical research must be conducted before it can be used in mental healthcare. Ayahuasca is a natural plant product with a wide variety of DMT and other compounds in each brew studied (Kaasik et al., 2021). To conduct proper research in a clinical setting, a brew with a precise ratio of ingredients is needed, which is not yet available. Moreover, little is known about the effect of different dosages, and we still know too little about the role of expectations and the ceremonial aspect with its associated rituals.

Unlike other psychedelic substances (such as psilocybin) that have long been studied for clinical use, ayahuasca is typically consumed in a naturalistic setting as part of a (religious) ceremony, often with therapeutic intent (Perkins et al., 2021). According to indigenous medicine practitioners, the group ritual, sacred music, and spiritual atmosphere are important factors in the healing process. Some of the observed effects of ayahuasca on mental health may therefore be a byproduct of this group ritual.

To what extent can the setting play a role in minimizing anxiety-provoking experiences and optimizing mystical ones? Pontual and colleagues (2022) asked participants in religious and neo-shamanic ayahuasca sessions to recall their most recent ayahuasca session and rate elements of the setting (feeling comfortable in the group, the expertise of the facilitators, the level of comfort, etc.) on a scale of 1-10. They were also asked to describe their last ayahuasca experience using a questionnaire on mystical and anxiety-provoking experiences (Pontual et al., 2022). Feeling safe in the group and a good infrastructure emerged as the two most important predictors of having a mystical experience for participants in neo-shamanic ayahuasca ceremonies. Group, comfort, and expert guidance, in turn, emerged as the most important predictors for avoiding anxiety-provoking experiences during the session in this group. Setting and ritual certainly seem to have an influence on the participant's experience (see also Perkins et al., 2021).

Besides the setting, the (mind)set is also important. If participants believe they received ayahuasca, but in reality received an inactive substance (placebo), and their symptoms improve afterward, this is called the "placebo effect." This placebo effect was found in as many as 30% of experienced ayahuasca drinkers (Uthaug et al., 2021). In the previously described group of depressed Dutch patients, 85% expected ayahuasca to alleviate their depression, which could possibly explain part of the improvement (Van Oorsouw et al., 2022). This was confirmed by Palhano-Fontes and colleagues (2018), who found an improvement in depressive symptoms in 26% of the placebo group, even in a clinical setting without ceremony and ritual. This demonstrates that belief and trust in the substance are also important.

What are the risks?

Despite the promising initial findings, it's also important to critically examine the availability and use of ayahuasca. Expert guidance has already been shown to be a key predictor of minimal anxiety-provoking experiences (Pontual et al., 2022; Perkins et al., 2021). Without this guidance, things can go wrong, as evidenced by a recent criminal case in the Netherlands, in which Karim, under the influence of ayahuasca, killed his housemate because he claimed to be "taken over by dark forces" (van der Lee, 2021; ECLI:NL: RBZWB: 2021:1283). It is therefore crucial that psychedelic use takes place in a supervised setting under expert guidance.

Schlag and colleagues (2022) recently examined anecdotal evidence regarding the side effects of psychedelics like ayahuasca against scientific standards. They concluded that the risks of addiction and neurotoxicity have been refuted in recent decades and that psychoses and overdoses are rare. Most side effects are acute (vomiting, palpitations, anxiety), although in some cases, unpredictable, severe physical or psychological reactions also occur, which are usually transient (Schlag et al., 2022). A recent study by Bouso and colleagues (2022) among 10.000 ayahuasca users found the same finding. Vomiting was the most common side effect. A third reported (temporary) cardiac arrhythmias. Physical side effects were more often reported by older individuals, those with underlying physical complaints, and those in an unsupervised setting. Negative psychological side effects were reported by half of the participants, but in 88% of cases, participants considered these beneficial for the growth and integration process. Twelve percent sought psychological support for this. Psychological side effects were more common in people with an underlying anxiety disorder (Bouso et al., 2022; Durante et al., 2021). If psychosis did occur, it was always temporary, and in most cases the person had an underlying psychotic disorder (Cerón et al., 2021; Dos Santos et al., 2017).

While side effects are usually temporary, it's important to emphasize that ayahuasca is not a "quick fix." The experiences and insights gained often require a period of processing (integration), and for participants in psychedelic sessions, (psychological) guidance is necessary, especially for patients (Mitchell et al., 2021). Several countries, including Belgium, are currently offering continuing education for therapists in this area, partly to accommodate the growth of clinical trials. However, the current lack of knowledge about psychedelics in mainstream medicine and the associated stigma means that adequate guidance is not always available (Schlag et al., 2022), and this too is a "risk" that must be considered before participating in an ayahuasca session.

Closing note

Ayahuasca shows promising results for improving depression and stress symptoms in both healthy and depressed participants, but the research is still too early to draw any far-reaching conclusions. Ayahuasca use is not without risk, especially for vulnerable individuals with underlying anxiety disorders. Setting and expectations also appear to play a role in health outcomes. Future research will need to determine the optimal conditions for safely offering ayahuasca for therapeutic purposes.