Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users

Ayahuasca is a traditional decoction prepared from the liana Banisteriopsis caapi and the shrub Psychotria viridis; the mixture combines β-carboline monoamine oxidase inhibitors (harmine, harmaline, tetrahydroharmine) from B. caapi with the hallucinogen N,N-dimethyltryptamine (DMT) from P. viridis. Prior research has established the pharmacology and acute subjective effects of ayahuasca, and preclinical work has suggested both potential therapeutic actions and possible cytotoxic effects of β-carbolines on liver cells. Because the liver is the main organ for metabolism and detoxification of orally ingested xenobiotics, concerns have been raised about whether chronic ritual use—common among members of ayahuasca churches who may consume the beverage for years—could impair hepatic function. Sueli and colleagues set out to evaluate biochemical markers of liver and renal function in long-term ritualistic users. Specifically, the study measured standard serum indicators (including ALT, AST, bilirubin, creatinine, urea, lactate dehydrogenase, alkaline phosphatase, and GGT) before and at multiple time points after a typical ritual dose of ayahuasca in volunteers who had consumed the beverage at least twice a month for one year or more. The intent was to determine whether chronic, religious-context consumption of ayahuasca is associated with hepatic dysfunction or acute changes during the immediate post-ingestion period.

The investigators conducted a descriptive cross-sectional study with within-subject repeated measurements. After ethics approval, 22 volunteers from the "Luz do Vegetal" Center of Integral Development were enrolled using the following inclusion criteria: age 21–65 years, either sex, no known renal or hepatic comorbidities, and ayahuasca consumption at least twice monthly for a minimum of one year. Exclusion criteria included pregnancy, use of other psychoactive substances (alcohol, cannabis, cocaine, amphetamines, hallucinogens), and abnormal results on a pre-evaluation of the biochemical parameters listed above. All participants provided informed consent and completed a structured questionnaire on demographics and ayahuasca use history. Participants ingested 1.5 mL of ayahuasca per kg body weight—reported as roughly 100 mL for a 70 kg individual—corresponding to the amount used in the religious ritual. The brew was prepared from B. caapi and P. viridis by decoction and concentration over several hours. The extracted text reports alkaloid concentrations measured by HPLC-DAD (N,N-dimethyltryptamine 2070 mg/mL; harmaline 147.5 mg/mL; harmine 2894 mg/mL; tetrahydroharmine 1893 mg/mL), though the units and magnitudes in the extraction appear unusual and may reflect formatting errors in the source text. Venous blood was collected before ingestion (T0) and at 4 h (T4), 24 h (T24), and 168 h (T168) after consumption. Serum was separated and frozen at −20°C. Biochemical assays were performed spectrophotometrically on a Roche/Hitachi modular analyser. The sample size was determined a priori for 85% power and an effect size of 27% (Cohen's f 2), yielding 22 participants by G*Power calculations. Data were reported as mean ± SD. Statistical analysis comprised one-way repeated-measures ANOVA to test time effects and General Linear Models (GLM) to examine baseline associations with sex (fixed factor) and age and duration of ayahuasca use (covariates); significance was set at P < 0.05. Analyses were performed in SPSS v.22.

Twenty-two participants (13 men, 9 women) provided samples; ages ranged from 21 to 56 years (mean = 39.5, SD = 10.9). Duration of reported ayahuasca use spanned 1 to 20 years (mean = 8.4, SD = 7.2). Blood was sampled at T0, T4, T24, and T168 and the measured biochemical parameters included ALT, AST, GGT, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), total bilirubin, creatinine, and urea. For the primary hepatic enzymes ALT and AST, mean serum activities remained below the upper reference limits at all time points, and one-way repeated-measures ANOVA found no statistically significant differences across the sampled intervals for men or women. GGT, LDH, ALP, and total bilirubin likewise stayed within reference ranges and showed no consistent time-related increases after ayahuasca ingestion. Creatinine and urea concentrations were within normal reference limits for both sexes at all measured times and did not change significantly after ingestion. When sexes were compared, average values for most parameters (except bilirubin and urea) were significantly higher in men than in women. The authors report isolated time-related differences when analysing all volunteers together: for total bilirubin (reported as a T0 to T7 change in the extracted text) and for LDH between T0 and T24. However, there were no statistically significant interactions between sex and time for any parameter, indicating no sex-specific temporal changes. In GLM analyses, sex, age, and duration of ayahuasca use did not generally affect baseline biochemical values; an exception was that sex was associated with differences in ALT and total bilirubin (p < 0.05). Overall, no measures provided evidence of clinically meaningful hepatic or renal dysfunction associated with the chronic ritual consumption studied.

Sueli and colleagues interpret their findings as indicating that long-term, ritualistic use of ayahuasca—at the consumption frequencies and doses represented in this cohort—does not appear to impair standard indicators of hepatic function. The measured enzymes and metabolites remained within normal reference ranges, including during the acute period captured at 4 h post-ingestion, so the investigators conclude there was no biochemical evidence of hepatocellular injury or cholestatic dysfunction in these volunteers. The authors position these results alongside earlier human and preclinical literature: they note systematic reviews and longitudinal community studies that have reported low toxicity and some neuropsychological benefits in long-term users, as well as reports of potential therapeutic effects such as antidepressant and antiaddictive actions. At the same time, they acknowledge preclinical data showing hepatocyte cytotoxicity of harmine and related β-carbolines in vitro and mitochondrial dysfunction in isolated cells, which motivated the present assessment of liver markers in humans. Key limitations acknowledged in the text include the small sample size (n = 22), which constrains statistical power and the generalisability of the findings. The extracted text also includes some possible formatting errors (for example, reported alkaloid concentrations and a time label T7 that do not align cleanly with the stated sampling schedule), and the authors indicate that larger studies are needed to more definitively assess safety and rule out less common or longer-latency hepatic effects. They further note that some biochemical measures can be nonspecific and that complementary investigations (such as imaging, serial long-term monitoring, or isoenzyme fractionation) could provide additional clinical insight. Despite these caveats, the study concludes that within the examined sample and context, ritualistic ayahuasca consumption did not produce detectable liver dysfunction.