OPEN Foundation

L. Tofoli

Chemical Composition of Traditional and Analog Ayahuasca

Abstract

Traditional ayahuasca can be defined as a brew made from Amazonian vine Banisteriopsis caapi and Amazonian admixture plants. Ayahuasca is used by indigenous groups in Amazonia, as a sacrament in syncretic Brazilian religions, and in healing and spiritual ceremonies internationally. The study aimed to determine concentrations of the main bio- and psychoactive components of ayahuasca used in different locations and traditions. We collected 102 samples of brews from ayahuasca-using communities. Concentrations of N,N-dimethyltryptamine (DMT), tetrahydroharmine, harmine, and harmaline were determined by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Qualitative analyses for non-traditional additives (moclobemide, psilocin, yuremamine) were performed by high resolution mass spectrometry. Higher and more variable concentrations of DMT in neoshamanic ayahuasca samples compared to indigenous samples may indicate use of higher and more variable proportions of DMT-containing admixture plants. From European samples, we found two related samples of analog ayahuasca containing moclobemide, psilocin, DMT, yuremamine, and very low concentrations of B. caapi alkaloids. Some analogs of ayahuasca (Peganum harmala, Mimosa tenuiflora) were used in Europe. No analogs were found from Brazil or Santo Daime ceremonies in Europe. We recommend awareness about the constituents of the brew and ethical self-regulation among practitioners of ayahuasca ceremonies.

Kaasik, H., Souza, R., Zandonadi, F. S., Tófoli, L. F., & Sussulini, A. (2021). Chemical Composition of Traditional and Analog Ayahuasca. Journal of psychoactive drugs, 53(1), 65–75. https://doi.org/10.1080/02791072.2020.1815911

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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial

Abstract

BACKGROUND:
Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression.
METHODS:
To test the antidepressant effects of ayahuasca, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 29 patients with treatment-resistant depression. Patients received a single dose of either ayahuasca or placebo. We assessed changes in depression severity with the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale at baseline, and at 1 (D1), 2 (D2), and 7 (D7) days after dosing.
RESULTS:
We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points. MADRS scores were significantly lower in the ayahuasca group compared with placebo at D1 and D2 (p = 0.04), and at D7 (p < 0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d = 0.84; D2: Cohen’s d = 0.84; D7: Cohen’s d = 1.49). Response rates were high for both groups at D1 and D2, and significantly higher in the ayahuasca group at D7 (64% v. 27%; p = 0.04). Remission rate showed a trend toward significance at D7 (36% v. 7%, p = 0.054).
CONCLUSIONS:
To our knowledge, this is the first controlled trial to test a psychedelic substance in treatment-resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., … & Tófoli, L. F. (2018). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological medicine, 1-9. 10.1017/S0033291718001356
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Assessment of Alcohol and Tobacco Use Disorders Among Religious Users of Ayahuasca.

Abstract

The aims of this study were to assess the impact of ceremonial use of ayahuasca-a psychedelic brew containing N,N-dimethyltryptamine (DMT) and β-carboline -and attendance at União do Vegetal (UDV) meetings on substance abuse; here we report the findings related to alcohol and tobacco use disorder. A total of 1,947 members of UDV 18+ years old were evaluated in terms of years of membership and ceremonial attendance during the previous 12 months. Participants were recruited from 10 states from all major regions of Brazil. Alcohol and tobacco use was evaluated through questionnaires first developed by the World Health Organization and the Substance Abuse and Mental Health Services Administration. Analyses compared levels of alcohol and tobacco use disorder between the UDV and a national normative sample (n = 7,939). Binomial tests for proportions indicated that lifetime use of alcohol and tobacco was higher in UDV sample compared to the Brazilian norms for age ranges of 25-34 and over 34 years old, but not for the age range of 18-24 years old. However, current use disorders for alcohol and tobacco were significantly lower in the UDV sample than the Brazilian norms. Regression analyses revealed a significant impact of attendance at ayahuasca ceremonies during the previous 12 months and years of UDV membership on the reduction of alcohol and tobacco use disorder.
Ribeiro Barbosa, P. C., Tofoli, L. F., Bogenschutz, M. P., Hoy, R., Berro, L. F., Marinho, E. A., … & Winkelman, M. J. (2018). Assessment of alcohol and tobacco use disorders among religious users of ayahuasca. Frontiers in psychiatry9, 136., 10.3389/fpsyt.2018.00136
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A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment

Abstract

Objective

This report documents the phenomenology of the subjective experiences of 22 patients with substance-related disorders who were involved in a treatment combining cognitive–behavioral therapy and hospital sessions with ibogaine in Brazil.

Methods

Participants underwent a one-to-one semi-structured interview exploring the subjective effects of ibogaine. We employed interpretative phenomenological analysis to identify relevant phenomenological categories, including physical sensations, perceptual (visual, auditory, and olfactory), emotional, cognitive, and spiritual. Participants also compared ibogaine with other drugs used in life, including psychedelics like ayahuasca, psilocybin mushrooms, and lysergic acid diethylamide.

Results

The findings reveal that the subjective experience with ibogaine has similarities with other psychedelic substances, but also important differences. These include very strong and unpleasant physical effects as well as, at least in this patient population, a very difficult and challenging experience.

Conclusions

Overall, the descriptions involve heightened memory retrieval, specially related to drug abuse and the perception of one’s own future with or without drug use. Strong perceptual phenomena, especially dreamlike visions, were commonly reported. Based on Revonsuo’s evolutionary hypothesis for the function of dreams and of previous suggestions that ibogaine has oneiric properties, we suggest the subjective experience of drug-dependent patients elicited by ibogaine may be framed as simulations of threat and danger.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Tófoli, L. F., Chaves, B. D. R., & da Silveira, D. X. (2017). A phenomenological analysis of the subjective experience elicited by ibogaine in the context of a drug dependence treatment. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2017.007
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Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomised placebo-controlled trial

Abstract

Major Depressive Disorder affects about 350 million people worldwide, and about one-third of the patients are considered treatment-resistant. Furthermore, available antidepressants take usually two weeks for the onset of their antidepressant effect. Recent open label trials show that psychedelics, such as ayahuasca and psilocybin, hold promise as fast-onset antidepressants. Although promising, these studies were not controlled for the placebo effect. To address this issue, and to further test the antidepressant effects of ayahuasca, we conducted a parallel arm, double blind randomised placebo-controlled trial, in patients with treatment-resistant major depression. Thirty-five patients with treatment-resistant major depression received a single dose of ayahuasca or placebo. We measured as primary outcome the change in the Hamilton Depression Rating scale (HAM-D) seven days after the dosing session, and as secondary outcomes the changes in Montgomery-Asberg Depression Rating Scale (MADRS), and response rates at one day (D1), two days (D2) and seven days (D7) after dosing, and remission rates at D7. This study is registered with http://clinicaltrials.gov (NCT02914769). We observed robust evidence of rapid antidepressant effects of a single dosing session with ayahuasca when compared to placebo. HAM-D scores at D7 were significantly lower in patients treated with ayahuasca than in those treated with placebo (p=0.019; Cohen’s d=0.98). MADRS scores were significantly reduced in the ayahuasca group compared to the placebo group at all endpoints (at D1 and D2, p=0.04; at D7, p<0.0001). Between-group effect sizes increased from D1 to D7 (D1: Cohen’s d=0.84; D2: Cohen’s d=0.84; D7: Cohen’s d=1.49). Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group only at D7 (64% vs. 27%; OR = 4.95; p = 0.04; NNT = 2.66). Remission rate was not significantly different between groups. Our study provides new evidence of rapid antidepressant effects of ayahuasca for treatment-resistant major depression.

Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M., Pessoa, J., … & Tofoli, L. (2017). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomised placebo-controlled trial. bioRxiv, 103531. 10.1101/103531
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Treating drug dependence with the aid of ibogaine: A qualitative study

Abstract

Background: Substance use disorders are important contributors to the global burden of disease, but current treatments are not associated with high rates of recovery. The lack of approved and effective treatments is acutely problematic for psychostimulants like cocaine and crack cocaine. One promising alternative in the treatment of drug dependence in general and psychostimulants in particular is the use of the psychedelic alkaloid ibogaine combined with psychotherapy. This was recently shown to induce prolonged periods of abstinence in polydrug users, including psychostimulants. However, drug dependence treatments cannot be comprehensively evaluated with reductions in consumption alone, with current recommendations including secondary outcome measures like craving, family and social relationship, quality of life, and self-efficacy.

Methods: We therefore employed a directed approach to qualitative content analysis to evaluate the outcomes of a treatment combining ibogaine with cognitive-behavioral therapy based on data gathered from patient’s reports obtained in semi-structured interviews.

Main findings: The results revealed that patients benefited from the treatment in all the secondary outcomes, reporting decreases in craving and improvements in personal relationships, quality of life, and self-efficacy, thus supporting existing notions that treatments combining ibogaine and psychotherapy do have a therapeutic potential in the treatment of substance use disorders.

Schenberg, E. E., de Castro Comis, M. A., Alexandre, J. F. M., Chaves, B. D. R., Tófoli, L. F., & da Silveira, D. X. (2016). Treating drug dependence with the aid of ibogaine: A qualitative study. Journal of Psychedelic Studies, (0), 1-10. 10.1556/2054.01.2016.002

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Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics

Abstract

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

Tófoli, L. F., & de Araujo, D. B. (2016). Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics. International Review of Neurobiology. 10.1016/bs.irn.2016.06.005
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The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network

Abstract

The experiences induced by psychedelics share a wide variety of subjective features, related to the complex changes in perception and cognition induced by this class of drugs. A remarkable increase in introspection is at the core of these altered states of consciousness. Self-oriented mental activity has been consistently linked to the Default Mode Network (DMN), a set of brain regions more active during rest than during the execution of a goal-directed task. Here we used fMRI technique to inspect the DMN during the psychedelic state induced by Ayahuasca in ten experienced subjects. Ayahuasca is a potion traditionally used by Amazonian Amerindians composed by a mixture of compounds that increase monoaminergic transmission. In particular, we examined whether Ayahuasca changes the activity and connectivity of the DMN and the connection between the DMN and the task-positive network (TPN). Ayahuasca caused a significant decrease in activity through most parts of the DMN, including its most consistent hubs: the Posterior Cingulate Cortex (PCC)/Precuneus and the medial Prefrontal Cortex (mPFC). Functional connectivity within the PCC/Precuneus decreased after Ayahuasca intake. No significant change was observed in the DMN-TPN orthogonality. Altogether, our results support the notion that the altered state of consciousness induced by Ayahuasca, like those induced by psilocybin (another serotonergic psychedelic), meditation and sleep, is linked to the modulation of the activity and the connectivity of the DMN.

Palhano-Fontes, F., Andrade, K. C., Tofoli, L. F., Santos, A. C., Crippa, J., Hallak, J. A., … Araujo, D. B. (2015). The Psychedelic State Induced by Ayahuasca Modulates the Activity and Connectivity of the Default Mode Network. PLoS One. https://dx.doi.org/10.1371/journal.pone.0118143
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