The International Journal of Neuropsychopharmacology
October 21, 2022
James J Gattuso, Daniel Perkins, Simon Ruffell et al.
233 citations
Classical psychedelics like LSD, psilocybin, and ayahuasca consistently disrupt resting-state connectivity within the Default Mode Network (DMN) and increase functional connectivity between canonical resting-state networks. The DMN, a set of brain regions active during self-referencing and mind wandering, is altered in various neuropsychiatric conditions. While DMN modulation is central to some cognitive models of psychedelics, its role in their therapeutic potential remains unclear. This systematic review provides a comprehensive overview to guide future research on the neurocognitive mechanisms of these agents.
Psychopharmacology
January 11, 2021
Nicole Leite Galvão‐coelho, Wolfgang Marx, Maria González et al.
143 citations
Classic serotonergic psychedelics such as psilocybin, LSD, and ayahuasca may improve mood and reduce depressive symptoms more than placebo, with effects appearing within hours and lasting up to 60 days. A meta-analysis of 12 randomized controlled trials involving 257 participants (124 healthy volunteers and 133 patients with mood disorders) found moderate significant effect sizes favoring psychedelics for acute mood improvements in both groups and for longer-term mood benefits in patients. For patients with mood disorders, significant reductions in depressive symptoms were seen acutely, at 2–7 days, and at 16–60 days after treatment. Although unblinding and expectancy are concerns, the strength, speed, and durability of effects support further placebo-controlled trials.
Journal of Psychopharmacology
July 10, 2020
Nicole Leite Galvão‐coelho, Ana Cecília de Menezes Galvão, Raíssa Nóbrega de Almeida et al.
124 citations
In a double-blind placebo-controlled trial, people with treatment-resistant depression had higher baseline levels of C-reactive protein than healthy controls, and a negative correlation between C-reactive protein and cortisol was observed. Ayahuasca, but not placebo, reduced C-reactive protein levels in both patients and healthy controls 48 hours after ingestion. Among patients treated with ayahuasca, larger reductions in C-reactive protein correlated with lower depressive symptoms. No significant changes were found for interleukin 6 or brain-derived neurotrophic factor, and these biomarkers did not predict antidepressant response or remission. The findings clarify biological mechanisms underlying ayahuasca's antidepressant effects.
PLOS global public health
January 1, 2022
José Carlos Bouso, Óscar Andión, Jerome J Sarris et al.
115 citations
A large global survey of over 10,800 ayahuasca users from more than 50 countries found that acute physical adverse effects, primarily vomiting, occurred in 69.9% of participants, with 2.3% needing medical attention. Adverse mental health effects in the weeks or months after use were reported by 55.9% of the sample, but about 88% of those viewed these effects as part of a positive growth or integration process; around 12% sought professional support. Physical adverse effects were linked to older age at first use, having a physical health condition, higher lifetime and recent use, a prior substance use disorder diagnosis, and using ayahuasca in unsupervised settings.
Front Pharmacol
April 21, 2021
Daniel Perkins, Violeta Schubert, Hana Šimonová et al.
73 citations
A large international survey of ayahuasca drinkers found that the context and setting in which ayahuasca is consumed—including preparation, guidance, and integration support—are strongly associated with mental health and wellbeing outcomes. Participants who reported professional or traditional guidance, structured preparation, and post-session integration were more likely to experience improvements in mood, reductions in anxiety, and overall psychological wellbeing. The findings suggest that the benefits of ayahuasca are not solely due to the substance itself but are significantly influenced by the surrounding environmental and support factors. Negative or null outcomes were more common among those who lacked such structured support.
Journal of Affective Disorders Reports
February 6, 2021
Jerome Sarris, Daniel Perkins, Lachlan Cribb et al.
72 citations
Among 1,571 people who reported depression and 1,125 who reported anxiety at the time of consuming ayahuasca, 78% of those with depression said their symptoms were 'very much' improved (46%) or 'completely resolved' (32%), while 70% of those with anxiety reported 'very much' improvement (54%) or complete resolution (16%). Greater improvement was linked to mystical experiences, more ayahuasca sessions, and personal psychological insights. A small minority—2.7% with depression and 4.5% with anxiety—reported worsened symptoms. The authors note this cross-sectional survey cannot establish treatment efficacy and call for randomized controlled trials.
Drug and Alcohol Review
July 25, 2021
Daniel Perkins, Emérita Sátiro Opaleye, Hana Šimonová et al.
54 citations
People who consumed ayahuasca in naturalistic settings reported lower current use of alcohol and other drugs, including risky drinking, compared to those who used it less often. The more times ayahuasca was consumed, the stronger the association with never or rarely drinking alcohol and not using a range of drugs in the past month. These effects were greater for individuals with a prior substance use disorder. The strength of subjective spiritual experience, number of personal insights gained, and drinking ayahuasca with an ayahuasca church were also linked to lower substance use in some analyses. The associations remained after adjusting for religious or social group effects.
Frontiers in pharmacology
January 1, 2022
Daniel Perkins, Broc A Pagni, Jerome Sarris et al.
53 citations
Fifty-three first-time ayahuasca users (32 women, 21 men) completed questionnaires before and one month after a facilitated ceremony. Depression, anxiety, stress, alcohol and cannabis use, body dissociation, self-alienation, impulsivity, and negative affect significantly decreased, while positive mood, self-efficacy, authentic living, extraversion, agreeableness, open-mindedness, spirituality, and relationship satisfaction increased. Baseline traits—especially high negative emotionality and body dissociation, and low self-efficacy—strongly predicted improvements in mental health and substance use, whereas the intensity of the mystical experience had little predictive value. The findings suggest ayahuasca may produce broad mental health benefits and that personal traits could guide personalized treatment.
Australian & New Zealand Journal of Psychiatry
March 21, 2021
Daniel Perkins, Jerome Sarris, Susan L. Rossell et al.
53 citations
Psychedelic substances such as psilocybin, ayahuasca, LSD, and MDMA are gaining renewed medical interest due to the need for new psychiatric treatments and promising study results. This viewpoint reflects on the Royal Australian and New Zealand College of Psychiatrists' Clinical Memorandum on Psychedelics and notes regulatory developments, including applications for down-scheduling and access approvals. The authors argue that rigorous research is needed to assess benefits, safety, and therapeutic mechanisms. They summarize recent findings on mechanisms of action and the psychedelic-assisted psychotherapy model, suggesting medicinal psychedelics could become a new class of psychiatric treatments when used under medical supervision with psychotherapeutic support. However, sufficiently powered trials and safety protocols are required before clinical use, and untrained practitioner access could be harmful.
Journal of Psychopharmacology
November 20, 2023
Andreas Halman, Geraldine Kong, Jerome Sarris et al.
42 citations
A systematic review of 52 studies published before September 2023 examined how classic psychedelics (LSD, psilocybin, mescaline, DMT, 5-MeO-DMT, and ayahuasca) interact with other drugs in humans. When combined with antidepressants, antipsychotics, anxiolytics, mood stabilizers, or recreational drugs, the psychedelics' effects were sometimes weakened, sometimes strengthened, and sometimes unchanged. Except for a few case reports, no serious adverse events were reported. The review maps the potential molecular pathways that may explain these interactions, highlighting a critical gap in knowledge about the safety and outcomes of combining psychedelics with other substances.
PCN reports : psychiatry and clinical neurosciences
December 1, 2023
Simon G D Ruffell, Max Crosland-Wood, Rob Palmer et al.
37 citations
Ayahuasca, a psychedelic plant brew from the Amazon made from Banisteriopsis caapi vine and a DMT-containing plant like Psychotria viridis, has attracted growing interest since the year 2000. This review covers its history, pharmacology, and the phenomenological responses it produces. Anecdotal reports range from positive to accounts of physical and psychological harm. The authors discuss effects on personality and mental health, and examine phenomenological analyses of the experience. They conclude that ayahuasca is a promising psychedelic agent deserving more empirical research into its neurochemical mechanisms and potential therapeutic use.
Frontiers in Neuroscience
January 31, 2023
Daniel Perkins, Kimberley Day, Jerome Sarris et al.
27 citations
Ayahuasca, a psychoactive Amazonian brew containing DMT and harmala alkaloids, is increasingly used worldwide in traditional and neo-shamanic settings. A review of existing literature and original qualitative data from a large cross-sectional study of ayahuasca drinkers proposes a model of five key psychotherapeutic processes inherent to the experience: somatic effects, introspection and emotional processing, increased self-connection, increased spiritual connection, and gaining insights and new perspectives. These processes, facilitated by neurobiological effects, are argued to lead to beneficial mental health and wellbeing outcomes. The model highlights differences from other classic psychedelics and implications for therapeutic use.
Nature medicine
June 3, 2025
Chloé Pronovost-Morgan, Kyle T. Greenway, Leor Roseman et al.
26 citations
A Delphi consensus study with 89 experts from 17 countries identified 30 extra-pharmacological variables that are important or very important for reporting the setting in psychedelic clinical trials. These variables, forming the ReSPCT guidelines, cover physical environment, dosing session procedure, therapeutic framework and protocol, and subjective experiences. The findings reveal significant ambiguities in current conceptualizations of set and setting. The guidelines provide a new standard for designing and documenting contextual factors in psychedelic research.
Psychoactives
June 13, 2023
Tessa Cowley‐court, Richard Chenhall, Jerome Sarris et al.
19 citations
Integrating ayahuasca experiences can be challenging and take considerable time, though working through these challenges may facilitate positive growth. A global online survey of 1630 ayahuasca drinkers (50.4% male, mean age 43) identified three main themes in integration experiences: overall appraisal (easy, challenging, or long-term/ongoing), beneficial tools (like-minded community, yoga, meditation, journaling), and challenges (feeling disconnected, returning to old life with new understandings). Findings challenge individual psychotherapy as the primary integration tool, suggesting communal and somatic elements may also be useful. An expanded definition of psychedelic integration is proposed that includes working with challenges and adjusting to life changes.
Psychoactives
October 3, 2023
Daniel Perkins, Emérita Sátiro Opaleye, José Carlos Bouso et al.
18 citations
Ayahuasca drinkers almost universally report gaining insights during their experiences, and these insights strongly predict subsequent beneficial life and lifestyle changes, including improvements in psychological wellbeing and mental health. In a large international survey of 8,907 ayahuasca drinkers, common changes attributed to ayahuasca included personal, vocational, religious or spiritual, and health-related shifts, along with healthier behaviors. Demographic factors and drinking patterns also predicted these outcomes. The findings suggest that insights and resulting life changes are central to the transformative effects of ayahuasca, occurring across diverse contexts and groups.
medRxiv
June 1, 2023
Andreas Halman, Geraldine Kong, Jerome Sarris et al.
17 citations
preprint
Classic psychedelics—LSD, psilocybin, mescaline, and DMT—are powerful psychoactive substances, but little is known about how they interact with other psychoactive drugs. This systematic review screened 8,487 records and identified 50 studies from 34 reports published before April 20, 2023, covering 31 studies on LSD, 11 on psilocybin, 4 on mescaline, 3 on DMT, and 1 on ayahuasca. The findings show that combining these psychedelics with antidepressants, antipsychotics, anxiolytics, mood stabilizers, or recreational drugs can attenuate, potentiate, or produce no change in effects. Except for a few case reports, no serious adverse drug events were reported.
Frontiers in Psychiatry
December 5, 2022
Geovan Menezes de Sousa, Vagner Deuel de Oliveira Tavares, Ana Cecília de Menezes Galvão et al.
14 citations
In a double-blind, placebo-controlled trial with 72 participants, ayahuasca's effects on depression-related biomarkers were examined two days after dosing. Larger reductions in depressive symptoms during the session were linked to higher serum cortisol levels in patients with treatment-resistant depression. Smaller changes in salivary cortisol during ayahuasca use were associated with higher brain-derived neurotrophic factor (BDNF) levels in patients who showed greater clinical improvement in depressive symptoms. No moderating effects were found for the cortisol awakening response, interleukin-6, or C-reactive protein in patients, nor for any biomarker in healthy controls or the placebo group. The findings suggest that acute emotional and physiological responses during ayahuasca sessions may influence key biomarkers of depression.
Clinical Pharmacology & Therapeutics
September 30, 2024
Andreas Halman, Rachel Conyers, Claire Moore et al.
13 citations
Genetic variations in drug-metabolizing enzymes, particularly cytochrome P450, can influence the intensity of acute effects from psychedelics like LSD and ibogaine, suggesting that dose reductions may be appropriate for CYP2D6 poor metabolizers. Preclinical evidence also indicates that CYP2D6 metabolizer status might alter psychedelic experiences with 5-MeO-DMT and psilocybin when combined with monoamine oxidase inhibitors. Although evidence is limited, especially for pharmacodynamics, pharmacogenomic testing warrants further investigation to potentially improve safety and personalize psychedelic-assisted therapies for psychiatric conditions.
International journal of toxicology
January 1, 2024
Eleanor White, Tom Kennedy, Simon Ruffell et al.
13 citations
A systematic thematic review of 78 articles found that ayahuasca and its main psychoactive alkaloid DMT are generally safe in controlled settings, with serious adverse effects rarely reported among healthy populations. However, some adverse human events have been documented. In animal models, higher doses of ayahuasca showed abortifacient and teratogenic effects, and isolated harmala alkaloid studies—especially with harmaline—revealed potential toxicity at higher doses, which may increase when co-administered with certain medications. The authors note that high-dose animal studies using synthetic isolates may not translate to human use of therapeutic plant-based extracts. The review concludes that traditional use of ayahuasca and DMT has an acceptable safety profile, but further randomized controlled trials with larger samples and longer follow-up are needed.
January 1, 2021
Daniel Perkins, Jerome Sarris
13 citations
Ayahuasca shows promise for improving mental health, with a study involving 100 participants revealing that 70% reported reduced anxiety and enhanced mood after treatment. Participants experienced significant positive changes in early childhood trauma responses, suggesting ayahuasca's potential in clinical psychology and psychiatry. The study also noted a low incidence of adverse effects, with only 10% experiencing mild discomfort. This highlights the need to explore psychedelics further, particularly their influence on neurotransmitter receptors and behavior, as well as their role in addressing stressors like anxiety.
Frontiers in behavioral neuroscience
January 1, 2022
Maria Lara Porpino de Meiroz Grilo, Geovan Menezes de Sousa, Lilían Andrade Carlos de Mendonça et al.
12 citations
Repeated ayahuasca administration before and during social isolation prevented depressive-like behaviors and cortisol alterations in common marmosets. Animals given ayahuasca showed higher cortisol reactivity and fecal cortisol levels similar to family-group controls, no signs of anhedonia, and no increase in chronic stress-related behaviors, unlike isolated animals that received no intervention. The findings suggest ayahuasca promotes resilient responses and may have a prophylactic action against depression.
Current Opinion in Psychiatry
November 15, 2021
Jerome Sarris, Diego Pinzon Rubiano, Kimberley Day et al.
12 citations
Serotonergic psychedelics, including psilocybin, ayahuasca, LSD, and MDMA, show promise for treating mood disorders and PTSD, often combined with psychotherapy. Psilocybin with psychological support has been effective for depression, including treatment-resistant cases, in randomized placebo-controlled trials. LSD has shown anxiolytic effects, and MDMA has Phase III evidence for PTSD. Microdosing has not been found to improve mood in a controlled trial. Challenges remain with blinding, small sample sizes, and lack of definitive Phase III studies (except MDMA for PTSD). Further research into novel formulations, pharmacogenomics, microbiome interactions, and inflammatory pathways is needed.
Drug Science Policy and Law
January 1, 2024
Simon Ruffell, Sam Gandy, WaiFung Tsang et al.
10 citations
Participating in ayahuasca retreats in a traditional Indigenous Amazonian context was associated with significant increases in nature relatedness and improvements in depression and stress, but not anxiety. A moderate negative correlation indicated that greater increases in nature relatedness were linked to lower stress levels. The study involved a mean of 6.31 ceremonies. It remains unclear whether changes resulted from the ayahuasca brew, the ceremonies, or the retreat setting. The findings suggest a potential therapeutic role for such retreats as a multidimensional intervention, but further research is needed to identify mediators and assess long-term effects.
JAMA
December 21, 2021
Luke A. Downey, Jerome Sarris, Daniel Perkins
8 citations
No Summary
Annals of the New York Academy of Sciences
September 23, 2024
Jerome Sarris, Andreas Halman, Anna Urokohara et al.
6 citations
Artificial intelligence and psychedelic medicines, two prominent disruptive innovations in mental healthcare, have potential to combine for novel treatments. A scoping review of literature up to August 2024 explored AI applications in psychedelic medicine, including drug discovery, clinical trial optimization, study design, understanding psychedelic experiences, personalizing treatments, clinical screening and follow-up via chatbots or apps, psychological preparation and integration, and enhancing treatment with brain modulatory devices like virtual reality and haptic suits. Challenges include data protection and ethical safeguards. Future possibilities involve administering psychedelics or algorithm-generated effects to inorganic AI-interfaced neural networks, potentially exceeding human cognitive capacity.