Publications

This article reviews the existing literature and draws on original qualitative data from a large cross-sectional study of ayahuasca drinkers. Our proposed model identifies five key psychotherapeutic processes or effects inherent to the ayahuasca experience; somatic effects; introspection and emotional processing; increased Self-connection; increased spiritual connection, and finally the gaining of insights and new perspectives. We note some important differences in these processes compared with other classic psychedelics as well as the implications of the model for the therapeutic use of ayahuasca. Improved understanding of the psychotherapeutic processes involved with the ayahuasca experience will better equip practitioners to work with this potentially transformative concoction and enable the optimization of therapeutic treatment models for potential clinical use.

Ayahuasca is a plant-based decoction native to Amazonia, where it has a long history of use in traditional medicine. Contemporary ritual use of ayahuasca has been expanding throughout the world for mental health purposes, and for spiritual and personal growth. Although researchers have been conducting clinical trials and observational studies reporting medical and psychological benefits, most of these do not report ayahuasca’s immediate or medium-term adverse effects, so these are underrepresented in the literature. With the expansion of ayahuasca ceremonies from their traditional contexts to countries around the world, there is an important public health question regarding the risk/benefit balance of its use…

Psilocybin is being studied for use in treatment-resistant depression. In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery–Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).

Naturalistic and placebo-controlled studies suggest ayahuasca, a potent psychedelic beverage originating from Indigenous Amazonian tradition, may improve mental health, alter personality structure, and reduce alcohol and drug intake. To better understand ayahuasca’s therapeutic potential and to identify factors that influence therapeutic efficacy, we conducted a naturalistic, longitudinal study of facilitated ayahuasca consumption in naïve participants using a comprehensive battery of self-report questionnaires…

Ayahuasca is a natural psychoactive brew, used in traditional ceremonies in the Amazon basin. Recent research has indicated that ayahuasca is pharmacologically safe and its use may be positively associated with improvements in psychiatric symptoms. The mechanistic effects of ayahuasca are yet to be fully established. In this prospective naturalistic study, 63 self-selected participants took part in ayahuasca ceremonies at a retreat centre in the Peruvian Amazon. Participants undertook the Beck Depression Inventory (BDI-II), State-Trait Anxiety Inventory (STAI), Self-compassion Scale (SCS), Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), as well as secondary measures, pre- and post-retreat and at 6-months. Participants also provided saliva samples for pre/post epigenetic analysis…

Purpose of review: Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions.

Recent findings: Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood.

Ayahuasca is a traditional plant decoction containing N,N-dimethyltryptamine (DMT) and various β-carbolines including harmine, harmaline, and tetrahydroharmine, which has been used ceremonially by Amazonian Indigenous groups for healing and spiritual purposes. Use of the brew has now spread far beyond its original context of consumption to North America, Europe, and Australia in neo-shamanic settings as well as Christian syncretic churches. While these groups have established their own rituals and protocols to guide use, it remains unknown the extent to which the use of traditional or non-traditional practices may affect drinkers’ acute experiences, and longer term wellbeing and mental health outcomes. Hence, this study aimed to provide the first detailed assessment of associations between ceremony/ritual characteristics, additional support practices, motivations for drinking, and mental health and wellbeing outcomes…

Major depressive disorder is one of the leading global causes of disability, for which the classic serotonergic psychedelics have recently reemerged as a potential therapeutic treatment option. We present the first meta-analytic review evaluating the clinical effects of classic serotonergic psychedelics vs placebo for mood state and symptoms of depression in both healthy and clinical populations (separately)…

Ayahuasca is a psychoactive Amazonian brew which has emerging data indicating that it has anti-depressant and anxiolytic properties. This paper uses data from the Global Ayahuasca Project (GAP), which was undertaken across 2017–2020 and involved 11912 people, to examine the perceived effects of Ayahuasca consumption on affective symptoms. The study focused on the subsample reporting depression or anxiety diagnoses at time of Ayahuasca consumption.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the ‘Clinical Memorandum on Psychedelics’ recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for downscheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme.

This systematic review searched literary databases for publications into the pharmacology of ayahuasca, with the objective of establishing a comprehensive understanding of the chemistry of the brew, and how it interacts in the body.

The review found data which suggests that the brews effects may result from synergistic properties, as well as additive. It concludes that surface level understanding exists and that further research is required.

Recent clinical trials are reporting marked improvements in mental health outcomes with psychedelic drug-assisted psychotherapy. Objectives: Here, we report on safety and efficacy outcomes for up to 6 months in an open-label trial of psilocybin for treatment-resistant depression. Methods: Twenty patients (six females) with (mostly) severe, unipolar, treatment-resistant major depression received two oral doses of psilocybin (10 and 25 mg, 7 days apart) in a supportive setting. Depressive symptoms were assessed from 1 week to 6 months post-treatment, with the self-rated QIDS-SR16 as the primary outcome measure. Results…[

Psychedelics are a hallucinogenic class of psychoactive drugs with the primary effect of activating non-ordinary states of consciousness. Due to the positive preliminary findings of these drugs in the treatment of psychiatric disorders, the number of registered clinical studies has risen significantly. In this paper, clinical studies registered on clinicaltrials.gov that evaluate the treatment of any psychiatric disorder with psychedelics (excluding ketamine) are summarized and analyzed. 70 registered studies were identified from a clinicaltrials.gov search on December 3, 2020…

Independently funded by the research team, this study provided foundational data which displayed that ayahuasca ceremonies had the power to alter personality, by reducing levels of Neuroticism on a standardised model of personality, the NEO-PI3; also known as the 'Big Five'.

Trend-level increases in Openness were also observed.

The aim of the current study was to review drug harms as they occur in Australia using the Multi-criteria Decision Analysis (MCDA) methodology adopted in earlier studies in other jurisdictions. A facilitated workshop with 25 experts from across Australia, was held to score 22 drugs on 16 criteria: 9 related to harms that a drug produces in the individual and 7 to harms to others. Participants were guided by facilitators through the methodology and principles of MCDA. In open discussion, each drug was scored on each criterion. Overall, alcohol was the most harmful drug when harm to users and harm to others was combined…

A qualitative exploration of participant experiences of ayahuasca ceremonies. These participants were also measured on quantitative scales, in the personality study featured above.

This project investigated themes within the content of the ayahuasca visionary states experienced by participants at the Ayahuasca Foundation, Iquitos - Peru.

Major depression is a highly prevalent mood disorder, affecting about 350 million people, and around 30% of the patients are resistant to currently available antidepressant medications. Recent evidence from a randomized controlled trial (RCT) supports the rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression. The aim of this study was to explore the effect of ayahuasca on plasma cortisol and awakening salivary cortisol response, in the same group of treatment-resistant patients (MD) and in healthy volunteers (C). Subjects received a single dose of ayahuasca or placebo (dosing session), and both plasma and awakening salivary cortisol response were measured at baseline (before dosing session) and 48 h after the dosing session…

Recent open-label trials show that psychedelics, such as ayahuasca, hold promise as fast-onset antidepressants in treatment-resistant depression. 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. We observed significant antidepressant effects of ayahuasca when compared with placebo at all-time points…

The last 20 years have seen major developments in the understanding of how childhood trauma (negative events that cause distress and overwhelm a person’s ability to cope) can have long-term effects on the health and well-being of adults who have experienced this. Child sexual abuse was first included in global burden of disease and disability estimates in 2004, and there has been a steady accumulation of research and evidence identifying the public health issues and costs associated with various traumatic childhood experiences.

A significant number of individuals affected by mental illness fail to respond to first-line treatment options. Therefore, there remains an unmet need for rapidly attenuating therapeutic options for mental health disorders with minimal social and economic burden. The paucity of novel treatment options warrants a renewed investigation of psychedelic-based psychotherapy. Herein, the authors will evaluate the therapeutic potential of traditional psychedelics, psilocybin, and MDMA, in the treatment of mental illness with a narrative review of available literature. Psychedelics, such as psilocybin and MDMA, offer an alternative avenue of therapy for many mental health disorders. Available evidence indicates that psychedelics may offer a single-dose, rapid effect model that have robust effects with treatment-resistant mental disorders and a unique advantage as a possible monotherapy for mental illness…

5-HT receptors expressed throughout the human body are targets for established therapeutics and various drugs in development. Their diversity of structure and function reflects the important role 5-HT receptors play in physiologic and pathophysiological processes. The present review offers a framework for the official receptor nomenclature and a detailed understanding of each of the 14 5-HT receptor subtypes, their roles in the systems of the body, and, where appropriate, the (potential) utility of therapeutics targeting these receptors. Significance Statement: This review provides a comprehensive account of the classification and function of 5-hydroxytryptamine receptors, including how they are targeted for therapeutic benefit.

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatmentresistant depression. Preclinical and clinical studies have suggested that serum brainderived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls (N = 45) and patients with treatment-resistant depression (N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia…