BMC Psychiatry
January 16, 2020
Jerome Sarris, Justin Sinclair, Diana Karamacoska et al.
247 citations
Evidence for medicinal cannabis in psychiatry is still early and not yet strong enough to recommend cannabinoid-based treatments. Isolated studies suggest cannabidiol (CBD) may help reduce social anxiety, and there is mixed but mainly positive evidence for its use alongside antipsychotics in schizophrenia. Case studies hint at benefits for sleep and post-traumatic stress disorder, but the evidence is weak. High-THC treatments show no benefit for depression, and CBD does not help mania. One study found a possible effect of an oral cannabinoid/terpene combination for ADHD. Caution is advised with high-THC formulas, especially in youth and people with anxiety or psychotic disorders, and gradual dosing and regular monitoring are recommended.
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.
Australian & New Zealand Journal of Psychiatry
November 15, 2010
Jerome Sarris, E. LaPorte, Isaac Schweitzer
157 citations
Kava, a South Pacific psychotropic plant, reduces anxiety by modulating GABA activity, altering lipid membrane structure and sodium channel function, inhibiting monoamine oxidase B, and blocking noradrenaline and dopamine reuptake. A review of six studies found significant anxiety reduction in four, with a mean Cohen's d of 1.1. Safety concerns include liver toxicity; traditional water-soluble extracts from the rhizome of appropriate cultivars are advised, along with avoiding alcohol and caution with other psychotropics. Routine liver function tests are recommended for regular users, and driving or operating heavy machinery should be avoided at high doses. More studies comparing kava's efficacy and safety with established pharmaceuticals are needed.
CNS drugs
April 1, 2013
Jerome Sarris, Erica Mcintyre, David A Camfield
154 citations
A narrative review of plant-based medicines with both preclinical and clinical evidence for anxiety identified 21 herbs tested in human trials. Chronic use of Piper methysticum, Matricaria recutita, Ginkgo biloba, Scutellaria lateriflora, Silybum marianum, Passiflora incarnata, Withania somniferum, Galphimia glauca, Centella asiatica, Rhodiola rosea, Echinacea spp., Melissa officinalis, and Echium amoenum showed support for treating various anxiety disorders. Acute anxiolytic activity was found for Centella asiatica, Salvia spp., Melissa officinalis, Passiflora incarnata, and Citrus aurantium. Bacopa monnieri showed anxiolytic effects in people with cognitive decline. Current evidence does not support Hypericum perforatum or Valeriana spp. for any anxiety disorder. Conclusions are tempered by methodological issues like small sample sizes and non-replication.
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.
Journal of Translational Medicine
October 2, 2020
Lara Sharpe, Justin Sinclair, Andrew Kramer et al.
122 citations
Acute doses of cannabidiol (CBD) reduce anxiety in both animals and humans without causing anxiety at higher doses, while tetrahydrocannabinol (THC) commonly produces anxiety, especially at higher doses. Epidemiological studies support an anxiolytic effect from CBD, THC, or whole-plant cannabis, but human clinical studies show THC often triggers anxiogenic responses. Cannabinoid therapies containing primarily CBD may be more suitable for people with pre-existing anxiety or as an adjunct for managing anxiety or stress-related disorders. Further research is needed on other cannabis constituents like terpenes, and more clinical trials involving patients with anxiety disorders are warranted.
Evidence-based Complementary and Alternative Medicine
January 1, 2011
Ramesh Manocha, Deborah Black, Jerome Sarris et al.
100 citations
An 8-week randomized controlled trial with 178 full-time workers compared a mental-silence meditation (Sahaja Yoga) to a relaxation active control and a wait-list control. The meditation group showed significantly greater improvements in work stress and depressed mood than both control groups. The findings suggest that approaches emphasizing thought reduction or mental silence may have specific benefits for occupational stress and depressive feelings.
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.
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.
Annals of the New York Academy of Sciences
March 1, 2022
Jerome Sarris
12 citations
Disruptive innovation, a concept from business, can be applied to psychiatry to describe approaches that challenge the status quo. The current mental health crisis and a lack of highly effective pharmacological treatments necessitate such innovative thinking. Promising therapeutic options include digital interventions, psychedelic medicines, microbiome-altering treatments, brain stimulation technology, and nanotechnology-based delivery systems. These could be further advanced through individualization using computational technology and genomics.
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.