Ayahuasca
- Researchers from University of São Paulo, Universitat Rovira i Virgili, Ribeirão Preto National Institute of Science and Technology-Translational Medicine, and Brazil ICEERS Foundation led a pilot randomized trial investigating the effects of ayahuasca vs placebo in 17 individuals with social anxiety disorder. Those who were administered ayahuasca had significant improvement in their perception of their public speaking. Results were published in Journal of Clinical Psychopharmacology.
- A 2021 prospective naturalistic study examined 63 subjects who had taken part in an ayahuasca ceremony in Peru to examine mental health and epigenetic outcomes. Both immediately and after 6-month delay, significant reductions in depression and anxiety measures, as well as increases in self-compassion, were observed. Epigenetic outcomes revealed small changes in SIGMAR1 regulation, with unclear implications. Results were published in Frontiers in Psychiatry by researchers from King’s College London, University of Exeter, University of West England, and University of Campinas.
- A 2021 placebo-controlled study published in Journal of Clinical Psychopharmacology examined the effect of ayahuasca on social cognition as measured by the recognition of emotions in facial expressions over a 3-month period. Twenty-two subjects naïve to ayahuasca were randomized to an ayahuasca group or placebo group. No differences on either positive or negative emotion recognition were observed between the two groups at any timepoint. Cardiovascular measures and levels of brain-derived neurotrophic factors were also examined, again with no differences found between groups. Ayahuasca was well-tolerated in the group that received it, with no serious adverse effects. The researchers who conducted this study are affiliated with the University of São Paulo; National Institute of Science and Technology; International Center for Ethnobotanical Education, Research, and Service; and Universitat Rovira i Virgili.
- A 2021 study published in Frontiers in Pharmacology studied 200 participants who took part in Shipibo ceremonial use of ayahuasca and undertook questionnaire assessments both before and 15 days after the retreat, with some participants participating in assessments up to 12 months after the retreat. None of the subjects had previous or current mental health diagnoses. Outcomes including psychological well-being, spiritual well-being, quality of life, and decentering demonstrated significant improvement at all follow-up timepoints. Decentering and psychological well-being were correlated from baseline to the first follow-up. Researchers affiliations include International Center for Ethnobotanic Education, Research and Service; PHI Association; Fundación BeckleyMed; Catholic University of Portugal; University of Rovira I Virgili, Institut de Recerca Germans Trias I Pujol; Universitat Autònoma de Barcelona; and University of São Paulo.
- This 2021 study analyzed online survey data from individuals with at least one experience with ayahuasca (N=6,877). The researchers found that therapeutic motivations were associated with higher self-insights and higher subjective spiritual experience, but also with greater fear during the ceremony and more difficulty with integration. Self-knowledge motivation was also associated with higher self-insights and higher subjective spiritual experience, as well as greater reported closeness to the ayahuasca community, but it was not related to fear or integration difficulty. Experiential motivation was associated with a lower spiritual experience and lower closeness to the community. Engaging in preparatory activities, seeking religious/spiritual counselling, practicing yoga/tai chi and seeing a psychologist all were associated with better current mental health, among other outcomes. Several other characteristics were examined. Results were published in Frontiers in Pharmacology by researchers from University of Melbourne; International Center for Ethnobotanic Education, Research and Service; University of Campinas; Mendel University; Western Sydney University; Federal University of Rio Grande do Norte; Universitat Rovira i Virgili; and University of São Paulo.
- A 2021 study examined personality change after use of ayahuasca in a ceremonial setting within a sample of 256 subjects. Within 1 week after ayahuasca use, self-report revealed significant decreases in neuroticism and increases in agreeableness, conscientiousness, extraversion, and openness compared to baseline. These differences persisted at 3-months. Informant report also demonstrated significant decreases in neuroticism and increases in openness after 3 months. Several moderating variables were examined. Results were published in Scientific Reports by researchers from the University of Georgia.
- A placebo-controlled observational study run by researchers at Maastricht University and Goethe University of Frankfurt examined the relationship between ayahuasca use and mental health outcomes. Both groups who used ayahuasca (n=14) and placebo (n=10) demonstrated improvements in symptoms of depression, anxiety, and stress after the ceremony, however only those in the ayahuasca group rated higher on a measure of increased empathy to negative emotional states. Some participants were experienced users while others were naive, and a measure of the overall psychedelic experience in the ayahuasca group was low, so results should be interpreted with caution.
- The Journal of Affective Disorders Reports published a cross-sectional study which utilized the Global Ayahuasca Project database to examine the relationship between ayahuasca use and affect. Over two thousand five hundred individuals with depression and anxiety at the time of ayahuasca use were examined. Depression and anxiety symptoms improved ‘very much’ or more for the majority of individuals (≥70%) per self-report. Researcher affiliations include Western Sydney University, University of Melbourne, Universidade Federal de São Paulo, University of Campinas, University of Zurich, Mendel University Brno, and University of Toronto.
- An observational study found that an addiction treatment program employing traditional Amazonian medicine, including ayahuasca, led to improvement in most clinical outcome measures. Furthermore, outcomes tended to persist over time. Author affiliations include James Cook University, University of Fribourg, Duke Kunshan University, and University of New England. Results were published in Therapeutic Advances in Psychopharmacology.
- A qualitative study led by researchers from the University of Campinas and the University of Auckland found that 14 individuals engaged in ritual use of ayahuasca for severe physical illness came to be more accepting of their illness through introspection, change in perspective, and other mechanisms. This study was published in the Journal of Psychoactive Drugs.
- Scientific Reports published a study that investigated the effect of ayahuasca on mental health and well-being in first-time users. While just under half of the 40 participants met criteria for a psychiatric disorder at baseline, symptoms were improved in the majority of these individuals 6 months after ayahuasca use. Further analyses were conducted in a subset of individuals who had reported acute adverse psychological reactions to ayahuasca use. Published in the Journal of Clinical Psychopharmacology, findings from this follow-up analysis revealed that psychiatric symptoms were still considerably reduced after 6 months in all four of the participants in this subset who also met criteria for a psychiatric disorder at baseline. Affiliations of study authors include the International Center for Ethnobotanical Education, Research, and Services; University of São Paulo; Madrid Autonomous University; Universitat Rovira i Virgili; Ribeirão Preto Medical School; and the National Institute for Translational Medicine.
- A small 2020 study published in Psychopharmacology found that a single dose trial of ayahuasca decreased suicidality up to 21 days after administration in patients with major depressive disorder and baseline suicidality. The researchers from Ryerson University, University of Toronto, University of São Paulo, and National Institute of Science and Technology for Translational Medicine concluded that randomized, controlled trials should be designed to evaluate the effect of ayahuasca on suicidality in the future.
- A randomized, placebo-controlled clinical trial at the Onofre Lopes University Hospital in Brazil, published in Psychological Medicine, has shown that a single dose of ayahuasca significantly alleviated symptoms of treatment-resistant depression just one day after receiving the dose.
- Collaborators from Spain and the Netherlands published this study in Psychopharmacology that revealed that ayahuasca facilitates increases in emotion regulation and mindfulness, and could conceivably be utilized to treat populations such as those with borderline personality disorder. Listen to the first author speak about their research here.
- Six months after ayahuasca use, positive changes in personality – including increased agreeableness and openness and decreased neuroticism – have been recently observed in a 2020 study published in Psychopharmacology by researchers at University of West of England and South London and the Maudsley.
- Several years after a 2013 study from the University of British Columbia revealed that problematic cocaine use was significantly decreased after ayahuasca use, a 2019 qualitative study published in Drug and Alcohol Review revealed that those same participants attributed their substance-use outcomes to feelings of increased connectedness and recognition of their addictive thought patterns.
- A biological basis for ayahuasca’s anti-addictive properties was explored by collaborators from Universidade Estadual de Santa Cruz, Universidade Federal de São Paulo, and the University of Mississippi Medical Center in a 2020 study published in Psychopharmacology, which found that ayahuasca blocked drug-seeking behavior in mice that had been conditioned with methylphenidate.
- This recent placebo-controlled fMRI study from UC San Francisco and the Federal University of Rio Grande do Norte in Brazil revealed changes in the default mode network and salience network of naive ayahuasca users 24 hours after ingestion. These changes correlated with scores of intensity of the psychedelic experience, suggesting a biological basis for the sustained influence of ayahuasca on emotion and affect. Results were published in Journal of Psychopharmacology.
Psilocybin
- Researchers from Johns Hopkins and the Behavioral Health Center of Excellence examined whether language could predict changes in drug use after a psychedelic experience, such as with psilocybin. Over one thousand individuals reported drug use reduction after a psychedelic experience online and volunteered a verbal description of their experience. Three machine learning algorithms detected language that differed by the drug that was quit and by what the long-term outcome was. Results were published in The American Journal of Drug and Alcohol Abuse.
- In 2021, results of a double-blind, randomized control trial were published in New England Journal of Medicine.The trial compared the effects of psilocybin (N=30) to the common antidepressant escitalopram (N=29) on patients with moderate to severe depression over a 6-week period. Neither primary nor secondary outcome measures demonstrated significant differences between the groups. Non-significant changes favored improvement in the psilocybin compared to the escitalopram group.
- Hypertension published a study from researchers at the University of Oxford, University of Alabama at Birmingham, Imperial College London, and Karolinska Institute, in which the relationship between hypertension and classic psychedelic use (including psilocybin and ayahuasca) was investigated. Using a subset of data from the National Survey on Drug Use and Health, they found that adults who had used a psychedelic at least one time over their lifetime were less likely to have hypertension in the past year. Researchers from some of the same institutions used a different subset of the National Survey on Drug Use and Health data to investigate the relationship between classic psychedelic use and physical health. They reported that adults who had used a psychedelic at least one time over their lifetime were more likely to report better overall health and less likely to be overweight or obese. These results were published in the Journal of Psychopharmacology. Relationships identified from both studies must be further investigated to understand possible causal effects.
- A paper published in Frontiers in Psychiatry detailed the development of a training program for psilocybin therapy geared toward treatment-resistant depression. Therapists who received training rated the experience as ‘very good’ or better and described training as comprehensive and well-structured. Author affiliations include the University of Manchester, New York State Psychiatric Institute, COMPASS Pathways, Helsinki University Central Hospital, Johns Hopkins Bayview Medical Center, Maryland Oncology Hematology, King’s College London, and Sheppard and Enoch Pratt Hospital.
- A meta-analysis of twelve randomized controlled trials of psilocybin, LSD, and ayahuasca use in subjects with and without mood disorders found that psychedelic use led to significant improvements in short and long-term mood, with moderate effect sizes. Results were published in Psychopharmacology. Author affiliations include Federal University of Rio Grande do Norte, National Institute of Science and Technology in Translational Medicine, Western Sydney University, Universidade Federal do Rio Grande do Norte, Deakin University, and University of Melbourne.
- Researchers from Johns Hopkins University examined the impact of music on the experience of psilocybin use in ten individuals, finding that individuals who listened to overtone-based music experienced slightly greater smoking abstinence and rated higher on mystical experience than those who listened to Western classical music. The authors highlighted the importance of further investigating the setting of psychedelic therapy. Results were published in ACS Pharmacology & Translational Science.
- A study in Drugs: Education, Prevention and Policy examined the effect of a psychedelic experience, including with psilocybin, on racial trauma among black, indigenous, and people of color. Significant reductions in stress, anxiety, and depression were observed and appeared to correlate with the intensity of psychedelic effects. Affiliations of study authors include the University of Ottawa, University of Connecticut, Johns Hopkins School of Medicine, Ohio State University, and Yale School of Medicine.
- Neurotherapeutics published a study on the effect of psilocybin on migraine suppression, led by researchers at the VA Connecticut Healthcare System, Yale School of Medicine, University of Wisconsin School of Medicine and Public Health, and Alexander Shulgin Research Institute. Ten individuals with migraines each received placebo and psilocybin in 2 sessions while maintaining a migraine diary. Weekly reduction in migraines was significantly greater across the psilocybin session than across the placebo session. This reduction was not associated with intensity of the psychedelic experience.
- Researchers from institutions including York University, University of Toronto, UCSF and University College London surveyed over six thousand individuals who endorsed microdosing LSD or psilocybin in the past year. Among other findings, they reported that microdosing was associated with improved mood and creativity. More often than not, no challenges associated with microdosing were described. The study was published in the Journal of Psychopharmacology in 2020.
- A small randomized clinical trial of psilocybin-assisted therapy in patients with major depressive disorder was published in JAMA Psychiatry in 2020. Depression scores were significantly lower in the treated group compared to a not-yet-treated group, both 1 week and 4 weeks post-treatment. This trial involved collaborators from Johns Hopkins School of Medicine and Ohio State University.
- In 2020, investigators from Aarhus University in Denmark published a study of psilocybin administration in rats in the Journal of Psychopharmacology. They found increased expression of several genes involved in neuroplasticity, especially in the prefrontal cortex.
- Researchers at UC San Francisco, UC Berkeley, San Francisco VA Medical Center, VA Palo Alto, and Oregon Health & Science University led a pilot study of psilocybin-assisted group therapy in older men living with HIV who were experiencing demoralization. Adherence to treatment protocol was high, and serious adverse events were unrelated to psilocybin. Participants saw improvements in demoralization, quality of life, depression symptoms, grief, PTSD symptoms, and trait anxiety, supporting the development future randomized clinical trials of psilocybin therapy. Results were published in EClinicalMedicine. Another paper published in ACS Pharmacology & Translational Science utilized data from this pilot study to demonstrate that attachment anxiety, though not avoidance, decreased significantly after the psilocybin-assisted group therapy experience. This may have implications for reductions in psychiatric symptomatology.
- In Eating and Weight Disorders – Studies on Anorexia, Bulimia and Obesity, researchers from Imperial College London reported that depression and mental health wellbeing scores were improved in individuals who had an eating disorder in their lifetime after single use of a psychedelic substance, including ayahuasca and psilocybin.
- A recent meta-analysis published in Psychiatry Research found a large and significant effect to support the therapeutic benefit of psilocybin use, in combination with behavioral therapy, to improve symptoms of anxiety and depression. Investigators were affiliates of the University of Wisconsin-Madison, University of Utah, VA Palo Alto, and Usona Institute; read additional coverage on the results of this study here.
- In 2016, a Johns Hopkins University School of Medicine clinical trial in patients with cancer-related depression and anxiety found that high doses of psilocybin produced lasting positive effects via increases in quality and meaning of life, and decreased anxiety surrounding death. In the same year, another clinical trial at NYU School of Medicine combined psilocybin with psychotherapy in this patient population and found similar results; and a follow-up in 2020 found that these positive antidepressant and anxiolytic effects of the psilocybin treatment remained even after 3-5 years. All results were published in the Journal of Psychopharmacology.
- A 2018 study in Journal of Psychopharmacology found that males who reported use of psilocybin and/or LSD has reduced odds of becoming violent with their partner, mediated by emotional regulation skills. This study was the result of collaborations between the University of British Columbia, Simon Fraser University, and Laurentian University in Canada; find more coverage here.
- A 2020 study led by investigators at Maastricht University was published in Neuropsychopharmacology and provided a biological and chemical basis for the therapeutic effects of psilocybin. Sixty participants with previous psychedelic experience were randomized to drug or placebo condition. Researchers found that increased medial prefrontal and reduced hippocampal glutamate in the psilocybin group vs control group was related to ego dissolution and was dependent upon whether the experience was positive or negative. Read more about the study here. In 2021, another study within this same sample investigated the effects of psilocybin on creativity, both immediately after administration and after a 1-week delay. They found that psilocybin reduced convergent thinking in comparison to the control group, both acutely and at the 1-week follow-up. They also found acute decreases in divergent thinking as measured by fluency in generating alternative uses for an object, but found that the psilocybin subjects experienced an increase in novel idea generation at the 1-week follow up. Results were published in Translational Psychiatry.
Iboga
- A 2021 observational study investigated the safety of ibogaine use in 14 patients with opioid use disorder. After administration of a single dose, a cardiac safety evaluation revealed that patients experienced QTc prolongation but no torsades des pointes. A cerebellar safety evaluation found that the Scale for the Assessment and Rating of Ataxia revealed inability to walk in all patients. Finally, a safety evaluation of drug effects revealed manageable and well-tolerated withdrawal effects as well as low ratings on the Delirium Observation Scale. All observed effects were reversible. The study was published in Addiction by Dutch researchers affiliated with the IrisZorg organization, the Nijmegen Institute for Science Practitioners in Addiction, Radboud University Medical Center, and the Pompekliniek.
- A 2021 case report published in Journal of Psychedelic Studies reported the treatment of opioid use disorder with ibogaine in two adults. For the first adult, a single 6-day ibogaine treatment resulted in complete abstinence from opioids after less than a week from treatment start, which was maintained for 3 years. Furthermore, this adult reported that after treatment, they no longer experienced the chronic pain that drove his opioid use. For the second adult, the first of 5 total ibogaine ceremonies resulted in abstinence from non-medical opioid use. The additional ceremonies, experienced over four months, helped to reduce all opioid use to the point of total abstinence for a 2-year period. The authors of this case report are affiliated with Interior Health in British Columbia.
- A study published in Nature investigated the effects of a synthesized non-hallucinogenic compound with structural features similar to alkaloids in iboga. Known as tabernanthalog, this compound is reported to promote neural plasticity, reduce drug-seeking behavior, and reduce signs of depression in rodents. Researchers are affiliates of UC Davis, UC Santa Cruz, UC San Francisco, University of Colorado Denver, and the Medical College of Wisconsin.
- This 2020 study, published in Chronic Stress by collaborators from Ohio State University, Johns Hopkins University, and Yale School of Medicine among other institutions, found that ibogaine and DMT treatment resulted in self-reported decreases in cognitive difficulty, PTSD symptoms, depression, and anxiety in veterans.
- A March 2020 study published in ACS Chemical Neuroscience found evidence that one dose of ibogaine produced anti-depressant effects in rats, an effect that was not replicated through a single dose of a typical anti-depressant. This was the result of collaborations between Universidad de la República and the Instituto de Investigaciones Biológicas Clemente Estable in Uruguay, and Columbia University in New York.
- UC San Diego and NYU researchers published a 2017 study in The American Journal of Drug and Alcohol Abuse, in which they administered ibogaine to individuals with opioid dependence and found that the individuals had reduced drug use as well as reduced withdrawal and addiction severity scores. A similar 2018 study, led by researchers at the Dunedin School of Medicine, University of Otago, and MAPS, also found reduced opioid addiction and withdrawal severity 12 months following ibogaine use, and additionally reported improvements in depressive symptoms. This study was also published in The American Journal of Drug and Alcohol Abuse.
- This March 2019 study in Frontiers in Pharmacology, led by investigators at Universidad de la República, Instituto de Investigaciones Biológicas Clemente Estable, and Columbia University, found increased brain levels of neuroprotective factors – molecules that facilitate neuron survival and plasticity – 24 hours after administration of ibogaine in mice. Findings varied by dose and brain region examined.