Psychopharmacology
August 13, 2018
Malin V. Uthaug, Kim van Oorsouw, Kim P. C. Kuypers et al.
213 citations
Ayahuasca, a psychotropic plant tea used ceremonially in South America, produces sub-acute and long-term improvements in affect and cognitive thinking style. In 57 ceremony attendees in the Netherlands and Colombia, ratings of depression and stress significantly decreased the day after the ceremony and these changes persisted for 4 weeks. Convergent thinking also improved post-ceremony and was maintained at 4 weeks. Satisfaction with life and several aspects of mindfulness increased the day after but were not significantly different from baseline at 4 weeks. Changes in affect, satisfaction with life, and mindfulness correlated with the degree of ego dissolution experienced during the ceremony, not with prior ayahuasca experience. These findings highlight ayahuasca's therapeutic potential for mental health disorders like depression.
Journal of Psychoactive Drugs
February 26, 2019
Natasha L. Mason, Elisabeth Mischler, Malin V. Uthaug et al.
176 citations
A single dose of psilocybin, given in a retreat setting, may boost creative thinking, empathy, and well-being for at least a week. The morning after use, divergent thinking and emotional empathy improved; seven days later, convergent thinking, certain types of emotional empathy, and life satisfaction remained enhanced. Changes in empathy were linked to changes in well-being. These sub-acute effects outlast acute intoxication and may help explain psilocybin's potential as a treatment for conditions like depression, where social interaction and well-being are impaired.
ACS Pharmacology & Translational Science
April 9, 2021
Gabrielle Agin-Liebes, Trevor F Haas, Rafael Lancelotta et al.
121 citations
Most people who used mescaline in natural settings reported lasting improvements in depression, anxiety, PTSD, and substance use disorders, with 68–86% of those with a history of these conditions noting subjective improvement after their most memorable experience. Those who improved reported stronger acute mystical-type, psychological insight, and ego dissolution effects (Cohen's d 0.7–1.5). For 35–50% of respondents, the mescaline experience ranked among the top five most spiritually significant or meaningful events of their lives. Psychological insight during the experience was linked to higher odds of improvement in depression, anxiety, and alcohol and drug use disorders. The authors call for controlled clinical trials to confirm these preliminary findings.
Psychopharmacology
March 10, 2021
Malin V. Uthaug, Natasha L. Mason, Stefan W. Toennes et al.
116 citations
Ayahuasca, a plant mixture containing DMT and β-carboline alkaloids, has been linked to mental health improvements in naturalistic settings, but prior studies lacked placebo controls. In this observational study, 30 experienced participants at ayahuasca retreats in the Netherlands, Spain, and Germany were assessed before and after sessions; 14 consumed ayahuasca and 16 a placebo. Symptoms of depression, anxiety, and stress reduced over time in both groups, independent of treatment. However, ayahuasca specifically increased implicit emotional empathy to negative stimuli. The findings indicate that mental health improvements can arise from both placebo effects and pharmacological actions of ayahuasca, highlighting the need for placebo-controlled designs.
Psychopharmacology
December 10, 2019
Malin V. Uthaug, Rafael Lancelotta, Attila Szabo et al.
116 citations
Inhalation of vaporized synthetic 5-methoxy-N,N-dimethyltryptamine significantly increased cortisol levels and decreased IL-6 concentrations in saliva immediately after the session. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience. Ratings of non-judgment increased and depression decreased from baseline to immediately post-session and at 7-day follow-up. Anxiety and stress ratings decreased from baseline to 7-day follow-up. Participant ratings of the psychedelic experience correlated negatively with affect ratings and positively with non-judgment ratings. The findings suggest that 5-methoxy-N,N-dimethyltryptamine produces changes in inflammatory markers and improves affect and non-judgment.
Journal of Neurochemistry
February 12, 2022
Johannes T. Reckweg, Malin V. Uthaug, Attila Szabo et al.
108 citations
5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a naturally occurring tryptamine that acts primarily as an agonist at 5-HT1A and 5-HT2A receptors, with highest affinity for the 5-HT1A subtype. Its subjective effects include distortions in auditory and time perception, amplification of emotional states, and feelings of ego dissolution that are usually short-lasting depending on route of administration. Individual dose escalation reliably induces a peak experience thought to be a core predictor of therapeutic efficacy. Observational studies and surveys suggest single exposure can cause rapid and sustained reductions in symptoms of depression, anxiety, and stress.
Frontiers in Pharmacology
October 1, 2021
Maggie Kiraga, Natasha L. Mason, Malin V. Uthaug et al.
83 citations
A single ayahuasca ceremony is associated with lasting improvements in cognitive empathy, satisfaction with life, and the ability to take a non-judgmental stance toward oneself (decentering), while decreasing neuroticism and divergent thinking. In a naturalistic study of 43 ceremony attendees, 20 completed the morning-after assessment and 19 completed the one-week follow-up. Compared to baseline, cognitive empathy, satisfaction with life, and decentering increased at both one day and one week post-ceremony; implicit emotional empathy increased only at one week; and trait neuroticism decreased. Divergent thinking (fluency corrected for originality) decreased. The findings suggest ayahuasca may enhance well-being and social cognition, but clinical trials are needed to confirm therapeutic potential.
Journal of psychopharmacology (Oxford, England)
January 1, 2024
Lisa Luan, Emma Eckernäs, Michael Ashton et al.
41 citations
A novel method of administering the psychedelic DMT via a bolus injection followed by a constant-rate infusion safely extends the experience to 30 minutes in a stable and tolerable fashion. In eleven healthy volunteers, subjective effects plateaued into a steady state while plasma DMT concentrations continued to rise, indicating acute psychological tolerance. Anxiety ratings remained low and heart rate habituated within 15 minutes, demonstrating psychological and physiological safety. This continuous intravenous administration method lays groundwork for further basic and clinical research into DMT's potential for treating mental health conditions and studying consciousness.
Neuroscience and Biobehavioral Reviews
December 1, 2023
Guy W. Fincham, Amy Kartar, Malin V. Uthaug et al.
41 citations
High Ventilation Breathwork (HVB)—volitional manipulation of breathing used historically for psychological distress—produces extraordinary changes in subjective experience and profound effects on central and autonomic nervous systems by modulating neurometabolic parameters and interoceptive sensory systems. Clinical observations and neurophysiological studies indicate these practices may have therapeutic potential for trauma-related, affective, and somatic disorders. The evidence base suggests that the phenomenological effects of HVB can be understood and potentially harnessed through volitional perturbation of psychophysiological state, but further research is needed for detailed mechanistic knowledge and rigorous clinical testing of these potential uses.
Journal of Psychedelic Studies
March 25, 2020
Malin V. Uthaug, Rafael Lancelotta, Ana María Ortiz Bernal et al.
25 citations
Among 27 respondents who used the psychedelic drug 5-MeO-DMT, those who received it by intramuscular injection (IM) reported a lower rate of reactivations (21%) compared to those who vaporized it (69%). The IM group also required fewer redoses, experienced release of physical tension more consistently, and had a slower onset of acute effects (1–6 minutes) versus the vaporization group (1–50 seconds). These findings suggest that the route of administration influences the frequency of reactivations, dosing patterns, physical sensations, and the timing of the drug's effects.
Frontiers in Psychiatry
July 7, 2022
Maggie Kiraga, Kim P. C. Kuypers, Malin V. Uthaug et al.
24 citations
A single dose of psilocybin-containing truffles, taken in a supportive group setting, produced rapid and lasting reductions in both state and trait anxiety among self-reported healthy volunteers. Medium reductions in anxiety were observed the morning after the ceremony and persisted for at least one week. At one week, participants also showed increased non-judging mindfulness and decreased neuroticism. The acute experience of ego dissolution and changes in neuroticism were the strongest predictors of anxiety reduction. Average psilocin consumption was 27.1 mg. Results suggest potential anxiolytic effects for sub-clinical anxiety and support further research in clinical populations.
Frontiers in Psychiatry
November 13, 2023
Tor-Morten Kvam, Malin V. Uthaug, Kristoffer A A Andersen et al.
21 citations
In a survey of 770 Norwegian adults who had a memorable experience with a classic psychedelic substance like psilocybin or LSD, most used the substance for recreational (46.1%) or therapeutic (42.3%) reasons. Psilocybin was the most common substance for the memorable experience. Many participants reported self-perceived symptoms of mental disorders and substance use disorders, and most said their condition improved after the experience. Adverse reactions were usually mild and short-lived, but 4.2% lasted a year or more, and 2.9% had persisting flashbacks for a year or more. The findings highlight both benefits and long-term risks in a self-selecting sample.
Journal of Psychedelic Studies
August 26, 2021
Kim van Oorsouw, Malin V. Uthaug, Natasha L. Mason et al.
16 citations
A single ayahuasca ceremony reduced self-reported stress, anxiety, and somatization, and increased non-judging awareness four weeks later in 73 ceremony attendants. Satisfaction with life and awareness improved the day after the ceremony but returned to baseline after four weeks. No reduction in depression was found, contrary to earlier work. The intensity of ego dissolution during the ceremony predicted sub-acute mental health improvements. Effects were similar for first-time and experienced users. The authors call for placebo-controlled trials to confirm ayahuasca's therapeutic potential.
Journal of Psychedelic Studies
December 15, 2021
Malin V. Uthaug, Natasha L. Mason, Martha N. Havenith et al.
15 citations
A naturalistic observational study of 58 Czech-speaking adults found that a single session of Holotropic Breathwork (a breathing technique intended to produce altered states of consciousness) was associated with lasting improvements in non-judgment, satisfaction with life, and reductions in stress-related symptoms. Although participants reported only low levels of psychedelic-like experience (averaging 0–34% on a 100% scale), the increase in non-judgment appeared sub-acutely and persisted for four weeks. Satisfaction with life increased and stress symptoms decreased at the four-week follow-up.
Commun Psychol
April 13, 2025
Martha N. Havenith, Max Leidenberger, Jelena Brasanac et al.
14 citations
Altered states of consciousness (ASCs) similar to those induced by psychedelics can be achieved through circular breathwork, a non-pharmacological practice. During breathwork sessions, deliberate hyperventilation reduces end-tidal CO2 pressure, which is significantly correlated with the onset of ASCs. The depth of these ASCs predicted subsequent improvements in well-being and reductions in depressive symptoms. Two forms of breathwork, Holotropic and Conscious-Connected, produced highly similar outcomes. The findings identify physiological conditions for ASCs outside of drug use, suggesting breathwork's potential as an accessible psychotherapeutic tool.
International Journal for the Psychology of Religion
December 5, 2022
Arne Bohn, Michiel H. H. Kiggen, Malin V. Uthaug et al.
10 citations
San Pedro, a cactus containing mescaline and used for millennia, is now popular in European ceremonial retreats. In a study of 42 participants at such retreats in the Netherlands, questionnaires measured 11 dimensions of altered consciousness, ego-dissolution, mystical experiences, and challenging experiences. Results indicate San Pedro produces deviations from normal waking consciousness on all 11 subscales, moderate ego-dissolution, and a complete mystical experience in two-thirds of participants. Spiritual experiences are strongly expressed, while disembodiment, anxiety, impaired control, and transcendence of space are low; physical distress and grief can occur during challenging experiences. Network analysis revealed two separate networks of positive and negative altered states.
PsyArXiv
April 13, 2023
Lisa Xiaolu Luan, Emma Eckernäs, Michael Ashton et al.
9 citations
preprint
A within-subjects, placebo-controlled study tested a novel method of administering N,N-Dimethyltryptamine (DMT) by combining a bolus injection with a constant-rate infusion to extend the experience to 30 minutes. The method effectively maintained stable and tolerable subjective effects over the infusion period. Anxiety ratings remained low, and heart rate habituated within 15 minutes, indicating psychological and physiological safety. Plasma DMT concentrations increased consistently starting ten minutes into administration, while psychological effects plateaued, suggesting acute psychological tolerance to DMT. These findings demonstrate the safety and effectiveness of continuous intravenous DMT administration for basic and clinical research.
Frontiers in Psychiatry
January 1, 2021
Sylvana Vilca-Melendez, Malin V. Uthaug, Julian L Griffin
5 citations
A systematic review found that proton nuclear magnetic resonance (1H NMR) spectroscopy has been used primarily for structural elucidation and analytical characterization of psychedelic molecules such as psilocin, LSD, DMT, and bufotenin, but no studies have applied 1H NMR to metabolic profiling of biofluids in psychedelic research, revealing a research gap. The review compared 1H NMR with mass spectrometry, noting both techniques are suitable for biofluid analysis in other fields. Future directions identified include real-time NMR, in vivo magnetic resonance spectroscopy, and gut microbiome studies. Further research is needed to determine whether 1H NMR will be an effective approach for analyzing metabolites in peripheral biofluids and in vivo.
Research Square
February 22, 2024
Martha N. Havenith, Max Leidenberger, Jelena Brasanac et al.
3 citations
Circular breathwork, which involves deliberate hyperventilation, can induce altered states of consciousness (ASCs) comparable to those produced by psychedelics, without the legal, medical, or financial barriers. A reduction in end-tidal CO2 pressure due to hyperventilation is instrumental in catalyzing these ASCs. The depth of the ASCs predicted psychological and physiological follow-on effects, including improved well-being and a reduction of depressive symptoms. Two popular forms of breathwork—Holotropic Breathwork® and Consciously-Connected breathwork—produced highly similar physiological, experiential, and psychological outcomes. These findings outline physiological boundary conditions for ASCs in a non-pharmacological context and suggest breathwork's potential as an accessible psychotherapeutic tool.
August 1, 2023
Guy W. Fincham, Amy Kartar, Malin V. Uthaug et al.
3 citations
preprint
High Ventilation Breathwork (HVB), which involves deliberate manipulation of breathing, has a long history of use for psychological distress. This review examines its potential as a treatment for psychiatric disorders by analyzing its phenomenological and neurophysiological effects. Clinical observations and neurophysiological data show HVB produces extraordinary changes in subjective experience and profoundly affects central and autonomic nervous system functions by modulating neurometabolic parameters and interoceptive sensory systems. These effects may guide understanding and harnessing of HVB's volitional perturbation of psychophysiological states. Reports of beneficial effects for trauma-related, affective, and somatic disorders warrant further mechanistic research and rigorous clinical testing.
Frontiers in Pharmacology
January 1, 2025
Paula Aarseth Tunstad, Tor-Morten Kvam, Malin V. Uthaug et al.
2 citations
An anonymous internet survey of Norwegian-speaking adults who had a memorable experience with a classic psychedelic substance found that 85% reported a small to large positive change in subjective wellbeing after the experience. Integration, ego dissolution, and emotional breakthrough had a clear positive predictive effect on self-reported wellbeing. Variables with smaller but significant effects included challenging experiences, nature or ceremony settings, and a therapeutic or seeking intention. The authors view these findings as hypothesis-generating rather than confirmatory due to study limitations.
Journal of Psychedelic Studies
June 26, 2026
Malin V. Uthaug, Jack G. Allocca, Martha N. Havenith et al.
A new construct called Pivotal Physical States (PiPS) is proposed as the bodily counterpart to Pivotal Mental States (PiMS). PiMS theory holds that psychedelics and stressors like fasting and hypoxia can trigger transformative mental states via serotonin receptor activation, enhancing cognitive flexibility and learning. The paper argues that these same stressors also induce profound bodily changes through the peripheral serotonin system and other somatic mechanisms, creating 'pivotal states' spanning the mind–body continuum. This dual action may enable psychological and physiological recalibration in positive or negative directions depending on moderators. The authors call for empirical validation of PiPS to guide integrated research and therapeutic applications.
medRxiv
March 2, 2022
Maggie Kiraga, Kim P. C. Kuypers, Malin V. Uthaug et al.
preprint
In a group of 52 healthy volunteers attending psilocybin ceremonies, consuming an average of 27.1 mg of psilocin led to medium to large reductions in both state and trait anxiety that persisted for at least one week. One week after the ceremony, participants showed increased non-judging mindfulness and decreased neuroticism. The strongest predictors of reduced trait anxiety were lower neuroticism, and for state anxiety, higher ego dissolution during the experience. The findings suggest rapid and lasting anxiolytic effects of psilocybin in a supportive setting, but further research is needed to confirm these effects in clinical populations.