Frontiers in Psychiatry
September 10, 2021
Cato M. H. de Vos, Natasha L. Mason, Kim P. C. Kuypers
259 citations
A review of 16 preclinical and 4 clinical studies (20 total) shows that a single dose of a psychedelic—such as ayahuasca, DMT, psilocybin, or LSD—rapidly alters molecular, neuronal, synaptic, and dendritic plasticity mechanisms. These changes include increased expression of plasticity-related genes and proteins like Brain-Derived Neurotrophic Factor (BDNF) and greater dendritic complexity that outlasts the drug's acute effects. Repeated administration directly stimulates neurogenesis and elevates BDNF mRNA levels for up to a month. The evidence suggests these neuroplasticity adaptations parallel and may underlie the antidepressant, anxiolytic, and antiaddictive clinical effects of psychedelics.
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
August 31, 2020
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
134 citations
Low doses of LSD (5, 10, and 20 μg) increase brain-derived neurotrophic factor (BDNF) levels in blood plasma, a marker of neuroplasticity. In a placebo-controlled within-subject study with healthy volunteers, BDNF levels rose at 4 hours after 5 μg and at 6 hours after both 5 and 20 μg, compared to placebo. This suggests that even low doses of LSD can acutely enhance neuroplasticity, supporting further research in patient populations for psychiatric conditions.
Translational Psychiatry
April 8, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
132 citations
A double-blind, placebo-controlled experiment with 0.17 mg/kg psilocybin shows that the drug affects creative thinking in time-dependent and task-specific ways. Immediately after consumption, psilocybin increased spontaneous creative insights but decreased deliberate, task-based creativity. Seven days later, participants generated more novel ideas. Brain imaging revealed that both acute and persisting effects were predicted by connectivity within and between networks of the default mode network. These results support historical claims that psychedelics can influence aspects of the creative process and may serve as tools for investigating creativity and its neural basis.
The International Journal of Neuropsychopharmacology
May 30, 2019
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
132 citations
A survey of 1,116 people who microdose psychedelics found that performance enhancement was the main motive (37%), with LSD (10 mcg) and psilocybin (0.5 g) used 2-4 times per week. Most users were unaware of their exact dose. Negative effects were mostly psychological and occurred acutely while under the influence, but the primary reason for stopping microdosing was that it was not effective. The authors call for placebo-controlled studies to quantify performance effects and assess longer-term negative effects.
European Neuropsychopharmacology
October 17, 2020
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
121 citations
Taking very low doses of LSD, known as microdosing, can selectively improve mood and cognition. In a placebo-controlled experiment with 24 healthy adults, doses of 5, 10, and 20 micrograms of LSD were tested. The 20 mcg dose increased positive mood, while 5 mcg and 20 mcg increased friendliness and reduced attentional lapses. Arousal increased at 5 mcg. Negative effects included increased confusion at 20 mcg and increased anxiety at both 5 and 20 mcg. Altered states of waking consciousness occurred at 10 and 20 mcg. The minimal dose producing noticeable effects was 5 mcg, with the clearest effects at 20 mcg.
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.
Journal of Neurochemistry
February 12, 2022
Johannes T. Reckweg, Malin V. Uthaug, Attila Szabó 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.
Journal of Psychopharmacology
August 25, 2020
Johannes G. Ramaekers, Nadia R. P. W. Hutten, Natasha L. Mason et al.
95 citations
A low dose of LSD (20 micrograms) that does not cause a psychedelic experience can increase pain tolerance and reduce the unpleasantness of pain in healthy volunteers. In a controlled experiment with 24 participants, those given 20 µg of LSD kept their hand in cold (3°C) water longer and reported less pain than when given a placebo. Smaller doses (5 and 10 µg) did not produce the same effect. The 20 µg dose caused slight increases in blood pressure, anxiety, and dissociation, but no profound mind-altering effects. These findings suggest that very low doses of LSD may offer a new approach to pain management without the intense psychological effects of higher doses.
Brain Behavior and Immunity
September 7, 2023
Natasha L. Mason, Attila Szabó, Kim P. C. Kuypers et al.
83 citations
A single dose of psilocybin (0.17 mg/kg) in 60 healthy participants immediately reduced the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while interleukin-1β, interleukin-6 (IL-6), and C-reactive protein (CRP) were unchanged. Seven days later, TNF-α returned to baseline, but IL-6 and CRP were persistently reduced. Greater reductions in IL-6 and CRP at seven days correlated with more positive mood and social effects. Acute TNF-α reductions linked to lower hippocampal glutamate. Psilocybin did not significantly alter the stress response to a psychosocial stressor. The findings suggest psilocybin has persisting anti-inflammatory effects that may relate to its therapeutic benefits.
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.
Frontiers in Psychiatry
September 13, 2019
Nadia R. P. W. Hutten, Natasha L. Mason, Patrick C. Dolder et al.
78 citations
People who microdose psychedelics report that it relieves symptoms of mental and physiological disorders more effectively than conventional treatments, especially for ADHD/ADD and anxiety disorders. However, regular (full) doses of psychedelics are rated as more effective than microdoses for mental disorders like anxiety and depression, while for physiological disorders there is no difference in effectiveness between microdoses and regular doses. These findings come from an online survey of 410 adults diagnosed with at least one disorder by a medical professional. The authors call for future randomized controlled trials to objectively test these claims.
Clinical Pharmacology & Therapeutics
September 25, 2020
Friederike Holze, Matthias E. Liechti, Nadia R. P. W. Hutten et al.
63 citations
Very low doses of LSD (5, 10, and 20 µg) were given to 23 healthy participants in a double-blind, placebo-controlled crossover trial. LSD concentrations in the blood increased in proportion to dose, with maximal levels reached after about 1.1 hours and an average elimination half-life of 2.7 hours. The 5 µg dose produced no significant subjective effects. The 10 µg dose significantly increased feelings of being under the influence and good drug effect, starting at 1.1 hours, peaking at 2.5 hours, and lasting until 5.1 hours. The 20 µg dose also increased bad drug effects. The threshold for psychotropic effects was 10 µg.
Contemporary Drug Problems
September 1, 2019
Hannes Kettner, Natasha L. Mason, Kim P. C. Kuypers
50 citations
Motives for using novel psychoactive substances (NPS) are largely similar to those for classical psychoactive substances (CPS), except for synthetic cannabinoids, whose main endorsed motive is getting intoxicated without regard to specific qualities. Across 12 substances, the most common motives are feeling euphoric (58.0%), enhancing an activity (52.3%), and broadening consciousness (48.1%). Coping-related reasons are more frequent among female participants, while males indicate a broader range of motives. These patterns can inform tailored educational campaigns and prevention strategies.
Journal of Psychopharmacology
February 1, 2022
Isabel Wießner, Marcelo Falchi-Carvalho, Lucas Oliveira Maia et al.
43 citations
A randomized, double-blind, placebo-controlled crossover study gave 24 healthy volunteers 50 micrograms of LSD or an inactive placebo and tested creativity near the drug's peak using multiple tasks. LSD changed creativity in three ways: it increased novelty, surprise, originality, and semantic distances (pattern break); decreased utility, convergent thinking, and marginally elaboration (disorganization); and increased symbolic thinking and ambiguity (meaning). The findings suggest LSD shifts cognitive resources away from normal patterns toward new ones, and that LSD-induced symbolic thinking might aid psychedelic-assisted therapy.
Clinical Pharmacology & Therapeutics
May 30, 2023
Pablo Mallaroni, Riccardo Paci, Sabrina Ritscher et al.
34 citations
2,5‐dimethoxy‐4‐bromophenethylamine (2C‐B), a hallucinogen derived from mescaline, produces psychedelic effects of moderate depth, shorter in duration than psilocybin. In a double‐blind, placebo‐controlled study of 22 healthy participants with prior psychedelic experience, 20 mg of 2C‐B elicited alterations of waking consciousness, though psilocybin (15 mg) caused greater dysphoria, subjective impairment, auditory alterations, and ego dissolution. Both compounds equally slowed psychomotor performance and impaired spatial memory compared with placebo, and neither produced empathogenic effects on the Multifaceted Empathy Test. 2C‐B raised blood pressure transiently, similar to psilocybin, and its effects largely resolved within six hours.
European Journal of Pain
August 20, 2023
Mauro Cavarra, Amanda Feilding, Pamela Kryskow et al.
28 citations
A survey of people with chronic pain conditions found that, except for sciatica, those who used psychedelics (full doses or microdoses) reported better pain relief than with conventional medication. Full doses outperformed conventional medication for fibromyalgia, arthritis, migraine, and tension-type headache. Microdoses provided significantly better relief than conventional medication for migraines and comparable relief for the other conditions. The findings suggest that psychedelics may hold value for treating some chronic pain conditions.
American Journal of Psychiatry
January 1, 2025
Johannes G. Ramaekers, Johannes T. Reckweg, Natasha L. Mason
25 citations
Psychedelics like psilocybin can produce a rapid antidepressant response, unlike classical antidepressants. Ultra-fast, short-acting psychedelics such as 5-MeO-DMT and DMT are being explored for their potential to induce rapid antidepressant effects after a brief, intense experience. These compounds primarily act on serotonergic receptors, including 5HT1A and 5HT2A. Early small clinical trials show that short interventions (15-30 minutes) are safe and well tolerated, leading to marked improvement in depression symptoms within 24 hours that lasts at least one week. Data on long-term efficacy are scarce but suggest a prolonged treatment response. Potential benefits include flexible dosing and independence from integrative therapy. Future challenges include establishing the duration of the antidepressant effect and optimizing treatment delivery.
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.
Network Neuroscience
November 1, 2023
Juan Carlos Farah, Pablo Mallaroni, Enrico Amico et al.
21 citations
Functional connectomes become more idiosyncratic under psilocybin, with greater dissimilarity between individuals than under placebo. While idiosyncratic features in placebo subjects appear mainly in the frontoparietal network, under psilocybin they concentrate in the default mode network (DMN). A DMN-focused pattern predicts subjective psilocybin experience, marked by reduced within-DMN and DMN-limbic connectivity and increased connectivity between the DMN and attentional systems. These findings link psilocybin's brain effects to subjective experience and demonstrate the value of brain-fingerprinting in pharmacological neuroimaging.
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.
European Neuropsychopharmacology
February 25, 2021
Natasha L. Mason, Kim P. C. Kuypers, Johannes T. Reckweg et al.
16 citations
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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.
Drug Science Policy and Law
January 1, 2020
Natasha L. Mason, Patrick C. Dolder, Kim P. C. Kuypers
15 citations
Psychedelics like LSD and psilocybin are most often used at home, while MDMA is more common at parties or festivals. Most people take these substances when already in a positive mood, and their mood stays positive or shifts to positive afterward. Individuals with low psychological well-being are more likely to experience a positive mood change after using LSD, psilocybin, or MDMA compared to those with normal well-being. Higher neuroticism scores are linked to both a greater likelihood of positive mood change and a greater likelihood of negative side effects. The findings suggest that psychedelic use can yield positive outcomes even in people with lower well-being and higher neuroticism.