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.
Psychopharmacology
July 19, 2016
Kim P. C. Kuypers, Jordi Riba, Mario de la Fuente Revenga et al.
204 citations
Ayahuasca enhances creative divergent thinking and appears to increase psychological flexibility, which may aid psychotherapeutic interventions and support clinical trial efforts.
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.
Frontiers in Psychology
June 10, 2022
Mauro Cavarra, Alessandra Falzone, Johannes G. Ramaekers et al.
156 citations
Modern clinical research on psychedelics shows promising outcomes for psychedelic-assisted psychotherapy with appropriately screened participants in controlled settings, though some patients relapse or respond poorly. Individual and contextual factors (set and setting) appear to shape the psychedelic experience and clinical outcomes, suggesting the therapeutic context may moderate efficacy. This review searched PubMed/Medline and Scopus for clinical studies describing structured psychotherapeutic interventions alongside psychedelics. Ad-hoc and adapted therapeutic methods were identified. Common principles, points of divergence, and future directions are discussed, focusing on therapeutic stance, degree of directiveness, and potential suggestive effects of information provided to patients.
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.
PLoS ONE
July 10, 2012
Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen et al.
121 citations
MDMA increases both positive moods (vigor, arousal, friendliness, elation) and negative moods (anxiety, confusion) while also slowing reaction times on impulsivity tasks, indicating greater impulse control. Blocking 5-HT(2) receptors with ketanserin prevented the positive mood effects but not the negative mood or impulsivity changes. Blocking 5-HT(1) receptors with pindolol had no effect on any MDMA-related mood or impulse measures. Thus, 5-HT(2) receptors are specifically involved in MDMA's positive mood enhancement, while 5-HT(1) receptors do not appear to play a role in these effects.
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 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.
Journal of Psychopharmacology
April 3, 2017
Kim P. C. Kuypers, Patrick C. Dolder, Johannes G. Ramaekers et al.
88 citations
A pooled analysis of six placebo-controlled studies with 118 participants confirmed that a single dose of MDMA (75 or 125 mg) increases emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy, which involves recognizing others' emotions. The empathy boost was strongest for positive emotions and was linked to higher MDMA blood levels before testing. The effect was consistent across different labs and doses, and was not influenced by sex, prior drug use, or participants' baseline trait empathy. Although MDMA raised oxytocin levels, those increases did not explain the empathy changes.
PLoS ONE
June 27, 2014
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
88 citations
A single 75 mg dose of MDMA selectively enhances emotional empathy—the ability to share and understand others' feelings—without affecting cognitive empathy (understanding others' mental states), trust, or reciprocity in social interactions. This effect was not altered by adding pindolol, a drug that blocks the 5-HT1A serotonin receptor. Oxytocin nasal spray, a hormone often linked to social bonding, had no effect on any empathy or social interaction measure. Changes in emotional empathy were unrelated to oxytocin levels in the blood. The findings suggest that MDMA's empathy-enhancing effects do not depend on peripheral oxytocin and may instead involve other receptors such as serotonin 2A or vasopressin 1A.
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.
Scientific Reports
November 18, 2021
Joseph M. Rootman, Pamela Kryskow, Kalin Harvey et al.
78 citations
Among self-selected users of a mobile app, people who microdose psychedelics (mostly psilocybin, 85%) were similar demographically to non-microdosers but more often reported a history of mental health concerns. Within that group, microdosers had lower levels of depression, anxiety, and stress across genders. Health and wellness motives were the most common reasons for microdosing, especially among women and those with mental health concerns. The findings highlight a need for rigorous longitudinal research on microdosing's mental health effects.
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.
Journal of Psychopharmacology
March 6, 2023
Emma I Kopra, Jason Ferris, Adam Winstock et al.
62 citations
A large international survey of 3364 people who used LSD or psilocybin mushrooms for self-treatment of mental health conditions or life worries found positive changes across all 17 measured outcomes, with the strongest benefits for insight and mood. However, 22.5% of respondents reported negative effects. Higher intensity of the psychedelic experience, seeking advice beforehand, using psilocybin mushrooms, and treating post-traumatic stress disorder were linked to better outcomes. Younger age, high experience intensity, and using LSD were associated with more negative effects. The findings suggest self-treatment outcomes are generally favorable but carry more frequent negative effects than clinical settings.
Scientific Reports
June 30, 2022
Joseph M. Rootman, Maggie Kiraga, Pamela Kryskow et al.
53 citations
A naturalistic observational study followed 953 people who microdosed psilocybin (taking small, non-hallucinogenic doses of psychedelic mushrooms) and 180 non-microdosers for about 30 days. Small to medium improvements in mood and mental health were observed among microdosers, consistent across gender, age, and pre-existing mental health concerns. Older adults showed specific improvements in psychomotor performance. Combining psilocybin with lion's mane mushrooms and niacin did not affect mood or mental health changes, but among older microdosers, this combination was linked to greater psychomotor improvements than psilocybin alone or with lion's mane. These findings add controlled evidence to the growing research on psychedelic microdosing.
Neuropsychopharmacology
May 11, 2011
Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen et al.
52 citations
Blocking the 5-HT(2A) receptor with ketanserin prevented MDMA-induced impairment on a word-learning task, but not on spatial or prospective memory tasks. Blocking the 5-HT(1A) receptor with pindolol had no effect on any memory task. MDMA alone significantly impaired performance in all three memory tasks. The findings indicate that MDMA-induced verbal memory impairment is mediated by 5-HT(2A) receptor stimulation.
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.
Psychopharmacology
January 18, 2010
Wendy M. Bosker, Kim P. C. Kuypers, Silke Conen et al.
45 citations
Sleep deprivation impairs psychomotor function, and the stimulant effects of MDMA are not sufficient to compensate for this impairment.
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.