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, a psychedelic plant tea used in Amazonian shamanism, may enhance creative divergent thinking—the ability to generate new ideas and strategies—while decreasing convergent thinking, which focuses on a single correct answer. In a study of 26 participants at two spiritual workshops, creativity tests before and during the acute effects of ayahuasca showed that the tea significantly increased divergent thinking and decreased convergent thinking, as measured by the picture concept test. No significant effects were found on the pattern/line meanings test. These results suggest ayahuasca increases psychological flexibility, potentially aiding psychotherapeutic interventions.
Psychopharmacology
May 1, 2019
Thomas R. Arkell, Nicholas Lintzeris, Richard C. Kevin et al.
177 citations
Both THC-dominant and THC/CBD equivalent cannabis increased lane weaving during simulated driving but had little effect on other driving measures. Impairment on the Digit Symbol Substitution Task, Divided Attention Task, and Paced Auditory Serial Addition Task occurred with both active cannabis types, with worse performance on the latter two tasks after THC/CBD equivalent cannabis. Subjective feelings of being "stoned" and confidence in driving ability did not differ by CBD content. Peak plasma THC concentrations were higher after THC/CBD equivalent cannabis, suggesting a possible pharmacokinetic interaction. Cannabis with equivalent CBD and THC appears no less impairing than THC-dominant cannabis, and CBD may exacerbate THC-induced impairment in some circumstances.
Psychopharmacology
October 30, 2010
Johannes G. Ramaekers, Eef L. Theunissen, Marjolein de Brouwer et al.
168 citations
Heavy cannabis users develop tolerance to the impairing effects of THC on neurocognitive tasks, but they do not develop cross-tolerance to the impairing effects of alcohol. In a double-blind study, 21 heavy cannabis users received alcohol at three levels (targeting blood alcohol concentrations of 0, 0.5, and 0.7 mg/ml) and smoked a THC cigarette (400 μg/kg) 3 hours after drinking began. Alcohol alone impaired performance on tests of perceptual motor control, divided attention, and motor inhibition, while THC alone generally did not affect performance. However, combining THC and alcohol produced greater impairments in divided attention than alcohol alone, indicating that alcohol can potentiate THC effects in tolerant users.
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.
Journal of Analytical Toxicology
March 4, 2015
Nathalie A. Desrosiers, Johannes G. Ramaekers, Émeline Chauchard et al.
136 citations
THC, the main psychoactive compound in cannabis, impairs psychomotor performance, cognition, and driving ability. Occasional cannabis smokers showed significantly more difficulty compensating for tracking error and greater decline in divided attention performance than frequent smokers after smoking one 6.8% THC cigarette. No differences between groups were found on working memory or risk-taking tasks. The results suggest that frequent users develop some tolerance to psychomotor impairment, with implications for driving under the influence cases.
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.
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.
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.
Journal of Psychopharmacology
December 1, 2003
C. T. J. Lamers, Johannes G. Ramaekers, N. D. Muntjewerff et al.
105 citations
A single 75 mg dose of MDMA improved psychomotor performance, including movement speed and tracking in both single and divided attention tasks, but impaired the ability to predict object movement under divided attention, which may indicate impairment of driving-relevant skills. No effect was found on visual search, planning, or semantic memory retrieval. Alcohol 0.5 g/kg was also tested but its effects are not described here. The findings suggest MDMA can both enhance and impair specific cognitive and motor functions relevant to driving.
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 Szabo, 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.
Psychopharmacology
October 5, 2011
Eef L. Theunissen, Gerold F. Kauert, Stefan W. Toennes et al.
82 citations
Heavy cannabis users develop tolerance to some impairing effects of cannabis, observable both in behavior and in brain electrical activity. In a double-blind, placebo-controlled crossover study, 12 occasional and 12 heavy cannabis users smoked a joint containing either 0 or 500 μg/kg body weight THC. During a divided attention task, THC reduced P100 amplitude in occasional users but not in heavy users, indicating tolerance at the neural level. P300 amplitude decreased in both groups. Performance on the stop signal task was impaired in both groups after THC, while divided attention task performance was impaired only in occasional users. Tolerance was evident in event-related potentials, suggesting it is not solely due to behavioral compensation.
Scientific Reports
May 26, 2016
Johannes G. Ramaekers, J. H. van Wel, Desirée Spronk et al.
81 citations
Acute cannabis intoxication impairs executive function, impulse control, attention, and psychomotor function, and increases subjective intoxication, regardless of how frequently a person uses cannabis. In a study of 122 drug users with cannabis use histories ranging from infrequent to daily, cannabis (300 μg/kg THC) produced these deficits compared to placebo, while cocaine (300 mg) improved psychomotor function and attention but impaired impulse control. The absence of tolerance to cannabis's neurocognitive effects suggests that frequent use and intoxication can interfere with performance in daily environments such as school, work, or traffic.
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.
Brain Imaging and Behavior
December 14, 2015
Johannes G. Ramaekers, J. H. van Wel, Desirée Spronk et al.
61 citations
The dopamine β-hydroxylase (DβH) enzyme converts dopamine into noradrenaline. People with low-activity DBH genotypes (rs1611115 CT/TT) appear more sensitive to cannabis and cocaine's effects on cognitive impulse control and brain connectivity. In 122 regular drug users, acute doses of cannabis (450 μg/kg THC) and cocaine (300 mg) increased cognitive impulsivity and reduced functional connectivity between the nucleus accumbens and limbic, prefrontal, striatal, and thalamic areas, primarily in those with CT/TT genotypes, not in those with the CC genotype. A negative association emerged between impulsivity and subcortical connectivity. The findings suggest DBH genotype influences how these drugs affect impulse control and brain networks, potentially explaining progression to drug seeking and informing targeted pharmacotherapy.
Addiction Biology
December 22, 2019
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al.
58 citations
Regular cannabis users develop tolerance to the drug's impairing and rewarding effects, but the underlying brain changes are unclear. In a double-blind, placebo-controlled study, 12 occasional and 12 chronic cannabis users received acute doses of cannabis (300 μg/kg delta-9-tetrahydrocannabinol) or placebo. In occasional users, cannabis decreased functional connectivity and increased striatal glutamate levels in reward circuitry, linked to greater subjective high and worse attention performance. Chronic users showed none of these changes, indicating reduced responsiveness of reward circuitry to cannabis intoxication, suggesting a pharmacodynamic mechanism for tolerance development.
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.