Cannabis and Cannabinoid Research
February 27, 2019
Eef L. Theunissen, Nadia R. P. W. Hutten, Natasha L. Mason et al.
22 citations
Synthetic cannabinoid JWH-018, inhaled by 17 healthy cannabis-experienced volunteers in a placebo-controlled crossover study, increased heart rate within the first hour and impaired critical tracking and memory performance. Participants who reported a subjective high (responders) had higher serum concentrations of JWH-018 and performed worse on reaction time tests, with increased confusion, amnesia, dissociation, derealization, depersonalization, and drug liking. Large variability in drug concentrations and subjective experience was observed, likely due to fluctuations in drug delivery, which may raise the risk of overdose among synthetic cannabinoid users.
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.
Psychopharmacology
January 26, 2021
Eef L. Theunissen, Johannes T. Reckweg, Nadia R. P. W. Hutten et al.
20 citations
A moderate dose of the synthetic cannabinoid JWH-018, inhaled by 24 healthy adults with no history of mental illness, produced pronounced psychedelic and dissociative effects, including altered perception, amnesia, derealization, depersonalization, and confusion. The average dose administered was 5.52 mg. These findings indicate that synthetic cannabinoids pose a serious risk for public health by inducing psychotomimetic symptoms even in people without prior mental health issues.
Frontiers in Pharmacology
March 18, 2020
Esther Papaseit, Marta Torrens, Mireia Ventura et al.
20 citations
2C-E, a psychedelic phenylethylamine similar to mescaline, acts as a partial agonist at serotonin 2A, 2B, and 2C receptors and inhibits norepinephrine and serotonin uptake. In an observational study, ten recreational psychedelic users self-administered single oral doses of 2C-E (6.5–25 mg). The drug induced alterations in perception, hallucinations, and euphoric mood, with saliva concentrations peaking 2 hours after administration. The effects resembled those of 2C-B and other serotonin-acting drugs.
Neuroscience of Consciousness
January 1, 2025
Christopher Timmermann, James W. Sanders, David Reydellet et al.
19 citations
The psychedelic 5-MeO-DMT can, in its most extreme cases, produce a complete absence of self-experience and other perceptual content while preserving a quality of aroused, waking awareness. In an exploratory observational study in naturalistic ceremonial settings, micro-phenomenological interviews, questionnaires, and EEG recordings revealed a dynamic progression of effects, including variable disruptions of bodily and narrative self, reduced phenomenal distinctions, and visual imagery. EEG showed global alpha and posterior beta power reductions, suggesting inhibition of top-down brain models. The findings indicate 5-MeO-DMT's potential as a pharmacological model for deconstructed consciousness, though retrospective questionnaires have limitations.
Psychopharmacology
June 27, 2019
Lilian Kloft, Henry Otgaar, Arjan Blokland et al.
19 citations
Cannabis intoxication and a history of regular cannabis use are linked to a more liberal response criterion in memory tasks, leading to higher false recognition of unrelated items. In a field study using the Deese/Roediger-McDermott (DRM) paradigm, regular cannabis consumers who were acutely intoxicated (n = 53), regular cannabis consumers who were sober (n = 50), and cannabis-naïve controls (n = 53) completed a memory test. False memory rates for critical lures did not statistically differ between groups, but both intoxicated and sober cannabis consumers falsely recognized more unrelated items than controls. Cannabis-naïve individuals showed higher memory accuracy compared with the intoxicated group.
Journal of Psychopharmacology
May 26, 2011
Kim P. C. Kuypers, Marleen Wingen, Armin Heinecke et al.
19 citations
A single 75 mg dose of MDMA impairs memory encoding by disrupting activity in the left middle frontal gyrus (BA10). In a double-blind, placebo-controlled study, 14 Ecstasy users completed a word-learning task during pharmaco-MRI. Under MDMA, performance on the experimental word list (which required encoding) was worse than under placebo. Encoding-related brain activity was found in frontal, temporal, and parietal regions, but MDMA specifically interfered with activation in the left middle frontal gyrus, right fusiform gyrus, and left cuneus. Only the middle frontal gyrus showed a correlation between brain activity and behavioral performance: during placebo, better performance corresponded with greater activation, but this relationship disappeared under MDMA.
Frontiers in Pharmacology
July 6, 2018
Elizabeth B. de Sousa Fernandes Perna, Eef L. Theunissen, Patrick C. Dolder et al.
18 citations
A single 100 mg dose of 4-fluoroamphetamine (4-FA), a phenethylamine novel psychoactive substance, produced strong elevation in blood pressure for 4-5 hours followed by sustained increased heart rate in healthy volunteers. Effects on mood and neurocognitive function peaked at 1 hour, including significant elevations of vigor, friendliness, elation, arousal, and positive mood, along with improvements in attention and motor performance. Negative affect also increased during the acute and subacute phases. The 150 mg dose was canceled after an interim safety review. The findings confirm clinical observations of acute toxicity and warrant warnings about health risks.
Neuroimage
January 1, 2024
Pablo Mallaroni, Natasha L. Mason, Lilian Kloft et al.
17 citations
Brain functional connectomes are unique fingerprints that persist across mental states, but their stability under altered states is unknown. After collective ayahuasca intake in 21 Santo Daime members, 7T fMRI showed reduced idiosyncrasy in static and dynamic functional connectivity, with a spatiotemporal reallocation of keypoint edges. Interindividual differences in higher-order connectivity motifs predicted perceptual drug effects, demonstrating that individualized connectivity markers can trace a subject's functional connectome across altered states of consciousness.
European Neuropsychopharmacology
February 3, 2022
Lilian Kloft, Henry Otgaar, Arjan Blokland et al.
17 citations
A double-blind, placebo-controlled trial with 60 healthy volunteers who had previously used MDMA examined the drug's effects on false memory. Participants received 75 mg of MDMA or a placebo and were tested using a word list task and two misinformation tasks involving a virtual reality crime scene. Memory was tested immediately and one week later. MDMA caused small impairments in true memory on the word list task at both time points. It increased false memory for related but non-critical lures immediately but decreased false memory for critical lures after a week. Episodic memory in the misinformation tasks was not consistently affected. The findings suggest no heightened vulnerability to external suggestion during MDMA intoxication.
Translational Psychiatry
July 15, 2024
Nadia R. P. W. Hutten, Conny W E M Quaedflieg, Natasha L. Mason et al.
16 citations
Repeated low doses of LSD (15 mcg) affect arousal, attention, and memory depending on a person's baseline cognitive state. In a randomized placebo-controlled trial with 53 healthy participants, LSD reduced resting-state EEG delta, theta, and alpha power (indicating stimulation) and enhanced pre-attentive processing during acute dosing sessions. LSD also blunted visual long-term potentiation (a marker of perceptual learning and memory) by the fourth dosing session. Stimulatory effects were strongest in individuals with low baseline arousal and attention, while inhibitory effects on memory were strongest in those with high baseline memory performance. Some EEG changes persisted at a one-week follow-up, suggesting possible neuroadaptations from repeated low-dose LSD.
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
No Summary
Biological psychiatry. Cognitive neuroscience and neuroimaging
July 1, 2024
Sepehr Mortaheb, Larry D. Fort, Natasha L. Mason et al.
15 citations
Psilocybin produces profound alterations in both brain connectivity and subjective experience. In a randomized study, healthy volunteers received psilocybin or placebo and underwent ultrahigh field 7T fMRI scanning during the peak drug effect. Psilocybin caused widespread increases in averaged brain functional connectivity and a recurrent hyperconnected brain pattern with low blood oxygen level-dependent signal amplitude, suggesting heightened cortical arousal. This hyperconnected pattern was linked to feelings of oceanic boundlessness and visionary restructuralization. The brain's tendency to enter this hyperconnected-hyperarousal state may underlie the variant mental associations characteristic of the psychedelic experience.
Journal of Cognitive Neuroscience
January 1, 2023
Johannes G. Ramaekers, Pablo Mallaroni, Lilian Kloft et al.
15 citations
In members of the Santo Daime church who regularly consume ayahuasca in a ritual setting, the brew's main psychoactive compound DMT drives feelings of oceanic boundlessness, visual restructuring, and ego dissolution, with these effects correlating with peak DMT concentration in the blood. However, measures of mental imagery—including visual perspective shifting, vividness of imagery, and associative thinking—did not noticeably differ between sober and ayahuasca conditions, though subjective cognitive flexibility was lower under ayahuasca. Two mental imagery measures (perspective shifts and cognitive flexibility) correlated with peak DMT levels. Long-term ayahuasca use may produce compensatory or neuroadaptive effects that dampen the acute impact on mental imagery.
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.
Biomedicine & Pharmacotherapy
March 24, 2022
Francisco Madrid-Gambin, Alex Gomez-Gomez, Arnau Busquets-García et al.
14 citations
Consumption of ayahuasca increases N-acyl-ethanolamine endocannabinoids, decreases 2-acyl-glycerol endocannabinoids, and alters several large-neutral amino acids (LNAAs) in human plasma. Most LNAAs were inversely associated with nine of eleven subscales of the 5-Dimension Altered States of Consciousness Rating Scale, except tryptophan, which was positively associated. Several endocannabinoids and hexosylceramides were directly associated with ayahuasca alkaloids. Enrichment analysis confirmed dysregulation in pathways involved in serotonin and dopamine synthesis. A crosstalk between circulating LNAAs and subjective effects is suggested, independent of alkaloid concentrations, providing insights into the metabolic fingerprint and mechanism of action underlying ayahuasca experiences.
Frontiers in Psychology
June 23, 2021
Alexandre Augusto de Deus Pontual, Luís Fernando Tófoli, Carlos Fernando Collares et al.
14 citations
A new questionnaire, the Setting Questionnaire for the Ayahuasca Experience (SQAE), measures the physical and social context in which ayahuasca is consumed. Developed from a literature review, interviews with 19 users, and a survey of 2,994 participants, the scale's structure was tested using exploratory graph analysis and multidimensional item response theory. Six dimensions emerged—Leadership, Decoration, Infrastructure, Comfort, Instruction, and Social—though the original theoretical model fit the data better than the exploratory model. The instrument shows evidence of validity and can support future research on how setting influences the ayahuasca experience, with potential applications for studying psychedelic use more broadly.
June 10, 2021
Drummond E-Wen Mcculloch, Gitte M. Knudsen, Frederick S. Barrett et al.
14 citations
preprint
Research into psychedelic drugs like psilocybin, LSD, and DMT is growing, with clinical trials showing promise for psychiatric conditions. Resting-state fMRI is a common method to study brain mechanisms in these contexts. A review of 42 articles from 17 datasets found high heterogeneity in methods and analyses; two datasets underlie over half the publications, and terms like "entropy" are used inconsistently. The authors suggest that the field needs greater methodological consistency and replicability to identify stable neural markers of psychedelic effects, and encourage development of new models and quantification methods.
Psychopharmacology
May 31, 2018
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Patrick C. Dolder et al.
14 citations
A single 100 mg dose of the new psychoactive substance 4-fluoroamphetamine (4-FA) increased self-reported drug liking, wanting, and good drug effect one hour after administration in 12 healthy poly-drug users, but these effects were absent 11 hours later. Impulsive behavior was not affected by 4-FA. The increase in liking and wanting suggests a potential for abuse, but the lack of effect on impulsivity and the small sample size limit the conclusions.
Journal of Psychoactive Drugs
January 24, 2019
Kim P. C. Kuypers, E. B. de Sousa Fernandes Perna, Eef L. Theunissen et al.
13 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with a chemical structure similar to amphetamine and MDMA, induces a mild psychedelic state. In a placebo-controlled crossover study of 12 healthy poly-drug users, the psychedelic state peaked one hour after administration, coinciding with highest serum concentrations, and declined over time as concentrations fell. No change in creative (flexible) thinking occurred. The intensity of the 4-FA-induced psychedelic state falls between that produced by amphetamine and MDMA, consistent with user reports. More research is needed to determine whether 4-FA can alter creative thinking.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
December 31, 2023
Francisco Madrid-Gambin, David Fabregat-Safont, Alex Gomez-Gomez et al.
12 citations
Psychedelics like LSD, mescaline, DMT, ayahuasca, 5-methoxy-DMT, and psilocybin induce altered states of consciousness and are being studied for treating mental health disorders. This review examines metabolic and metabolomics studies in humans after administration of these drugs. The main metabolites for classical psychedelics have been robustly established, but the metabolic alterations they induce need further exploration. Integrating metabolomics with pharmacokinetics may help understand the therapeutic role of psychedelics by revealing molecular interactions with multiple targets.
Scientific Reports
January 12, 2018
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
12 citations
MDMA's mood effects depend partly on a genetic variation in the serotonin transporter gene (5-HTTLPR). People with the short variant of this gene typically show more anxiety and negative mood, while those with two long alleles (l-group) tend to be less anxious. In a pooled analysis of four placebo-controlled studies with 63 polydrug ecstasy users, MDMA (75 mg) generally improved mood but also increased anxiety and confusion. Unexpectedly, the l-group reported higher anxiety regardless of MDMA or placebo. MDMA reduced depressive feelings only in females from the l-group, suggesting a sex- and genotype-dependent effect.
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.
Drug Testing and Analysis
March 26, 2019
Stefan W. Toennes, David J. Schneider, Werner Pogoda et al.
9 citations
The pharmacokinetics of 4-fluoroamphetamine (4-FA) in humans resemble those of amphetamine, with peak serum concentrations occurring about 2 hours after ingestion and an elimination half-life of roughly 8-9 hours, though this varies widely (5.5-16.8 hours). After a 100 mg dose, median maximum serum concentration was 195 ng/mL (range 155-316 ng/mL). Concentrations in oral fluid were higher than in serum, especially during the first 3 hours, likely due to oral contamination. Serum concentrations observed in forensic cases matched those in the study, suggesting recreational doses are similar, but such doses may already cause prominent adverse effects and life-threatening consequences.