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. In a randomized, double-blind, placebo-controlled crossover study, 16 recreational MDMA users received single doses of 25, 50, and 100 mg. While MDMA did not generally affect performance, the highest dose improved rapid information processing in the morning after administration. In the evening, MDMA increased subjective ratings of positive mood at every dose and subjective arousal at the highest dose, but these subjective effects were no longer present after a night of sleep loss.
British Journal of Pharmacology
November 22, 2017
Eef L. Theunissen, Nadia R. P. W. Hutten, Natasha L. Mason et al.
38 citations
A placebo-controlled crossover study gave six healthy adults with prior cannabis experience two low doses (2 mg and 3 mg) of the synthetic cannabinoid JWH-018. Serum concentrations of the drug were highest after the 2 mg dose but remained low overall. Both doses were well tolerated with no serious side effects. Participants reported feeling more 'high' at 1 and 2 hours after administration, especially after 2 mg. Despite low serum levels, behavioral impairments emerged: the 2 mg dose impaired performance on tracking, divided attention, and stop signal tasks. Higher doses are needed to obtain a more representative risk profile.
British Journal of Pharmacology
October 11, 2013
Janelle H. P. van Wel, Kim P. C. Kuypers, Eef L. Theunissen et al.
38 citations
Heavy cannabis users show broad impairments in neuropsychological function during THC intoxication, including reduced psychomotor performance and more errors on impulsivity tasks. These impairments appear less severe in psychomotor tasks than those previously seen in occasional users, suggesting some tolerance. Cocaine temporarily improves psychomotor function and speeds reaction times but increases errors, indicating a trade-off between stimulation and impulse control. The decline in impulse control may increase the risk of repeated drug use and addiction.
Psychopharmacology
October 13, 2022
Nadia R. P. W. Hutten, Thomas R. Arkell, Frederick Vinckenbosch et al.
36 citations
Vaporized cannabis containing both THC and cannabidiol (CBD) produces less anxiety than THC alone, but this effect depends on a person's baseline anxiety level. In a placebo-controlled trial with 26 healthy recreational cannabis users, THC-dominant cannabis (13.75 mg THC) and THC/CBD-equivalent cannabis (13.75 mg each) both increased self-rated state anxiety compared to placebo, though the combination caused significantly less anxiety than THC alone. When baseline anxiety was low, CBD completely counteracted THC-induced anxiety; when baseline anxiety was high, CBD did not counteract it. Trait anxiety did not influence the results, and objective measures of attention bias showed no effects.
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.
Frontiers in Pharmacology
July 11, 2017
Drew J. Puxty, Johannes G. Ramaekers, Rafael de la Torre et al.
33 citations
A single 75 mg dose of MDMA produces a dissociative state, marked by feelings of depersonalization and derealization, in healthy recreational users. Blocking the 5-HT2 receptor with ketanserin did not prevent this effect, indicating that the 5-HT2 receptor does not mediate MDMA-induced dissociation. Heart rate correlated with the dissociative state after MDMA alone, but not when ketanserin was given, suggesting heart rate changes do not directly cause dissociation. Cortisol levels and MDMA blood concentrations showed no clear relationship with dissociation. The exact neurobiological mechanism remains unknown and may be relevant to MDMA's therapeutic use.
Psychopharmacology
September 27, 2011
Wendy M. Bosker, Kim P. C. Kuypers, Silke Conen et al.
32 citations
Taking MDMA (ecstasy) during the night does not improve driving performance the next morning after sleep loss, nor does it counteract the impairing effects of sleep deprivation. In a controlled driving test, weaving (measured as standard deviation of lateral position) was significantly increased during morning drives after a night without sleep, regardless of whether participants had taken 0, 25, 50, or 100 mg of MDMA the previous evening. The degree of impairment was clinically relevant and comparable to that seen with a blood alcohol concentration above 0.8 mg/mL. MDMA cannot compensate for sleep-loss-induced driving impairment, and sleep-deprived drivers who have taken MDMA are unfit to drive.
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.
Journal of Psychedelic Studies
June 1, 2018
Natasha L. Mason, Kim P. C. Kuypers
27 citations
Among nearly 2,000 psychedelic users surveyed, 46% reported having or having had a mental disorder, with 77% of those diagnosed by a medical professional. For 99% of diagnosed cases, treatment was offered, yet 77% sought alternatives outside professional recommendations, and 81% used psychedelics to treat symptoms. Self-administered psychedelic treatment was rated as more effective than professional treatment, with greater symptom reduction and quality of life improvement. Lifetime prevalence of psychopathologies in this sample was higher than in the general population. Self-medication with psychedelics was not highly frequent, but when it occurred, it was considered significantly more effective than professional treatment.
Journal of Psychopharmacology
August 25, 2016
EB de Sousa Fernandes Perna, Esther Papaseit, Clara Pérez‐mañá et al.
26 citations
Mephedrone, a recreational drug similar to MDMA, impairs short-term spatial memory one hour after intake but improves critical tracking performance four hours later. When combined with alcohol, mephedrone reduces reaction time compared to alcohol alone, but does not counteract alcohol's impairing effects on divided attention or spatial memory. Alcohol alone impairs both short- and long-term spatial memory and divided attention. The findings suggest mephedrone enhances psychomotor performance while harming memory, and its stimulatory effects are insufficient to offset alcohol-induced deficits on most cognitive tasks.
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.
Psychopharmacology
July 22, 2017
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
24 citations
MDMA reduced the arousal normally elicited by negative sounds, and this effect was blocked by pre-treatment with ketanserin, a 5-HT2 receptor antagonist, indicating the involvement of the serotonin 2A receptor. The drug did not produce a bias toward emotional or social stimuli in the tasks used. MDMA increased both positive and negative mood ratings and elevated oxytocin plasma concentrations. The reduction in arousal to negative sounds was unrelated to subjective arousal levels. This decrease in defensive arousal may contribute to MDMA's therapeutic effects.
Neuroscience & Biobehavioral Reviews
June 6, 2022
Corinna L. Felsch, Kim P. C. Kuypers
23 citations
Current first-line treatments for social anxiety disorder (SAD) have limited efficacy, prompting a need for novel approaches. This systematic review proposes combining meditation-based interventions with a psychedelic, such as psilocybin, as a future alternative. Thirty experimental studies on neural effects of meditation or psilocybin in healthy and patient samples suggest that psilocybin-assisted meditation could alter cognitive processes like biased attention to threat by modulating salience network connectivity, balancing cortical-midline structure activity, and increasing frontoparietal control over amygdala reactivity. The authors conclude that future studies should investigate whether this combination provides therapeutic benefits for SAD patients who do not remit with conventional therapy.
PLoS One
February 23, 2016
Kim P. C. Kuypers, Eef L. Theunissen, Janelle H. P. van Wel et al.
23 citations
Verbal memory performance in people who use Ecstasy (MDMA) does not differ from that of healthy non-users when they are not under the drug's influence, and there is substantial evidence supporting no long-term memory deficit. Clinically significant memory impairment—defined as performance more than 1.5 standard deviations below the average of healthy controls—was absent during abstinence. However, during acute MDMA intoxication, verbal memory was impaired. Pooled data from four experimental studies compared 65 Ecstasy users tested on placebo with 65 matched drug-naïve controls. History of use did not predict memory impairment. The findings suggest that Ecstasy/MDMA use does not cause clinically deficient long-term verbal memory.
Journal of Psychopharmacology
January 8, 2015
JHP van Wel, DB Spronk, Kim P. C. Kuypers et al.
23 citations
Regular drug users with normal or high trait impulsivity levels showed largely similar subjective responses to cocaine, cannabis, and placebo. Cannabis increased dissociation, psychedelic symptoms, fatigue, confusion, depression, and anxiety while decreasing arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic symptoms, vigor, friendliness, elation, positive mood, anxiety, and arousal while decreasing fatigue. Only a few subjective measures differed by impulsivity level; psychedelic symptoms were most intense in high-impulsivity subjects. Trait impulsivity correlated negatively with vigor (r = -.197) and positively with loss of thought control (r = .237) during cannabis intoxication, but a broad association between trait impulsivity and psychedelic drug experience was absent.
British Journal of Pharmacology
September 4, 2012
Kim P. C. Kuypers, Rafael de la Torre, Magı́ Farré et al.
23 citations
MDMA acutely impairs memory, but this effect is not caused by the rise in cortisol that MDMA also triggers. In a placebo-controlled, within-subject experiment with 17 polydrug MDMA users, blocking the cortisol increase with metyrapone (a cortisol synthesis inhibitor) did not prevent the memory deficit produced by a 75 mg dose of MDMA. Memory was tested at peak drug concentrations. The finding suggests that the neuropharmacological mechanism behind MDMA-induced memory impairment is independent of cortisol.
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.
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.
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.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2024
Mesud Sarmanlu, Kim P. C. Kuypers, Patrick Vizeli et al.
17 citations
MDMA-assisted psychotherapy for PTSD shows promising safety and efficacy in clinical trials, but its underlying mechanisms are not well understood. This review examines preclinical and clinical evidence suggesting that MDMA's effects on memory processes—specifically fear extinction and fear reconsolidation—may contribute to the treatment's success. The authors integrate findings from cognitive psychology and psychopharmacology to support this view and provide recommendations for future research.
Neurosci Appl
October 26, 2022
Eline Haijen, Petra P M Hurks, Kim P. C. Kuypers
17 citations
Adults with ADHD who microdosed classic psychedelics on their own initiative reported reduced ADHD symptoms and improved well-being after two and four weeks, compared with their baseline. Performance on a time perception task did not improve. Taking conventional ADHD medication alongside microdosing or having other mental health conditions did not alter the effects on symptoms or well-being after four weeks. The authors call for placebo-controlled experiments to determine whether microdosing offers a genuine benefit beyond the placebo effect.