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.
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.
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 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 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.
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.
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.
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.
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.
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.
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.
medRxiv
November 1, 2022
Natasha L. Mason, Attila Szabo, Kim P. C. Kuypers et al.
6 citations
preprint
Psilocybin immediately reduced concentrations of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α), while other inflammatory markers (interleukin-1α, IL-1β, IL-6, and C-reactive protein) remained unchanged. Seven days later, TNF-α returned to baseline, but IL-6 and CRP were persistently reduced in the psilocybin group. Changes in immune profile were linked to acute neurometabolic activity: reductions in TNF-α were associated with lower hippocampal glutamate concentrations. Greater reductions in IL-6 and CRP at seven days correlated with persisting positive mood and social effects. Psilocybin also blunted the cortisol response to a psychosocial stressor compared to placebo.
Human Psychopharmacology Clinical and Experimental
October 25, 2018
Patrick C. Dolder, Elizabeth B. de Sousa Fernandes Perna, Natasha L. Mason et al.
6 citations
4-Fluoroamphetamine (4-FA), a novel psychoactive substance with effects between MDMA and amphetamine, reduced cognitive empathy while leaving emotional empathy unaffected in healthy poly-drug users. Plasma oxytocin levels increased one hour after a 100 mg dose compared with placebo, but this hormonal change was unrelated to the behavioral effects on empathy. The findings indicate that 4-FA affects empathy differently from MDMA and amphetamine, and confirm that drug-induced changes in peripheral oxytocin are not associated with empathy.
bioRxiv (Cold Spring Harbor Laboratory)
July 19, 2019
Natasha L. Mason, Eef L. Theunissen, Nadia R. P. W. Hutten et al.
4 citations
preprint
Regular cannabis users develop tolerance to the drug's impairing and rewarding effects, but the underlying brain changes are unclear. In a double-blind, randomized, placebo-controlled crossover study, 12 occasional and 12 chronic cannabis users received acute doses of cannabis (300 μg/kg THC) and placebo, then underwent ultra-high field fMRI and magnetic resonance spectroscopy. In occasional users, cannabis caused decreased functional connectivity and increased striatal glutamate concentrations in reward circuitry, linked to greater subjective high and worse sustained attention. These changes were absent in chronic users, suggesting reduced responsiveness of reward circuitry to cannabis intoxication and a pharmacodynamic mechanism for tolerance development.
Br J Pain
September 4, 2025
Mauro Cavarra, Nadia R. P. W. Hutten, Jan Schepers et al.
A single 15 μg dose of lysergic acid diethylamide (LSD) did not significantly alter pain perception in healthy volunteers compared to placebo in a randomized controlled trial. The study used a double-blind design to test whether a microdose of LSD would produce analgesic effects, but found no meaningful difference between the LSD and placebo conditions on measures of pain tolerance or threshold.