Frontiers in Psychiatry
June 20, 2023
Johannes T Reckweg, Cees J van Leeuwen, Cécile Henquet et al.
86 citations
In a small clinical trial with 16 adults suffering from treatment-resistant depression, an inhaled form of the psychedelic drug 5-MeO-DMT (GH001) was well tolerated and produced rapid antidepressant effects. An individualized dosing regimen of up to three increasing doses within a single day led to 87.5% of patients achieving remission (a depression score of 10 or less on the MADRS scale) by day 7, compared to 50% and 25% for single doses of 12 mg and 18 mg, respectively. Remission occurred as early as two hours after dosing for some patients. The findings suggest that individualized dosing may be more effective than a single dose.
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.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2025
Johannes G Ramaekers, Johannes T Reckweg, Natasha L Mason et al.
8 citations
In a first-in-human trial, low to moderate doses of the synthetic cathinone 3-MMC were well tolerated and safe, with potential health risks only at high or excessive doses. 3-MMC caused dose-dependent increases in heart rate and blood pressure that were not clinically significant, along with feelings of subjective high. It also enhanced performance on several neurocognitive tasks, including processing speed, cognitive flexibility, psychomotor function, attention, and memory, while impulse control was unaffected. Participants reported mild dissociative and psychedelic effects, decreased appetite, and transient liking and wanting for the drug. The cardiovascular, psychostimulant, and psychotomimetic profile resembles that of amphetamine-related compounds.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
May 1, 2025
Francisco Madrid-Gambin, Noemí Haro, Natasha L Mason et al.
4 citations
The metabolome—the collection of small molecules in blood—differs between occasional and chronic cannabis users both when sober and after acute THC intoxication. Fourteen metabolites, mainly involved in endocannabinoid and amino acid metabolism, distinguished the two groups with 80% accuracy. During intoxication, occasional users showed attentional impairment and elevated subjective high, accompanied by increases in organic acids, β-hydroxybutyrate, and ceramides; chronic users did not show these changes. The findings demonstrate that metabolomic profiling can identify metabolic alterations specific to the neurocognitive state of cannabis intoxication and to cannabis use frequency.
Frontiers in psychology
January 1, 2025
Johannes T Reckweg, Natasha L Mason, Eef L Theunissen et al.
2 citations
A three-item Peak Experience Scale (PES) was developed to quickly gauge the intensity of the psychoactive experience with the psychedelic 5-MeO-DMT and to guide dosing. Data came from three studies involving 84 healthy volunteers and patients with treatment-resistant depression who inhaled a 5-MeO-DMT formulation at doses of 0 (placebo), 2, 6, 12, or 18 mg, or an incremental individualized dosing regimen. PES ratings increased significantly with dose, peaking after the individualized regimen. The scale showed strong internal consistency and high correlation with other psychedelic assessment tools like the Mystical Experience Questionnaire and Ego Dissolution Inventory, but not with the Challenging Experience Questionnaire. The PES is an effective, simple tool for rapidly assessing psychedelic experience strength and may help guide dosing of rapid-acting psychedelics.
Nature reviews. Neuroscience
July 1, 2021
Johannes G Ramaekers, Natasha L Mason, Lilian Kloft et al.
Acute cannabis intoxication can impair neurocognitive function, potentially leading to human error, injury, and psychological distress. However, the impairing effect varies among individuals and may not occur in all users. The neurocognitive response is driven by changes in mesocorticolimbic and salience network activity and can be exacerbated or mitigated by biological and pharmacological factors, product formulations, and frequency of use, and it can differ between recreational and therapeutic use. These determinants should be considered when defining cannabis impairment in legal contexts, prescribing cannabis therapeutically, and informing the public about safe and responsible use.
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
December 1, 2019
Natasha L Mason, Eef L Theunissen, Nadia R P W Hutten et al.
THC increases striatal glutamate concentrations and reduces functional connectivity between the nucleus accumbens and cortical areas, indicating increased dopaminergic activity. These changes were dose dependent, occurring in the full dose group where THC serum concentrations exceeded 2 ng/ml at T-max. Average glutamate changes correlated strongly with functional connectivity alterations. THC-induced changes in functional connectivity correlated with feelings of subjective high and decreased performance on an attention task. The findings suggest THC elicits subjective and cognitive alterations via increased striatal dopaminergic activity and loss of corticostriatal connectivity, associated with increased striatal glutamate.