Journal of psychopharmacology (Oxford, England)
March 1, 2022
Harriet de Wit, Anya K. Bershad, Charles S. Grob
11 citations
The psychological processes by which mind-altering drugs improve mood or behavior remain poorly understood. Controlled laboratory studies using well-defined psychological constructs can help reveal how these drugs produce therapeutic benefits, but substantial methodological differences exist between clinical studies of therapeutic outcomes and laboratory studies of underlying mechanisms. Using MDMA as an example, this review examines differences in expectancies, social and physical context, participant characteristics, pharmacological factors, and outcome measures between studies with and without psychiatric participants. It describes challenges and opportunities in translating laboratory findings to clinical settings and identifies ways to bridge the gap between these research approaches.
Journal of psychopharmacology (Oxford, England)
March 1, 2024
Anya K. Bershad, David T Hsu, Harriet de Wit
9 citations
MDMA, a compound being studied for treating PTSD, increases positive feelings in response to social feedback, such as receiving likes or rejections in a dating-app-like task. In a double-blind, placebo-controlled trial with 36 healthy adults aged 18-40, a high dose of MDMA (1.5 mg/kg) boosted positive affective responses to both positive and negative social feedback, compared to placebo and methamphetamine. This suggests MDMA may enhance social connection by making social interactions feel more rewarding, which could explain its therapeutic benefits. Further research is needed to test these effects in clinical populations and with different types of social feedback.
bioRxiv (Cold Spring Harbor Laboratory)
May 24, 2022
Manoj K. Doss, Jason Samaha, Frederick S. Barrett et al.
6 citations
preprint
Different classes of psychoactive drugs—sedatives, dissociatives, psychedelics, stimulants, and cannabinoids—each produce unique patterns of effects on the conscious processes underlying episodic memory, depending on whether they act during encoding, consolidation, or retrieval. Reanalyzing confidence data from 10 published datasets (28 drug conditions) with signal detection models, the authors found that all drugs except stimulants impaired recollection when given at encoding; sedatives, dissociatives, and cannabinoids also impaired familiarity at encoding. Psychedelics at encoding enhanced familiarity and did not affect metamemory, while dissociatives and cannabinoids tended to enhance metamemory. Stimulants enhanced metamemory at encoding and retrieval but impaired it at consolidation. These distinct profiles may help explain drug-specific subjective phenomena such as sedative-induced blackouts or psychedelic déjà vu.
Nat Med
June 1, 2021
David Nutt, Harriet de Wit
6 citations
The text is a brief, playful title that reinterprets the abbreviation MDMA, suggesting a connection to medical doctors (MD) rather than providing substantive content. It does not present a finding, argument, or data.
Biological Psychiatry
May 15, 2025
Anya K. Bershad, Harriet de Wit
3 citations
Disrupted social homeostasis underlies many behavioral disorders, including problematic drug use. This narrative review examines whether single doses of psychoactive drugs can relieve the discomfort of social isolation and promote social connection. For opioid drugs, mu opioid agonists and kappa opioid antagonists reduce distress from social isolation, and mu opioid agonists enhance social reward. Amphetamine-like stimulant drugs, including MDMA, do not reduce the distress of social isolation but increase motivation for social contact and the pleasure derived from social interaction. Many questions remain, including whether these effects contribute to problematic drug use and the effects of drug withdrawal or dependence on social function.
Psychedelic medicine (New Rochelle, N.Y.)
December 1, 2024
Connor J Haggarty, Hanna Molla, James Glazer et al.
2 citations
A low dose of LSD (26 µg) alters the brain's electrical response to neutral and happy faces, but not angry faces. In a double-blind, placebo-controlled experiment with 39 healthy adults, LSD reduced the amplitude of the N170 brain wave to neutral faces and reduced the P300 brain wave to neutral and happy faces, while angry faces were unaffected. These results suggest that low-dose LSD specifically changes how the brain processes non-threatening social cues, which may help explain reports of improved mood.
bioRxiv (Cold Spring Harbor Laboratory)
September 23, 2019
Kirsten C. S. Adam, Manoj K. Doss, Elisa Pabon et al.
2 citations
preprint
THC, the main psychoactive component in cannabis, impairs visual working memory—the ability to temporarily hold visual information in mind. Two double-blind, randomized crossover experiments with 23 healthy adults each found that oral THC (7.5 or 15 mg) reduced working memory performance, increased self-reported mind wandering, and decreased metacognitive accuracy about ongoing task performance. The authors also showed that short task durations and small sample sizes reduce the likelihood of detecting such drug effects.
Psychopharmacology
February 1, 2026
Ana Deutsch, Connor J Haggarty, Gavin N Petrie et al.
1 citation
A single oral dose of methamphetamine (20 mg) reduced blood levels of the endocannabinoid 2-AG in healthy adults, while MDMA (100 mg) did not. Neither drug affected anandamide (AEA) levels. Under placebo, higher AEA concentrations were linked to disliking the drug effects, suggesting a connection between AEA and negative expectations. These findings show how stimulants act on the endocannabinoid system and may inform treatments for substance use disorders.
Journal of Psychopharmacology
September 16, 2025
Ramona L. Martinez, Nina Radošić, Hanna Molla et al.
1 citation
MDMA increases feelings of trust in the social world beyond specific interaction partners in a lab setting. The findings align with user reports of generalized social well-being effects and suggest that MDMA may have clinical value from a social psychological perspective.
Scientific Reports
December 28, 2024
Harriet de Wit, Evan Hahn, Shahd Smadi et al.
1 citation
Psychoactive drugs like alcohol and stimulants are often used in social settings, but little is known about how they alter social interactions. This study tested whether MDMA, methamphetamine, and alcohol increase feelings of connection between strangers having a conversation, and also compared conversations with deeper topics versus small talk without drugs. All four conditions—deeper conversations, MDMA, methamphetamine, and alcohol—significantly increased feelings of connection and closeness compared to control conditions (small talk or placebo). The authors suggest these feelings of connection may contribute to the rewarding effects of drugs when used socially.
The European journal of neuroscience
June 1, 2024
Connor J Haggarty, Anya K. Bershad, Mahesh K Kumar et al.
1 citation
MDMA, but not methamphetamine, enhances the brain's early visual processing of happy and angry facial expressions, as measured by the N170 event-related potential in an EEG oddball paradigm. This effect was specific to emotional faces compared to neutral ones. Methamphetamine did not affect this neural measure, and neither drug altered other components of the response to emotional faces. The findings suggest a unique neural mechanism for MDMA's effects on socio-emotional processing, which may underlie its therapeutic potential for social anxiety and other psychiatric disorders.
BMJ Open
May 11, 2026
Julia Colcott, Alexandre A. Guerin, Olivia Carter et al.
A new tool, the MDMA-Assisted Psychotherapy Side Effects Tool (M-SET), was developed to systematically capture side effects during MDMA-assisted psychotherapy. Experts in MDMA-AP and neuropsychopharmacology participated in a two-round online Delphi process to refine a list of 165 items across four questionnaires covering screening, baseline, medication session days, and follow-up. The tool aims to improve safety monitoring and build a more robust evidence base on the tolerability of MDMA-AP for research and clinical use.
Biological psychiatry. Cognitive neuroscience and neuroimaging
May 1, 2026
Zachary Anderson, Matthew Gunn, Emily Jones et al.
A moderate oral dose of THC (7.5 mg) reduced resting-state functional connectivity within several brain networks, including corticostriatal circuits and networks involved in sensory processing, interoception, and spatial reasoning, in 33 healthy occasional young adult cannabis users. THC also decreased connectivity between two specific networks: one involving the anterior cingulate cortex and dorsal insula, and another involving the ventral insula and lingual gyrus. These connectivity changes were not related to subjective drug effects or recent cannabis use. The findings indicate that even a single moderate THC dose broadly disrupts intrinsic brain network connectivity.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2026
Jonah Griffin-Stolbach, Hanna Molla, Donald Hedeker et al.
Questionnaires designed for high-dose psychedelic experiences fail to capture the subtle subjective effects of very low doses of LSD. Using data from 199 healthy volunteers given 6.5, 13, and 26 µg doses, a new 31-item questionnaire—the micro-dimensional Altered States of Consciousness (m-DASC)—was developed. It identifies four components: Transcendent Experience, Auditory Somatic Disturbance, Animated Intoxication, and Synesthesia, accounting for 44% of the variance. The m-DASC detected significant effects at 13 and 26 µg and correlated highly with longer questionnaires, offering a more sensitive tool for future low-dose psychedelic research.
Journal of psychopharmacology (Oxford, England)
January 13, 2026
James Glazer, Hanna Molla, Royce Lee et al.
A low dose of LSD (26 micrograms) altered brain responses to reward feedback in people with mild-to-moderate depression, compared to those without depression. In depressed participants, LSD increased a brain signal called the late positive potential (LPP) when they received loss feedback, suggesting enhanced emotional processing of rewards. This change was linked to immediate positive mood and lower depressed mood two days later. Across all participants, LSD reduced other reward-related brain signals. The findings cautiously support the idea that low-dose LSD may have antidepressant effects.
Imaging neuroscience (Cambridge, Mass.)
January 1, 2024
Hanna Molla, Giovanni Novembre, Anya K. Bershad et al.
MDMA increases the perceived pleasantness of touch, but the neural mechanisms are not well understood. In a double-blind, randomized, within-subject fMRI study with 18 healthy participants, MDMA (1.5 mg/kg) compared to placebo enhanced affective ratings of gentle touch at both a slower, more pleasant speed (3 cm/s) and a faster, less pleasant speed (30 cm/s). Plasma oxytocin levels also increased more during the MDMA session. On the neural level, primary sensorimotor areas showed greater hemodynamic changes during MDMA for both touch speeds, indicating an early influence within somatosensory pathways. Changes in oxytocin levels interacted with the drug in area MT+, associated with motion perception. However, the posterior insula did not show preferential activation for the slower stroking speed.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2022
Conor H. Murray, Zhengyi Huang, Royce Lee et al.
Adolescents aged 18-20 are more sensitive than adults aged 30-40 to the performance-impairing effects of THC, the main active component of cannabis. In a double-blind, placebo-controlled study with 12 adolescents and 12 adults who had used THC fewer than 20 times, THC doses of 7.5 and 15 mg impaired reaction time, response accuracy, and time perception more in adolescents. THC also decreased P300 brain-wave amplitude in adolescents but not adults, indicating greater cognitive and brain-function disruption at doses that produced similar subjective intoxication and heart-rate effects in both age groups.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
October 1, 2020
Kirsten C. S. Adam, Manoj K. Doss, Elisa Pabon et al.
THC, the main psychoactive component of cannabis, impairs visual working memory—the ability to temporarily hold information in mind. In two double-blind, randomized crossover experiments, healthy adults performed a visual working memory task after taking oral THC (7.5 or 15 mg) or a placebo. THC reduced working memory performance (effect size d = 0.65), increased self-reported mind wandering, and decreased the accuracy of participants' awareness of their own task performance. The findings suggest that THC disrupts working memory both by increasing mind wandering and by reducing metacognitive monitoring. The study also demonstrated that short task durations and small sample sizes can mask such drug effects.
Biological psychiatry. Cognitive neuroscience and neuroimaging
January 1, 2020
Manoj K. Doss, Jessica Weafer, David A Gallo et al.
A double-blind, placebo-controlled experiment with 24 healthy infrequent cannabis users tested how THC (15 mg oral) affects context-based memory illusions. Participants memorized object pictures on scenes (e.g., a cat on a beach) after THC or placebo. Two days later sober, they discriminated seen objects from similar lures, with context reinstated or changed. THC impaired memory for perceptual details compared to placebo. Context reinstatement increased both correct recognition and false recognition in both conditions. THC did not interact with context effects overall, but post hoc analyses showed THC magnified the context illusion when objects were semantically congruent with their encoding contexts and abolished it when incongruent. Results suggest THC impairs encoding of specific object information more than item-context associations, potentially sparing or increasing distorting effects of context.
Journal of psychopharmacology (Oxford, England)
September 1, 2019
Elisa Pabon, Harriet de Wit
Two double-blind, within-subjects studies tested whether a mobile phone app could detect cognitive impairment from oral doses of ∆9-tetrahydrocannabinol (0, 7.5, 15 mg). In 24 healthy non-daily cannabis users per study, tasks measuring cognitive speed, reaction time, fine motor ability, working memory, and time perception were completed during four-hour sessions at peak drug effect. ∆9-Tetrahydrocannabinol impaired performance on most standardized computer tasks but not on most brief phone tasks. The phone tasks' brevity likely reduced their sensitivity. The findings confirm impairment at two recreational doses but raise doubts about developing a phone-based field sobriety test for cannabis.