Annals of Internal Medicine
December 19, 2000
Steven J. Lester, Matthew J. Baggott, Susette Welm et al.
140 citations
A modest oral dose of MDMA (1.5 mg/kg) increases heart rate by 28 beats per minute, systolic blood pressure by 25 mm Hg, diastolic blood pressure by 7 mm Hg, and cardiac output by 2 L per minute in healthy adults who have used the drug before. These cardiovascular effects are similar to those of the heart stimulant dobutamine at doses of 20 to 40 micrograms per kilogram per minute. Unlike dobutamine, MDMA shows no measurable effect on the heart's pumping strength (inotropism). The findings suggest that even moderate MDMA use raises myocardial oxygen demand without enhancing the heart's contractile force.
Journal of Psychopharmacology
August 26, 2016
Anya K. Bershad, Melissa A. Miller, Matthew J. Baggott et al.
104 citations
MDMA, a recreational drug, enhances sociability and feelings of closeness more than other stimulants like dextroamphetamine, methamphetamine, and methylphenidate. This review compares human laboratory studies on the social effects of MDMA versus other stimulants, from simple ratings of sociability to complex social behaviors, and examines the neurochemical mechanisms involved. The findings suggest that MDMA's distinct prosocial effects may underlie its recreational use and potential as a psychotherapy aid, distinguishing it from typical stimulants.
Drug and Alcohol Dependence
October 1, 2010
Matthew J. Baggott, Earth Erowid, Fire Erowid et al.
78 citations
A survey of 500 individuals who had used Salvia divinorum found that 92.6% typically smoked or vaporized the plant, with acute effects lasting about 14 minutes on average. Most participants (80.6%) said they would use it again, and 38.4% described the experience as unique. On at least one occasion, 25.8% reported persisting positive effects lasting 24 hours or more, often an increased sense of well-being, while 4.4% reported persisting negative effects, most commonly anxiety. These findings suggest that Salvia divinorum may produce subacute improvements in mood, which is unusual for a non-medically used drug.
Journal of Psychopharmacology
April 29, 2015
Matthew J. Baggott, Matthew G. Kirkpatrick, Gillinder Bedi et al.
69 citations
MDMA increases the use of social, sexual, and emotional words during conversation. In a double-blind, within-subjects study, 35 healthy volunteers who had previously used MDMA received either 1.5 mg/kg oral MDMA or a placebo and then discussed a close personal relationship for five minutes. Both a standard dictionary method and a machine learning analysis showed that MDMA altered speech content: it boosted social and sexual words, and also increased words related to both positive and negative emotions. These changes in speech content may help explain how MDMA enhances sociability and emotional connection during social interactions.
Matthew J. Baggott
50 citations
After a 40-year pause, researchers are again asking whether psychedelics can boost creativity. This critical review examines the conceptual challenges in studying psychedelic-induced creativity, summarizing limited evidence and proposing two broader frameworks. Key challenges include separating creativity from other drug effects that might be mistaken for it and developing operational measures to quantify it. The article reviews major studies, including a reanalysis of raw data from one study. Results are modest and inconclusive but consistent with reports that psychedelics produce unusual or novel thoughts. Given the lack of robust changes in creativity measures, creativity may be too specific a construct to capture the beneficial cognitive changes users report. Feelings of creativity may stem from a more general effect, such as altered mental representations or changes in Bayesian inference.
JAMA Network Open
June 3, 2024
Amy L. Mcguire, I Glenn Cohen, Dominic Sisti et al.
41 citations
A consensus statement from a 2023 meeting of 27 experts identifies 20 points of consensus across five ethical issues for integrating psychedelic medicines into mainstream medical practice: reparations and reciprocity, equity, and respect; informed consent; professional boundaries and physical touch; personal experience; and gatekeeping. The meeting included clinicians, researchers, Indigenous groups, industry, philanthropy, veterans, retreat facilitators, training programs, and bioethicists. The statement focuses on government-approved medical use in the US and abroad, emphasizing that policymakers must address challenges ahead while acknowledging the hopeful moment.
Psychopharmacology
April 1, 2011
John Mendelson, Jeremy Coyle, Juan Carlos Lopez et al.
40 citations
Salvinorin A (SA), the psychoactive compound in the hallucinogenic plant Salvia divinorum, was administered sublingually at doses up to 4 mg to eight experienced users in a placebo-controlled ascending-dose study. No dose produced significantly greater physiological or subjective effects than placebo, and the effects did not resemble those of smoked Salvia divinorum. SA was detectable in plasma and urine but mostly below the reliable quantification limit of 0.5 ng/mL. The results suggest that sublingual bioavailability of SA is low, indicating that higher doses, alternate formulations, or other routes of administration are needed to study its effects in humans.
Neuropsychopharmacology
January 24, 2020
Carla Agurto, Guillermo Cecchi, Raquel Norel et al.
33 citations
Computer-extracted speech features from acoustic, semantic, and psycholinguistic domains can detect mental states after controlled administration of MDMA and intranasal oxytocin. In a double-blind, placebo-controlled study with 31 healthy adults, speech tasks during peak drug effects yielded cross-validated accuracies up to 87% in the training/validation set and 92% in independent datasets for classifying drug conditions. Oxytocin-driven changes were mostly captured by acoustic features related to emotion and prosody, while MDMA-related mental states manifested across multiple speech domains. The experimental task—whether involving interaction with another individual—also affected speech responses. These results suggest speech analysis can provide objective markers of drug-induced mental states.
PLoS One
December 2, 2010
Gantt P. Galloway, Jennifer D. Siegrist, Lynn C. Robertson et al.
22 citations
A double-blind placebo-controlled study found that the hallucinogen MDA increases closed-eye visions and mystical-type experiences. People who had more intense visions tended to perform worse on tests of contour integration and object recognition, suggesting that drug-induced hallucinations may be stronger in individuals with poorer perceptual processing. This points to possible shared mechanisms with hallucinations in psychiatric and neurological conditions.
bioRxiv (Cold Spring Harbor Laboratory)
June 23, 2015
Matthew J. Baggott, Jeremy Coyle, Jennifer D. Siegrist et al.
21 citations
preprint
MDMA produces a prosocial syndrome that facilitates emotional disclosure by increasing feelings of authenticity and decreasing concerns about negative evaluation by others. In a within-subjects double-blind placebo controlled study of 1.5 mg/kg oral MDMA, the drug showed both sedative- and stimulant-like effects, including increased self-report anxiety, but positively altered self-evaluation and reduced social anxiety. MDMA also increased how comfortable participants felt describing emotional memories, consistent with the suggestion that it represents a novel pharmacological class.
Journal of Psychoactive Drugs
March 15, 2019
Matthew J. Baggott, Kathleen J. Garrison, Jeremy Coyle et al.
20 citations
The drug MDA, an entactogen similar to MDMA (ecstasy), produces longer-lasting emotional and physiological effects than MDMA. In a controlled experiment with healthy volunteers, a single oral dose of 1.4 mg/kg MDA increased heart rate, blood pressure, and stress hormones (cortisol and prolactin) to levels comparable to those from a 1.5 mg/kg dose of MDMA. However, participants' self-reported drug effects from MDA remained elevated for at least 8 hours, whereas MDMA effects subsided by 6 hours. Blood measurements showed that MDA and its metabolite HMA reached peak concentrations of about 229 µg/L and 92 µg/L, respectively. Because the two drugs had similar blood-level profiles, the longer duration of MDA's effects likely stems from differences in how it acts on the brain rather than from slower elimination.
Therapeutic Advances in Psychopharmacology
September 1, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
8 citations
Psychedelic-assisted therapy (PAT) is a complex intervention combining pharmacological, psychotherapeutic, and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional randomized controlled trials may fail to capture these complexities. This position paper advocates applying the UK Medical Research Council's framework for complex interventions to PAT development and evaluation, emphasizing the need to articulate the theory of therapeutic change, structure intervention development into phases, account for contextual interactions, and incorporate stakeholder perspectives.
The Journal of pharmacology and experimental therapeutics
September 18, 2024
Candace B Johnson, Donna Walther, Matthew J. Baggott et al.
5 citations
MDMA is effective as a treatment for PTSD but carries cardiovascular and neurological risks. Researchers tested two new compounds, 5-MABB and 6-MABB, in rat brain tissue and in live rats trained to recognize MDMA. The S isomers of both compounds released serotonin, norepinephrine, and dopamine, similar to MDMA. The R isomers released serotonin and partially released norepinephrine but not dopamine. All compounds caused rats to respond as if they had received MDMA, with effects increasing with dose. The R isomers were less potent behaviorally. The findings suggest the aminoalkyl benzofuran structure is a promising starting point for developing safer MDMA-like drugs.
PsyArXiv
February 23, 2025
Suresh Muthukumaraswamy, Matthew J. Baggott, Eduardo Ekman Schenberg et al.
3 citations
preprint
Psychedelic-assisted therapy (PAT) is a complex, multi-component intervention, yet most clinical trials evaluate it as a simple pharmaceutical treatment, limiting real-world validity. This position piece advocates applying the UK Medical Research Council's complex intervention framework to PAT, emphasizing theory of change, structured development, context, and stakeholder input. Pragmatic randomized controlled trials, informed by the PRECIS-2 tool, are proposed to align trial designs with real-world healthcare settings. The authors contrast drug-centric and psychotherapy-augmented views of PAT's efficacy, and recommend integrating qualitative data, adaptive designs, and comparative effectiveness research. A pluralistic evidentiary model is suggested to advance psychedelic medicine while avoiding past developmental pitfalls.
History of Pharmacy and Pharmaceuticals
October 1, 2023
Matthew J. Baggott
2 citations
In 1967, a synthetic psychedelic drug nicknamed STP escaped from Dow Chemical's archives and caused a public health crisis in San Francisco's Haight-Ashbury neighborhood. Young hip doctors, underground chemists, and users each interpreted the drug differently, but only the doctors were recognized as experts by media reports. This article combines contemporary media accounts, pharmacology, and first-person narratives to examine how STP came to be understood as dangerous. The episode serves as a case study in how knowledge about new unsanctioned psychoactive substances is formed and which sources are acknowledged or overlooked, offering timely lessons as psychedelics regain attention.
bioRxiv (Cold Spring Harbor Laboratory)
Matthew J. Baggott, Kathleen J. Garrison
1 citation
preprint
MDMA (ecstasy) use can cause dangerously low blood sodium levels (hyponatremia), especially when people drink too much water. In two double-blind, placebo-controlled studies, healthy volunteers who took MDMA did not show increased levels of the hormone that normally regulates water balance (ADH or copeptin), but their blood sodium dropped more than with placebo when they drank standardized amounts of water. Women tended to have lower baseline sodium, but this did not significantly interact with MDMA. The findings indicate that consuming hypotonic fluids during MDMA use poses a significant risk of hyponatremia, which should be anticipated and managed in clinical and recreational settings.
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.
Psychopharmacology
March 4, 2026
Ava M. Mac, Srinivasu Kallakuri, Alixandria T. Mascarin et al.
Repeated low doses of MDMA (2.5 mg/kg) caused mild anxiety-like behavior in rats one day after exposure, but this effect was confounded by reduced movement and did not persist at 15 days. Higher doses (5 mg/kg) did not produce anxiety-like behavior. Sucrose preference, a measure of anhedonia, increased over time and was unaffected by MDMA or sex. Brain analysis showed reduced serotonin levels in the nucleus accumbens one day after both MDMA doses, but not in the prefrontal cortex or dorsal hippocampus. These transient effects suggest that low-dose MDMA used clinically may be tolerated without limiting therapeutic benefit.
arXiv Preprint Archive
June 1, 2012
Jeremy Coyle, David E. Presti, Matthew J. Baggott
Machine learning applied to 1000 written reports of 10 different drugs from the Erowid website identified distinct patterns in how people describe their experiences with each drug. A random-forest classifier using just 110 key words achieved 51.1% accuracy in identifying which drug a report described, far above the 10% expected by chance. Reports of MDMA were most distinctive (86.9% accuracy), while those for DPT were hardest to classify (20.1%). Hierarchical clustering revealed similarities between certain drugs, such as DMT and Salvia divinorum. The findings suggest that automated text analysis can uncover consistent, drug-specific features in subjective experience reports, potentially aiding hypothesis generation about new or poorly understood compounds.