Journal of Psychopharmacology
January 12, 2024
Antonin Rouaud, Gregor Hasler, Abigail E. Calder
36 citations
Microdosing psychedelics like LSD and psilocybin has become popular, but its long-term effects on heart health are unknown. These drugs share structural similarities with medications that raise the risk of cardiac fibrosis and valvulopathy when taken regularly. This review evaluates the evidence that microdosing for months or more could increase the risk of cardiac fibrosis, discusses the role of the 5-HT2B receptor in drug-induced cardiac fibrosis, and recommends safety evaluations for future studies.
Journal of Psychopharmacology
March 28, 2021
Mitch Earleywine, Luna F. Ueno, Maha N. Mian et al.
36 citations
High doses of cannabis can produce subjective effects similar to those of the psychedelic psilocybin, but at a lower rate. In a survey, 17–19% of cannabis users reported a “breakthrough” experience, compared to 59% in psilocybin clinical trials. Heavier cannabis users reported lower scores. These effects may parallel the therapeutic benefits seen with psilocybin, suggesting potential for cannabis-assisted psychotherapy.
Journal of Psychopharmacology
May 1, 2024
Max Wolff, Ricarda Evens, Lea J. Mertens et al.
34 citations
A new questionnaire, the General Change Mechanisms Questionnaire (GCMQ), reliably measures five psychotherapy processes—resource activation, therapeutic relationship, problem actuation, clarification, and mastery—during psychedelic experiences. Validated in 1153 English-speaking and 714 German-speaking users, the GCMQ showed good internal consistency and convergent validity. Experiences varied with setting and use motives (therapeutic, hedonic, escapist). Resource activation, clarification, and mastery moderated the link between stressful life events and well-being, suggesting potential therapeutic benefits. Five distinct user profiles emerged, which may inform clinical use and harm reduction.
Journal of Psychopharmacology
August 1, 2022
Javier Hidalgo Jiménez, José Carlos Bouso
34 citations
DMT, a potent psychedelic naturally produced by many plants and animals including humans, may play significant roles in mammalian physiology. This review integrates historical and recent evidence to address ongoing debates about DMT's relevance. Arguments dismissing endogenous DMT are often based on obsolete data or misleading assumptions. Evidence strongly suggests DMT functions as a neurotransmitter, neuromodulator, hormone, and immunomodulator, and is important in pregnancy and development. Key experiments are proposed to definitively determine DMT's specific physiological roles.
Journal of Psychopharmacology
July 17, 2020
Carl Roberts, Isaac Osborne-Miller, Jon C. Cole et al.
33 citations
Both people who have used magic mushrooms and those who have not perceive mushrooms as less dangerous than heroin, cocaine, prescription painkillers, GHB, ecstasy, tobacco, and alcohol. However, those without experience rate mushrooms as significantly more dangerous than users do, and they expect more negative intoxication effects. Users expect greater entactogenic, prosocial, aesthetic, and mood effects, as well as perceptual alterations. Motivations for use predict expected effects—for example, using mushrooms for personal psychotherapy is linked to expecting increased entactogenic and decreased negative effects. The findings align with data on low actual harm but conflict with legal classifications.
Journal of Psychopharmacology
January 24, 2011
Jéssica Ruiz‐medina, Catherine Ledent, Olga Carretón et al.
33 citations
Adenosine A2a receptors are crucial for the rewarding and neuroinflammatory effects of MDMA. In mice lacking these receptors, MDMA failed to support self-administration, indicating a complete loss of its reinforcing properties. Additionally, the neurotoxic regimen of MDMA caused increased glial activation in the striatum of normal mice, but this inflammatory response was attenuated in mice without A2a receptors. Acute effects on body temperature, locomotion, and anxiety were similar in both genotypes. This work identifies the A2a adenosine receptor as a key mediator of MDMA's addictive potential and neurotoxicity.
Journal of Psychopharmacology
July 31, 2024
Roman Palitsky, Deanna M. Kaplan, John Perna et al.
32 citations
A multidisciplinary working group identified 54 potential adverse events that warrant systematic assessment in psychedelic-assisted therapies, finding that existing measurement tools substantially fail to cover these constructs. The group developed recommendations for when and how to assess these adverse events across preparation, dosing, integration, and follow-up phases, and demonstrated a preliminary assessment protocol. The framework addresses the need to capture post-acute dosing adverse events, accounting for both the pharmacotherapy and psychotherapy components of psychedelic-assisted therapy, as well as documented impacts on worldviews and spirituality.
Journal of Psychopharmacology
August 31, 2023
Pravesh Sharma, Quang Anh Nguyen, Erin Carpenter et al.
32 citations
Psilocybin, the psychoactive compound in hallucinogenic mushrooms, shows modest evidence for treating depression and anxiety disorders, and early data suggest it may reduce harmful drinking in alcohol use disorder. When administered under supervision, side effects are mild and transient, and severe adverse events are uncommon. However, a recent clinical trial found increased suicidal ideations and non-suicidal self-injurious behaviors in the psilocybin arm. Further investigation is needed to identify which patient subgroups benefit most and which are at risk for adverse outcomes.
Journal of Psychopharmacology
November 16, 2023
Oliver Rumle Hovmand, Emil Deleuran Poulsen, Sidse Arnfred
31 citations
Classical psychedelics such as psilocybin, peyote, ayahuasca, and LSD can temporarily alter consciousness, affecting perception, mood, and sense of self. Reliable measurement tools are needed because the acute subjective experience may influence treatment outcomes. A review of 93 trials identified 17 different rating scales used to assess these altered states. The five most common instruments were the Five-Dimensional Altered States of Consciousness Questionnaire, visual analog or Likert scales developed for specific trials, the Hallucinogen Rating Scale, the States of Consciousness Questionnaire, and the Abnormer Psychischer Zustand. The authors recommend developing a core set of outcome measures to allow comparisons across different psychedelics, participants, and settings, and suggest designing instruments that assess the setting of the experience.
Journal of Psychopharmacology
October 2, 2008
Sj Kish, Paul S. Fitzmaurice, Lj Chang et al.
31 citations
A post-mortem analysis of a high-dose MDMA user's brain found that protein levels of the serotonin transporter (SERT) were markedly reduced in the striatum and occipital cortex (by 48–58%) and less affected in frontal and temporal cortices (by 25%), while tryptophan hydroxylase (TPH), the enzyme that synthesizes serotonin, was severely decreased in the caudate and putamen (by 68% and 95%, respectively). The reduction in striatal SERT protein was larger than the binding decreases typically reported in imaging studies. These results suggest high-dose MDMA exposure may cause loss of two key protein markers of serotonin neurons, possibly indicating physical damage or downregulation of neuronal components.
Journal of Psychopharmacology
January 21, 2008
Christopher D. Verrico, Laurie J. Lynch, Michele A. Fahey et al.
31 citations
Oral MDMA impairs executive function in monkeys for several days, a finding potentially relevant to human MDMA users. The cognitive deficits were reversed by inhibitors of the serotonin transporter (citalopram) and the norepinephrine transporter (desipramine), but not by a dopamine/norepinephrine transporter inhibitor (methylphenidate). MDMA also altered sleep latency. The results implicate the norepinephrine transporter and norepinephrine in MDMA-induced cognitive impairment, suggesting that serotonin deficits alone may not explain the cognitive effects. The study used cynomolgus monkeys trained in a reversal learning task and tested with oral or intramuscular MDMA, with or without transporter inhibitor pretreatments.
Journal of Psychopharmacology
January 1, 2022
Grant M Jones, Matthew K Nock
30 citations
Lifetime use of psilocybin was linked to lower odds of arrest for seven of eleven crime categories, with adjusted odds ratios ranging from 0.30 to 0.73. Peyote use was associated with reduced odds of motor vehicle theft (aOR = 0.30) and driving under the influence (aOR = 0.52), while mescaline use was associated with reduced odds of drug possession or sale (aOR = 0.51). Most other substances showed no relationship or were linked to higher odds of arrest. The findings suggest classic psychedelic substances may be associated with lowered criminal behavior, but further research is needed to explore causal or third-variable explanations.
Journal of Psychopharmacology
July 1, 2023
Justin N Bonnieux, Baeleigh VanderZwaag, Zahra Premji et al.
29 citations
A scoping review of 42 studies on psilocybin's effects on cognition and creativity in adults found that macrodoses tended to impair cognitive performance and creativity during the acute phase (minutes to hours after intake), while microdoses tended toward creative enhancement. The few macrodosing studies that included post-acute measures (1–85 days) reported primarily null but some positive effects. Psilocybin was mostly administered orally (83%) in bodyweight-adjusted doses (74%) to healthy participants (90%). Only 26% of studies explicitly reported safety outcomes, and among those, only one reported serious adverse reactions. The findings are limited by methodological concerns and inadequate assessment of long-term effects.
Journal of Psychopharmacology
June 21, 2022
T. Ching, Monnica T. Williams, Julie B. Wang et al.
29 citations
In a pooled analysis of two Phase 2 open-label trials and one Phase 3 randomized placebo-controlled trial of MDMA-assisted therapy for PTSD, no significant difference in symptom reduction was found between BIPOC and non-Hispanic White participants who received MDMA. Among those given placebo-assisted therapy, BIPOC participants showed a trend toward greater improvement than non-Hispanic Whites. Non-Hispanic Whites had significantly larger reductions in PTSD symptoms with MDMA than with placebo, but no such treatment difference emerged among BIPOC participants. Adverse events were mostly mild or moderate across all groups. The findings suggest MDMA-assisted therapy is effective and safe across ethnoracial groups, though subgroup sizes were imbalanced.
Journal of Psychopharmacology
October 31, 2022
Grant M Jones
28 citations
Race and ethnicity influence how naturalistic use of MDMA/ecstasy and psilocybin relates to major depressive episodes. Among White adults, use of either substance was linked to lower odds of lifetime, past year, and past year severe major depressive episodes. For Hispanic adults, use of either substance was associated with lower odds only for a past year major depressive episode. For non-Hispanic racial minority adults, neither MDMA/ecstasy nor psilocybin use was associated with lower odds of any depressive outcome. The findings suggest that the potential mental health benefits of these psychedelics may not be uniform across racial and ethnic groups.
Journal of Psychopharmacology
October 10, 2012
Cheryl M Collins, Joris Kloek, J.m. Elliott
28 citations
In rats, MDMA (20 mg/kg) caused a parallel drop in serotonin levels in the frontal cortex and blood, with decreases of 63% and 46% respectively at 2 hours, partial recovery by 8 hours (42% and 38% below control), and further recovery by 18 hours (19% and 24% below control). A tryptophan supplement (82.5 mg/kg) raised serotonin in both brain (39%) and blood (26%) in naïve rats, but after MDMA, the same supplement raised brain serotonin only 26% and had no effect on blood serotonin. Blood serotonin appears to be a useful marker for brain serotonin levels after acute MDMA, suggesting platelet serotonin could serve similarly in human studies.
Journal of Psychopharmacology
February 28, 2008
KPC Kuypers, M. Wingen, Jg Ramaekers
28 citations
Memory performance worsens progressively overnight due to sleep loss, and taking MDMA (ecstasy) in the evening adds to that impairment. In a double-blind, placebo-controlled crossover study with 14 healthy adults, MDMA (75 mg and 50 mg split over the evening) caused additional deficits in verbal and spatial memory beyond those from sleep deprivation alone. During the night, MDMA improved response speed and increased feelings of vigor, friendliness, elation, anxiety, confusion, arousal, and positive mood, but these effects returned to placebo-like levels by morning. Evening MDMA selectively impairs memory, and this harm is separate from and adds to the memory impairment caused by sleep deprivation.
Journal of Psychopharmacology
March 22, 2024
Tommaso Barba, David Erritzøe, Meg J. Spriggs et al.
26 citations
In a clinical trial comparing psilocybin plus psychological support to escitalopram plus psychological support for major depressive disorder, patients who discontinued their SSRI or SNRI medication before receiving psilocybin showed a reduced treatment effect on all depression severity and well-being measures compared with those who were unmedicated at trial entry. Discontinuation did not affect the intensity of the acute psychedelic experience. The findings are exploratory and hypothesis-generating, not confirmatory, and the study did not test SSRI/SNRI continuation. A controlled trial comparing discontinuation versus continuation before psilocybin is needed.
Journal of Psychopharmacology
February 21, 2019
Adam L. Halberstadt, Muhammad Chatha, Stephen J. Chapman et al.
25 citations
In mice, the hallucinogenic compound mescaline and several of its chemical analogs produce a distinctive head-twitch response that depends on activation of the 5-HT2A receptor. Adding a methyl group to mescaline (making TMA) doubled its potency, and replacing the 4-methoxy group with larger ethoxy or propoxy groups also increased potency for both mescaline and TMA. However, for a different set of isomers (TMA-2 and its analogs), changing the 4-alkoxy group did not alter potency, even though TMA-2 itself was twice as potent as mescaline. These potency patterns in mice closely match known human hallucinogenic data and show that different substitution patterns on the phenyl ring produce distinct structure-activity relationships.
Journal of Psychopharmacology
April 25, 2023
Brandon Weiss, David Erritzoe, Bruna Giribaldi et al.
24 citations
A reanalysis of data from a trial comparing psilocybin therapy (PT) to escitalopram (ET) for major depressive disorder found that 14 of 16 outcome measures favored PT, but the QIDS-SR-16 did not. The QIDS-SR-16 showed higher variance, imprecision from compound items and sum-scoring, vague response options, and lack of focus on a core depression factor. When the trial data were examined at item, facet, and factor levels, results suggested PT was superior in reducing depressed mood, anhedonia, a core depression factor, and specific symptoms like sexual dysfunction. This raises concerns about relying on individual scales that miss depression's multidimensional structure.
Journal of Psychopharmacology
October 20, 2022
23 citations
A systematized review of 83 sources found consensus that adequate preparation before substance-assisted psychotherapy (SAPT) sessions is important for safety and therapeutic effect. Preparatory practices include screening participants, optimizing set and setting, and preparing therapists with appropriate competencies and roles. However, the extent and specific approaches vary across models, and more rigorous qualitative and quantitative research is needed to determine optimal preparation techniques.
Journal of Psychopharmacology
March 1, 2022
Neiloufar Family, Peter S. Hendricks, Luke T. J. Williams et al.
23 citations
LSD doses of 50, 75, and 100 micrograms are tolerable and safe in healthy adults when administered in a novel group-based intervention paradigm with one attendant per participant. Thirty-two adults (mean age 28.8 years) received LSD or placebo across open-label and double-blind designs. No serious adverse events occurred; 28% of participants reported at least one mild expected adverse event and one moderate event. Peak blood plasma levels appeared 1.2 to 2 hours after administration, with an apparent half-life of 2.8 to 4.3 hours. LSD produced greater subjective effects than placebo, including mystical-type experiences. Further research is needed in clinical populations.
Journal of Psychopharmacology
August 5, 2020
Will Lawn, J. P. Hill, Chandni Hindocha et al.
23 citations
A single 600 mg oral dose of cannabidiol did not alter brain activity related to anticipating or receiving rewards in healthy adults. Using functional magnetic resonance imaging during a monetary incentive delay task, the expected reward-related brain regions—including the insula, caudate, nucleus accumbens, anterior cingulate, and orbitofrontal cortex—were activated, but no difference was observed between cannabidiol and placebo. Bayesian analyses confirmed that activity in these regions was similar under both conditions, and behavioral measures of motivation for reward also showed no significant difference. The findings suggest that acute cannabidiol does not affect the neural correlates of reward anticipation or feedback in healthy individuals.
Journal of Psychopharmacology
January 1, 2024
Lisa Bouchet, Zachary Sager, Antoine Yrondi et al.
22 citations
Older adults (65+) account for less than 1.4% of participants in psychedelic clinical trials, despite these compounds showing potential for conditions common in this age group, such as depression, anxiety, and existential distress. A systematic review of 36 trials involving 1,400 patients found only 19 were aged 65 or older. Safety data for 10 of these older adults showed no serious adverse events; only transient mild-to-moderate effects like anxiety, gastrointestinal upset, and hypertension occurred during dosing sessions. The authors conclude that psychedelic-assisted psychotherapy appears safe and well tolerated in older adults and warrants more rigorous investigation for psychiatric treatment in this population.
Journal of Psychopharmacology
October 31, 2023
Kurt Stocker, Matthias Hartmann, Laura Ley et al.
22 citations
A questionnaire that measures psychedelic experiences, the Psychedelic Experience Scale (PES), contains more useful subscales than the well-known Mystical Experience Questionnaire (MEQ30). Analyzing 239 measurements from 140 healthy participants given LSD or psilocybin, researchers identified four additional factors beyond the original four: paradoxicality, connectedness, visual experience, and distressing experience. Paradoxicality and connectedness correlated strongly with the mystical subscale. Adding these new subscales to the MEQ30 increased the variance explained alongside another measure, the 5D-ASC. A cluster analysis supported these findings. The results provide a validated 6-factor structure (MEQ40) covering mystical experience more comprehensively and a broader 48-item version (PES48), with the full 100-item PES available for future research.