European Psychiatry
August 1, 2000
C. Burgess, Alan O'Donohoe, Michael Gill
108 citations
Ecstasy, a recreational drug often thought to be safe, can cause serious acute adverse effects including hyperthermia, seizures, cardiac arrhythmias, liver toxicity, low sodium levels, and various psychiatric disorders. These effects are not due to overdose alone or the typical environment where the drug is used. In animal studies, Ecstasy damages serotonin-producing neurons at doses similar to those taken by humans, though its long-term effects on the human brain remain unknown. Because of the drug's popularity, both immediate and potential lasting harms warrant concern, and Ecstasy toxicity should be considered when diagnosing certain medical and psychiatric conditions.
European Psychiatry
March 1, 2001
Z. Zemishlany, Dov Aizenberg, Abraham Weizman
70 citations
MDMA (Ecstasy) moderately to profoundly increases sexual desire and satisfaction in more than 90% of users, and orgasm is delayed but perceived as more intense. However, erection is impaired in 40% of men, indicating that MDMA enhances subjective sexual experience while impairing sexual performance.
European Psychiatry
June 18, 2005
Marie-Laure Espiard, Laurent Lecardeur, Pascale Abadie et al.
61 citations
Flashbacks can recur without recent hallucinogen use, a condition recognized as hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last five years or more and cause significant psychosocial distress. This report describes an 18-year-old man who developed HPPD after mixing psilocybin and cannabis, with symptomatic recurrences persisting for over eight months. The report also discusses differential diagnoses considered and the therapeutic strategies employed.
European Psychiatry
December 1, 2000
F. Salomé, P Boyer, Michel Fayol
21 citations
A review of eighteen studies on psychoactive drugs and neuroleptics (NL) shows that in healthy subjects, alcohol, amphetamine, and secobarbital increase language production, d-amphetamine makes speech more complex, L-dopa focuses it, psilocybin makes it unfocused, and ketamine clearly impairs it. No studies examine neuroleptic effects on language in healthy people. In schizophrenic patients, conventional neuroleptics at therapeutic doses reduce language disorders clinically, linguistically, and psycholinguistically. When combined with other molecules, moderate chronic NL plus amphetamine improves verbal flow and reduces pauses and positive thought disorder, while NL plus fenfluramine impairs language measurements.
European Psychiatry
March 1, 2015
Katrin H. Preller, Thomas Pokorny, Rainer Krähenmann et al.
20 citations
Social cognition, including empathy and reactions to social exclusion, is often impaired in psychiatric disorders like depression but is poorly addressed by current treatments. In a double-blind, randomized, cross-over study with healthy volunteers, psilocybin (0.215 mg/kg) reduced the neural response to social exclusion in the anterior cingulate cortex, a brain region linked to social pain, compared to placebo. Emotional empathy was enhanced after psilocybin, while cognitive empathy showed no significant change. These findings suggest that 5HT-1A/2A receptor subtypes modulate socio-cognitive functioning and may be relevant for treating social cognition deficits, particularly in depressed patients.
European Psychiatry
January 1, 2024
Eline Haijen, Petra P. M. Hurks, Kim P. C. Kuypers
10 citations
Adults with severe ADHD symptoms who microdosed psychedelics reported better emotion regulation and some empathy improvements in an initial uncontrolled study. A second study with a control group found that after four weeks, ADHD symptoms were lower in the microdosing group than in those taking conventional ADHD medication. However, only one emotion regulation measure—expressive suppression—remained improved after accounting for the control group. The findings suggest microdosing may help with ADHD symptoms and certain emotion regulation strategies, but there was no evidence for effects on empathy.
European Psychiatry
January 1, 2025
Marianne Destoop, Pavel Mohr, Florence Butlen‐ducuing et al.
7 citations
The European Psychiatric Association (EPA) acknowledges the therapeutic potential of psychedelic substances for mental disorders, such as psilocybin for depression, which are nearing regulatory approval in the US and Europe. This policy paper highlights both the benefits and challenges of psychedelic treatments, emphasizing the importance of psychosocial components and ethical, professional aspects for real-world implementation. Four recommendations are formulated to guide further research and clinical integration, aiming for safe, ethical, and equitable access for all patients who may benefit.
European Psychiatry
June 1, 2022
Kaushal Shah, C. Trivedi, D. Kamrai et al.
6 citations
Among 172,745 U.S. adolescents aged 12-17 surveyed from 2008-2018, 2,469 reported ever using psilocybin (magic mushrooms). Users were more likely to be 17 years old, male, and non-Hispanic White. 31% of psilocybin users had a lifetime major depressive episode (MDE), compared to 16% of non-users. The odds of MDE were 2.17 times higher among psilocybin users (95% confidence interval: 1.93-2.44). The authors conclude there is a significant association between psilocybin use and MDE in adolescents, raising public health concerns about illegal use, abuse, and toxicity.
European Psychiatry
June 1, 2022
Pierre Chue, A. Andreiev, E. Bucuci et al.
6 citations
Aeruginascin, a naturally occurring tryptamine compound found in certain mushroom species, has much weaker activity at serotonin receptors compared to psilocybin, with binding affinities several orders of magnitude lower. Its active metabolite, 4-HO-TMT, binds at 5-HT1A, 5-HT2A, and 5-HT2B receptors with inhibition constants of 4400, 670, and 120 nM respectively, versus psilocybin's 567.4, 107.2, and 4.6 nM. As a quaternary trimethylammonium compound, it is less likely to cross the blood-brain barrier. The limited data suggest aeruginascin's direct contribution to any entourage effect in psychedelic mushrooms is limited.
European Psychiatry
August 5, 2019
Thomas M. Kelley, William F. Pettit, Jack Pransky et al.
6 citations
A general factor of psychopathology may arise through two opposing forms of neural plasticity. Early plasticity, called TEMP (Temperature or Entropy Mediated Plasticity), increases model variance, learning rate, and entropy, making the system more malleable. Later, Hebbian-like canalization increases precision and narrows the phenotypic state-space, entrenching pathological patterns as a defensive response to adversity. The model suggests that TEMP, combined with gentle psychological support, can counter canalization. The article discusses when canalization is adaptive versus maladaptive and proposes concrete experiments to test the model's hypotheses.
European Psychiatry
January 1, 2026
4 citations
Ketamine's antidepressant effects in treatment-resistant depression may be partially mediated by the opioid system, but the evidence is mixed. Because opioid receptor antagonists inconsistently reduce these effects, the opioid system likely acts as a context-dependent modulator rather than a primary mediator, especially at standard antidepressant doses.
European Psychiatry
April 1, 2025
M. Sabé
3 citations
Among people without a history of psychotic symptoms, psychedelic-induced psychosis is very rare: 0.002% in population studies, 0.2% in uncontrolled trials, and 0.6% in randomized controlled trials. In uncontrolled trials that included people with schizophrenia, 3.8% developed long-lasting psychotic symptoms. Among those who experienced psychedelic-induced psychosis, 13.1% later developed schizophrenia. The evidence suggests that schizophrenia may not be an absolute exclusion for psychedelic therapy trials, but the authors recommend a conservative approach due to low study quality and limited data.
European Psychiatry
April 1, 2024
K. P. Kuypers
3 citations
Microdosing psychedelics—taking small, non-hallucinogenic doses of LSD or psilocybin over weeks or months—may enhance certain behaviors, emotions, or treat psychiatric conditions. Recent studies in healthy individuals show nuanced effects on pain perception, mood, neuroplasticity, sleep, brain connectivity, and default mode network synchronicity, though some parameters show null effects after single or repeated administration. Survey research found that people with ADHD reported symptom relief from microdosing, deeming it more effective than conventional treatments. A naturalistic 4-week study with ADHD individuals showed reduced symptoms, increased trait mindfulness, and decreased neuroticism compared to baseline. These results require validation in a clinical trial, which has been conducted and is being analyzed.
European Psychiatry
March 1, 2023
Saundarai Bhanot, Michelle Cq Lin, S. Bains et al.
3 citations
Psilocybin, a naturally occurring psychedelic compound, shows promise for treating various headaches, including migraines and cluster headaches. A systematic review of eight studies found that psilocybin use was associated with improvements in headache frequency, intensity, duration, and remission periods, with clinically significant improvements reported in six studies and statistically significant results in three. Macrodosing provided greater pain relief than microdosing or conventional medications, with 12.3% more participants experiencing pain reduction three days after a macrodose. However, side effects included hallucinations in 18% of essential headache patients and temporary increases in anxiety and pain (5.3% with microdosing, 14.1% with macrodosing). Psilocybin remains illegal in many countries, limiting further research.
European Psychiatry
June 1, 2022
Johannes T. Reckweg, N. Mason, C. van Leeuwen et al.
3 citations
A vaporized formulation of 5-MeO-DMT, a fast-acting psychedelic, was tested in 22 healthy volunteers at single doses of 6, 12, and 18 mg and with an individualized dose escalation regimen. The drug produced dose-related increases in the intensity of psychedelic experiences, as measured by several questionnaires, except for challenging experiences. Maximal effects on mystical, ego dissolution, and altered states of consciousness ratings occurred after individualized dose escalation. Cognition, mood, and well-being were not affected. Vital signs remained stable, and adverse events were mild and resolved on their own. Individualized dose escalation may be preferable for clinical applications aiming to enhance short-term psychoactive effects for a strong therapeutic response.
European Psychiatry
April 1, 2021
R. Pinilla, Carmen Rocamora Rodriguez, D. Batet-Sanchez et al.
3 citations
Ayahuasca shows potential therapeutic benefits for dependencies, anxiety, depression, and near-death experiences in terminal illness, based on a literature review. It induces an introspective state that promotes reflection and new perspectives, described by users as similar to psychotherapy. Neuropharmacologically, 5HT2A agonists stimulate genes linked to neuronal plasticity and cognitive functions; MAOIs and 5HT2A agonism have anxiolytic and antidepressant effects; sigma-1 agonism promotes neuroplasticity. Decreased alcohol and cocaine consumption and remission have been reported. Significant decreases in depressive symptoms were found in observational studies, case-controls, and a double-blind placebo-controlled trial. Improvements on mindfulness scales similar to meditators suggest an association between mindfulness and ayahuasca experiences. More studies with larger samples are needed.
European Psychiatry
March 1, 2016
Laura Orsolini, Alessandro Valchera, Duccio Papanti et al.
3 citations
Hallucinogen Persisting Perception Disorder (HPPD) is a syndrome marked by prolonged or recurring perceptual symptoms similar to acute hallucinogen effects, associated with substances like LSD, cannabis, MDMA, psilocybin, and mescaline. Symptoms mainly involve visual disturbances such as geometric pseudo-hallucinations, halos, flashes of light, motion-perception deficits, afterimages, and micropsy, though depressive and thought disorders may co-occur. First described in 1954, HPPD was formally established as a syndrome in the DSM-IV-TR in 2000. The neuronal substrate, risk factors, etiology, and pathogenesis remain unknown and under investigation. This critical review covers psychopathological bases, etiological hypotheses, and psychopharmacological approaches, presenting a case report and offering practical clinical recommendations.
European Psychiatry
March 1, 2015
D. Nutt
3 citations
Cortical 5HT2A receptors are largely expressed in layer 5 pyramidal neurons and gate top-down inputs to local cortical microcircuits. Their number is increased in some people with depression, and blockade of these receptors partly explains the augmenting action of atypical antipsychotics. Agonists at these receptors—the psychedelic drugs psilocybin and LSD—profoundly reduce brain activity, especially in regions that highly express the 5HT2A receptor such as the default mode network (DMN). Since the DMN is overactive in depression, this reduction may explain improvements in mood that users of psychedelics often report. A study of psilocybin in resistant depression has been funded by the UK MRC and will start in early 2015.
European Psychiatry
March 1, 2023
V. W. L. Tsang, R. Moyer, P. Kryskow et al.
2 citations
A group therapy program called Roots to Thrive (RTT) produced significant reductions in PTSD, depression, and anxiety symptoms among 49 healthcare practitioners with treatment-resistant mental health conditions. Participants' average PTSD scores dropped from 39.3 to 20.99, depression scores from 15.5 to 7.7, and anxiety scores from 15.5 to 6.2 over 12 weeks. Adding ketamine-assisted therapy did not lead to statistically greater improvements than the group therapy alone. The findings suggest that the group therapy model itself may be effective, and that the role of ketamine in this context requires further investigation.
European Psychiatry
March 1, 2023
K. P. Kuypers
2 citations
Classical psychedelics like psilocybin and LSD showed therapeutic potential for psychiatric disorders decades ago, and ayahuasca has been used for healing in western Amazonia for thousands of years. Recent research into these substances has re-emerged, with preliminary findings indicating that one or two administrations can lead to remission in depressed patients previously labeled treatment-resistant. This is notable because conventional antidepressants like SSRIs take longer to work and fail to achieve remission in one-third of patients. The fast onset of effects has increased interest in understanding the mechanism of action, with debate over the role of psychological experience versus neurobiological correlates.
European Psychiatry
April 1, 2021
I. Figueiredo, Filipa Viegas, F. Ferreira et al.
2 citations
Post-traumatic stress disorder (PTSD) often persists despite available evidence-based treatments, and psychotherapy remains the first-line approach, though many patients have high rates of psychiatric and medical comorbidity. Psychedelic-assisted psychotherapy may offer new treatment opportunities. A literature review of the Medline database found that MDMA-assisted psychotherapy appears to be a potentially safe, effective, and durable treatment for individuals with treatment-refractory PTSD. Ketamine administration, based on a small number of studies, appears to provide temporary symptom relief and, combined with psychotherapy, may lead to lasting reductions in PTSD symptoms. Psilocybin and LSD have psychoactive effects that could contribute to psychotherapeutic treatment, though controlled studies are lacking. More research on safety, efficacy, cost-effectiveness, and therapist training is needed.
European Psychiatry
April 1, 2021
S. Torres
2 citations
Psychedelics such as LSD, psilocybin, DMT, ayahuasca, and mescaline have a long history of use across civilizations and briefly entered psychiatry after LSD's discovery in 1950 before being prohibited due to recreational use in the mid-1960s. Renewed scientific interest over the last decade, termed the 'Psychedelic Renaissance', has led to a review of their pharmacology and therapeutic potential. These drugs act as agonists on 5-HT2A receptors in brain regions involved in mood and emotion, increasing glutamatergic tone and neuroplasticity while reducing amygdala activity. Experimental, open-label, and randomized controlled trials show anxiolytic, antidepressive, and antiaddictive effects, including reduced anxiety and depression in cancer patients and reduced alcohol and tobacco dependence. Evidence remains preliminary, pending larger long-term studies.
European Psychiatry
April 1, 2017
Amira Trabsa, E. Monteagudo, D.d. Mariona et al.
2 citations
Among 8324 drug samples submitted to a Spanish harm-reduction organization between 2014 and 2015, nine were gummy formulations—a novel delivery form for psychoactive substances. Analysis by gas chromatography-mass spectrometry showed that 55.5% of these gummies contained multiple drugs. The most common substance was 25N-NBOMe, found in 66.7% of samples; other detected substances included 2C-E, 2C-D, allylescaline, cocaine, THC, ketamine, MDMA, and caffeine. Only 25N-NBOMe was present in an active dosage. Two-thirds of the gummies did not contain the substance the consumer expected, indicating risks of unintended effects.
European Psychiatry
April 1, 2025
1 citation
A systematic review of 45 studies on psychedelic-assisted psychotherapy for mental disorders found that the quality of reporting on psychological interventions was mostly low. The studies assessed psilocybin, MDMA, LSD, or ayahuasca. Psychological interventions varied widely across studies, and completeness of information reported about these interventions was low, according to an adaptation of the Template for Intervention Description and Replication checklist. In studies including MDMA, psychotherapy was more homogeneous and more procedural details were provided. Improved reporting on psychological interventions is necessary to support replicability, generalisability, and accurate interpretation of research, as well as to enhance feasibility and safety of future clinical research and real-world implementation.
European Psychiatry
April 1, 2024
Venessa Tsang, C. Roney
1 citation
Patients awaiting psilocybin-assisted therapy (PAT) face complex application processes, fear of judgement, logistical and financial constraints, and systemic inequities. Health Canada's strict control through clinical trials and the Special Access Program creates challenges for primary care providers and limits involvement of trained practitioners. Moral distress from delayed or denied access underscores the urgency of addressing these barriers. Advocates recommend streamlined referrals, expedited services for end-of-life patients, formal billing infrastructure, practitioner education, expanded coverage, legislative adjustments, post-therapy support, and collaboration with non-profits and Indigenous Healers to promote equitable and effective PAT.