European Psychiatry
August 27, 2024
D. Zullino, L. Penzenstadler, S. Rothen et al.
Enhancement is the most common motive for using MDMA, followed by expansion motives—altering perceptions and increasing self-awareness—which reflects growing interest in MDMA-assisted therapy for conditions like PTSD. Social motives are third, coping fourth, and conformity least common. Compared to alcohol and cannabis, MDMA shows a distinct pattern of motives: social motives are less common for MDMA, and conformity motives are also less significant, possibly due to user maturity. These differences highlight the need for tailored harm reduction and intervention strategies. Data come from an online survey of 99 participants.
European Psychiatry
August 27, 2024
E. Kavakbasi, M. Yilmaz, Ö. Bulut et al.
In a retrospective chart review of 76 inpatients with treatment-resistant depression at a German university hospital, a series of esketamine nasal spray sessions (average 10.9) combined with usual care led to large reductions in depression severity and suicidal ideation. Scores on the Beck Depression Inventory (BDI-II) dropped by an average of 10.1 points, and Montgomery–Åsberg Depression Rating Scale (MADRS) scores fell by 10.0 points; suicidal ideation, measured by MADRS item 10, decreased by 0.9 points. All changes were statistically significant with large effect sizes. Treatment was generally well tolerated, though 5.3% of patients discontinued early due to dissociation.
European Psychiatry
April 1, 2024
V. Tsang
A program offering weekly virtual group therapy sessions combined with a single psilocybin session helped patients with terminal health conditions. Twenty-one of twenty-five participants (84%) completed the program. Feedback highlighted improved preparation, benefits such as perspective and peace, the group as a key source of connection, and the need for a curriculum focused on death and loss. Psilocybin was delivered safely in a group setting, and the virtual community of practice supported set, setting, and integration.
European Psychiatry
April 1, 2024
J. S. Seo
In Korea, debate over medical marijuana has preceded a similar discussion about psychedelics. Mescaline was first isolated from peyote in 1890, but psychedelics were prohibited in the US in 1970. Recent studies suggest psychedelic mushrooms may help with treatment-resistant depression, alcohol dependence, and anxiety in terminal cancer patients. This review catalogs wild hallucinogenic mushrooms in Korea. Psilocybin from magic mushrooms causes hallucinations and other symptoms lasting 2–4 hours. Of 114 psilocybin-containing Psilocybe species worldwide, only five grow in Korea: P. argentipes, P. coprophila, P. perdaria, and P. subcarulipes. Acute poisoning cases with GI symptoms occur, but abuse or dependence records are rare. The Korean government classifies psilocybin and psilocin as psychotropic drugs, and clinical trials require FDA approval.
European Psychiatry
April 1, 2024
C. Zu Eulenburg, E. Papanastasiou, K. Schmid et al.
A novel oral prolonged-release ketamine formulation (KET01) produces a low and delayed peak concentration of ketamine, high hydroxynorketamine levels, and minimal dissociative effects. In a phase 2 trial in outpatients with treatment-resistant depression, 240 mg/day KET01 added to ongoing treatment reduced depressive symptoms within 7 hours, with a statistically significant separation from placebo on day 4 and day 7, though the difference was not significant at day 21. In a separate phase 1 trial in healthy volunteers, the mean maximum dissociative score was 0.7 for KET01 versus 29.6 for intranasal esketamine. The formulation appears to be a safe, take-at-home adjunct treatment with minimal dissociation.
European Psychiatry
April 1, 2024
V. Tsang
A small study tested whether a device called Apollo reduces anxiety compared to no intervention. Participants were matched by age, sex, and initial anxiety scores. The median anxiety reduction was larger in the Apollo group (a drop of 8.5 points on the GAD-7 scale) than in the control group, but the difference was not statistically significant. The authors conclude that the Apollo device did not produce a significant effect in this sample and suggest that future work should include more participants and balanced group sizes.
European Psychiatry
November 17, 2023
V. Gallese
Schizophrenia involves disturbances in the minimal, bodily self—the pre-reflective sense of one's own body as one's own. Anomalies in multisensory integration and in the differential processing of self-related versus other-related bodily information may blur the distinction between self and other. This imbalance in the embodied self's pre-reflective relationship to the social world could underlie the self-disturbances and social deficits characteristic of schizophrenia. Cognitive neuroscience can now correlate first-person experiential aspects of psychiatric diseases with their neurobiological roots, adding a new descriptive level to classic psychopathology.
European Psychiatry
November 17, 2023
J. Curto Ramos, H. Dolengevich, M.a. Morillas Romerosa et al.
A patient who used 2C-B during chemsex—intentional drug use before or during sex—arrived at an emergency room with psychotic symptoms and was diagnosed with stimulant acute intoxication and acute psychotic symptoms induced by stimulants. 2C-B increases dopamine, serotonin, and norepinephrine, producing both stimulating and hallucinogenic effects. Men who have sex with men (MSM) are especially vulnerable to problematic drug use in sexual contexts. Chemsex users face mental health problems including psychotic symptoms, suicidal ideation, encephalopathy, and delirium. Polysubstance use is common in chemsex, making identification of specific drugs during acute intoxication challenging, but psychiatrists should investigate use of drugs beyond classic chemsex substances like mephedrone, GHB, and methamphetamine, including 2C-B, cocaine, MDMA, ketamine, and other cathinones.
European Psychiatry
November 17, 2023
M. I. Husain, D. M. Blumberger, D. J. Castle et al.
The antidepressant effects of psilocybin, the active compound in magic mushrooms, may not require its psychedelic effects. Psilocybin's psychedelic effects depend on activation of the serotonin 2A receptor, and blocking that receptor with drugs like risperidone or ketanserin eliminates the psychedelic experience in healthy volunteers. A mouse study showed that ketanserin did not reduce psilocybin's antidepressant effect. This proposed three-arm, double-blind, proof-of-concept randomized controlled trial in adults with treatment-resistant depression will test whether giving psilocybin with risperidone blocks psychedelic effects without reducing antidepressant effects. If so, psilocybin-assisted psychotherapy, which currently requires intensive therapist support, could become more scalable and accessible.
European Psychiatry
October 23, 2023
O. Martin-Santiago, G. Guerra-Valera, C. Alario-Ruiz et al.
A single dose of the hallucinogenic drug 25I-NBOMe can trigger psychosis lasting months, as shown in a case of a 30-year-old man who required psychiatric admission five months after use. He developed paranoid delusions, self-referential experiences, and intrusive flashbacks, becoming isolated and irritable. He previously worked and had a strong social network, with occasional adolescent use of alcohol, cannabis, and cocaine, and a family history of schizophrenia. Treatment with long-acting injectable aripiprazole reduced symptoms, allowing him to return to work within a year. The drug's expanding use may increase chronic psychosis cases, especially in vulnerable individuals, partly due to its phenylethylamine-like structure and the mistaken belief it is less dangerous.
European Psychiatry
October 23, 2023
I. B. Nita, O. D. Ilie, A. S. Ciobica et al.
A review of 246 studies from 2010 to 2022 examined how various substances induce schizophrenia-like symptoms in zebrafish. The compounds included NMDA inhibitors (MK-801, ketamine, phencyclidine), psychedelics (mescaline, LSD), amphetamine, and amino acids (proline, methionine). Most research focused on MK-801, ketamine, amphetamine, proline, methionine, and phencyclidine, with fewer studies on mescaline and LSD. Findings were inconsistent, showing both increases and decreases in behaviors such as locomotion, aggression, sociability, circling, and memory. The authors conclude that additional studies are needed to clarify these effects and guide future research on pharmacodynamics and kinetics.
European Psychiatry
March 1, 2023
R. Sousa, Luís Costa, J. Brás et al.
Substance use disorders (SUDs) remain a major health concern, with about 50–60% of patients relapsing within 6–12 months after treatment. Hallucinogens such as lysergic acid diethylamide (LSD) and psilocybin have shown potential anti-craving properties and may reduce substance use. Psilocybin has been found to increase trait openness, cognitive and behavioral flexibility, and positive attitudes and mood, with some studies reporting persistent positive changes. These effects suggest psilocybin could help treat SUDs and prevent relapse, possibly by improving negative emotional states and stress or by reducing cognitive inflexibility and compulsivity. However, research is still limited to a handful of studies, and many questions about its mechanisms and use alongside current treatments remain unanswered.
European Psychiatry
March 1, 2023
René Zeiss
Psilocybin, a classical psychedelic, is being studied as an alternative treatment for mental disorders. A narrative review of recent studies found no serious side effects under controlled conditions. Common adverse drug reactions include headache, nausea, vomiting, diarrhea, rapid heart rate, and high blood pressure. The lethal dose is many times higher than the therapeutic dose, with no overdose deaths identified. Hallucinogen persisting perception disorder did not occur in the studies reviewed and is more associated with recreational use. Results are preliminary because risk populations were mostly excluded. Risks like delusional experiences and bad trips are more likely in uncontrolled recreational use. The authors caution that high expectations and fame surrounding psilocybin could blur the line between therapeutic and abusive use.
European Psychiatry
March 1, 2023
J. Ramírez González, I. Fernández Márquez, Serafín González et al.
Psilocybin microdoses (10–25 mg) combined with psychotherapy improve depressive symptoms in patients with drug-resistant depressive disorder, with benefits lasting at least six months. A review of 19 recent studies found that one or two such doses produce statistically significant improvement. These findings offer optimism for new mental health treatments.
European Psychiatry
March 1, 2023
J. H. Shepherd, C.t.m. Baten, A. C. Klassen et al.
Serotonergic psychedelics such as LSD, psilocybin, and MDMA significantly alter neural activation in several regions of the cerebral cortex and basal ganglia. Some effects are common across these drugs, while others are unique to each substance. This meta-analysis combined functional MRI studies of both clinical and healthy participants, using multilevel kernel density analysis with ensemble thresholding. The findings clarify the functional neuroanatomy associated with these drugs and may guide future research into their therapeutic and adverse effects, particularly for emerging psychiatric treatments.
European Psychiatry
June 1, 2022
L. Silva, L. Bravo
Ayahuasca, a hallucinogenic tea containing monoamine oxidase inhibitors and DMT, shows potential benefits for psychiatric symptoms such as depression, anxiety, and drug addiction. In a randomized placebo-controlled trial, ayahuasca had a significant antidepressant effect compared to placebo. Long-term use was associated with structural brain alterations in medial regions, with no evidence of increased psychopathology or impaired neuropsychological functioning. Prolonged psychotic reactions among users are rare, and causal links to ayahuasca are difficult to establish. More controlled double-blinded studies with larger populations are needed to clarify therapeutic potentials and side effects.
European Psychiatry
June 1, 2022
A. Fraga, B. Mesquita, João Facucho-Oliveira et al.
A narrative review examined whether ketamine, a dissociative anesthetic, could improve the antidepressant effects of electroconvulsive therapy (ECT) for treatment-resistant depression. ECT is a standard end-line therapy but can cause memory impairment, possibly from overstimulation of glutamate receptors in the hippocampus. Ketamine blocks NMDA receptors and stimulates glutamate release, so it was proposed as an ECT adjuvant to reduce cognitive side effects and speed response. However, response and remission rates with ketamine in ECT showed no significant difference from comparator groups, and it was linked to more psychiatric and cardiovascular adverse events. The findings do not support combining ketamine and propofol as anesthetics for ECT in major depressive disorder.
European Psychiatry
June 1, 2022
H. Yaniv, V. Savlev
A 44-year-old man with longstanding major depressive disorder who had not improved after multiple medications showed clinical improvement after six months of Esketamine treatment combined with a 30-minute therapy group held after each session. He reported a positive mood, fewer thoughts of death, and better functioning at work and home. He attributed the improvement partly to the group, which provided a peer group and a place to process the treatment experience. Vignettes from the sessions illustrate these changes.
European Psychiatry
June 1, 2022
S. Pratas Penedos, M.j. Freire, I. Fonseca et al.
MDMA-assisted psychotherapy shows promise for treating refractory PTSD. Pre-clinical and imaging studies suggest mechanisms involving memory reconsolidation and fear extinction, driven by increased serotonergic activity and release of oxytocin and brain-derived neurotrophic factor, which reduce amygdala and insula activation while increasing amygdala-hippocampus connectivity. This may create a neuroplastic 'tolerance window' for emotional engagement. A phase 3 randomized, double-blind, placebo-controlled trial reported full remission in 67% of patients at 2 months, with a safety profile comparable to SSRIs and no increase in suicidality, cardiovascular events, or abuse behavior. Emerging models emphasize unmedicated sessions for preparation and integration.
European Psychiatry
June 1, 2022
B. Baune, Z. Susam, V. Falcone et al.
Intranasal S-ketamine (Spravato) can be safely and effectively administered in an acute psychiatric emergency setting to treat depressive crises in patients with treatment-resistant major depressive disorder who have severe suicidal ideation. In a case series of 10 patients (70% female, mean age 49.5 years), average MADRS scores dropped from 37 pre-treatment to 18 post-treatment, and BDI scores dropped from 39 to 24. Side effects such as dissociation were short-lived.
European Psychiatry
April 1, 2021
B. Van der Kolk
A randomized, double-blind, Phase 3 trial tested three sessions of flexible-dose MDMA or placebo as an adjunct to psychotherapy in 100 participants with severe PTSD. The primary outcome was change in PTSD symptoms and functional impairment at 18 weeks. MDMA was well tolerated, with some treatment-emergent adverse events more frequent in the MDMA group, and three serious adverse events of suicidal ideation or behavior occurred. The authors will present effect sizes and responder analyses. If MDMA-assisted psychotherapy significantly reduces PTSD symptoms and functional impairment, the results could support marketing authorization applications worldwide.
European Psychiatry
April 1, 2021
Pushpendra Kumar Jain, Varchasvi Mudgal, Ujwal Sardesai et al.
Dissociative identity disorder (DID) is rare despite its popularity in the public imagination. A 30-year-old woman from a low socioeconomic background presented with episodic altered behavior. Evaluation confirmed DID, and treatment combined psychotherapy facilitated by hypnosis, escitalopram (up to 20 mg daily), and a short course of clonazepam. The patient improved, with decreased Dissociative Experiences Scale scores. The authors suggest that unconscious conflicts, such as the Elektra complex in Freudian theory, may underlie DID. They urge clinicians, especially in countries like India where trance and possession syndromes are common, to consider DID as a differential diagnosis.
European Psychiatry
April 1, 2021
Jackelyne Gabrielle Jesus de Miranda, Mario Barbosa, I. Figueiredo et al.
Classic psychedelics such as LSD, mescaline, and psilocybin have been used in sacramental contexts since ancient times and were studied in psychiatry in the 1950s–1960s before research halted due to countercultural associations. Modern research has renewed interest in these substances for treating cancer-related distress and addiction. This review of articles from 2010–2020 finds that psychedelics, as 5HT2AR agonists, can occasion mystical experiences—characterized by a strong sense of unity—that may produce abrupt, sustained changes in behavior and perception. Research on psychedelics for substance use disorders is at an early stage, but results show promise with no clinically significant adverse events when high-risk individuals are excluded. Psilocybin for specific addictions may become available in the near future if safety and efficacy continue to be demonstrated.
European Psychiatry
April 1, 2017
L. Bartova, A. Weidenauer, M. Dold et al.
A severely depressed and chronically suicidal patient who had not responded to many antidepressant treatments, including electroconvulsive therapy (ECT) and ketamine alone, was given a combination of ECT (up to 150% bilateral stimulation) 2–3 times per week and intravenous racemic ketamine (up to 75 mg per infusion) on ECT-free days. Robust anti-suicidal and antidepressant effects appeared during the first week. After 9 ECT treatments and 7 ketamine infusions, the patient achieved a stable state and was discharged. A maintenance plan of monthly ECT with two ketamine infusions (up to 100 mg) around each ECT prevented relapse. The alternating regimen proved safe and long-term effective in this case.
European Psychiatry
March 1, 2016
M. Mithoefer
MDMA-assisted psychotherapy shows promise for treating PTSD in people who have not responded to established treatments. In a double-blind trial, PTSD resolved in 83% of those receiving MDMA plus psychotherapy versus 25% of those receiving placebo plus psychotherapy. Improvement was maintained for at least 74% of subjects at long-term follow-up averaging 45 months later. A later unpublished trial found large reductions in PTSD symptoms for both high and medium doses of MDMA. Phase III trials are needed to confirm safety and efficacy.