Frontiers in Psychiatry
January 23, 2024
Johannes Hauser, Jan Sarlon, Timur Liwinski et al.
10 citations
Listening to music during intranasal (es)ketamine treatment for therapy-resistant depression is linked to reduced anxiety and lower blood pressure, stable or increased dissociation, and tolerance for higher doses. In a review of 494 sessions from 37 patients, those who listened to music received higher average doses (131.5 mg vs. 116.7 mg), reported less anxiety (0.4 vs. 1.4 points), and had lower peak systolic blood pressure (137.9 vs. 140.3 mmHg) compared to those who did not. Music did not affect depression scores between sessions.
Frontiers in Psychiatry
January 8, 2024
N. Jones, Laura M. Wagner, Molly C. Pellitteri Hahn et al.
10 citations
Psilocybin, a psychedelic compound used in psychotherapy research, is converted in the body to the active metabolite psilocin. Psilacetin (4-AcO-DMT) has long been thought to be an alternative prodrug for psilocin, but direct evidence was lacking. In mice, psilocybin produced 10–25% higher psilocin concentrations than psilacetin at 15 minutes after injection. The half-life of psilocin was about 30 minutes from either prodrug. Overall, psilacetin fumarate yielded about 70% of the psilocin exposure that psilocybin did. These results confirm that psilacetin acts as a psilocin prodrug in vivo and suggest it can be used as a substitute for psilocybin in mechanistic research with mice.
Frontiers in Psychiatry
December 8, 2023
Alina Wilkowska, Wiesław Jerzy Cubała
10 citations
Bipolar depression is a serious psychiatric condition linked to high suicide risk, treatment resistance, chronicity, and poor quality of life. Approved treatments are limited and often insufficient, creating an urgent need for new strategies. Intranasal esketamine, a ketamine enantiomer, is a rapid-acting antidepressant proven effective for treatment-resistant depression. Research on bipolar depression, though less extensive, suggests esketamine may be a safe alternative with low risk of mood polarity shifts. Reports indicate ketamine treatment may reduce suicidal thoughts, anhedonia, and anxiety. Ketamine's potential mood-stabilizing properties are hypothesized. This narrative review examines ketamine as an add-on to standard medication for acute bipolar depression.
Frontiers in Psychiatry
August 24, 2023
Grant Jones, Patrick Mair, Maha Al‐suwaidi et al.
10 citations
Lifetime psilocybin use is associated with lower odds of arrest for property crime, assault, serious violence, and miscellaneous crimes in a large US sample. However, race and ethnicity moderate these associations: psilocybin conferred reduced odds of at least one crime arrest outcome for White, Indigenous, Asian, and Multiracial participants, but not for Black or Hispanic participants. The authors suggest that structural factors such as systemic racism may underlie these differences and call for intersectional research on sociodemographic factors, psychedelic use, and crime.
Frontiers in Psychiatry
February 9, 2023
Anya Ragnhildstveit, Miriam Kaiyo, Matthew Brian Snyder et al.
10 citations
A 28-year-old woman with complex dissociative posttraumatic stress disorder (D-PTSD) underwent ten sessions of cannabis-assisted psychotherapy (CAP) over five months, combined with cognitive behavioral therapy. After treatment, her pathological dissociation score, measured by the Multidimensional Inventory of Dissociation, dropped by 98.5%, and she no longer met criteria for D-PTSD. She also experienced reduced cognitive distractibility, less emotional suffering, and improved psychosocial functioning. The patient has maintained these gains for over two years. The authors suggest CAP, which produced subjective effects similar to psychedelics like psilocybin and ketamine, warrants further research as a potential treatment for D-PTSD.
Frontiers in Psychiatry
January 9, 2024
Terence H W Ching, Lucia Amoroso, Calvin Bohner et al.
9 citations
A randomized controlled trial will test whether two doses of psilocybin (25 mg followed by either 25 or 30 mg), given with non-directive support, reduce obsessive-compulsive disorder (OCD) symptoms more than a single dose or a waitlist control. Thirty adults with treatment-refractory OCD will be enrolled. OCD symptoms will be measured with the Yale-Brown Obsessive-Compulsive Scale – Second Edition by a blinded rater at baseline and after the second dosing week. Participants will be followed for up to 12 months. The trial also aims to identify psychological mechanisms that may explain psilocybin's effects on OCD.
Frontiers in Psychiatry
September 20, 2022
Lawrence G. Fischman
9 citations
People who undergo MDMA- and psychedelic-assisted psychotherapy often adopt new beliefs about themselves and the world, and these changes are linked to mystical-type experiences during drug sessions. This paper argues that the sense of authenticity accompanying these belief changes arises from a simultaneous feeling of knowing and being known. The medications reduce defensive barriers, enabling the subject to share powerful feelings intersubjectively with the therapist or internalized others. The author draws on concepts such as existential feeling, ipseity, the True Self, transitional phenomena, implicit relational knowing, and predictive processing to propose a transitional space model for working through dissociated experience.
Frontiers in Psychiatry
June 17, 2022
Andrew Beswerchij, Dominic Sisti
9 citations
Adopting precise, non-stigmatizing terminology grounded in the medical model can advance both the science and public acceptance of psychedelics. Researchers and clinicians should distinguish between medical, recreational, and spiritual uses to set clear boundaries and expectations for patients. Replacing colloquial names with scientific names for medicines and therapies may help correct misconceptions held by professionals and the public. A harmonized medical lexicon provides a common language for important communication, such as informed consent. Recommendations draw on communications research in addiction medicine to encourage development and implementation of non-stigmatizing terminology in psychedelic research and treatment.
Frontiers in Psychiatry
June 3, 2020
Alina Wilkowska, Łukasz P. Szałach, Jakub Słupski et al.
9 citations
Ketamine can rapidly reduce depression in people with treatment-resistant bipolar disorder, but it also carries a risk of triggering mania. This case describes a patient with bipolar I disorder who, after eight low doses of oral ketamine added to their usual treatment, switched from a depressive episode to a manic episode with mixed features. The manic symptoms began two days before the switch became full-blown. The finding highlights the need for careful monitoring of mood changes when using ketamine in bipolar depression.
Frontiers in Psychiatry
October 24, 2019
Patrick Vizeli, Matthias E. Liechti
9 citations
MDMA (ecstasy), a recreational drug also studied as a treatment for PTSD, stimulates the dopamine system, which may contribute to its mood effects. Genetic differences in dopamine-related genes—including the D2 and D4 receptors and the dopamine transporter—were tested for their influence on subjective and autonomic responses to 125 mg of MDMA in 149 healthy volunteers across placebo-controlled crossover studies. After adjusting for multiple comparisons and individual differences in MDMA blood levels, none of the genetic variants significantly altered the drug's effects. Genetic variations in dopamine system genes are unlikely to explain why people respond differently to MDMA.
Frontiers in Psychiatry
August 13, 2017
Luisa Ponzoni, Daniela Braida, Gianpietro Bondiolotti et al.
9 citations
MDMA and its derivatives DOB and PMA increase social, rewarding, and anxiety-reducing behaviors in adult zebrafish. These effects are blocked by a V1a vasopressin antagonist (SR49059), suggesting the oxytocin/vasopressin system plays a key role. The drugs also raised brain levels of isotocin (fish oxytocin) 3–5 times above control levels. The findings indicate that the oxytocin/vasopressin system mediates the behavioral effects of these substances, linking it to substance abuse disorders.
Frontiers in Psychiatry
August 13, 2024
Mu-Hong Chen, Shu-Li Cheng, Yu-Chen Kao et al.
8 citations
A Bayesian meta-analysis of 10 clinical trials involving 515 adults with diagnosed depression found that psilocybin-assisted therapy produced a pooled mean reduction of 10.08 points on the 17-Item Hamilton Depression Rating Scale. The psychological protocols used alongside psilocybin varied: manualized directive psychotherapy, manualized nondirective psychological support, non-manualized nondirective psychological support, and non-manualized supportive psychotherapy. Compared with manualized nondirective psychological support, the other three approaches did not differ significantly in their effect on depressive symptoms. The improvement in depressive symptoms was not associated with the type of psychological protocol employed.
Frontiers in Psychiatry
November 3, 2022
Devon Christie, Berra Yazar-Klosinski, Ekaterina Nosova et al.
8 citations
Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur and worsen each other. In a Phase 2 open-label trial of MDMA-assisted therapy for PTSD, 84% of 32 participants reported pain and 75% reported pain-related disability. After treatment, those with the highest baseline pain showed significant reductions in pain intensity, disability, and overall severity grade; those with medium baseline pain also showed significant reductions in pain intensity. The findings suggest MDMA-assisted therapy may reduce chronic pain in people with severe PTSD, but the data are preliminary and encourage further research.
Frontiers in Psychiatry
December 6, 2024
Jonathan Brett, Elizabeth Knock, Kathy Watson et al.
7 citations
A daily methamphetamine user, a 36-year-old transwoman, achieved sustained abstinence and improved mental health after a single session of psilocybin-assisted psychotherapy following inpatient withdrawal management. She reported increased self-esteem, mindfulness, and distress tolerance over three months. The case suggests that psilocybin-assisted therapy may offer a scalable, safe, and effective approach for treating methamphetamine dependence, though further research is needed to confirm generalizability.
Frontiers in Psychiatry
November 21, 2023
Peter Wipf, Nikhil R. Tasker, Ethan J. Pazur
7 citations
Clavine alkaloids, a subclass of ergot alkaloids found widely in nature, have potent physiological effects but remain understudied compared to well-known psychedelics like LSD and psilocybin. This review summarizes their biological properties, compares their pharmacology to ergolines and related psychedelics, and highlights opportunities for developing new structure–activity relationship profiles. Such advances could expand the currently limited structural variety of psychedelic therapeutics, opening new avenues for medicinal chemistry.
Frontiers in Psychiatry
June 30, 2023
Colleen E. Charlton, Povilas Karvelis, Roger S. McIntyre et al.
7 citations
Suicide claims over 700,000 lives each year. Ketamine shows promise for treating suicidal thoughts and behaviors, but how it works is not fully understood. Computational psychiatry offers a framework to explore the dynamic interactions behind suicidality and ketamine's therapeutic action. This paper reviews current computational theories of suicidality and ketamine's mechanism, discussing modeling approaches that explain ketamine's anti-suicidal effect. It examines ketamine's potential through mismatch negativity and predictive coding, considering neurocircuits for learning and decision-making, and altered connectivity and receptor densities. Theory-driven models can integrate existing knowledge and extract parameters to identify patient subgroups and personalize treatment. Future studies should optimize task design and evaluate set, setting, and psychedelic-assisted therapy.
Frontiers in Psychiatry
May 19, 2022
Eef L. Theunissen, Kim P. C. Kuypers, Natasha L. Mason et al.
7 citations
At equal levels of subjective intoxication, natural cannabis (THC) and the synthetic cannabinoid JWH-018 both impair psychomotor function, divided attention, and impulse control to a similar degree. Both drugs also produce psychotomimetic effects, but JWH-018 causes considerably more pronounced dissociative effects than THC. The study matched participants from two placebo-controlled experiments by their subjective high to compare the drugs' neurocognitive and psychotomimetic profiles, concluding that psychotropic dose equivalence offers a uniform method for comparing CB1 receptor agonists.
Frontiers in Psychiatry
October 31, 2023
Albino J. Oliveira-Maia, Benoit Rive, Joachim Morrens et al.
6 citations
An adjusted indirect comparison of treatment strategies for treatment-resistant depression found that esketamine nasal spray plus an antidepressant led to a higher probability of response (49.7%) and remission (33.6%) at six months compared with real-world polypharmacy strategies (26.8% response, 19.4% remission). Esketamine was about 1.86 times as likely to produce a response and 1.74 times as likely to produce remission. Threshold and sensitivity analyses indicated these results were robust to potential unmeasured confounders.
Frontiers in Psychiatry
October 16, 2023
Eline Haijen, Petra P. M. Hurks, Kim P. C. Kuypers
6 citations
Adults with ADHD who microdosed psychedelics for four weeks showed increased trait mindfulness—specifically the ability to describe and not judge inner experiences—and decreased neuroticism, while other personality traits like conscientiousness, extraversion, agreeableness, and openness remained unchanged. These changes occurred regardless of whether participants also used conventional ADHD medication or had other mental health diagnoses. The findings suggest that microdosing may alter otherwise stable psychological traits in this population, though placebo-controlled studies are needed to confirm the effects.
Frontiers in Psychiatry
October 9, 2023
A. Zavaliangos-Petropulu, Shawn M. Mcclintock, S. Joshi et al.
6 citations
In patients with treatment-resistant depression, smaller hippocampal subfield volumes (left CA4 and GC-ML-DG) were observed before ketamine treatment compared to healthy controls. Four ketamine infusions over two weeks did not change hippocampal subfield volumes, and pre-treatment volumes did not predict improvement in depressive symptoms. However, smaller pre-treatment left CA4 and GC-ML-DG volumes were associated with greater improvement in processing speed after ketamine, and larger right CA3 volume was linked to better working memory at follow-up. Baseline hippocampal subfield volumes may serve as biomarkers for cognitive, but not antidepressant, response to ketamine.
Frontiers in Psychiatry
June 29, 2023
Winston De La Haye, Geoffrey Walcott, Jordan Eaton et al.
6 citations
Psilocybin and other psychedelics have shown efficacy in treating several mental illnesses, including treatment-resistant cases, through clinical trials. In psychedelic assisted psychotherapy, these substances enhance psychotherapeutic processes. Psychohistoriographic Brief Therapy, developed in Jamaica, has successfully treated personality disorders by documenting life experiences in a psychohistoriogram. The De La Haye psilocybin Treatment Protocol combines micro-doses of psilocybin mushrooms over eight weeks with this documentation, followed by a supervised larger dose in the ninth week. Given Jamaica's legal status for psilocybin, a regulated industry could support rigorous clinical research and benefit clients in this new psychiatric frontier.
Frontiers in Psychiatry
May 18, 2023
Tigran Makunts, Diane Dahill, Lisa Jerome et al.
6 citations
MDMA is being tested as a treatment aid for PTSD and anxiety disorders, and regulatory approval is expected soon. Its main effects involve increasing serotonin, norepinephrine, and dopamine activity, which can raise heart rate and blood pressure. Clinical trials have limited data on cardiac side effects due to small participant numbers and restricted use of other drugs. An analysis of FDA adverse event reports found 17 cardiovascular cases where people took MDMA plus other substances. All accompanying drugs—opioids, stimulants, anticholinergics, and amphetamines—are already linked to heart problems. In none of these reports was MDMA considered the primary cause.
Frontiers in Psychiatry
June 9, 2022
H. Bringmann, Martin Bogdanski, G. Seifert et al.
6 citations
A meditation and yoga program (Meditation-Based Lifestyle Modification, MBLM) improved heart rate variability (HRV) in outpatients with mild to moderate depression compared with standard clinical care. In an exploratory randomized trial, MBLM participants (22 people) showed gains in vagal tone (RMSSD) and symbolic dynamics entropy, while a minimal-treatment group (17 people on drugs only) showed almost no changes. The findings suggest that MBLM may benefit selected HRV parameters, but further 24-hour monitoring is needed to confirm long-term effects.
Frontiers in Psychiatry
April 14, 2022
Johannes G. Ramaekers, Eef L. Theunissen, Peter van Ruitenbeek et al.
6 citations
Comparing brain function between chronic cannabis users and non-users may be confounded by factors like polydrug use, alcohol, withdrawal, or lifestyle. A proposed methodology uses acute Δ9-tetrahydrocannabinol (THC) dosing studies to directly assess neuroadaptations in chronic users. This approach quantifies neurochemical, receptor, and functional brain network changes in response to an acute cannabis challenge and stratifies users from occasional to dependent. It enables evaluation of THC-induced neuroadaptive and neurocognitive changes across cannabis use history, informing neurobiological models of reward-driven, compulsive cannabis use.
Frontiers in Psychiatry
August 4, 2025
Fernando Mora, J. Ramos-Quiroga, Enrique Baca-García et al.
5 citations
Treatment-resistant depression (TRD) occurs when a patient fails to respond to at least two adequate antidepressant trials, and it imposes a greater social and economic burden than non-resistant depression. A committee of ten Spanish psychiatrists reviewed recent literature and developed consensus statements on TRD definitions, clinical response criteria, and the role of intranasal esketamine, which improves neuroplasticity and synaptogenesis. They highlighted therapeutic inertia—its causes and consequences—and produced a treatment algorithm that includes specific response evaluation steps to avoid inertia and ensure adequate treatment. This is the first Spanish consensus on theoretical aspects of TRD and intranasal esketamine's place in therapy.