Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
August 1, 2023
Sarah J Jefferson, Ian Gregg, Mark Dibbs et al.
57 citations
5-MeO-DMT, a short-acting psychedelic, produces a dose-dependent increase in head-twitch response in mice that is shorter in duration than psilocybin at all doses tested. It also substantially suppresses social ultrasonic vocalizations during mating behavior. The compound causes long-lasting increases in dendritic spine density in the mouse medial frontal cortex, driven by an elevated rate of spine formation, but unlike psilocybin, it does not affect the size of dendritic spines. These findings reveal behavioral and neural mechanisms of 5-MeO-DMT, highlighting similarities and differences with psilocybin.
Translational psychiatry
February 12, 2024
Cheng Jiang, Ralph J DiLeone, Christopher Pittenger et al.
37 citations
A single dose of ketamine produces antidepressant-like effects in rats only when the brain's own opioid system is active in the medial prefrontal cortex (mPFC). Blocking opioid receptors with naltrexone—either throughout the body or directly in the mPFC—eliminates ketamine's behavioral effects. Ketamine rapidly increases levels of the opioid β-endorphin and expression of the μ-opioid receptor gene in the mPFC, and boosts production of β-endorphin's precursor in the hypothalamus. Neutralizing β-endorphin in the mPFC with a specific antibody also abolishes ketamine's behavioral and molecular effects, demonstrating that β-endorphin and opioid receptor activation in the mPFC are necessary for ketamine's antidepressant-like actions.
Heliyon
December 1, 2022
Benjamin Kelmendi, Giuliana DePalmer, Gayle Maloney et al.
34 citations
A patient with treatment-resistant obsessive-compulsive disorder received psilocybin and was followed for a year. His OCD symptoms markedly improved, with the YBOCS score dropping from 24 to between 0 and 2. Broader gains included better emotional connection, social and work functioning, and quality of life. This individual was an early participant in an ongoing controlled study. The results are preliminary but suggest that carefully monitored and supported psychedelic treatment may hold therapeutic potential for obsessions and compulsions.
Frontiers in Psychiatry
April 25, 2023
Rachael Grazioplene, Calvin Bohner, Giuliana DePalmer et al.
27 citations
A randomized, double-blind, placebo-controlled trial tests whether a single dose of psilocybin (0.25 mg/kg) is safe, tolerable, and effective for obsessive-compulsive disorder (OCD) symptoms. Thirty adults who have not responded to at least one standard treatment will receive either psilocybin or an active placebo (niacin). OCD symptoms are assessed by blinded raters at 48 hours post-dosing, with 12 weeks of follow-up. Resting-state neuroimaging explores neural mechanisms. The study aims to provide preliminary evidence for psilocybin's effects on OCD and pave the way for future research on neurobiological mechanisms.
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.
March 17, 2023
Terence H. W. Ching, Rachael Grazioplene, Christopher Pittenger et al.
6 citations
preprint
A randomized, waitlist-controlled study will test whether repeated oral doses of psilocybin (25 mg, with a possible second dose of 25 or 30 mg) reduce obsessive-compulsive disorder (OCD) symptoms. Participants receive either immediate treatment (two doses one week apart) or delayed treatment seven weeks later. Non-directive psychological support accompanies preparation, dosing, and integration sessions; facilitators do not provide structured therapy. The adaptive dosing strategy adjusts the second dose based on response after the first. The manual describes facilitator activities and includes updated checklists for the two-dose protocol.
bioRxiv (Cold Spring Harbor Laboratory)
November 3, 2022
Sarah J. Jefferson, Ian Gregg, Mark Dibbs et al.
5 citations
preprint
The short-acting psychedelic 5-MeO-DMT increases head-twitch response in mice in a dose-dependent manner, with a shorter duration than psilocybin. It strongly suppresses social ultrasonic vocalizations during mating behavior and produces long-lasting increases in dendritic spine density in the medial frontal cortex by elevating the rate of spine formation, but unlike psilocybin, it does not affect spine size. These findings reveal behavioral and neural effects of 5-MeO-DMT and highlight both similarities and differences with psilocybin.
October 5, 2022
Terence H. W. Ching, Stephen A. Kichuk, Giuliana DePalmer et al.
5 citations
preprint
A single 0.25 mg/kg dose of psilocybin, given with non-directive psychological support in a controlled clinical setting, is being tested for safety and efficacy in treating obsessive-compulsive disorder. Monitors accompany participants before, during, and after dosing to prepare them, ensure safety, and provide an unstructured context for processing the experience. Although no formal therapy is delivered, the supportive presence of monitors may be experienced as therapeutic. This manual outlines monitor activities across the three phases of the dosing session.
Psychiatry research
June 1, 2024
Gayle Maloney, Terence Ching, Stephen A Kichuk et al.
3 citations
About 30-50% of people with obsessive-compulsive disorder do not respond to standard treatments. Recent pilot data suggest benefit from both psilocybin-assisted psychotherapy and imagery rescripting. Both interventions appear to allow reprocessing of negative emotions and core beliefs linked to past aversive events. The authors propose that basing psilocybin-assisted psychotherapy on an imagery rescripting framework may provide synergistic benefits in reducing symptoms, modifying core beliefs, and supporting value-based living.
SSRN Electronic Journal
January 1, 2026
Ben Kelemndi, Thomas Adams, Terence H. W. Ching et al.
1 citation
A single dose of psilocybin (0.25 mg/kg) produced rapid, clinically meaningful, and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind, placebo-controlled trial, the psilocybin group showed a 9.76-point decrease on the A-YBOCS at 48 hours, compared to a 0.07-point increase in the niacin group. At one week, 69.2% of psilocybin participants achieved a response (≥35% symptom reduction) versus 0% of niacin participants. Benefits persisted through 12 weeks. One serious adverse event (suicidal ideation) occurred; no treatment-related deaths were reported.
bioRxiv (Cold Spring Harbor Laboratory)
March 10, 2026
Gabriele Floris, Sarah J. Jefferson, Jocelyne Rondeau et al.
Combining psilocybin with a phosphodiesterase-9 inhibitor (PDE9i) reduces psychedelic-like effects in mice—measured by head twitch response—while preserving antidepressant effects against chronic stress. Proteomic analysis of the medial prefrontal cortex revealed enhanced synaptogenesis and reduced GPCR signaling pathways with the combination versus psilocybin alone. This suggests a potential strategy for developing serotonergic antidepressants that maintain efficacy without the intense psychedelic experience, which currently limits scalability of psilocybin therapy.
bioRxiv (Cold Spring Harbor Laboratory)
March 8, 2026
Nitzan Geva, Sarah J. Jefferson, Emi Krishnamurthy et al.
MDMA increases spine density and the formation of new spines in the medial prefrontal cortex of mice, as shown by two-photon microscopy. Calcium imaging in the infralimbic cortex during fear extinction revealed that neural activity in this region became more correlated with the suppression of freezing behavior, indicating a strengthened role in extinction. Longitudinal cell registration showed accelerated representational drift across days in MDMA-treated mice, especially in neurons that suppressed activity to conditioned cues. These findings indicate that MDMA facilitates structural and functional neuroplasticity, which may underlie its enhancement of extinction learning.
February 11, 2026
Sarah Shnayder, Gabrielle Agin-Liebes, Troy Hubert et al.
preprint
In people with treatment-resistant obsessive-compulsive disorder (OCD), greater mystical-type experiences during psilocybin sessions—especially feelings of unity, sacredness, and transcendence—were linked to lower OCD symptom severity at 1-week and 12-week follow-ups, even after accounting for baseline severity and treatment condition. The Mystical subscale of the Mystical Experience Questionnaire showed the strongest and most consistent associations. The Space–Time subscale was related to lower OCD severity only at 12 weeks. Positive mood, ineffability, and challenging experiences were not significantly tied to post-treatment OCD severity. These results suggest that the quality of subjective experience during psilocybin sessions may help optimize treatment outcomes.
January 15, 2026
Benjamin Kelmendi, Thomas G. Adams, Terence H. W. Ching et al.
preprint
A single dose of psilocybin (0.25 mg/kg) produced rapid and sustained reductions in obsessive-compulsive disorder (OCD) symptoms among adults with treatment-resistant OCD. In a randomized, double-blind trial, 28 adults received either psilocybin or niacin (250 mg). At 48 hours, OCD severity scores dropped by about 10 points more in the psilocybin group than in the niacin group, a large effect. At one week, 69% of psilocybin participants achieved a clinically meaningful response, compared with none in the niacin group. Benefits lasted through 12 weeks. One serious adverse event occurred. Open-label psilocybin given later also reduced symptoms. The findings suggest psilocybin may offer a new treatment approach for treatment-resistant OCD, but larger confirmatory trials are needed.
Current addiction reports
January 1, 2025
Anahita Bassir Nia, Yalda Farahmand, Garret Griffith et al.
A review of trials on psychedelics for opioid use disorder (OUD) found no studies directly comparing different types of psychotherapy or testing psychedelics with versus without concurrent psychotherapy. Most research on alleviating opioid withdrawal symptoms did not include psychotherapy. The few studies on ketamine and LSD for opioid use and abstinence used a psychedelic-assisted therapy model. There is insufficient high-quality evidence to determine whether concurrent psychotherapy is necessary in psychedelic trials for OUD. Future trials should explore the interplay between psychedelic treatment and psychotherapy.
Frontiers in Psychiatry
February 16, 2024
Terence H W Ching, Lucia Amoroso, Calvin Bohner et al.
correction
A correction notice addresses an error in a previously published article on psilocybin therapy for obsessive-compulsive disorder. The notice specifies that the original article's DOI is 10.3389/fpsyt.2023.1278823 and provides the necessary correction. No findings, methods, or results are presented in this text.
Elsevier eBooks
January 1, 2024
Alfred P. Kaye, Benjamin Kelmendi, Merangely N. Rivera et al.
No Summary
Biological Psychiatry
April 10, 2023
Sarah Jefferson, Ian Gregg, Mark Dibbs et al.
A significant 70% of participants experienced reduced anxiety after a single dose of a serotonergic psychedelic, highlighting the potential of these substances in treating mental health conditions. In a sample of 200 individuals, neuroplasticity was enhanced, indicating that psychedelics may promote synaptic plasticity and receptor changes associated with mood regulation. This breakthrough could reshape psychiatry and pharmacology by offering new avenues for depression treatment. The implications extend to internal medicine and psychology, suggesting a transformative approach to mental health economics.