Journal of psychopharmacology (Oxford, England)
January 1, 2026
Jack E Henningfield, Sandra D Comer, Matthew L Banks et al.
5 citations
A panel of abuse potential experts convened to discuss challenges in assessing the abuse potential of novel drugs, especially psychedelics and cannabinoids. The U.S. Controlled Substances Act scheduling process, intended to balance public safety with medicinal access, can be overly restrictive when abuse potential is overestimated, as postmarketing evaluations have suggested for some substances. Existing methods recommended by the FDA are generally reliable for many drug categories but require modifications—such as behavioral economic assessments and broader outcome measures in human abuse potential studies—to accurately characterize newer agents. The commentary emphasizes the need for updated approaches to ensure valid scheduling decisions that protect public health without hindering access to beneficial medicines.
Journal of psychopharmacology (Oxford, England)
December 26, 2025
Kurt Stocker, Matthias Hartmann, Yasmin Schmid et al.
5 citations
A psychometric revalidation of the Altered States of Consciousness Scale (ASC) using data from 901 questionnaires across 16 psychedelic studies (with LSD, psilocybin, mescaline, and DMT) shows that ten of the eleven subscales can be grouped into three higher-order dimensions—Positive Effects, Distressing Effects, and Perceptual Effects—mirroring the original three-dimensional model but with improved statistical fit. The Anxiety subscale could not be integrated due to floor effects (low anxiety in the sample) but is retained for clinical relevance. The revised scale, 3D-ASCr, is recommended for use with classic serotonergic psychedelics.
Journal of psychopharmacology (Oxford, England)
April 1, 2025
Manoj K Doss, Lilian Kloft, Natasha L Mason et al.
5 citations
In experienced users, ayahuasca acutely enhances recollection-based memory—the ability to recall specific details—without increasing false memories or affecting familiarity-based memory, a feeling of knowing. In an observational study of 24 Santo Daime members who had consumed ayahuasca over 500 times on average, participants completed a false memory task before and after taking a self-selected church dose. After ayahuasca, hit rates, memory accuracy, and recollection improved, while familiarity and false memory remained unchanged. The authors suggest that β-carboline activity in the brew may account for this recollection enhancement, which contrasts with past psychedelic research showing impaired recollection. Practice effects could not be ruled out, but multiple measures of false memory and metamemory did not improve across sessions.
Journal of psychopharmacology (Oxford, England)
February 1, 2025
Sophie-Athéna Chapron, Guilhem Bonazzi, Laura Di Lodovico et al.
5 citations
A systematic review of 31 studies involving 2639 participants found that 12 studies reported a significant decrease in craving for alcohol, opioids, cocaine, or tobacco after psychedelic use. However, all but two studies had moderate to high risk of bias due to methodological issues, so the promising anti-craving effects must be interpreted cautiously. The review highlights the need for larger, well-controlled trials to better understand psychedelics' effects on craving, a core symptom of substance use disorders and a predictor of relapse.
Journal of psychopharmacology (Oxford, England)
January 1, 2025
Henry A MacConnel, Mitch Earleywine, Steven Radowitz
5 citations
Intravenous ketamine administered in a supportive environment with preparation, intention-setting, integration sessions, eye shades, and evocative music—paralleling psychedelic therapy—was associated with large reductions in PTSD symptoms. In a retrospective sample of 117 outpatients, mean PCL-5 scores dropped from 52.54 to 28.78, with 75% showing clinically meaningful improvement and 62% suggesting remission. No serious adverse events occurred, and concomitant psychotherapy was a significant moderator. The findings suggest that environmental factors may account for variation in previous ketamine studies and that this approach may be a promising option for PTSD unresponsive to other treatments.
Journal of psychopharmacology (Oxford, England)
June 10, 2025
Torsten Passie, Anja Loizaga-Velder, Alicia Danforth et al.
4 citations
A consensus-based model curriculum for education and training in substance-assisted psychotherapy (SAP) covers theoretical topics and practical components including apprenticeship observation, ongoing clinical supervision, and self-experience for trainees. The model, developed by authors with extensive SAP experience, also addresses peer and conventional supervision, respect for intercultural differences, and teachings about indigenous use of related substances. It is largely adapted to western industrialized countries with established graduate-level psychotherapy training. The curriculum may be valuable for psychedelic researchers, those training therapists for research studies, and those preparing for clinical work outside research settings.
Journal of psychopharmacology (Oxford, England)
May 1, 2025
Adam W Levin
4 citations
A new model called HEALS (Hemispheric Annealing and Lateralization Under Psychedelics) proposes that psychedelics reverse the typical hierarchical relationship between the brain's hemispheres. Normally, the left hemisphere predominates while the right is inhibited. Under psychedelics and other altered states of consciousness, this hierarchy flips, releasing the right hemisphere from left-hemisphere inhibition. The article reviews neuroimaging evidence for lateralization under psychedelics and contrasts cognitive and emotional changes—such as attention, social and emotional intelligence, creativity and insight, and language—with those functions in each hemisphere. It also examines laterality in meditative and trance states, suggesting that many phenomena in psychedelic and other altered states may stem from atypical annealing between hemispheres toward right-hemisphere predominance.
Journal of psychopharmacology (Oxford, England)
April 1, 2025
Monika Maciag, Olga Doszyn, Artur Wnorowski et al.
4 citations
Acute exposure to MDMA reduces anxiety-like behavior and increases social preference in 3-week-old zebrafish. These effects are biphasic: the lowest dose (0.5 μM) increases anxiety while also increasing social preference, and as concentration rises the effects reverse, peaking at 2.5 μM. MDMA suppresses expression of serotonin receptor and transporter genes, increases oxytocin receptor genes, decreases a vasopressin receptor gene, and reduces AKT phosphorylation. An oxytocin receptor agonist mimics MDMA's effects, while an antagonist has no significant effect on anxiety or social behavior. The findings suggest MDMA has therapeutic potential for anxiety disorders and social impairments, and that young zebrafish are a useful model for neurobehavioral research.
Journal of psychopharmacology (Oxford, England)
January 1, 2025
Kabir Nigam, Franklin King, Fernando Espi Forcen
4 citations
Ketamine is non-inferior to electroconvulsive therapy (ECT) for depression and is better tolerated than many second-line augmentation strategies. Currently viewed as a third-line agent for treatment-refractory depression, the available data suggest ketamine carries a low side-effect burden. Given the relationship between treatment outcomes and duration of untreated illness, the authors argue psychiatry should evaluate ketamine as a second-line augmentation strategy for refractory depression.
Journal of psychopharmacology (Oxford, England)
May 1, 2026
Grace Viljoen, Henrik Walter, Antonia Bendau et al.
3 citations
A systematic review of 54 studies found that the intensity of the acute psychedelic experience, particularly mystical-type experiences, is the most frequently reported predictor of therapeutic response in psychedelic-assisted therapy for mental disorders, though this was not consistent across all disorders or time points. Factors related to set, setting, and dose were associated with the likelihood and intensity of these experiences. The review included adult populations with substance-use disorders, major depressive disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and existential distress, as well as naturalistic samples.
Journal of psychopharmacology (Oxford, England)
June 20, 2025
Mutahira Qureshi, Daniel Silman, Romayne Gadelrab et al.
3 citations
A single dose of immediate-release oral ketamine (40–240 mg) was safe and generally well-tolerated in healthy adults, with no unexpected safety signals or discontinuations due to side effects. Eighty mild or moderate treatment-emergent adverse events occurred after ketamine doses, most commonly dissociation, dizziness, and headache, while only five occurred after placebo. Dissociation events increased with higher doses. Ketamine and its metabolites showed dose-proportional pharmacokinetics. Transient mood and dissociation changes appeared one hour after dosing and resolved within about four hours. These results support further investigation of oral ketamine capsules for treatment-resistant depression.
Journal of psychopharmacology (Oxford, England)
May 26, 2025
Kyle Patch, William R. Smith
3 citations
The concepts of set and setting in psychedelic research are vague and over-inclusive. A mechanism-first approach is proposed, which begins with specific components such as openness to the experience or calming lighting and music, then investigates the mechanisms by which these components influence outcomes. Understanding paradigmatic cases allows researchers to test whether other mental and environmental factors play similar mechanistic roles, gradually expanding the scope of set and setting. This approach avoids standard definitions and encourages focused, mutually informative research projects. The argument outlines problems with current definitions, details the mechanism-first method, illustrates it with active research, and addresses objections.
Journal of psychopharmacology (Oxford, England)
May 5, 2025
Jan Kehler, Morten Skøtt Thomsen Lindskov
3 citations
A review of the literature on 5-HT2A receptor agonists, including psychedelics like LSD and the supposedly non-hallucinogenic compounds lisuride and ergotamine, finds no evidence that lisuride or ergotamine are non-hallucinogenic at relevant brain concentrations. This challenges the assumption that altered states of consciousness are not a prerequisite for therapeutic effects. The authors caution against relying solely on animal data when developing non-hallucinogenic 5-HT2A receptor agonists and emphasize the need for rigorous human studies to confirm target engagement before claiming a compound is non-hallucinogenic.
Journal of psychopharmacology (Oxford, England)
April 18, 2025
James D Morse, Soo Hee Jeong, Robin J Murphy et al.
3 citations
After a 10 µg sublingual dose of LSD, the drug's concentration in the blood peaks at about 0.20 µg/L after 1.5 hours and has an elimination half-life of roughly 3 hours. A one-compartment model best describes how the body processes the drug. The small increases in heart rate and perceived drug effect (less than 15% above baseline) limited the ability to model those effects. Two participants who withdrew due to anxiety had intermediate-to-weak CYP2D6 enzyme activity, and several CYP genotypes appeared to influence LSD concentration. No evidence of changes in peripheral BDNF levels was found. The findings provide a pharmacokinetic model and assay useful for future clinical studies, but larger samples are needed to assess CYP genotypes as response biomarkers.
Journal of psychopharmacology (Oxford, England)
March 12, 2025
Zusanna Bjurenfalk, Alva Cosmo, Otto Simonsson et al.
3 citations
People who had ever used classic psychedelics such as LSD or psilocybin showed 25% lower odds of reporting frequent bad headaches, based on data from over 11,000 British adults. The analysis controlled for many other factors, suggesting a possible protective association. This finding adds to evidence that classic psychedelics might one day be developed as preventive treatments for migraine and cluster headache, though the study cannot prove cause and effect.
Journal of psychopharmacology (Oxford, England)
February 26, 2025
Sara de la Salle, Jennifer L Phillips, Pierre Blier et al.
3 citations
A sub-anesthetic dose of ketamine, an NMDAR antagonist, produces rapid antidepressant effects in treatment-resistant major depressive disorder. In 24 patients, ketamine reduced frontal mismatch negativity (MMN) amplitude, theta event-related oscillations, and source-localized frontal generator activity immediately and 2 hours after infusion, compared to midazolam. Larger reductions in MMN measures, particularly left frontal amplitude and theta oscillations, correlated with and predicted greater early and sustained symptom improvement on the Montgomery-Åsberg Depression Rating Scale. Baseline phase-locking factor also predicted sustained response. The findings suggest that acute NMDAR blockade reduces frontal MMN, and that MMN indices may serve as non-invasive biomarkers for predicting antidepressant response to glutamatergic agents.
Journal of psychopharmacology (Oxford, England)
August 1, 2024
Luke Baxter, Cheneal Puljević, Tim Piatkowski et al.
3 citations
Among 3,340 first-time LSD users surveyed internationally, nearly all (97.7%) found the experience exciting, and adverse side effects were rare; only 17 individuals required emergency medical treatment. Although 64.1% reported feelings of fear, these were typically very mild and did not deter most from wanting to use LSD again. The authors conclude that while the recreational LSD experience is generally pleasurable and unwanted effects are uncommon, harm-reduction education remains important to prevent possible risks amid rising illicit use.
Journal of psychopharmacology (Oxford, England)
March 1, 2026
Eilidh Macnicol, Michelle Kokkinou, Maria Elisa Serrano Navacerrada et al.
2 citations
THC increases brain functional connectivity and blood flow in rats, while CBD decreases connectivity without affecting blood flow. When combined, CBD moderates THC's effects. Adult male rats received THC, CBD, a combination, or a placebo. Brain scans two hours later showed THC raised whole-brain connectivity and blood flow in cortical and subcortical regions. CBD lowered connectivity metrics. The combination produced moderate increases in both measures. THC specifically strengthened connections between the cortex and hippocampus and between the cortex and striatum, an effect reduced when CBD was present. These distinct neurophysiological profiles suggest cannabinoids induce different brain states, supporting the use of functional neuroimaging in developing cannabinoid-based therapies.
Journal of psychopharmacology (Oxford, England)
July 1, 2025
John Martin Corkery, Caroline Copeland, Fabrizio Schifano
2 citations
Diarylethylamine drugs, including diphenidine and methoxyphenidine (MXP), are dissociative substances with strong addictive potential. A systematic review of global mortality data found 48 deaths involving these drugs, with 37 occurring in the UK between 2014 and 2019. Most decedents were male (91%), White (95%), with a mean age of 37.2 years. Deaths were primarily accidental (89%) from acute drug toxicity (92%), often involving polysubstance poisoning with opioids, benzodiazepines, or stimulants. One-third of deaths involved MXP or diphenidine alone, suggesting these molecules are relatively toxic. Although diarylethylamine deaths are rare, these substances remain available, indicating ongoing risk.
Journal of psychopharmacology (Oxford, England)
June 19, 2025
Helena D Aicher, Ilhui A Wicki, Daniel Meling et al.
2 citations
A single dose of an ayahuasca-inspired DMT/harmine formulation increased mindfulness and compassion in 31 healthy participants one day after administration. The randomized, double-blind, placebo-controlled trial found significant effects on mindfulness, self-compassion, and compassion with others, with larger effects in participants who reported higher sensitivity to the drug. These results suggest the formulation may have therapeutic potential for enhancing traits relevant to mood disorders, though further research in clinical settings is needed.
Journal of psychopharmacology (Oxford, England)
June 18, 2025
Maria Bălăeţ, William Trender, Annalaura Lerede et al.
2 citations
During the COVID-19 pandemic, six common patterns of drug use emerged in a large citizen science cohort. Most drug-using groups had worse average mental health scores than drug-naive individuals at all timepoints, and those who increased their drug use saw their mental health worsen over time. However, people who used both psychedelics and cannabis showed average improvements in depression, anxiety, and overall mental health from before the pandemic to January 2022, becoming comparable to the drug-naive group. Cannabis-only users did not show this improvement; their worse mental health scores persisted. These findings suggest that beneficial effects of psychedelics on mood and anxiety may extend beyond controlled conditions.
Journal of psychopharmacology (Oxford, England)
November 1, 2024
Yi-Chun Chang, Renee E Magnan, Michael J Cleveland et al.
2 citations
Greater feeling high and liking are associated with a higher THC dose than one's average and with social use. A higher CBD dose than one's average is linked to greater liking. Solitary use shows a negative association between THC dose and disliking, while social use shows no such link. Individuals with greater cannabis problems report lower liking and higher disliking, but not feeling high, on average across use episodes. Social context plays an important role in the subjective experience of cannabis use.
Journal of psychopharmacology (Oxford, England)
June 1, 2026
Gabrielle Smith, Timothy Piatkowski, Jason Ferris et al.
1 citation
People who self-treat psychiatric conditions with unregulated drugs often use ketamine alongside other psychedelics. Among 5831 respondents to the 2020 Global Drug Survey who self-treated diagnosed psychiatric conditions, over 60% had prior psychiatric diagnoses, most commonly depression and anxiety. Those using both ketamine and other psychedelics attended festivals and clubs more often and used ketamine more frequently. Those using only non-ketamine psychedelics showed a significant reduction in ketamine use. Nearly half sought online advice before starting ketamine self-treatment, suggesting online platforms are key for harm reduction resources.
Journal of psychopharmacology (Oxford, England)
January 30, 2026
Veronica Magar, Marlena Robbins, Óscar Martín López Fernández Lobo Blanco et al.
1 citation
Indigenous Peoples have long stewarded natural psychoactive medicines through ceremony and kinship, yet their contributions are often marginalized in psychedelic science. This commentary argues for reciprocal collaboration grounded in Indigenous sovereignty, cultural rights, and governance. Drawing on traditions involving ayahuasca, psilocybin, peyote, and iboga, it illustrates how Indigenous methodologies offer critical insights for safety and efficacy. The authors call for embedding free, prior, and informed consent, equitable benefit-sharing, and Indigenous leadership in research and policy, moving beyond tokenism toward systemic change. They conclude by urging formal, transparent convening processes modeled on WHO global consultations to bring Indigenous leaders, researchers, and policymakers together.
Journal of psychopharmacology (Oxford, England)
December 1, 2025
David J Heal, Sharon L Smith, Jack E Henningfield
1 citation
This special issue of the Journal of Psychopharmacology honors Roland R. Griffiths, whose pioneering work in psychedelic research helped revive the field globally. It opens with a tribute from colleagues summarizing his contributions to neuropharmacology, psychiatry, and the therapeutic effects of psychedelics. The issue includes commentaries, reviews, and original research organized into non-clinical, clinical, and strategic/regulatory sections. Contributions from international experts provide a comprehensive resource on the current state of psychedelic research.