Research Square
March 31, 2026
Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.
A compound derived from ibogaine, oxa-noribogaine, reduces alcohol consumption in rats by strengthening learning from negative drinking outcomes. It produces sustained decreases in alcohol intake and relapse-like drinking, matching or exceeding ibogaine's efficacy without detectable motor or cardiac side effects. These effects involve transient changes in prefrontal brain activity, lasting alterations in glutamatergic signaling after aversion-related learning, and normalization of neurotrophic signaling in cortico-striatal circuits. The results generalize across multiple models, genetically diverse animals, and independent study sites, identifying oxa-noribogaine as a promising treatment candidate for alcohol use disorder.
International Review of Psychiatry
March 31, 2026
Anne Anne Lingford-Hughes
Alcohol and drug addictions impose heavy burdens on individuals and society, a situation likely to persist. Addiction psychiatry in the UK faces challenges including under-investment, reduced psychiatric input in the workforce, and stigma, while needing better integration with mental and physical health services. Psychological therapies remain the mainstay of treatment, with few new pharmacological options emerging in recent decades. Emerging approaches such as novel pharmacological targets, psychedelics, and neuromodulation show promise but require larger, better-designed trials in clinically representative populations. Neuroimaging is highlighted as a key tool for understanding mechanisms and accelerating treatment development. Driving innovation requires senior leadership, robust research infrastructure, global collaboration, reduced stigma, and a research-capable workforce.
Psychiatry and Clinical Psychopharmacology
March 30, 2026
Kenji Hashimoto, Feyza Arıcıoğlu, Mesut Çetin
Classical serotonergic psychedelics—psilocybin, DMT, 5-methoxy-DMT, and LSD—can produce rapid and sometimes durable improvements in mood under supervised conditions. The review synthesizes clinical evidence for these compounds in depression and related disorders, noting challenges such as small sample sizes, expectancy effects, and limitations in maintaining blinding. Mechanistic frameworks extend beyond 5-HT2A receptor activity, involving multiple serotonergic subtypes, glutamatergic modulation, synaptic plasticity, and brain network reorganization. Preclinical and clinical evidence points to neurotrophic mechanisms, particularly BDNF-TrkB signaling, as contributors to sustained effects. Acute mystical-type experiences may enhance response but are not strictly required, suggesting plasticity-promoting mechanisms can be partially dissociated from hallucinogenic effects. Peripheral contributions, including gut-brain axis interactions, may influence treatment durability.
PsyArXiv
March 26, 2026
preprint
An open-label extension of a Phase II randomized controlled trial examined the safety and efficacy of psilocybin-assisted therapy for alcohol use disorder. Participants who had received either psilocybin or placebo in the main trial were offered two open-label psilocybin sessions. The treatment was well tolerated, with no serious adverse events attributed to psilocybin. Heavy drinking days decreased substantially from baseline, and the reduction was sustained through the 32-week follow-up. The findings suggest that psilocybin-assisted therapy may produce durable reductions in alcohol consumption among individuals with alcohol use disorder.
Behavioral Sciences
March 24, 2026
J. Richard Kendrick, Ghonwa Ahmad, Audrey Wood et al.
An analysis of 500 high-engagement threads (12,852 comments) from the r/TherapeuticKetamine subreddit found that people primarily use ketamine for mood-related concerns (53%). Positive effects, most often improved emotional well-being (65%), were reported alongside adverse effects that were predominantly psychological or mood-related (56%). 70% of reported doses exceeded 149 mg, indicating a trend toward higher doses. Intravenous administration (40%) and sublingual troches (23%) were the most common routes. Concurrent use of prescribed psychotropics, cannabis, and psychedelics was also reported. The findings suggest substantial heterogeneity in individual experiences and underscore the importance of clinical monitoring for addiction potential and drug interactions.
Frontiers in Neuroscience
March 23, 2026
Malkanthi Evans, Andrew Charrette
Psychedelic therapies show promise for treatment-resistant depression, PTSD, anxiety, and substance-use disorders, but significant methodological and ethical challenges remain. Issues include inadequate masking in trials, expectancy effects, and reproducibility concerns. Early-phase studies indicate rapid symptom improvement, supported by neuroimaging insights, but large multisite trials with harmonized protocols and long-term follow-up are still needed. The role of psychotherapy in psychedelic-assisted treatment is debated; some developers include only psychological support. Subjective aesthetic experiences—perceptual richness, emotional resonance, beauty—are strongly linked to emotional breakthroughs and clinical outcomes. Neuroimaging shows DMT modulates brain connectivity in socio-emotional circuits. Psilocybin promotes emotional openness and cognitive flexibility. Future research must clarify mechanisms, optimize protocols, and ensure safety and generalizability.
Preprints.org
March 17, 2026
Yuki Ueda
preprint
Oxytocin, a hormone involved in social bonding, may help create the brain conditions for non-dual awareness—a state of consciousness without intentional content. The review proposes that oxytocin down-regulates the amygdala and modulates the Default Mode Network, reducing self-referential processing and supporting ego-dissolution. This neuro-chemical substrate could explain how contemplative traditions achieve pure consciousness. The authors discuss ethical concerns about using neuro-pharmacology to influence meditative states and suggest future clinical applications for psychiatric disorders involving rigid self-narratives.
Frontiers in Pharmacology
March 16, 2026
Alessandra Linardi, Ariadiny Lima Caetano, Rodrigo Portes Ureshino
Scientific interest in psychedelic substances has revived, offering new perspectives on treating neuropsychiatric and neurological disorders. Psychedelics induce neuroplasticity and alleviate symptoms of depression, anxiety, PTSD, and neurodegenerative diseases like Alzheimer's and Parkinson's. A review of six abused recreational drugs—methamphetamine, cocaine, synthetic cathinones, ketamine, nitrous oxide, and heroin—shows they share convergent neurotoxic mechanisms involving oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. Original research demonstrates that social hierarchy modulates methamphetamine reinforcement in rats and is associated with distinct phosphoproteomic signatures in the nucleus accumbens, with HDAC4 phosphorylation differing between dominant and subordinate rats. A mini-review discusses trace amine-associated receptors, particularly TAAR1, as potential therapeutic targets for anxiety and depression.
Pharmacological Reports
March 11, 2026
1 citation
People with both substance use disorders and treatment-resistant depression are more likely to respond to ketamine, which is effective for depression but also has misuse potential. The authors contrast a biological mechanism with a possible expectancy effect to explain this link, and advise weighing risks and benefits when using ketamine for these patients.
Healthcare
March 3, 2026
Paul Lie, Titus Lie, Madeleine Nguyen et al.
1 citation
Suicide rates are rising, and standard antidepressant medications (SSRIs) take 2–6 weeks to work, leaving a 1–3 month danger zone of high risk. Ketamine, a fast-acting NMDA receptor antagonist, works through the mTORC1 pathway to relieve depressive symptoms much more quickly, potentially eliminating this lag. This review proposes a hypothetical Bridge Protocol using a controlled, supervised subanesthetic dose of ketamine in a clinical setting, which the literature suggests has low addiction risk. However, the framework remains untested, and rigorous longitudinal studies are needed before widespread adoption.
SVOA Medical Research
March 2, 2026
Olumuyiwa A. Bamgbade, Olumide O. Asaolu, Daniel O. Bamgbade et al.
In a small group of 20 adults with chronic pain and substance misuse, regular monthly injections of a low dose of ketamine (0.25 mg/kg) combined with lidocaine and magnesium nerve blocks were associated with improvements in pain, mood, and substance dependence. Opioid misuse was the most common category (45% of patients), followed by benzodiazepines, cocaine, and kratom. After repeated treatments, all patients showed reduced substance misuse, pain scores dropped from severe to moderate, depression scores (PHQ-9) improved from moderately severe to mild, and dependence severity reached satisfactory levels. The findings suggest ketamine-based therapy may help manage both chronic pain and substance misuse together.
BMJ Open
March 1, 2026
Christina Mcanulty, Philippe Lavoie, Samuel Cyr et al.
A new treatment combining ketamine infusions with acceptance and commitment therapy (ACT) may be feasible for people who have both alcohol use disorder and treatment-resistant depression. In an open-label trial at a Montreal hospital, 30 participants will receive six ketamine infusions plus eight weekly therapy sessions, either in person or online. The study primarily tests whether the combined approach is practical and acceptable by measuring completion rates, safety, and data quality. Exploratory measures will track changes in depressive symptoms, alcohol use, and quality of life. Some participants will also be interviewed about their experiences.
Psychedelic medicine (New Rochelle, N.Y.)
March 1, 2026
Veronica Szpak, Samuel Maddams, Amanda Kim et al.
Adults with opioid use disorder who have survived injection-related infections generally support psychedelic-assisted therapy as a treatment for substance use disorders, but they also express concerns. In interviews with 17 participants, common supportive themes included that hospitalization helped them recognize the severity of their disorder, that psychedelic-assisted therapy could foster insight and openness to recovery, and that professional monitoring during sessions was reassuring. Participants also valued addressing underlying mental health issues and the role of spirituality. Concerns centered on the possibility of a "bad trip," adverse effects, relapse risk, and misuse of psychedelics. Further research is needed, especially when standard medications have failed.
The Nursing clinics of North America
March 1, 2026
Amanda Canada
Posttraumatic Stress Disorder (PTSD) and Alcohol Use Disorder (AUD) frequently co-occur, leading to worse outcomes and higher relapse rates. Ketamine can produce rapid and lasting reductions in PTSD symptoms and AUD relapse. Prazosin effectively treats PTSD-related nightmares and may lower alcohol consumption in people with high autonomic reactivity. Because these drugs work through complementary mechanisms—modulating glutamatergic transmission and reducing noradrenergic hyperactivity—combining them may improve stabilization, readiness for trauma-focused therapy, and broader symptom control. Although this combination has not been tested in clinical trials, it warrants nurse practitioner-led research to evaluate safety, efficacy, and integration into multidisciplinary care.