Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2018
Allison A. Feduccia, Michael C. Mithoefer
213 citations
MDMA-assisted psychotherapy for PTSD has advanced to Phase 3 trials and received FDA Breakthrough Therapy designation. Phase 2 trials showed it is effective and safe, with 68% of participants achieving durable remission from PTSD. This review explores how MDMA may work by enhancing memory reconsolidation and fear extinction. MDMA boosts serotonin, norepinephrine, dopamine, oxytocin, cortisol, and BDNF, which modulate emotional memory circuits. It reduces activity in fear-related brain regions like the amygdala and insula while increasing amygdala-hippocampus connectivity, potentially allowing reprocessing of traumatic memories. The authors suggest a neurobiological rationale for MDMA's large effect sizes in treating PTSD.
Progress in neuro-psychopharmacology & biological psychiatry
February 2, 2018
Simon Reiche, Leo Hermle, Stefan Gutwinski et al.
125 citations
Anxiety and depression are common in people with life-threatening diseases, harming quality of life and prognosis. Serotonergic hallucinogens like LSD and psilocybin were first studied in the 1960s, and interest has recently revived. A systematic review of clinical trials from 1960 to 2017 identified 11 eligible trials with 445 participants: 7 on LSD (323 participants), 3 on psilocybin (92), and 1 on DPT (30). Four more recent randomized controlled trials (104 participants) had higher methodological quality than earlier studies. Evidence supports that these substances reduce anxiety and depression in patients with life-threatening diseases, with anecdotal reports of improved quality of life and reduced fear of death. Side effects were low in studies following safety guidelines.
Progress in neuro-psychopharmacology & biological psychiatry
January 4, 2016
Alicia L Danforth, Christopher M Struble, Berra Yazar-Klosinski et al.
110 citations
A clinical trial of MDMA-assisted therapy for social anxiety in autistic adults began in spring 2014. MDMA has been administered to over 1133 individuals in research without unexpected serious adverse events requiring expedited FDA reporting. The authors argue that established safety parameters justify developing MDMA-assisted interventions to help autistic adults improve social adaptability. MDMA, like classic psychedelics, can catalyze lasting openness and introspection without ongoing administration, reducing adverse event frequency and improving the risk/benefit ratio compared to daily medications. Clinicians could employ new treatment models using one to several MDMA sessions within supportive psychotherapy for social anxiety or similar distress.
Progress in neuro-psychopharmacology & biological psychiatry
December 3, 2012
John M Corkery, Emma Durkin, Simon Elliott et al.
105 citations
5-MeO-DALT is a psychoactive tryptamine sold online as a 'research chemical' with little scientific study. A review of available knowledge and a first reported death involving the substance is described: a man in his mid-20s died in mid-2010 after being hit by a lorry while under the influence of 5-MeO-DALT, as concluded by the coroner. The authors call for documentation of other cases to build an evidence base.
Progress in neuro-psychopharmacology & biological psychiatry
August 1, 2003
Mirna Bainy Leal, Kátia Michelin, Diogo Onofre Souza et al.
50 citations
Ibogaine, a noncompetitive NMDA receptor antagonist, inhibits the behavioral signs of morphine withdrawal in mice. Jumping, a key withdrawal behavior, was reduced by 64.2% and 96.9% with 40 and 80 mg/kg of ibogaine, respectively, and by 67.3% and 97.7% with the NMDA antagonist MK-801. Combining lower doses of both drugs produced a 94.7% inhibition, similar to higher doses of either alone. Ibogaine and MK-801 also blocked NMDA-induced jumping when given 30 minutes before, but not 24 hours before, in non-addicted mice. No changes in NMDA receptor binding were observed across treatment groups, suggesting a functional, transient alteration of NMDA receptors underlies ibogaine's effect on withdrawal.
Progress in neuro-psychopharmacology & biological psychiatry
June 8, 2024
Han Qin, Miao Yu, Nianjiao Han et al.
27 citations
Esketamine, a drug approved for treatment-resistant depression, may also treat postpartum depression (PPD) and reduce depression risk in offspring. In a mouse model of chronic unpredictable mild stress during pregnancy, both mothers with PPD and their adult offspring showed anxiety- and depression-like behaviors. Injecting esketamine into postpartum mice improved these behaviors: it enhanced exploration in unfamiliar environments, increased preference for sucrose, and restored impaired BDNF/AKT/mTOR signaling in the frontal lobe and hippocampus. The findings suggest esketamine has potential for treating PPD and lowering the incidence of depression in the next generation.
Progress in neuro-psychopharmacology & biological psychiatry
August 30, 2024
Antonella Campanale, Antonio Inserra, Stefano Comai
18 citations
The kynurenine pathway (KP) plays a crucial role in the altered gut-brain axis balance in severe mental illness (SMI), including depression, bipolar disorder, and schizophrenia, as well as in cardiometabolic comorbidities. Serotonergic psychedelics may hold therapeutic potential by modulating the KP, either directly through influencing rate-limiting enzymes and tryptophan levels, or indirectly via effects on the gut microbiome, metabolism, and immune system. Preliminary evidence suggests psychedelics improve outcomes in preclinical models of obesity, metabolic syndrome, and vascular inflammation. However, the mechanisms and outcomes remain largely unknown, and concerns about side effects in specific SMI cohorts require further investigation.
Progress in neuro-psychopharmacology & biological psychiatry
July 13, 2023
Dimitri Daldegan-Bueno, Natalia Maria Simionato, Vanessa Manchim Favaro et al.
18 citations
Ayahuasca, a psychedelic brew, is being studied for therapeutic uses. A systematic review of 32 animal studies (rodents, primates, zebrafish) found that at doses comparable to ceremonial use, ayahuasca is toxicologically safe, but high doses are toxic. Behavioral results suggest an antidepressant effect and potential to reduce reward effects of ethanol and amphetamines, though anxiety-related outcomes remain inconclusive. Ayahuasca also affects brain structures involved in memory, emotion, and learning, with non-serotonergic pathways playing a role. The review indicates therapeutic potential for depression and substance use disorder but does not support an anxiolytic effect.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2024
Mesud Sarmanlu, Kim P C Kuypers, Patrick Vizeli et al.
17 citations
MDMA-assisted psychotherapy for PTSD shows promising safety and efficacy in clinical trials, but its underlying mechanisms are not well understood. This review examines preclinical and clinical evidence suggesting that MDMA's effects on memory processes—specifically fear extinction and fear reconsolidation—may contribute to the treatment's success. The authors integrate findings from cognitive psychology and psychopharmacology to support this view and provide recommendations for future research.
Progress in neuro-psychopharmacology & biological psychiatry
February 1, 2002
Linda A Parke, Page Burton, Robert V Mcdonald et al.
17 citations
Ibogaine reduces both the physical signs and the motivational distress of opioid withdrawal in rats. In two experiments, rats given morphine only twice and then injected with naloxone to trigger withdrawal showed less aversion to a place associated with withdrawal and fewer physical withdrawal reactions when they had received ibogaine four hours earlier, compared with rats given saline. The results suggest ibogaine can interfere with withdrawal even after limited opioid exposure, targeting not just somatic symptoms but also the motivational aspects that make withdrawal distressing.
Progress in neuro-psychopharmacology & biological psychiatry
July 1, 1996
T Luxton, L A Parker, S Siegel
13 citations
Ibogaine, a proposed anti-addictive agent, does not reduce the expression of a previously established morphine-induced place preference in rats. Single injections of 40 mg/kg ibogaine given 24, 12, or 4 hours before testing, or 80 mg/kg given 24 hours before, failed to interfere with the conditioned preference. Two injections of 40 mg/kg at intervals of 48 and 24 hours or 24 and 4 hours before testing also had no effect. Ibogaine appears incapable of attenuating the expression of a one-trial morphine place preference once it has been established.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
S Chiappini, A Guirguis, N Schifano et al.
12 citations
Intranasal esketamine, the S-enantiomer of ketamine, is approved with oral antidepressants for treatment-resistant depression and offers rapid absorption. Analysis of FDA Adverse Events Reporting System data up to May 2024 compared urological safety profiles of esketamine, ketamine, and several other antidepressants and antipsychotics. Risperidone had the highest total adverse drug reactions (107,418) and serious cases (71,515), including acute kidney injury and urinary incontinence. Esketamine and ketamine were associated with lower urinary tract symptoms and nephrolithiasis. Disproportionality analysis showed ketamine had higher odds of renal and urinary disorders, while esketamine had lower or comparable odds, suggesting a relatively favorable tolerability profile for esketamine.
Progress in neuro-psychopharmacology & biological psychiatry
April 20, 2024
Juliana Marino Maia, Bruna Stefane Alves De Oliveira, Luiz G S Branco et al.
11 citations
Psychedelics, also known as serotonergic hallucinogens, alter perception, mood, and cognitive functions by activating 5-HT2A receptors. They show potential therapeutic effects for disorders such as depression, addiction, anxiety, and post-traumatic stress disorder. While clinical studies report effectiveness with minimal side effects, the relationship between these drugs and human brain modulation remains poorly understood. This article reviews promising findings on the putative therapeutic effects of psychedelics.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
Agnieszka Bysiek, Adam Wojtas, Izabela Szpręgiel et al.
10 citations
Psilocybin increased the release of dopamine, noradrenaline, serotonin, and acetylcholine in the frontal cortex of rats, with the 0.3 mg/kg dose producing the weakest effect. Glutamate release rose only for the first two hours after injection then fell, while γ-aminobutyric acid release increased. Unlike the 5-HT2A receptor agonist 25I-NBOMe, psilocybin did not cause hallucinogenic wet dog shakes or disrupt sensorimotor gating. It showed an anxiolytic effect in the light dark box test one hour after administration, transiently raised serum corticosterone, altered hypothalamic neurotransmitter turnover, and did not produce oxidative DNA damage in the frontal cortex or hippocampus.
Progress in neuro-psychopharmacology & biological psychiatry
July 25, 2025
Kiana Askariyan, Mohammad Taghi Joghataei, Samaneh Dehghan et al.
9 citations
Psychedelic-assisted psychotherapy, using compounds like psilocybin, LSD, MDMA, and ketamine, represents a significant shift in mental health treatment. These agents modulate serotonin receptors and brain network connectivity, with each having distinct pharmacological profiles: psilocybin and LSD share serotonergic pathways but differ in receptor specificity, MDMA offers empathogenic properties, and ketamine provides rapid antidepressant action. Recent FDA breakthrough therapy designations for psilocybin and MDMA signal growing evidence-based acceptance. However, the field faces challenges including methodological limitations, regulatory barriers, and ethical concerns. This narrative review synthesizes historical developments, mechanisms, and clinical outcomes, calling for rigorous research and diverse patient cohorts to integrate psychedelics with psychotherapy effectively.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Emma I Kopra, Jenni Penttinen, James J Rucker et al.
9 citations
Between 1997 and 2022, only 28 deaths in England, Wales, and Northern Ireland involved psychedelic drugs, with 75% directly implicated and 25% potentially implicated. Most deaths were accidental (86%), involved multiple drugs (68%), and occurred in people under 30 (82%). The most common psychedelics were LSD (39%), psilocybin (21%), and NBOMes (18%). Polysubstance use was the most frequent contributing factor (82% of cases), followed by unsafe physical environments. While psychedelic-related deaths are very rare compared to other recreational drugs, their unpredictable effects create unique risks, often compounded by polydrug use.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Wanting Feng, Chengfeng Chen, Yexian Zeng et al.
9 citations
A meta-analysis of 49 clinical trials with 3,982 participants found that a single dose of ketamine significantly reduces suicidal ideation within 4 hours, with the strongest effect at 24 hours, and benefits lasting up to one month. Repeated doses also produced similar anti-suicidal effects at treatment endpoint and beyond one month. There was no statistical difference in efficacy or duration between single and multiple doses. The analysis suggests that even a single ketamine administration may provide a rapid and lasting reduction in suicidal thoughts.
Progress in neuro-psychopharmacology & biological psychiatry
December 20, 2024
Veronica Grasso, Gilmar Gutierrez, Najat Alzbeidi et al.
9 citations
Unipolar treatment-resistant depression is linked to cognitive impairment. A systematic review of fourteen studies found that intravenous ketamine treatment shows promise for improving neurocognitive function in these patients, including processing speed, working memory, verbal and visual memory, executive function, attention, emotional processing, and auditory verbal episodic memory. One study reported negative effects on verbal memory. The evidence had a low risk of bias, but limitations include small sample sizes, heterogeneity, and a predominantly female, Western, and Caucasian population, constraining generalizability. Further research is needed on long-term effects and confounders.
Progress in neuro-psychopharmacology & biological psychiatry
December 20, 2024
Guilherme Lodetti, Rafael Mariano de Bitencourt, Eduardo Pacheco Rico
9 citations
Alcohol is a harmful drug, and dependence on it is often resistant to treatment, with no completely effective model available. Classic psychedelics like LSD, psilocybin, and ayahuasca have shown promising pharmacotherapeutic effects in treating treatment-resistant conditions, including addiction, particularly alcohol dependence. This narrative review examines emerging research on psychedelics for alcohol use disorder treatment. These substances may treat addiction by modulating neuroplasticity in the brain. Since serotonergic psychedelics do not produce physical dependence or withdrawal symptoms with repeated use, they are considered promising treatment options. However, great inter-individual variability exists in the duration of effects, and further studies using different doses and protocols are needed.
Progress in neuro-psychopharmacology & biological psychiatry
February 1, 1999
S Helsley, R A Rabin, J C Winter
9 citations
In rats trained to recognize ibogaine's effects, activating 5-HT2C receptors with MK-212 or mCPP produced ibogaine-like responses (79.6% and 76.4% of the time), and this substitution was blocked by the 5-HT2C antagonist metergoline. However, metergoline did not block ibogaine itself, indicating that while ibogaine may activate 5-HT2C receptors, this action is not necessary for its distinctive cue. Neither a 5-HT3 agonist nor antagonist, nor a 5-HT1A agonist or antagonist, substituted for ibogaine, and a 5-HT1A antagonist did not block ibogaine's effects. Thus, 5-HT1A and 5-HT3 receptors appear uninvolved in ibogaine's discriminative stimulus.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo et al.
7 citations
A systematic review compared metformin and psilocybin as potential prophylactic treatments for Parkinson's disease. Metformin may slow disease progression by reducing oxidative stress and α-synuclein damage in mitochondria. Psilocybin may repair damaged neurons through 5-HT2A receptor activation, increasing brain-derived neurotropic factor and reducing α-synuclein accumulation. The review calls for further research into off-label metformin use and serotonergic compounds for neurodegenerative disease prevention.
Progress in neuro-psychopharmacology & biological psychiatry
July 5, 2025
Verina Guirguis, Sanvi Korsapathy, Francesca Pupillo et al.
6 citations
Nasal esketamine, a rapid-acting antidepressant, alters brain network activity by reducing top-down control and shifting the excitation/inhibition balance toward excitation. In eight individuals with major depressive disorder, EEG recordings before and up to 90 minutes after esketamine administration showed decreased frontoparietal alpha power and central beta power, along with increased frontal midline delta and low gamma power. The aperiodic exponent decreased, indicating cortical disinhibition. These neural changes correlated with increased subjective ratings of highness and happiness and decreased tension, linking the drug's neurophysiological effects to the immediate subjective experience.
Progress in neuro-psychopharmacology & biological psychiatry
April 2, 2025
C J Healy, Aaron Frazier, Stephen Kirsch et al.
6 citations
Adults with histories of childhood maltreatment who used psychedelic drugs with therapeutic intent at ceremonies or raves showed significant improvements in PTSD symptoms, complex PTSD symptoms, trait shame, social connectedness, and general connectedness from before the experience to two months afterward. The size of these improvements was large. Changes in these outcomes were linked to specific aspects of the acute psychedelic experience, such as subjective effects. The findings suggest that the social and psychological context of group psychedelic use may contribute to lasting mental health benefits for this population.
Progress in neuro-psychopharmacology & biological psychiatry
January 10, 2025
Juliana Lima Constantino, Jens H van Dalfsen, Sara Massetti et al.
6 citations
A systematic review of nine studies found that psilocybin consistently decreases interleukin-6, C-reactive protein, and eosinophils, and increases cortisol, prolactin, oxytocin, thyroid-stimulating hormone, adrenocorticotropic hormone, brain-derived neurotrophic factor, and free fatty acids in healthy participants. These biomarker changes align with preclinical evidence and suggest psilocybin may have beneficial effects on biological processes involved in major depressive disorder. However, results are preliminary due to the small number of studies and exclusive use of healthy volunteers. Further research with clinical populations, larger samples, and longer follow-up is needed before drawing firm conclusions.
Progress in neuro-psychopharmacology & biological psychiatry
July 13, 2025
Jasmine Jade Butler, Margherita Virgili, Giuseppe Di Giovanni et al.
5 citations
Serotonergic psychedelics disrupt the normally organized pattern of correlations among serotonin, dopamine, and noradrenaline concentrations across 28 brain regions in mice during forced exploratory behavior. Both the 5-HT2A receptor agonist TCB-2 and the antagonist MDL-100,907 decreased correlations between regional neurochemical levels, while combining them partially restored those correlations. TCB-2 dose-dependently reduced serotonin turnover across all brain regions and dopamine turnover in the striatum, and enhanced markers of dopamine and noradrenaline systems in the anterior cingulate cortex. MDL-100,907 alone had minimal effects on monoamine levels but reduced TCB-2-induced head twitches and increased monoamine concentrations in the anterior cingulate cortex without affecting the serotonin turnover decrease. The functional connectivity of monoaminergic systems during exploration is highly sensitive to modulation through 5-HT2A receptor activation or blockade.