Rapid and sustained reduction of treatment-resistant PTSD symptoms after intravenous ketamine in a real-world, psychedelic paradigm

Post-traumatic stress disorder (PTSD) is a chronic, disabling condition characterised by intrusive memories, avoidance, negative mood and heightened arousal. Conventional therapies—trauma-focused psychotherapies and pharmacotherapy (primarily SSRIs)—have substantial limitations: many patients do not achieve remission, dropout rates can be high, and pharmacological benefits often take weeks to appear. Interest in rapid-acting treatments has therefore increased, and ketamine, an N-methyl-D-aspartate (NMDA) antagonist with rapid antidepressant effects at subanaesthetic doses, has been investigated for PTSD with mixed findings across trials. Macconnel and colleagues set out to examine clinical outcomes after delivering intravenous ketamine within a treatment model that intentionally incorporated elements common to psychedelic-assisted therapies—psychological preparation, sensory immersion (music and eye shades), integration sessions and supportive staffing—at a real‑world clinic. The study reports a retrospective chart review of patients treated at a single clinic and aims to assess change in PTSD symptoms measured by the PCL-5 and to explore moderators such as concomitant psychotherapy, demographic factors and prior medication trials in this psychedelic-style delivery context.

This study is a retrospective chart review of outpatients treated at Nushama Psychedelic Wellness Center between September 2021 and October 2023. Institutional review board oversight at the University at Albany deemed the work exempt because analyses used de-identified, pre-consented clinical records. Clinic screening excluded individuals with psychosis, current mania or uncontrolled medical conditions. Extracted chart variables included demographics, trauma type, diagnoses, PCL-5 scores, past medications, psychotherapy history, suicidal ideation history, number of infusions and infusion dosages. Treatment procedures combined medical monitoring with psychedelic-style psychological support. A multidisciplinary team (physician, nurse practitioner, nurse, medical assistant and integration coach) assessed and monitored patients. Integration coaches spent about 15–30 minutes with patients both before and after each infusion. Sessions included eye shades and evocative music, and the usual infusion schedule began with twice-weekly treatments for three weeks followed by a tailored maintenance schedule. Initial ketamine dosing typically started at 0.8 mg/kg infused over 60 minutes with patient‑guided escalation by 0.1–0.2 mg/kg in subsequent sessions to reach a higher subanaesthetic, “psychedelic” dose range. Usual precautions included withholding certain medications (lamotrigine for 24 hours, stimulants, benzodiazepines and gabapentin on the morning of infusion) and offering antiemetics where needed. Blood pressure was monitored and treated if necessary. For outcome measurement and analysis, the clinic used the PTSD Checklist for DSM-5 (PCL-5). Researchers screened 337 patients who completed an intake PCL-5; 257 started ketamine treatment, 170 of whom had intake scores >31, and 117 of those 170 completed at least one subsequent PCL-5 and comprised the analytic sample. A reduction of 10 points or more on the PCL-5 defined clinically meaningful response; remission was defined as a PCL-5 score of 33 or lower at last measurement. A repeated-measures analysis of variance (ANOVA) compared baseline (FirstPCL) and follow-up (LastPCL) scores while adjusting for covariates: age, gender, days between PCL assessments, number of past psychiatric medication trials, concomitant psychotherapy at intake, current suicidal ideation at intake and prior suicidal ideation. Normality of residuals was assessed with Shapiro–Wilk tests and Q–Q plots. Analyses used SPSS v29, with two‑tailed p < 0.05 as the threshold for statistical significance.

The final sample comprised 117 patients (72.6% female) with a mean age of 41.9 years (±13.1). Most patients (96.6%) had at least one psychiatric comorbidity and had tried multiple medication trials previously (mean 4.68 ± 1.97). Between the first and last recorded PCL-5, patients received on average 4.79 ± 1.7 ketamine infusions (range 2–9, mode 3). The mean dose across infusion series was 1.28 mg/kg ± 0.20 (range 0.50–2.40 mg/kg); the highest administered dose averaged 1.62 mg/kg ± 0.27. On the primary outcome, mean PCL-5 scores fell markedly from 52.39 (SD = 11.90) at intake to 29.42 (SD = 16.52) at the last recorded assessment, yielding a standardised pre–post effect size of approximately Cohen’s d = 1.60. The repeated-measures ANOVA showed a significant main effect of time, F(1,103) = 10.737, p = .001, partial η² = .094, and multivariate tests likewise supported a significant time effect (reported F = 196.651, p < .001, partial η² = .656). The pairwise mean difference was −23.757 (95% CI reported in the paper) and p < .001. Using the predefined thresholds, 88 of 117 patients (75.21%) achieved a clinically meaningful improvement (≥10‑point PCL reduction) and 72 of 117 (61.54%) met the study’s remission criterion (PCL-5 ≤ 33) at their final measure. Time between first and last PCL varied widely (7–314 days; mean 55 ± 60 days). Safety and retention findings indicated no serious adverse events; occasional nausea was treated with ondansetron or meclizine and blood pressure elevations were managed per protocol. Of the 117 analysed patients, 111 (94%) completed the full course of ketamine treatment recorded in clinic charts. The investigators reported an overall dropout of 35% when considering the broader cohort that began treatment (170 with intake PCL >31 to 111 finishing), and noted scheduling and cost as common non‑medical reasons for discontinuation. Regarding moderators, no significant interactions were found for time with age, gender, days between assessments, psychiatric medication count, current suicidal ideation or past suicidal ideation. Concomitant psychotherapy at intake did interact with time, F(1,103) = 4.957, p = .028, partial η² = .046, indicating greater PCL reductions among those already engaged in external psychotherapy. An independent-samples t-test showed patients with an external psychotherapist (n = 80) had larger mean PCL reductions (M = −25.3, SD = 16.7) than those without (n = 37; M = −17.8, SD = 19.9), t(115) = −2.11, p = .037, Cohen’s d ≈ −0.42. Between-subjects tests also associated age with average PCL scores, F(1,103) = 8.175, p = .005, partial η² = .074. The extracted text did not provide item‑level symptom breakdowns or standardised measures of acute subjective (mystical‑type) experiences for the sample.

Macconnel and colleagues interpret the findings as preliminary evidence that intravenous ketamine delivered within a psychedelic‑style care model preceded large and sustained reductions in self-reported PTSD symptoms in this real‑world outpatient sample. They highlight that the treatment combined moderately high subanaesthetic ketamine doses, sensory immersion (music and eye shades), preparation and integration sessions and a supportive clinical team—elements the authors identify as likely contributors to outcome variability seen across prior ketamine trials. The apparent moderating effect of concomitant external psychotherapy is noted as an initial signal that adjunctive psychological care may enhance clinical benefit. The authors contrast their results with mixed findings from prior randomised trials and suggest that contextual factors—treatment setting, dose range and psychological supports—might partly explain heterogeneity in ketamine PTSD outcomes. They further propose several possible mechanisms informed by existing literature: neuroplastic enhancement of psychotherapy, exposure/priming of trauma memories around dosing, and therapeutic effects mediated by mystical‑type or insight experiences, though the current dataset did not systematically capture subjective experience measures. Key limitations that the authors acknowledge include the retrospective design, absence of a placebo or control group, heterogeneity in follow-up timing, lack of standardised measurement of acute subjective effects, and limited generalisability given a sample skewed toward female patients with socioeconomic resources and incomplete ethnicity data. They caution that these constraints prevent causal attribution of effects to ketamine and call for randomised, controlled and dismantling studies to parse the contributions of pharmacology, dose and psychological context. Finally, the authors observe that ketamine’s practical advantages—affordability as a generic drug, brief 60‑minute infusion format and compatibility with concomitant psychiatric medications—may support broader access, but emphasise that rigorous prospective trials are necessary to validate and extend these real‑world findings.