We read with great interest the letter submitted by Schirmer, Hofmann, and Weinmann. We thank them for their careful reading of our case report and for their thoughtful critical remarks. We fully recognize the value of clarifying methodological and interpretative issues. At the same time, we believe it is important to restate that the core conclusions of our report remain well supported by the clinical course and the toxicological and autopsy findings. This reply should be read as a postpublication clarification of the rationale underlying our interpretations. THC vs. THCA-A in the seized hashish and in gastric content The authors of the letter emphasize that, in cannabis products, THCA-A may exceed Δ9-THC and that failure to distinguish these forms could affect any quantitative reconstruction of the ingested dose. Clarification: In our article, we reported the THC percentage of the seized material (28%) as provided by the official forensic analysis (that was not performed by the authors). In real-world forensic practice, this figure is often expressed as “THC total” or Δ9-THC equivalent depending on the laboratory, and we agree that the distinction between active THC and total THC (THC + THCA-A) is relevant in principle. However, even if THCA-A constituted a substantial fraction of the product, this does not undermine our causal interpretation. The ante-mortem clinical picture (progressive neurological depression with bradypnea leading to apnea) is typical of intoxication by active cannabinoids, and we documented active THC and metabolites in biological matrices at levels consistent with acute exposure. Potential in vitro decarboxylation during gastric extraction It is suggested that solvent evaporation of gastric extracts might have induced partial conversion of THCA-A into THC, altering measured concentrations. Response: We acknowledge this as a theoretical limitation. Our evaporation conditions were controlled and not intended to promote substantial decarboxylation, but any postsampling conversion cannot be excluded entirely. Importantly, the gastric findings were not used as stand-alone proof of lethality; they were interpreted together with blood and tissue results and with the clinical trajectory. Dose estimation and LD50 extrapolation The letter questions comparing our reconstructed dose with animal LD50 values and recommends relying instead on pediatric clinical series of THC edibles. We agree that pediatric data are more directly informative where available, and we explicitly treated LD50 comparisons as only approximate. Yet the analogy with commercial edibles is not fully equivalent to our case, given the variability of resin products, the uncertainty about decarboxylation state, and the child's particular vulnerability. The overall evidentiary set remains consistent with a severe acute cannabinoid intoxication. THCA-A metabolites and hydrolysis protocol Concerns are raised that alkaline hydrolysis at 60°C could transform THCA-A metabolites into THC metabolites. Response: Our analytical approach follows standard forensic toxicology practice for cannabinoid determination in complex postmortem matrices. We do not deny that conversion phenomena are a topic of ongoing methodological discussion; nevertheless, the presence of unmodified THC in ante-mortem blood, combined with the clinical syndrome, already documents exposure to active THC irrespective of any potential contribution of THCA-A. Postmortem redistribution and THC stability The letter notes that more recent literature does not support a systematic postmortem decrease in THC and questions any inference of higher premortem levels. Clarification: We accept that postmortem behavior of THC is complex and that ante-mortem concentrations should be weighted most heavily. Our causal reasoning indeed rests primarily on the ante-mortem toxicology and on the clinical course, not on speculative adjustment of postmortem values. Low body weight We agree that a body weight of ~10 kg under 3 years is low. We did not intend to minimize this factor; rather, we consider it a further element increasing pharmacokinetic/pharmacodynamic vulnerability (mg/kg effect), which strengthens—rather than weakens—the plausibility of a fatal outcome for a given exposure. On allegedly inappropriate citations We appreciate the specific bibliographic remarks. Some references cited in the discussion may not have been the most targeted for pediatric physiology or for pH-related stability issues. Since the paper is already published, we cannot revise the reference list, but we acknowledge the point and reiterate that these secondary discussion elements do not affect the main evidentiary backbone of the case. Public health comments on regulation and packaging Our discussion aimed to highlight the epidemiological rise in availability of high tenor Cannabis and thus in risk of accidental intake; it was not meant to deny the potential protective role of regulation when appropriately designed. We agree that child-resistant packaging and clear regulation can mitigate accidental pediatric exposures; however, when there is a danger, the risk cannot be zero; the higher the frequency of having Cannabis in our homes, the higher the risk. Additional Clarification on Gastric THC Findings and the Seized Hashish We would like to add a crucial interpretative point. In our report, the gastric THC finding was used only as an indicative element to support the logical exclusion of an inhalational route (i.e., smoking). The presence of cannabinoid material in the stomach, together with the clinical scenario and blood toxicology, made an oral intake more plausible than a purely respiratory exposure. We did not use gastric concentration to claim a precise ingested dose. Furthermore, we cannot state with certainty that the specific hashish seized in the home was the same material ingested by the child. The seized product was analyzed because it represented what was available in the environment, but we do not know whether that exact specimen—or another hashish preparation—was consumed. In forensic terms, each cannabis resin product is a case in itself, with wide variability in THC/THCA-A ratio, potency, and prior decarboxylation state. For this reason, any quantitative back-calculation from a single seized sample must be considered cautious and contextual. Conclusion To summarize, we welcome several of the correspondents' points as useful methodological clarifications (THC vs. THCA-A distinctions, possible in vitro conversion, and limits of quantitative extrapolation). Yet, we respectfully reject the implication that these issues overturn the central conclusion. The child showed a clinical pattern compatible with acute active-cannabinoid toxicity, ante-mortem blood and postmortem matrices documented active THC exposure, and no alternative cause sufficiently explained the fatal respiratory depression. We thank the correspondents again for the opportunity to clarify these aspects for readers. Sincerely, (On behalf of all Authors) Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.
Favretto et al. (Wed,) studied this question.