Catalepsy is a biological state in which the person lies motionless, in apparent death without vital signs; however, they are in a conscious state that can vary due to reflex actions. Although the symptoms of catalepsy are similar to that of apparent death, the recordings of the electrical signal of the heart with an electrocardiogram (ECG) will be the definitive proof that will allow death to be certified. In the film he confirms that the physician’s expertise fails due to the absence of an electrocardiography during the acute episode of catalepsy. The state of apparent death induced by the voodoo drug drastically reduces breathing, reflex stimuli, blood pressure and pulse with rates so low that they are confused with clinical death. Drugged patients show syncope due to a clear clinical case of orthostatic hypotension², which is defined as a drop of ≥20 mmHg in systolic blood pressure and/or ≥10 mmHg in diastolic blood pressure within 3 minutes of active standing. After tilt-induced syncope, blood pressure generally recovers rapidly after returning to the horizontal position^{3, 4}. However, in some patients, hemodynamic recovery is delayed, a condition recently termed “prolonged postfainting hypotension”. The mechanism is believed to be mediated by a delay in the recovery of cardiac output as a consequence of increased vagal flow⁴, rather than exaggerated peripheral vasodilation and sympathetic withdrawal. Durand’s survival in the face of prolonged hypotension is because he was in a horizontal position, allowing blood to be easily pumped in the same plane.

Complementation with recordings of the brain’s electrical activity by electroencephalogram (EEG) would have helped reduce these errors. A clinical study with animals demonstrates that catalepsy induced by another drug, morphine, consists of two complementary⁵, but opposite extreme behaviors (rigid immobility and sudden locomotor bursts), each of which can be controlled by different kinds of external stimuli. Phasic (discrete) stimulation produces behavioral and/or EEG activation, however, in a very similar way to the resurrected Durand, when the stimuli involving pain and/or nociceptive skin pressure are tonic (continuous), the EEG deactivation induced by morphine and behavioral immobility, even to the point of stimulation-linked reversible coma. Furthermore, this apparent death of the character due to the drug is also similar to that of animals that become immobilized before a predator. The sensorimotor characteristics and EEG reactions suggest that there may be similarities between morphine-induced catalepsy and the defensive reactions of immobility and escape in drug-free animals (i.e., the adaptive reflex of feigning death)⁵.

Long before the appearance of recordings of bioelectric signals, until a few decades ago, the limits of life and death were determined by the existence or not of cardiac and respiratory activity. The concept of death was expanded when it was discovered that the brain had a vital role in governing physiological functions, therefore, the reversible cessation of the functions of the central nervous system (CNS) must also be considered death⁶. Although the definition of clinical death is apparently obvious, it is more complex than it seems. The need to unify criteria led to the establishment in the United States (USA, 1981)^{7, 8} of two possibilities for diagnosis (President´s Commission): 1) Irreversible absence of cardiovascular and respiratory functions, or 2) Irreversible cessation of all brain functions (brain and brainstem). Since the brain is the organ that coordinates the physiology of the entire organism, when brain death occurs, profound pathophysiological changes appear that lead to the deterioration and subsequent cessation of the functions of the different organs and systems. These changes are associated with alterations^{6, 9, 10}: 1) hemodynamics with a previous parasympathetic appearance and explosive sympathetic response; 2) respiratory due to the presence of apnea; 3) thermoregulation due to destruction of the thermoregulatory centers of the hypothalamus with frequent occurrence of hypothermia; 4) endocrine metabolic with the appearance of diabetes insipidus, loss of electrolytes in urine, hyperglycemia due to the release of catecholamines and low demand for cellular metabolism. In some patients who meet the criteria for brain death, spinal reflexes may falsely suggest persistence of brain function^{8, 9}.

For clinical neurological examination, it is necessary to perform different tests in an orderly manner to avoid interference in the results. To certify brain death it is necessary to identify¹⁰:

In this way, the zombie of Haitian society is a living dead achieved with ethnopharmacological preparations. The poisonings that arise from the therapeutic activities belonging to the voodoo cult are similar to that of the drug of modern medicine. Although Haitian voodoo priests control herbal healing, for the practice of poisoning poisons are extracted from tissues (plant and animal) and then administered to victims as a means of punishment established by a clandestine justice system¹². The zombie drug used as a powder acts as a dissociative anesthetic agent, possessing primary psychoactive hallucinogenic and neurotoxic effects with plasma clearance that may take hours to weeks. Of the four ingredients identified in the film, the analgesic and anesthetic effects of the drug come from the sea toad and the TTX-producing fish, especially the latter. In non-fiction, the formula of the poison is known in four widely separated localities in Haiti, including as an ingredient one or more species of puffer fish (Diodon hystrix, Diodon holacanthus or Sphoeroides testudineus) that contain lethal amounts of the neurotoxin TTX, capable of pharmacologically induce the zombie state¹³. Pufferfish contain TTX in the organs, especially the region of the liver and ovaries, and also in the skin. TTX binds to voltage-gated sodium channels of human muscles and excitable nervous tissues, blocking it and thereby inhibiting the entry of sodium ions and arresting impulse conduction by impairing action potential propagation, resulting in hypotension (more due to peripheral vasodilation than depression of cardiac activity), numbness, nervous paralysis of the diaphragmatic muscles and immobilization¹⁴. The venom paralyzes the muscles while the victim remains fully conscious and eventually dies from respiratory paralysis (asphyxiation), accompanied by paresthesia, headache, blurred vision, vertigo, nausea, vomiting and hypothermia^{15, 16}. Intoxication is easily detectable by a TTX-specific enzyme-linked immunoassay (ELISA) in blood and urine¹⁷.

There is currently no known antidote, and the standard medical approach is supportive treatment to attempt to support the respiratory (assisted ventilation) and circulatory (hemodialysis) systems until the poison is eliminated^{15, 16}. Chances of survival improve with gastric lavage and/or oral ingestion of activated charcoal, intravenous hydration, and neostigmine injections to increase activity at the neuromuscular junction¹⁸. Neostigmine, a parasympathomimetic that acts as a reversible inhibitor of the enzyme cholinesterase¹⁹, continues to be investigated as a possible treatment.

Food poisoning due to pufferfish is very common, where prevention is born with the implementation of measures to increase awareness, control markets and establish toxicological tests¹⁷. In 2008, advances in fugu research and cultivation have allowed some fish farmers to massively produce non-toxic specimens. The researchers found that the TTX in fugu came from eating other animals that had TTX-producing bacteria²⁰, and they developed immunity over time.

More research agrees that this powder contains an alkaline degradation product of TTX^{12, 21}, achieved through extraction with acetic acid and passing it through a cationic exchange column for chromatographic analysis. However, there are other results that contradict TTX as the main active ingredient, given that the presence of neurotoxins in local fish and amphibians of the Caribbean continues not to be recognized in chromatographic analyses¹². It is also possible to find high concentrations of TTX and its analogues 4-epiTTX and 4,9-anhidroTTX in cooked puffer fish using fluorescence detection and chromatography¹⁷. This inability to discriminate between active and inactive components, without recognizing who the real toxic elements really are, suggests that chemical analyzes and toxicological studies must be carried out on each ingredient individually. Later the studies would be done as combinations of ingredients contained in these voodoo potions. This voodoo drug acts relatively similar to ketamine, tiletamine, dextromethorphan, and phencyclidine (PCP), the latter being a very toxic NMDA receptor antagonist drug²² commonly known as “Angel Dust”, “Peace Pill” or “Weed” (when consumed in combination with marijuana). PCP and TTX are capable of producing hallucinogenic effects and paralysis by blocking ion, potassium and sodium channels, respectively²³. High concentrations of PCP induce the release of [3H]dopamine from cultures of dissociated rat midbrain cells, being independent of Ca²⁺ and insensitive to TTX²⁴. TTX alone has no effect on the spontaneous release of [3H]dopamine²⁴. Many of these hallucinations are also attributed to epileptic seizures, where they have a historical association with religion, mainly through the concept of spirit possession²⁵.

The film describes a poisonous marine toad, which could be the same “giant toad”, “cane toad” or “marine toad” (Bufo marinus, also know as Rhinella marina), being a species of anuran amphibian of the family Bufonidae. One of the chemicals excreted by this toad is bufotenin²⁶, classified as a drug of the same classification as heroin and cocaine. Wade Davis himself published an anthropological article where he hypothesizes that for a long time the ancient people of Mesoamerica used Bufo marinus as a ritual intoxicant²⁶, but this toad is also rejected as a candidate for such use due to the toxicity of its venom, being another candidate most likely the Sonoran Desert toad, Bufo alvarius, which secretes large amounts of the potent hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT). Although the venom of B. alvarius is toxic when consumed orally, it can be smoked safely and is powerfully psychoactive by that route of administration, giving rise to a hallucinogenic and psychoactive agent, known as the “God molecule”, which could have been used by pre-Columbian peoples of the New World²⁶. The hallucinogenic effects of bufotenine are believed to last less than an hour, showing activity similar to that of LSD and other known hallucinogens (psilocin and 5-MeO-DMT) at the putative hallucinogenic serotonin (5-HT) receptors, 5-HT2A and 5-HT2C²⁷. The binding and activation of hallucinogenic receptors does not have a complete scope, this evidences the idea that the lack of the classic hallucinogenic response of the drug in experiments with humans is due to the poor ability to cross the blood-brain barrier²⁷. It is known that certain serious mental disorders such as schizophrenia and autism spectrum disorders (ASD) are associated with the endogenous synthesis and urinary excretion of a psychomimetic molecule bufotenine (NN-dimethyl-5-hydroxytryptamine)^{28, 29}, a product of the serotonin degradation pathway. Therefore, the presence and levels of bufotenin could be useful and important markers of some psychiatric disorders.