Alternative therapy including herbal drugs and complementary medicine is becoming increasingly popular. However, the rise in the incidence of herb-drug interactions is causing concern, especially in the absence of warning labels addressing potential adverse effects. We present the case of a 55-year-old male who suffered a fatal breakthrough seizure, with no evidence of non-compliance with his anticonvulsant medications. The autopsy report revealed subtherapeutic serum levels for both anticonvulsants Depakote and Dilantin. Concomitant with his prescribed medications, the decedent was also self-medicating with a cornucopia of herbal supplements and nutraceuticals, prominent among which was Ginkgo biloba. Ginkgo, an herbal extract from the leaves of the Ginkgo biloba tree, has been used medicinally for centuries and has been touted as a cure for a variety of medical conditions. The induction of Cytochrome P450 enzymes by components of herbal drugs has been known to affect the metabolism of various drugs. Dilantin is primarily metabolized by CYP2C9, and secondarily metabolized by CYP2C19. Valproate metabolism is also modulated in part by CYP2C9 and CYP2C19. A recent study revealed significant inductive effect of ginkgo on CYP2C19 activity. CYP2C19 induction by ginkgo could be a plausible explanation for the subtherapeutic levels of Dilantin and Depakote. Additionally, ginkgo nuts contain a potent neurotoxin, which is known to induce seizure activity. Evidence of other herbal drugs diminishing the efficacy of anticonvulsant medication does exist; however, there has been only one other documented instance of ginkgo potentiating seizure activity in the presence of anticonvulsant therapy. Highlighting the potential adverse effects and drug interactions of ginkgo on the packaging of the drug may help prevent inadvertent use in vulnerable individuals.

Encoding and consolidating information through learning and memory is vital in adaptation and survival. Dopamine (DA) is a critical neurotransmitter that modulates behavior. However, the role of DA in learning and memory processes is not well defined.Herein, we used the olfactory adaptive learning paradigm in Caenorhabditis elegans to elucidate the role of DA in the memory pathway. Cat-2 mutant worms with low DA synthesis showed a significant reduction in chemotaxis index (CI) compared to the wild type (WT) after short-term conditioning. In dat-1::ICE worms, having degeneration of DA neurons, there was a significant reduction in adaptive learning and memory. When the worms were trained in the presence of exogenous DA (10 mM) instead of food, a substantial increase in CI value was observed. Furthermore, our results suggest that both dop-1 and dop-3 DA receptors are involved in memory retention. The release of DA during conditioning is essential to initiate the learning pathway. We also noted an enhanced cholinergic receptor activity in the absence of dopaminergic neurons. The strains expressing GCaMP6 in DA neurons (pdat-1::GCaMP-6::mCherry) showed a rise in intracellular calcium influx in the presence of the conditional stimulus after training, suggesting DA neurons are activated during memory recall. These results reveal the critical role of DA in adaptive learning and memory, indicating that DA neurons play a crucial role in the effective processing of cognitive function.

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Pharmacogenomics is the study of the linkage between an individual's genotype and the disposition of drugs in the body. The first association between adverse drug reactions and inherited variations was recognized in the 1950s, and since then, pharmacogenomics has come a long way. The importance of pharmacogenomics is accentuated by the incidence of adverse drug reactions, which may account for hospital expenditures of up to 5.6 billion dollars annually. Interindividual variations in drug metabolism are often the result of genetic variants or genetic polymorphisms, and polymorphisms have been known to alter the relationship between dose and plasma drug concentration. Drug disposition can be affected by polymorphisms in drug metabolizing enzymes, drug transport proteins, and drug targets. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of a large number of drugs. Polymorphisms of the CYP enzymes have been well documented, and CYP2D6 is the most polymorphic CYP enzyme. However, there is a relative dearth of research on the role of transport proteins and drug targets. This review attempts to provide a brief synopsis of the pharmacogenomics of some common drug-metabolizing enzymes, transport proteins, and targets. The examples of tramadol, methadone, and oxycodone are used to illustrate the potential role of pharmacogenomics in forensic toxicology. Pharmacogenomics may present a practicable hypothesis in cases of incongruence between dose and plasma drug concentration, and the possibility of genotype-mediated drug plasma levels needs to be considered.

A 6-year-old male child was scheduled for a dental procedure requiring conscious sedation. Prior to the procedure, the child was administered a dental cocktail containing chloral hydrate, hydroxyzine, and methadone. After returning from the dentist, the child appeared groggy and was allowed to sleep. A few hours later, he was found unresponsive, and following resuscitation attempts at a local medical center, he was pronounced dead. Toxicological analyses of femoral blood indicated the presence of hydroxyzine at less than 0.54 μg/mL, trichloroethanol (TCE) at 8.3 μg/mL, and methadone at 0.51 μg/mL. No meperidine was detected. The cause of death was reported to be due to the toxic effects of methadone. The toxicological analysis was corroborated by the analysis of the contents of the dental cocktail, which revealed the presence of hydroxyzine, chloral hydrate, and methadone. Residue from a control sample obtained from the same pharmacy, but administered to a different subject, was found to contain hydroxyzine, chloral hydrate, and meperidine. This report represents the first known fatality due to accidental substitution of methadone in a dental cocktail.