This week on The Tox Lab, we're diving into the world of Kanna alkaloids.

We begin by exploring Kanna, its traditional use in southern Africa, and the growing interest in its potential effects on anxiety and depression. We take a closer look at the alkaloids found within Kanna, including mesembrine, and consider the pharmacology behind some of its reported effects.

We then turn to the potential harms associated with Kanna, examining in-silico toxicity prediction data for mesembrine and discussing what these predictions can, and cannot, tell us about the potential toxicity of the compound.

We also look at National Poison Data System data and the apparent increase in reported Kanna exposures, before exploring research into the potential cognitive effects of Kanna and whether these compounds could have a future role in treating conditions such as Alzheimer's dementia.

Join us as we explore the chemistry, pharmacology and toxicology of Kanna alkaloids, and consider whether this traditional plant could have a place in modern medicine.

Hope you enjoy!

This episode is very kindly sponsored by Cayman Chemical. Check out their Kanna Alkaloid Mix here: https://www.caymanchem.com/product/45074/kanna-alkaloids-mixture

Links to the papers we discussed:

https://www.thieme-connect.com/products/ejournals/abstract/10.1055/a-2809-5144

https://www.sciencedirect.com/science/article/pii/S0378874123009819?via%3Dihub

https://www.sciencedirect.com/science/article/abs/pii/S0009279725002789?via%3Dihub

https://www.acmt.net/wp-content/uploads/2026/04/2026-ASM-abstracts.pdf

https://onlinelibrary.wiley.com/doi/10.1155/2014/682014

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This week on The Tox Lab, we're diving into the world of psychedelic therapies and exploring the use of psilocybin to treat depression.

We begin with a recent trial investigating whether psilocybin-assisted therapy could actually be delivered within an NHS setting. We explore the practical challenges of delivering psychedelic therapy, the results of the trial, and what the findings might mean for the future of psilocybin treatment for people with treatment-resistant depression.

We then look at how psilocybin could produce antidepressant effects that persist long after the drug itself has left the body. We discuss what happens when psilocybin is converted to psilocin, its effects on serotonin receptors, and some of the proposed mechanisms behind its longer-term effects, including changes in brain activity, connectivity and neuroplasticity.

Finally, we examine the evidence from a trial comparing psilocybin with escitalopram, asking how the two treatments compare and what this tells us about the potential role of psilocybin in treating depression. We also discuss one of the fundamental challenges in psychedelic research: can you really blind a trial when participants can often tell whether they've received a psychedelic?

Join us as we explore the science behind psychedelic therapy, the evidence for psilocybin in depression, and the challenges of moving these treatments from clinical trials into real-world healthcare.

Hope you enjoy!

Links to the papers we discussed:

https://www.nature.com/articles/s41591-026-04541-0

https://www.nejm.org/doi/full/10.1056/NEJMoa2032994

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This week on The Tox Lab, we're diving into the world of mad honey and grayanotoxin poisoning.

We examine where mad honey comes from and its cultural uses before turning to the compounds responsible for its toxic effects: grayanotoxins. We discuss how these compounds affect voltage-gated sodium channels and how this can lead to severe bradycardia, hypotension, cardiac conduction abnormalities, dizziness, neurological symptoms and, in some cases, hallucinations.

The episode also examines reported cases of mad honey poisoning, including a severe case in Nepal and a case from the UK involving imported raw honey. We consider why the concentration of grayanotoxins can make the effects of mad honey difficult to predict and explore the clinical features of grayanotoxin poisoning.

Join us as we explore the chemistry, pharmacology, history and toxicology of mad honey, and discover how something as familiar as honey can cause significant cardiovascular and neurological toxicity.

Hope you enjoy!

Links to the papers we discussed:

https://pmc.ncbi.nlm.nih.gov/articles/PMC9978999/pdf/EFS2-21-e07866.pdf

https://www.mdpi.com/1420-3049/30/19/3925

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jat.4855

https://pmc.ncbi.nlm.nih.gov/articles/PMC6293183/pdf/CCR3-6-2355.pdf

https://www.cureus.com/articles/488288-mad-honey-poisoning-caused-by-grayanotoxin-toxicity-in-a-75-year-old-male-patient-presenting-with-hypotension-and-bradycardia-in-the-united-kingdom-a-case-report#!/

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This week on The Tox Lab, we're taking a closer look at one of the most challenging parts of toxicology: interpreting the results.

If we give you a number, can you tell us what it means?

We begin by exploring why interpreting a toxicology result is rarely as simple as comparing a concentration with a reference value. We discuss the range of clinical, analytical, pharmacological, and contextual information needed to understand what a result actually means, as well as the biases that can influence the way toxicology results are interpreted.

We then turn to recent published work evaluating the performance of AI and large language models in toxicology interpretation. Can these tools accurately interpret toxicology results, or do they reflect the same pitfalls seen when results are considered without sufficient clinical context? We explore some of the common errors and limitations reported in the literature when AI is applied to toxicology result interpretation.

Finally, we examine the use of reference intervals in toxicology and ask whether they can really help clinicians interpret drug concentrations. We discuss why reference intervals are not always straightforward and why context matters when deciding whether a toxicology result is clinically significant.

Join us as we explore the complexities of toxicology result interpretation, the risks of relying on numbers without context, and whether AI could actually help us make sense of toxicology results.

Hope you enjoy!

Links to the papers we discussed:

https://www.tandfonline.com/doi/full/10.1080/15563650.2026.2698028

https://www.sciencedirect.com/science/article/pii/S0379073826001052?via%3Dihub

https://pmc.ncbi.nlm.nih.gov/articles/PMC13152082/

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This week on The Tox Lab, we're taking a closer look at fentanyl, exploring its clinical use, toxicological risks, and the analytical challenges associated with detecting and interpreting fentanyl exposure.

We begin by examining fentanyl patch-related deaths reported in England, Wales and Northern Ireland, including cases highlighted through Prevention of Future Deaths reports. We discuss how fentanyl patches can contribute to fatal toxicity and consider what these cases can tell us about preventing future deaths.

We then turn to the laboratory, exploring fentanyl immunoassay cut-offs and why the concentration used to define a positive result matters. We discuss the importance of understanding and clinically assessing analytical cut-offs in different toxicological scenarios, rather than treating a single threshold as universally applicable.

Finally, we examine 4-ANPP, a minor metabolite of fentanyl that is also an important precursor and impurity associated with illicit fentanyl manufacture. We explore whether detecting 4-ANPP could help distinguish between exposure to pharmaceutical fentanyl and illicitly manufactured fentanyl, and consider the challenges in interpreting this marker.

Join us as we explore fentanyl toxicity, analytical interpretation, and the challenges of distinguishing different sources of fentanyl exposure, and consider what these findings mean for clinical and forensic toxicology.

Hope you enjoy!

Links to the papers we discussed:

https://bpspubs.onlinelibrary.wiley.com/doi/10.1002/bcp.70525

https://academic.oup.com/jat/article-abstract/50/5/bkag025/8658822?redirectedFrom=fulltext

https://academic.oup.com/jat/article-abstract/50/3/bkaf111/8415903?redirectedFrom=fulltext

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This week on The Tox Lab, we're diving into the world of absinthe, the infamous "Green Fairy".

We begin by exploring what absinthe actually is, from its botanical origins and traditional preparation to its rise in popularity and the myths that eventually surrounded it. We discuss why absinthe became associated with hallucinations, madness, and toxicity, and how these stories contributed to its controversial reputation and prohibition.

We then turn to the toxicology of absinthe and examine thujone, the compound often identified as the toxin responsible for "absinthism". We explore how thujone affects the central nervous system, what the evidence actually tells us about thujone toxicity, and whether reported cases of absinthe-related illness can really be attributed to the compound itself. We also take a closer look at what is known about thujone exposure and toxicity in general, discussing how neurological symptoms can arise at high doses and why interpreting reports of adverse effects is challenging when modern toxicological data is limited or based on experimental models rather than real-world exposure.

Finally, we bring these threads together by separating fact from fiction, unpacking some of the most persistent myths surrounding absinthe, including whether it truly causes hallucinations and what ultimately led to its bans in many countries.

Join us as we explore the chemistry, pharmacology, and toxicology of absinthe, and ask whether the notorious "Green Fairy" really deserved its dangerous reputation, or if its legacy is more myth than science.

Hope you enjoy!

Links to papers we discussed:

https://pmc.ncbi.nlm.nih.gov/articles/PMC1475830/

https://ift.onlinelibrary.wiley.com/doi/epdf/10.1111/1750-3841.14273

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This week on The Tox Lab, we're taking a look at the dark side of decongestants and exploring how seemingly harmless over-the-counter nasal sprays and eye drops can cause severe toxicity.

We begin by discussing the pharmacology of imidazoline decongestants, including their effects on alpha-adrenergic receptors and how systemic exposure can lead to cardiovascular and central nervous system toxicity.

We then examine a fatal case involving xylometazoline, in which exposure was associated with a haemorrhagic stroke. We explore the possible mechanisms underlying this rare but serious complication, including the effects of sympathomimetic decongestants on vascular tone and blood pressure.

Finally, we turn to tetrahydrozoline, an ingredient found in products such as Visine eye drops and some nasal decongestants. We discuss accidental and intentional ingestions, severe bradycardia, hypotension, CNS depression, and cardiac conduction abnormalities, as well as the challenges associated with recognising and detecting tetrahydrozoline toxicity. We also explore the darker forensic history of tetrahydrozoline, including its involvement in cases of drug-facilitated sexual assault and murder, and consider why the role of these compounds in unexpected deaths and criminal investigations may be underestimated.

Join us as we examine how everyday over-the-counter decongestants can cause coma, profound cardiovascular toxicity, and even death, and explore the toxicological and forensic challenges posed by compounds that are not routinely included in standard drug screening.

Hope you enjoy!

Links to the papers we discussed:

https://onlinelibrary.wiley.com/doi/abs/10.1111/1556-4029.15416

https://link.springer.com/article/10.1007/s12024-023-00680-9

https://pmc.ncbi.nlm.nih.gov/articles/PMC8118060/

Disclaimer: All opinions are our own.

Find us on instagram: @the_tox_lab

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This week on The Tox Lab, we're diving into wastewater-based epidemiology and exploring how wastewater analysis can be used to monitor drug use and emerging drug trends.

We begin by discussing the UK national wastewater analysis programme and examining what wastewater data revealed about the use of commonly encountered recreational drugs in 2022. We explore what these measurements can tell us about population-level drug use and how wastewater analysis can provide a different perspective from more traditional sources of toxicological data.

We then turn to the use of wastewater analysis for monitoring novel psychoactive substances, discussing the detection of emerging compounds including nitazenes and xylazine.

Finally, we examine the recent detection of N-propionitrile chlorphine, also known as cychlorphine, in wastewater in the United States. We discuss what these findings may tell us about the emergence of this novel synthetic opioid and the potential for wastewater monitoring to identify new substances as they begin to appear in the illicit drug supply.

Join us as we explore how wastewater analysis is being used to monitor drug use, track emerging synthetic opioids and novel psychoactive substances, and consider whether wastewater could play an increasingly important role in early warning systems, harm reduction, and public health.

Hope you enjoy!

Links to papers we discussed:

https://onlinelibrary.wiley.com/doi/10.1111/add.70398

https://pubs.acs.org/doi/10.1021/acsestwater.5c01173?ref=PDF

https://pmc.ncbi.nlm.nih.gov/articles/PMC12319643/

https://pubs.acs.org/doi/10.1021/acs.estlett.6c00529

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This week on The Tox Lab, we're discussing silver toxicity and the toxicological consequences of using silver outside its established medical applications.

We begin by exploring the legitimate uses of silver in medicine, including wound dressings, topical preparations, and antimicrobial coatings on medical devices. We then turn to the claims surrounding colloidal silver, including its promotion as a treatment for a wide range of conditions despite a lack of evidence supporting many of these uses.

We then examine argyria, a condition caused by the accumulation of silver in the body that can lead to permanent blue-grey discolouration of the skin. We discuss the case of Paul Karason, better known as "Papa Smurf", and explore how his use of colloidal silver made him one of the most recognisable examples of the potential consequences of long-term silver exposure.

Finally, we examine a case of severe anaemia associated with colloidal silver ingestion, discussing the potential mechanisms of toxicity and the challenges of recognising the role of alternative and unregulated products in serious clinical presentations.

Join us as we explore the medical uses, alternative claims, and toxicological consequences of silver exposure, and consider how a substance with legitimate applications in medicine can become harmful when used in ways that are not supported by the evidence.

Hope you enjoy!

Link to papers we discussed:

https://jamanetwork.com/journals/jamadermatology/fullarticle/2214158  

https://onlinelibrary.wiley.com/doi/10.5694/mja2.52687  

https://www.sciencedirect.com/science/article/pii/S221475002300104X?via%3Dihub  

Disclaimer: All opinions are our own.

Find us on instagram: @the_tox_lab

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This week on The Tox Lab, we're discussing cross-tolerance, focusing on the relationship between benzodiazepines and alcohol.

We begin by exploring how alcohol acts at the GABA-A receptor, the neuroadaptations that occur with chronic alcohol use, and why the sudden cessation of alcohol can lead to withdrawal. We then discuss why benzodiazepines are the mainstay of treatment for alcohol withdrawal and the pharmacological basis for their effectiveness.

We then turn to the concept of cross-tolerance, examining how long-term alcohol use can influence the response to benzodiazepines, and whether chronic benzodiazepine use provides similar cross-tolerance to the effects of alcohol. We discuss the pharmacological mechanisms underlying these interactions, the similarities and important differences between the two drugs, and why cross-tolerance is only partial.

Finally, we consider the clinical implications of these findings, including why combining alcohol and benzodiazepines remains particularly dangerous despite any degree of tolerance.

Join us as we examine the pharmacology, clinical toxicology, and misconceptions surrounding benzodiazepine and alcohol cross-tolerance, and consider what these interactions mean for patient care and overdose risk.

Hope you enjoy!

Link to papers we discussed:

https://pmc.ncbi.nlm.nih.gov/articles/PMC3321276/ 

https://journals.healio.com/doi/10.3928/00485713-20251202-02?__cf_chl_f_tk=QOyw_fXXLTUEXO4ZHEuX5s6eAN_jQeaCPemdwZ_Ygdc-1783254633-1.0.1.1-n9t5ECBcZIAn9EM4ia88JllcRLiCinRKSrG5LRy3D94

Disclaimer: All opinions are our own.

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Check out our new website: https://thetoxlab.co.uk/ 

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