Nitisinone (Orfadin)

  • used to treat hereditary tyrosinaemia type 1 (HT-1), a rare genetic disease caused by a deficiency in fumarylacetoacetase (FAH), an enzyme involved in the metabolism of tyrosine
    • tyrosine metabolism consists of a series of steps, with FAH being in charge of the last one
    • FAH deficiency causes the buildup of tyrosine metabolites produced by prior metabolic steps, several of which happen to be toxic to cells
      • since FAH is highly expressed in liver cells, HT-1 usually presents as liver failure or chronic liver disease
  • does its thing by inhibiting 4-hydroxyphenyl pyruvate dehydrogenase (HPPD), an enzyme with an annoyingly long name that is responsible for an early step in tyrosine metabolism (upstream of FAH), thus preventing toxic tyrosine metabolite production
  • initially developed as a maize herbicide
    • is a derivative of leptospermone, a natural compound present in the roots of bottlebrush (Callistemon citrinus), a shrub native to Australia that kinda resembles one of those things that you clean your toilet with if you aren’t a typical male university student sharing an apartment with two other typical male university students (yes, we are gross)
    • HPPD is also present in plants, where it has a role in the synthesis of plastoquinone from tyrosine
    • plastoquinone is a cofactor required for the biosynthesis of carotenoids, which in turn are required for photosynthesis (making food from sunlight) and the prevention of chlorophyll (the stuff that makes plants green) destruction
    • weeds sprayed with mesotrione, another derivative of leptospermone that is used expressly as a herbicide, acquire a bleached appearance due to the destruction of chlorophyll prior to biting the dust
    • maize is tolerant because it is able to rapidly break down leptospermone-like compounds
Callisto: a very successful maize herbicide inspired by allelochemistry
McKiernan PJ. Nitisinone in the treatment of hereditary tyrosinaemia type 1. Drugs. 2006;66(6):743-50.



  • monoterpene present in essential oils (see: silly aromatherapy nonsense) from plants of the Lamiaceae (mint) family
    • particularly high levels are found in the European (Mentha pulegium) and American (Hedeoma pulegioides) varieties of pennyroyal
  • has an odour similar to peppermint and camphor
  • used as a flavouring agent, an ingredient in perfumes, and a flea repellent (so perfect for hippies)
  • pennyroyal tea (and oil) is/was used in traditional folk medicine to promote menstruation and as an abortifacient to initiate self-abortion
    • there is a crappy Nirvana song about this (bring it, haters!)
    • there is no scientific evidence available to support its efficacy in this regard (read: this is a bad idea)
  • ingestion of high doses has been reported to cause organ toxicity and death
  • pulegone and one of its metabolites (menthofuran) are bioactivated by liver enzymes to reactive intermediates that permanently bind to cellular proteins and cause liver damage
Anderson IB et al. Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature. Ann Intern Med. 1996 Apr 15;124(8):726-34.

Coprine - Why you sometimes don't want to pair a wine with a mushroom dish

  • a rare amino acid (derivative of glutamic acid, natch) present in several edible species of mushroom belonging to the genus Coprinus ("inky caps") including the common ink cap (Coprinus atramentarius), a lawn mushroom that is, most unexpectedly, fairly common
  • is thought that it or one of it's metabolites (cyclopropanone hydrate) inhibits the enzyme aldehyde dehydrogenase (ALDH)
    • alcohol (ethanol) is primarily metabolized in the body by the enzyme alcohol dehydrogenase (ADH) into acetaldehyde, a fairly toxic substance that is responsible for many of the symptoms of a hangover
    • acetaldehyde is then further metabolized by ALDH into not nearly as toxic acetic acid, the stuff in vinegar that makes it taste and smell the delightful way that it does
    • inhibition of ALDH results in the accumulation of acetaldehyde when alcohol is consumed, essentially giving you an insta-hangover
  • gettin' smashed or even just having a single drink up to 72 hours after eating mushrooms containing coprine will cause acetaldehyde poisoning, symptoms of which include flushing, nausea and vomiting, headache, and palpitations
    • symptoms usually only last 2-4 hours but may last up to 2 days (yay!)
    • the same reaction is seen in individuals who: (a) are taking disulfiram (Antabuse), an anti-drinking drug used in the treatment of alcohol dependence (alcoholism) that inhibits ALDH or (b) possess a super effective form of ADH and/or a crappy form of ALDH due to variation in the genes that encode these enzymes (these people are often of East Asian descent)
  • has no known toxic effects on its own - is only poisonous when ingested prior to alcohol consumption, and even then it is the metabolized alcohol that is causing the problems
Berger KJ, Guss DA. Mycotoxins revisited: Part II. J Emerg Med. 2005 Feb;28(2):175-83.


Clomifene (Clomid, Serophene, Milophene)

  • what "fertility pills" are usually made of
  • used to treat female infertility due to anovulation (lack of ovulation)
    • doesn't work if infertility is caused by the dude (defective or lack of spermies) or woman's infertility is caused by ovarian dysfunction
  • inhibits the negative feedback action of estrogen in the anterior pituitary gland, resulting in increased release of follicle-stimulating hormone (FSH) - this leads to a higher rate of ovulation and hence increased potential for pregnancy
  • can actually cause multiple ovulation, increasing the risk of multiple births
    • sometimes four or five ova are released and fertilized - say hello to the local news crew, quintuplets!
  • actually is a mixture of two geometric isomers, enclomifene and zuclomifene
  • used (abused?) by some male bodybuilders to block the estrogen-like effects (e.g. man titties!) produced by anabolic steroids and restore the body's natural production of testosterone (which is lost with steroid use)


To barf, or not to barf: Drugs that control vomiting

Your brain is almost entirely closed off from the rest of your body by a layer of tightly linked cells called the blood brain barrier (often abbreviated the BBB). Although nothing can pass between the cells of this layer, small and/or lipid-soluble chemicals such as water and THC are able to pass through the cells, and thus access your brain. There are a limited number of sites in the brain where the BBB is intentionally circumvented, for here lie neural structures that require access to the general circulation to carry out their functions.

One of these sites is called the area postrema. It is a small tongue-shaped area that lies on the floor of the fourth ventricle in the brainstem, and is involved the co-ordination of emesis, or vomiting. It is also called the chemical trigger zone (CTZ), which references its ability to stimulate other parts of the brain (the nucleus tractus solitarius and dorsal motor nucleus of the vagus - more info here) to cause you to puke if it detects a toxic substance in your blood. This provides the us with a built-in mechanism by which we can potentially get rid of substances that have the potential to do us harm. Trauma, bad reactions to drugs, and certain motions are capable of hijacking the vomiting reflex, which is why they often make you ralph.

Emetics are drugs that stimulate vomiting. They are currently used to help remove ingested poisons from dogs and cats and abused as a dangerous method of weight loss. Historically, emetics were used to induce vomiting in humans as a means of dealing with poisonings by ingestion, but this approach has since been replaced by the use of activated charcoal and/or whole bowel irrigation. Antiemetics are drugs that suppress nausea and vomiting. This is their primary application, and it's a damn good one. Many of the drugs belonging to these classes act via dopamine receptors in the area postrema or the other parts of the brain involved in the vomiting reflex to do their thing.

Some emetics and antiemetics:


  • potent emetic that was used in the past in humans to induce spewing
    • currently only used for this purpose in dogs that have ingested toxic and/or foreign substances
  • nonselective dopamine agonist
  • activates dopamine receptors in the striatum, enabling its use to treat Parkinson's disease
    • Parkinson's is the result of the loss of dopamine-secreting cells such that there is insufficient dopamine to activate receptors in the striatum as part of the normal control of movements by the brain
  • derivative of morphine (a common side effect of opioid use is nausea and vomiting)
  • appears clear in solution but stains things green!

Domperidone (Motilium) and Metoclopramide (Maxolon, Reglan, and Degan)

  • antiemetic dopamine receptor antagonists (block dopamine receptors in the area postrema)
  • in addition to arresting upchucking, they are used to treat gastroparesis
  • metoclopramide crosses the BBB but domperidone does not
    • metoclopramide can worsen the symptoms of Parkinson's disease



  • a group of related compounds present in the leaves of Salvia divinorum ('Mexican mint', 'magic mint'), a rare variety of sage that is used by the Mazatec Indians of Mexico for religious and medicinal purposes and only became known to western society in 1962
    • the leaves or leaf extracts can be smoked to induce powerful hallucinations that last for a relatively brief period of time
    • when smoked, you start feeling it about 30 seconds after taking a hit, peaks in 5-10 minutes, and then effects disappear over next 20-30 minutes
  • only salvinorins A and D through F are hallucinogenic, producing effects similar to those of LSD
    • salvinorin A is the best studied of these and has a potency similar to LSD
    • unlike LSD, which acts via 5-HT2 receptors, these compounds are kappa opioid receptor agonists (there are three types of opioid receptors: mu, kappa, and delta - morphine is primarily a mu opioid receptor agonist)
  • potential toxicity has not been fully investigated in lab animals or humans - so far no toxic effects are known to exist



  • cancer-zapping agent discovered in the 1950s as an unexpected result of a research effort to find a cheap plant-derived source for cortisone synthesis
    • cortisone was found to be a potent anti-inflammatory agent in the 1940s, creating a huge demand for it
    • at the time, the only available source for cortisone was from animals, making it mega expensive (a single dose cost $1000 and required bile from 40 slaughtered oxes)
    • eventually Mexican yams (genus Dioscorea) containing diosgenin, a plant steroid that could be converted into cortisone, were identified as an ideal source for inexpensive cortisone production - Mexico subsequently became the primary supplier of cortisone in the 1960s
  • present in the wood, bark, and fruit of Camptotheca acuminata, a deciduous tree found in southern China that has a long history of use in traditional Chinese medicine
  • clinical trials (testing it on humans) in the early 1970s revealed that, although it wrecked terrible havoc upon tumours, it wrecked terrible havoc upon normal tissues as well, leading to all sorts of impressive side effects (neutropenia - loss of white blood cells, thrombocytopenia - loss of platelets, hemorrhagic cystitis - bladder damage that makes you pee blood, and GI upset with severe diarrhea - no further explanation required) that brought it's development as an anticancer drug to an abrupt end
  • in the 1980s, researchers discovered that it acts upon topoisomerase I, a cellular enzyme that normally functions to untangle supercoiled (tangled up) DNA strands
    • topoisomerase I is most active during replication and transcription, as these processes generate excessive supercoiling
    • untangling is accomplished by cutting, unwinding, and then attaching the stands back to together
    • camptothecin binds to topoisomerase I and inhibits it's ability to rejoin the strands that it breaks apart, causing the normally protective enzyme to start busting DNA stands all to pieces, leading to fragmentation of chromosomes and the death of rapidly dividing cells such as cancer cells
  • this lead to the development of less toxic synthetic derivatives including irinotecan (Campto, Camptosar), topotecan (Hycamtin), and 9-aminocamptothecin (9-AC)
    • these have been used to treat ovarian, colon, and small-cell lung cancers
    • intense diarrhea and immunosupression (due to neutropenia) are still significant side effects
History and Use of Dioscorea as a Food and Herbal Medicine
Oberlies NH, Kroll DJ. Camptothecin and taxol: historic achievements in natural products research. J Nat Prod. 2004 Feb;67(2):129-35.
O'Leary J, Muggia FM. Camptothecins: a review of their development and schedules of administration. Eur J Cancer. 1998 Sep;34(10):1500-8.

Loperamide - Because no one likes pooping emergencies

Imodium Anti-Diarrheal Caplets
  • trade names include Lopex, Imodium, and Dimor
  • analogue of meperidine (a synthetic opioid) used to deal with diarrhea / suppress the squirts / prevent the poops / revert the runs / thwart the trots / squash the skitters
    • acts on opioid receptors in the gastrointestinal tract to decrease fluid secretion and peristalsis
  • also used to treat fecal incontinence (loss of the ability to restrain from just pooping whenever there is poop to be pooped) since it increases anal sphincter tone
  • is metabolized in the intestinal wall, so very little of it is absorbed into the systemic circulation and delivered to the rest of the body
  • is mostly charged at physiological pH, so it cannot cross readily into the brain, meaning that even though it is an opioid like morphine or heroin it cannot get you stoned and has no potential for causing dependence



  • potent polypeptide anticoagulant derived from the saliva of the blood-sucking leech Hirudo medicinalis
    • use of this leech for medicinal purposes dates back to ancient Egypt
    • leech application has been used in reconstructive microsurgery to alleviate venous congestion (pooling of blood in veins) in flaps and free pieces of tissue (read: partially torn or completely cut off fingers, ears, lips, nasal tips, etc.) that are being reattached, improving their survival
  • inhibits thrombin, the central enzyme responsible for controlling the coagulation process (clotting of blood), by binding to it at a site separate from it's active site (the site where it does it's enzyme stuff) and then covering the active site over - is the most potent known natural thrombin inhibitor and one of the most potent natural anticoagulants
  • first isolated and named in 1884, but it's structure and mechanism of action weren't discovered until 1955
  • lepirudin and desirudin are recombinant (see this post) forms of hirudin produced in yeast cells (hirudin would be hideously expensive if it had to be harvested from leeches) that are used to prevent deep vein thrombosis in certain surgeries, but are less effective and more toxic compared to heparin when used to treat coronary heart problems
  • since it is a peptide it must be given parenterally (with a needle into a body part - muscle, vein, beneath the skin, etc.)
  • has served as a model for the design of new anticoagulant drugs, such as bivalirudin, a peptide that consists of a thrombin active site inhibitor linked via a short amino acid chain to a dodecapeptide (12 amino acids) analogue of a section of hirudin
Kikelj D. Peptidomimetic thrombin inhibitors. Pathophysiol Haemost Thromb. 2003 Sep-2004 Dec;33(5-6):487-91.

Whitaker IS et al. By what mechanism do leeches help to salvage ischaemic tissues? A review. Br J Oral Maxillofac Surg. 2005 Apr;43(2):155-60.


Q & A #2

Yes, folks, it's that time again. That time when I scroll through the long list of search queries that brought people to this blog and pick out ones that were posed as questions that I would like to answer. Check out my first instalment of this fun little exercise here. As always, incorrect spelling and grammar have been subjected to the righteous fury of a semi-literate man. Myself.

Can I use Tylenol to kill a cat ?

Yes. But don't, because cats are nice and overdosing on Tylenol (acetaminophen) is a mean way to die, not to mention the fact that YOU'D BE KILLING A CAT. Jesus, if you really don't want it, drop it off at the local humane society or take it to a vet to get it put down. But don't do it yourself. By the way, cats are apparently highly sensitive to the hepatotoxic effects of acetaminophen, to the point that even a small portion of a single pill can do them in!

What organs are affected by LSD ?

LSD affects any tissues that express serotonin 5-HT2 receptors, since these are the primary target for this drug in the body. In addition to their presence in the brain, these receptors are found in platelets and in the smooth muscle of the gastrointestinal tract, uterus, and blood vessels. As a result, LSD can induce platelet aggregation, uterine contractions (induction of labour in pregnant women), abdominal cramps and soreness, and vasoconstriction. LSD also affects the heart (increases heart rate), eyes (mydriasis), and the salivary and mucous glands (increases the production of both secretions). I'm guessing that it's effects on these organs is produced indirectly, via central (occurring in the brain) stimulation of the autonomic nervous system.

(soaking marijuana in codeine)

This wasn't a question, but I just wanted to point out the crazy things that people will consider doing recreationally with drugs. Given the nature of humanity, I expect that this has been tried before. I suppose it would be kind of fun, getting stoned two different ways at once, provided you dosed things correctly. Best wishes!

Do sharpies make you high ?

Yes. But they also damage your brain. And you get black rims around your nostrils that make you look like someone who gets off on sniffing sharpies. Stick with white-out, folks. At least then people might think you're doing coke.

Does Benadryl affect heparin / Can Bendaryl delay your period ?

First off, I should point out that in the United States, Benadryl is a trade name for diphenhydramine, a first generation antihistamine. However, in Britain, depending on the particular formulation, Benadryl may contain diphenhydramine, acrivastine, or cetirizine (the latter two being second generation antihistamines, which basically means that they don't make you drowsy because they only target the site of your allergies instead of also acting on your brain). Antihistamines have been shown to prevent adverse hemodynamic responses to heparin (e.g. hemorrhaging) if they are given prophylactically (i.e. before the heparin is given). I can't find anything else in the scientific literature. Irregular menses (e.g. a delay in your period) is not associated with antihistamine (e.g. Benadryl) use, although certain drugs, such as opioids (e.g. heroin, morphine), can cause this effect.

Kanbak M et al. Prophylactic administration of histamine 1 and/or histamine 2 receptor blockers in the prevention of heparin- and protamine-related haemodynamic effects. Anaesth Intensive Care. 1996 Oct;24(5):559-63.

Leysen JE et al. Serotonin-S2 receptor binding sites and functional correlates. Neuropharmacology. 1984 Dec;23(12B):1493-501.


Darbepoetin alfa (Aranesp)

  • synthetic form of recombinant human erythropoietin (epoetin)
  • erythropoietin is an glycoprotein (protein with a bunch of sugars attached to it) hormone produced mostly by the kidney that stimulates erythropoiesis (production of red blood cells by the bone marrow)
  • epoetin and darbepoetin are manufactured using recombinant DNA technology:
    1. a gene encoding the protein/drug is inserted into a bunch of mammalian cells (usually Chinese Hamster Ovary cells)
    2. cells that begin to produce the drug are isolated and cultured in a bioreactor (placed in a controlled artificial environment and permitted to multiply)
    3. cultures of cells are processed to harvest the drug (see why they call it molecular farming?)
  • the gene encoding epoetin is identical to that which is found in humans, but the gene encoding darbepoetin has been tinkered with such that darbepoetin contains more sialic acid (a type of sugar) groups than epoetin - this modification increases its half-life three-fold and enhances its activity relative to epoetin
  • used to correct anemia (reduction in the amount of circulating red blood cells) associated with chronic kidney disease and cancer chemotherapy - these feature damage to the kidneys and bone marrow, respectively, which blunts the normal response of the body to anemia (increased release of erythropoietin from the kidney leading to increased red blood cell synthesis in the bone marrow)
  • has been abused by a number of athletes in endurance sports, particularly during the 2002 winter Olympics, as a variety of blood doping - increasing the number of red blood cells in order to enable the blood to carry more oxygen and thus enhance athletic performance
  • since it contains no components of human blood, may be okayed for use by those crazy Jehovah's Witnesses as a possible alternative to blood transfusion
  • excessive use can cause polycythemia (too many red blood cells to the point that they begin to significantly thicken the blood) - the heart has to work harder to pump the blood, increasing the risk of heart failure and other cardiovascular problems
Joy MS. Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother. 2002 Jul-Aug;36(7-8):1183-92.


Precious medicines: Platinum, gold, and silver as therapeutic agents

It's true. Precious metals are used as drugs. As a complete and utter pharmacology nerd, I happen to think that this is awesome. Let me tell you some things.


Platinum-containing compounds represent an important class of anticancer / antitumour / antineoplastic agents, the prototype of which is cisplatin (Platinol). Cisplatin was first synthesized in 1844, but it was not until 1965 that it's ability to inhibit cell division was discovered. Like the discovery of penicillin, it was made totally by accident.

A dude named Barnett Rosenberg was delivering electric current to cultures of bacteria as part of a series of experiments that he was doing. Rosenberg made the observation that the ability of the bacteria to multiply was inhibited in these cultures. It was soon realized that the inhibition of bacterial growth was due to the presence of platinum coordination complexes, among them cisplatin, in the cultures. These complexes were being generated by the platinum electrodes that were being used to deliver the electrical currents. After further investigation, cisplatin was found to possess anticancer activity in a number of different animal tumour models. It was first approved for human use in Canada in 1978, and is now employed worldwide against a number of different cancers, including: germ cell, ovary, bladder, cervix, head and neck, esophageal, gastric, prostate, lung (NSC), and neuroblastoma.

Platinum-containing anticancer drugs are alkylating agents, meaning that they react with the nitrogenous bases in DNA strands to cause the formation of cross-linkages within and between strands. It is thought that the resulting DNA adducts mess up cellular repair mechanisms, with the accumulating genetic damage activating apoptosis (controlled cell death) preferentially in fast growing cells such as cancer cells. As a result of their high level and broad spectrum of activity (effectiveness against a variety of different types of cancer), platinum-containing drugs based on cisplatin continue to be developed for use in the treatment of cancer.


Gold has a long and sordid (well, maybe not so sordid) history of being used medicinally in most cultures around the world. The Chinese used it as early as 2500 BCE. There are records dating back to 500 BCE of gold salts being used to treat leprosy. Indian physicians used various preparations containing gold as antiepileptic agents.

In the late 19th century, gold cyanide compounds were shown to kill Mycobacterium tuberculosis (the bacteria responsible for most causes tuberculosis) in test tubes but were found to be too toxic to use in people. Over the course of the 20th century, organogold drugs have been used (albeit often unsuccessfully) to treat a wide variety of autoimmune diseases, kala-azar, tuberculosis, and malaria. Gold-chloroquinone drugs are currently being developed to combat malaria.

Gold drugs have been shown to have anti-tumour, anti-HIV, anti-microbial, and anti-fungal activities. However, the primary therapeutic application for gold in today's world is in the treatment of rheumatoid arthritis. This is an incurable chronic inflammatory autoimmune condition that progressively destroys the articular cartilage that lines the surfaces of bones where they meet in joints. Since cartilage is necessary for joints to work, this disease can lead to the loss of joint function (i.e. the bones at the affected joint(s) fuse together). It is estimated that 1-2% of all people everywhere have this form of arthritis, and we still don't understand exactly what causes it. Rheumatoid arthritis is routinely treated with gold drugs, which have anti-inflammatory and other properties that help to combat the disease. In most cases, monovalent organogold salt formulations are injected into the joints. The use of gold drugs in this application is called chrysotherapy, and has been in use for over 70 years. The major side effect of these drugs is dermatitis. In the exciting and ever-so-controversial world of alternative medicine, gold needles are used by many acupuncturists in patients with rheumatoid arthritis.


Silver has long been employed as an antiseptic. The ancient Phoenicians used silver bottles to store their beverages to prevent them from spoiling. Alexander the Great reportedly would only drink from silver vessels. Both Hippocrates (the dude who invented how to be a good doctor) and Paracelsus (hero to toxicologists everywhere) noted the healing effects of silver in their writings. Once bacteria were discovered, silver was recognized to be effective at knocking them off. This lead to silver being used as an antimicrobial agent, which remains its primary therapeutic application to date. Silver is toxic to many bacteria, viruses, algae, and fungi. Yet it does not appear to pose a significant threat to human cells or humans as a whole. This selective toxicity makes silver a great antimicrobial agent, although we still don't understand the mechanism behind it.

K. S. F. Crede, a German obstetrician, is credited with introducing (in 1884) the practice of applying eye drops containing silver nitrate to the eyes of newly-born children to prevent them from becoming infected with gonorrhea (yeah, that STD we all know and love). Early on in the twentieth century, a surgeon by the name of William S. Halstead figured out that silver foil bandages for wounds helped to prevent the development of infection. These bandages, as well as topical creams containing silver salts, were used during World War I. With the development of systemically-acting sulfa drugs and penicillin, and the spread of their use worldwide following World War II, the use of silver as a general antimicrobial agent fell out of favour. It remains a mainstay in the treatment of burns, traumatic wounds, and diabetic ulcers. Ointments containing silver sulfadiazine (Silvazine and Flamazine) were the treatment of choice for controlling bacterial infections in patients with serious burns up until the late 1990s, at which point bandages containing slow-release silver compounds became popular. A 10% solution of silver nitrate has recently been show to be an effective treatment for warts.

Although silver, as noted previously, is essentially non-toxic to humans, it can cause a rare permanently disfiguring condition called argyria. Silver is absorbed into the blood and deposited in tissues, such that the skin, eyes, and mucous membranes acquire a grey to blue-black colouring.

Eisler R. Chrysotherapy: a synoptic review. Inflamm Res. 2003 Dec;52(12):487-501.

Kalant H, Grant D, and Mitchell J. Principles of Medical Pharmacology 7th ed. Toronto: Saunders Canada, 2006.

Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer. 1998 Sep;34(10):1522-34.

Silver S, Phung le T, Silver G. Silver as biocides in burn and wound dressings and bacterial resistance to silver compounds. J Ind Microbiol Biotechnol. 2006 Jul;33(7):627-34. Epub 2006 May 25.



  • rhymes with arteriole, bronchiole, and vacuole
  • also known as shikimol or 5-allylbenzo-1,3-dioxole
  • a colourless to slightly yellow (think the colour range of healthy pee) oily liquid at room temperature
  • extracted from the root bark of the sassafras tree and also present in low levels in numerous other plants
  • has been used as a flavouring agent in root beer (the original flavour), sassafras tea, and other foods
  • in 1960, the FDA banned its use in the USA as a food additive after is was found that it causes liver cancer in rats
  • no reported cases of liver toxicity or cancer in humans have been attributed to sassafras consumption - it is important to realize that not all substances that are carcinogenic in lab animals cause cancer in humans (i.e. animal models do not always predict the toxic effects of a substance in humans)
  • is used in the synthesis of piperonyl butoxide (added to insecticides to increase their potency) and the mood-modifying amphetamines MDMA (Ecstacy) and MDE (Eve)


Exenatide (Byetta)

  • a synthetic version of a peptide (small protein) found in the saliva of the Gila monster (which is for some reason pronounced HEE-la), an intricately-patterned North American lizard capable of storing food in its tail
  • is structurally similar to and so mimics the action of glucagon-like peptide 1 (GLP-1), an endogenous (made by the body) incretin (hormone made by the intestine that enhances the secretion of insulin after meals) that is important for regulation of glucose levels in the body and is deficient in diabetics
  • enhances glucose-induced insulin release from beta cells in the pancreas
  • used to treat type II diabetes (doesn't work on type I since people with this form generally have no beta cells, which is why they are diabetic in the first place)
  • administered in combination with other anti-diabetic drugs (i.e. as an add-on or adjunctive therapy) to permit better control of glucose levels
  • main side effects are nausea and vomiting
Mikhail N. Exenatide: a novel approach for treatment of type 2 diabetes. South Med J. 2006 Nov;99(11):1271-9.



  • a group of nuclear proteins found in the sperm of many animals
  • may have a role in the maturation of spermies and/or protect the genetic material (haploid chromosomal DNA, natch) that they carry - thus they may have a role in male infertility (i.e. if your protamines are mutated or expressed at abnormal levels, you're probably going to have to adopt)
  • are used to make neutral protamine Hagedorn (NPH) insulin, an intermediate-acting form of insulin that is formulated such that when it is injected subcutaneously (under the skin) the insulin will be absorbed in a manner that closely resembles how it is normally released by the pancreas into the body AND it will last longer than regular old insulin and so reduces the number of daily injections required by diabetics
  • protamine sulphate is used as an antidote to an overdose of heparin, specifically the uncontrolled bleeding that this entails, acting to bind heparin in a stable complex that blocks its anticoagulant activity - this effect is selective for heparin, so it won't work for other anticoagulants(e.g. if you drink a bunch of rat poison/warfarin, tough)
  • are a component of the liposomal preparation LPD (liposomes/protamine/DNA), a gene delivery system under development for use in cancer gene therapy (this stuff is the future, mark my words)
El-Aneed A. An overview of current delivery systems in cancer gene therapy. J Control Release. 2004 Jan 8;94(1):1-14.



  • trade name is Aldara (5% topical cream)
  • topical immunomodulator (applied to and acts only on the superficial layers of the skin to modify the local immune response)
  • used to treat external genital warts (oh great, another addition to my list of MEDICAL CONDITIONS I REALLY REALLY DON'T WANT TO GET EVER), actinic keratoses (a skin condition that often precedes the development of skin cancer), and superficial skin cancers (basal cell and squamous cell carcinomas and melanoma that appear as a red scaling patch on the skin)
  • increases the production of cytokines (signalling molecules that are similar in function to hormones), which activate the immune system (both innate and adaptive immunity), thus increasing the ability of the body (specifically, the skin) to deal with viral infections and cancerous growths
  • since it has a relatively non-specific mechanism of action, it is likely also effective against other viral infections of the skin and superficial skin cancers
  • may soon find work as an anti-aging agent since it has been shown to repair chronically sun-damaged skin associated with lentigo maligna (melanoma that hasn't begun to spread)


Delta-9-tetrahydrocannabinol (THC)

When I started this blog, way back in November of 2006, I made it my priority to post in a vague and interesting manner about drugs and poisons that the average person would probably know little to nothing about. However, the time has come, good reader, for my coverage of one of the big boys of the drug and poison world. Based on the queries that you have been making using that search box over yonder, I figured it was 'high' time that I discuss the drug we've all been waiting for... delta-9-tetrahydrocannabinol, or THC, as you kids like to call it.

Now, I don't want to have to 'hash' out every last detail for y'all, so I'm gonna cover the basics, tell you to click here or here for more information, and then try to tell you something you didn't already know about THC. Given the subject matter, I felt that it was appropriate to discard my detached, sarcastic, and yet infinitely lovable persona and try to explain THC to you through the red eyes and giggle-injected ramblings of a terminal stoner. However, upon attempting to do so, I became distracted by an intense need for nachos. Ergo, back to normal.

Briefly, THC is the primary psychoactive (acts on your brain) compound found in marijuana / ganja / bhang / maconha, the leaf or flowering part of the plant Cannabis sativa. THC is what gets you stoned. When it is used on its own as a legal drug, THC is called dronabinol. Hashish / hash / kief / charas is resin from the Cannabis plant, while hash oil/honey oil is a concentrated extract of hashish. Both contain more THC than the plant itself. THC readily dissolves in fat, which is why people can cook marijuana in butter, use the butter to bake brownies or make rice krispie squares or what have you, and then eat the results to get stoned (see also: Neil Young's honey slides). THC is a cannabinoid, and acts via specific receptors for this class of compounds in a number of regions in the brain to produce its effects, which I expect you are all familiar with. It also is capable of directly stimulating the cardiac tissue of the heart, which is why tachycardia (increased heart rate) is a common symptom of marijuana use.

Click here or here for more information on marijuana/THC.

Things you may have not known about THC:

  • apparently some folks soak their jays in formaldehyde to increase the potency (strength) of the THC - they call this delightful preparation "dank", "boat", or "AMP" - I have no idea why they call it these things, or if it even works (let me know in the comments), but I do know that formaldehyde is toxic and probably carcinogenic
  • following the inhalation of marijuana smoke, THC typically reaches the brain within 15 seconds, since the lungs and the brain receive a lot of blood and THC can dissolve rapidly through tissues
  • giving THC by injection (e.g. intravenous injection of hashish oil) can cause cardiovascular collapse (heart stops working), disseminated intravascular coagulopathy (all of the blood in your bloody starts to clot), and/or death


Phosgene - Assassinator of alveoli and butcher of bronchioles

  • also called carbonyl chloride (it's an acyl halide) or CG (I'm partial to phosgene, myself)
  • a colourless gas with a musty odour that was developed and employed as a chemical warfare agent during WWI, first being used by the German army in December of 1915
    • was the most effective lethal chemical agent used in WWI, accounting for about 80% of the approximately 100,000 gas-induced casualties
  • is used in the manufacture of plastics and is produced as a by-product of welding and from the combustion of chlorine-containing household products
  • following inhalation it is transported deep into the gas-exchanging region of the lungs, where it slowly reacts with water to produce hydrochloric acid and carbon dioxide - the acid causes tissue damage, leading to the development of pulmonary edema (accumulation of fluid in the lungs, a potentially life-threatening condition)
  • is an alkylating agent and so is carcinogenic
  • acute exposure presents as eye, skin, pulmonary, and gastrointestinal irritation, with pulmonary edema often developing as a delayed symptom preceded by a relatively asymptomatic (no symptoms, you appear to be getting better) period
    • can progress to adult respiratory distress syndrome (ARDS) and death
  • there is no specific and effective antidote for its toxic effect