March 2011

by James J. Galligan, Ph.D., Associate Chair,2c-i image from wikipedia
Department of Pharmacology and Toxicology

There was a recent news story about 1 death and several hospitalizations that might have resulted from the use of a drug known as 2C-I.  This happened after a spring break house party in suburban Minneapolis.

What is 2C-I?  2C-I is 2,5-dimethoxy-4-iodophenethylamine.  The key part of this chemical name is “phenylethylamine”.  This is important because the brain neurotransmitters, norepinephrine and dopamine are also phenylethylamines.  The brain neurotransmitter, serotonin is also very similar in chemical structure to the phenylethylamines.  Many legal and illegal drugs are also phenylethyamines including: amphetamine, methamphetamine and MDMA (“Ecstasy).

Let’s first discuss methamphetamine and amphetamine.  These drugs are stimulant drugs as they increase alertness.  This effect is caused by activation of the norepinephrine systems in the brain.  Amphetamine and methamphetamine also activate norepinephrine nerves that supply the heart and blood vessels.  Amphetamine and methamphetamine stimulate the heart to beat faster and they contract blood vessels.  These effects cause an increase in blood pressure and they also make some people susceptible to altered heart rhythms and potential heart attacks.  Both drugs cause pleasant feelings (euphoria) and this is what makes them addictive.  The euphoria is caused by activation of dopamine systems in the brain.

While MDMA is similar to amphetamine and methamphetamine in chemical structure, it has little activity at the dopamine and norepineprhine systems.  Instead, MDMA prefers to interact with the serotonin system.  The serotonin system is partly responsible for feelings of anxiety and also for monitoring visual and auditory (sound) sensations.  This is why MDMA is classified as a hallucinogen (like LSD-25) but also why it is used as a “club drug”.  MDMA reduces anxiety and increases feelings of interpersonal warmth and empathy.

Back to 2C-I:

Although 2-CI is a phenylethylamine, it does not have the same level of activity at the norepinephrine or dopamine systems as amphetamine and methamphetamine.  2C-I is more like MDMA in its pharmacological effects as 2C-I prefers the serotonin systems.  So, 2C-I can produce hallucinations (like LSD-25) and also feelings of interpersonal warmth and empathy.

LSD-25 is a Schedule I drug and this means it has no legitimate medical use.  MDMA does have some legitimate medical uses but it is still highly regulated and it is illegal to sell these drugs over the internet.  2C-I is chemically different from these regulated drugs and therefore it does not fall under the same stringent controls.  This makes it possible to sell 2C-I through online chemical suppliers or as a research chemical.  The problems arise in unknown quality control in producing the chemical so it difficult to know how much of the active drug is actually in the sample increasing the risk of overdose.  In addition, MDMA can be toxic to serotonin neurons in the brain and 2C-I may also kill serotonin neurons.

Let the buyer beware!

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

cnn image of nuclear reactor


There is tremendous interest in the potential risks of radiation exposure that might come from  the earthquake and tsunami damaged Fukushima Daiichi nuclear plant in Japan.

Last week I discussed the mechanisms responsible for protection of the thyroid gland provided by potassium iodide tablets.  I want to clarify a few points about that blog.

  • Firstly, I provide basic information about the pharmacology and toxicology of drugs.  I focus on stories that appear in the popular press and my goal is to provide a little scientific background to these stories.  I do not and will not make any recommendations about what drugs readers should or should not take.
  • Secondly, readers need to understand that potassium iodide tablets provide very specific protection against one type of radiation danger.    Potassium iodide will only protect the thyroid gland against radiation exposure that would occur if the thyroid gland absorbs radioactive iodine emitted from the damaged reactor.

There is a wide range of the types of radiation that might be emitted and potassium iodide tablets do not protect against most radioactive emissions.


by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

The recent earthquake and tsunami in Japan has caused severe destruction and has damaged a nuclear power plant.  This poses the danger of release of radioactive materials into the atmosphere and subsequent exposure to the people living near the damaged plant.  You may have heard on the continuous news coverage of this catastrophe that medical personnel are providing potassium iodine to people at risk for radiation exposure.

Why is potassium iodine useful for protection against radiation toxicity?  To answer this question we first need to discuss the thyroid gland.  The thyroid gland produces thyroid hormone which is released into the circulation to regulate metabolism of cells throughout the body.  Cellular metabolism generates body heat and energy utilization.  Thyroid hormone contains iodide and without iodide there is not thyroid hormone and this disrupts normal cell metabolism.  Normally iodine comes from dietary sources (including iodized salt) and this is sufficient to maintain normal thyroid function.  One of the toxic substances released from a damaged nuclear reactor is radioactive iodine.  When people breathe in radioactive iodine contaminated air, they are giving themselves a dose of this toxic substance.  Radioactive iodine accumulates in high concentrations in the thyroid gland and the radiation can then damage the thyroid or cause thyroid cancer.  IOSAT Photo

Interestingly, radioactive iodine is used to treat thyroid cancer as the radiation will kill off the tumor cells and iodine accumulates in the thyroid gland.  Anyway, people who are at risk will be protected against accumulation of radioactive iodine in the thyroid gland by potassium iodine supplements.  Potassium iodine fills up the thyroid stores of iodine leaving no room for radioactive iodine to accumulate.  Because potassium iodine is safe and non-toxic, there is no risk to using this preventative treatment.

Let’s hope that there is a quick and uneventful resolution to the current nuclear danger in Japan.  In the meantime, supplements of potassium iodine will help reduce the long term risks of exposure to any leaking radiation.

nicotine replacement therapy image

by James J. Galligan, Ph.D., Associate Chair,
Department of Pharmacology and Toxicology

Quitting cold turkey is a common regimen for kicking the cigarette smoking/nicotine habit.  Cold turkey does work for many cigarette smokers.  However, there are also many smokers who find that quitting is easy because they have done it hundreds of times.

Nicotine replacement therapy (NRT) is a common treatment for smokers in this latter category.  NRT comes in nasal sprays (very messy), chewing gum and “the patch”.  NRT involves a step down strategy over a 8-12 week period where the smoker gives up cigarettes and initially goes on a high dose nicotine treatment for 2-3 weeks followed by successive 2-3 week nicotine dose reductions.  This strategy is designed to gradually reduce the nicotine dependence and uncomfortable withdrawal symptoms (irritability, craving, disruption of sleep, etc.) until smokers no longer crave nicotine.  Studies have shown that NRT doubles the smoker’s chances of quitting by the end of the 12 week period although the success rate is still not great.  In placebo controlled studies, NRT produces about a 40% success rate while subjects on the placebo treatment quit about 20% of the time.  The big problem is that 80-90% of the quitters relapse in about 1 year. Current Food and Drug Administration (FDA) approval for NRT indicates a maximum 12 week treatment.

Part of the problem with cigarette smoking/nicotine addiction is the behavioral aspect of the addiction.  For example, the post meal coffee and cigarette is a very satisfying experience for smokers and there are strong social reinforcements associated with several smokers sharing this experience.  Studies have shown that even crack cocaine addiction has a strong behavioral-social component to the drug smoking experience and addiction.  So, unless the cigarette smoker changes his or her friends and family the smoker will continue to be exposed to the drug (nicotine)-related cues.

Drug addiction therapists and the FDA are beginning to re-think the 12 week limitation on NRT.  Nicotine raises blood pressure in some individuals but overall the data indicate that nicotine itself is not particularly dangerous to your health.  Cigarette smoking is clearly dangerous to your health as cigarette smoke contains an array of toxic chemicals.

Cigarette smoking is the major cause of lung cancer and it is also a major cause of deadly cardiovascular diseases such as high blood pressure, clogged arteries, heart attacks and strokes.  At this time, the long-term risks of NRT have not been studied in large groups of subjects.  However, the risks of cigarette smoking are unambiguous.  About 20% of Americans are cigarette smokers; this translates into 62 million people who are at great risk for lung cancer and cardiovascular disease which places a huge burden on our healthcare system.  It may be time to permit long-term NRT in an effort to reduce cigarette smoking relapse rates.  Of course this must be done with mechanisms in place to carefully monitor any unanticipated adverse effects that might appear when large numbers of people are using long-term NRT to kick the habit.

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