Bees Benefit From Caffeine

Caffeinated plants provide an unforgettable experience.

Honeybees rewarded with caffeine remember the smell of specific flowers longer than bees given only sucrose, according to a study published in Science. “By using a drug to enhance memories of reward,” the study says, “plants secure pollinator fidelity and improve reproductive success.”

Many drugs used by humans come from plants. But what role do the drugs play for the plants themselves? Frequently, they play the role of toxic avenger, providing a chemical defense against attacks by herbivores. But in smaller doses, they often have pharmacological effects on mammals. The researchers looked at two genera of caffeine-producing plants—Coffea and Citrus. “If caffeine confers a selective advantage when these pants interact with pollinators,” the investigators reasoned, “we might expect it to be commonly encountered in nectar.” And it was. Caffeine at very low doses was measured in the nectar of several of the caffeine-producing plant species, including several Coffea species, as well as some citrus nectars—grapefruit, lemons, and oranges among them.

Next, the researchers wanted to find out if the caffeine-laced nectar could affect learning and memory in pollinating bees. They trained individual honeybees to associate various floral scents with sucrose containing various concentrations of caffeine. This pairing of odor and reward, with high-concentration sucrose as the control, demonstrated that low doses of caffeine had almost no effect on the rate of honeybee learning—but a profound effect on long-term memory. Three times as many caffeinated bees remembered the conditioned floral scent 24 hours later, “and responded as if it predicted reward.” Twice as many bees remembered the scent at the 72-hour mark.

What’s the trick? Caffeine’s ability to influence mammalian behavior is due to its action as an adenosine receptor antagonist. “In the hippocampal region,” the authors write, “inhibition of adenosine receptors by caffeine induces long-term potentiation, a key mechanism of memory formation." The Kenyon cells in mushroom bodies of the insect brain, which showed “increased excitability” under the influence of caffeine, are similar in function to hippocampal neurons, they write. “Remembering floral traits is difficult for bees to perform at a fast pace as they fly from flower to flower and we have found that caffeine helps the bee remember where the flowers are,” said Geraldine Wright of the UK’s Newcastle University, who was lead author on the study. “So, caffeine in nectar is likely to improve the bee’s foraging prowess while providing the plant with a more faithful pollinator.”

It is an interesting balancing act by nature: Too much caffeine makes the nectar toxic and repellent to honeybees. Too little, and there is no behavioral effect on bee memory. “This implies that pollinators drive selection toward concentrations of caffeine that are not repellent but still pharmacologically active,” says the report.  Humans have selected for a not-too-much, not-too-little dose of caffeine in the form of soda drinks and coffee. Is it possible that the humble coffee bean is pharmacologically manipulating us into taking good care of it? And do we drink it when we read or study because, for one thing, it enhances long-term memory? And speaking of memory, people often forget where they tucked the oregano, but they usually have little difficulty remembering where they stashed the coffee.

More pragmatically, honeybees on caffeine may lead researchers toward a better understanding of the foraging strategies of pollinator insects, and allow for improved management of crops and landscapes.

Wright G.A., Baker D.D., Palmer M.J., Stabler D., Mustard J.A., Power E.F., Borland A.M. & Stevenson P.C. (2013). Caffeine in Floral Nectar Enhances a Pollinator's Memory of Reward, Science, 339 (6124) 1202-1204. DOI: 10.1126/science.1228806

Photo credit: http://www.coorgblog.orangecounty.in

Khat: A Psychologist's Field Trip

Looking for a chew in London.
 
I ran across a great story by Vaughan Bell at Mind Hacks, about his stroll around London, looking for khat, the East African stimulant plant that is chewed much like coca leaves.

 Research psychologist Vaughan Bell is not your average armchair academician. Currently a Senior Research Fellow at the Institute of Psychiatry, King’s College, London, Bell is well known online for his contributions to the Mind Hacks blog, which covers unusual and intriguing findings in neuroscience and psychology. He recently taught clinical psychiatry at Hospital Universitario San Vicente de Paúl and the Universidad de Antioquia in Medellín, Colombia, where he remains an honorary professor. He has also worked for Médecins sans Frontières (Doctors Without Borders) as a mental health coordinator for Colombia. (See my interview with Bell last year).

Reprinted with permission:


Finding myself at a loose end yesterday I decided I’d try and track down one of London’s mafrishes – a type of cafe where people from the capital’s Ethiopian, Somali and Yemeni community chew the psychoactive plant khat.

I’d heard about a Somali cafe on Lewisham Way and thought that was as good a place as any to try. The cafe owner first looked a bit baffled when I walked in and asked about khat but he sat me down, gave me tea, and went out back to ask his associates.

“Sorry, there’s no khat in Lewishman. We have internet?” he suggested while gesturing towards the empty computers at the back. I kindly declined but in reply he suggested I go to Streatham. “There are lots of restaurants there,” he assured me.

Streatham is huge, so I arrived at one of the rail stations and just decided to walk south. Slowly I became aware that there were more Somali-looking faces around but there were no cafes to be seen.
Just through chance I noticed some Somali cafes off a side street and walked into the first one I saw. “There’s none here, but next door”, I was told. The people in the next cafe said the same, as did the next, and the next, until I came to an unmarked door.

“Just go in,” a cafe owner called to me from across the street, so I walked in.

The place was little dark but quite spacious. My fantasies of an East African cafe translocated to London quickly faded as my eyes adjusted to the trucker’s cafe decor. Inside, there were four guys watching the news on a wall-mounted TV.

The cafe owner greeted me as I entered. I asked my usual question about khat and he looked at me, a little puzzled.

“You know, khat, to chew?” I ventured. A furrowed brow. Thinking. “Oh, chat. Yes, we have bundles for three pounds and bundles for seven. Which do you want?”

“Give me one for seven” I said. “No problem” he replied cheerily. “Have a seat”.

This wasn’t the first time I had tried khat. Many years ago, when I was an undergraduate in the Midlands, I discovered khat in an alternative shop. It was sold as a natural curative soul lifting wonder plant from the fields of Africa.

I bought some, didn’t really know what to do with it, and just began to ‘gently chew’, as the leaflet advised, while walking through the streets of Nottingham.

So when my bundle of khat arrived, I just picked out some stems and began chomping on one end. “Wait, wait, stop!” they shouted in unison. “We’ll help you” said one and I was joined by the cafe owner and a friend. “Anyway, he said”, “you’re not allowed chew alone, it’s a social thing.”
I was given a bin to put beside my table, was shown how to strip off the stems and pick out the soft parts, and how to chew slowly. I was provided tea and water on the house and told to keep drinking fluids. Apparently, it can be a little strong on the stomach and the plant makes you go to the toilet a lot as, I was told, ‘it speeds up the body’.

I had the company of the cafe owner, a Somali Muslim, and his friend, an Ethiopian Christian.
Over the next two hours we chewed and talked. Ethiopian politics, football, living in another country, khat in Somalia, Haile Selassie, religion, languages, Mo Farah, stereotypes of Africa and family life in London.

People strolled in an out of the cafe. Some in jeans and t-shirt, others looking like they’d just walked in from the Somali desert. Everyone shook my hand. Some bought khat and left, others joined us, all the while chewing gently and drinking sweet tea. At one point I asked the Christian guy why he wore an Islamic cap. He whipped off his hat. “I’m bald” he said “and it’s the only cap you can wear inside” which sent me into fits of laughter.

Khat itself has a very tannin taste and it is exactly like you’d imagine how chewing on an indigestible bush would be. It’s bitty and it fills your mouth with green gunk. The sweet tea is there for a reason.
The effect of the khat came on gently but slowly intensified. It’s stimulating like coffee but is slightly more pleasurable. There’s no jitteriness.

It reminded me of the coca plant from South America both in its ‘mouth full of tree’ chewing experience and its persistent background stimulation. But while coca gave me caffeine-like focus that always turned into a feeling of anxiety, khat was gently euphoric.

My companions told me that it lifts the spirits and makes you talkative. They had a word, which for the life of me I can’t remember, which describes the point at which it ‘opens your mind’ to new ideas and debate.

The active ingredient in khat is cathinone which has become infamous as the basis of ‘bath salts’ legal highs which chemists have learnt to create synthetically and modify. But like coca, from which cocaine is made, the plant is not mental nitroglycerine. It has noticeable effects but they don’t dominate the psyche. It’s a lift rather than a launch.

The guys in the cafe were not unaware of its downsides though. “Don’t chew too often” they told me “it can become a habit for some”. I was also told it can have idiosyncratic effects on sexual performance. Some find it helps, others not so much.

Not everyone was there for khat. Some guys chewed regularly, some not at all, some had given up, some only on special occasions. Some just came to hang out, drink tea and watch the box.

Towards the end when I felt we had got to know each other a bit better I asked why the cafe was unmarked. The owner told me that while khat is legal they were aware of the scare stories and were worried about the backlash from less enlightened members of the community. ‘Immigrants sell foreign drug’ shifts more papers, it seems, than ‘guys chew leaves and watch football’.

Eventually, I said my goodbyes and decided I could use my buzz to go for a walk. I made London Bridge in a couple of hours. But I think my newfound energy came as much from the welcome as it did from the khat.


An Interview with Pharmacologist David Kroll

On synthetic marijuana, organic medicines, and drugs of the future.

(Second post in the “Five-Question Interview” series.)

Back in July, Addiction Inbox ran a fascinating 5-question interview with clinical and research psychologist Vaughan Bell. The post touched on abnormal brain function, drugs, hallucinations, and addiction. It was a blast.

The huge and multi-talented staff here at Addiction Inbox has hopes of making this a semi-regular feature, since there is no shortage of interesting and accomplished people out there who can sometimes be successfully pestered into answering broad-ranging questions about drugs and addiction for an obscure science blog.

Herewith, a 5-question interview with pharmacologist David Kroll, Ph.D., Professor and Chair of Pharmaceutical Science at North Carolina Central University in Durham, and a well-known blogger in the online science community.

A cancer pharmacologist whose field is natural products—he’s currently involved in a project to explore the potential anticancer action of chemicals found in milk thistle and various sorts of fungi—Dr. Kroll received his Ph.D. from the University of Florida, and completed his postdoctoral fellowship in Medical Oncology and Molecular Endocrinology at the University of Colorado School of Medicine. He went on to spend the first nine years of his independent research and teaching career at the University of Colorado School of Pharmacy, where he taught all aspects of pharmacology, from central nervous system-active drugs, to anticancer and antiviral medications. He has also worked as a research pharmacologist for the Research Triangle Institute, and for SmithKline and French Laboratories. He’s responsible for Terra Sigillata—a natural products pharmacology and chemistry blog—and Take As Directed, his personal blog. He is also co-author of Breast Cancer Recurrence and Advanced Disease: Comprehensive Expert Guidance.


1. You’ve been writing about the new synthetic marijuana products on your blog, Terra Sigillata, since they first leaked into the drug underground. Can you briefly explain the origin of these “fake” cannabis chemicals, and the work done by the Huffman lab?

Every area of CNS pharmacology has chemists who try to figure out the smallest possible chemical structure that can have a biological effect. In fact, this is a longstanding practice of any area of pharmacology. Huffman was an excellent chemist who in the 1990s was trying to figure out the most important part of the active component of marijuana that might have psychotropic effects. These compounds made by him and his students, surprisingly simple ones, I prefer to call cannabimimetics since they mimic the effect of the more complex cannabinoids in marijuana. These basic chemistry and pharmacology studies are what ultimately lead to new drugs in every field - a facet of chemistry called "structure-activity relationships" or SAR.

But since they are simple, they are relatively easy to make - some of Huffman's work at Clemson was actually done by undergraduate chemistry majors. So, it was no surprise that they would be picked up by clandestine drug marketers, even though cannabis (UK) and marijuana (US) are freely available. The attraction to users was, until recently, that Huffman compounds (prefixed with "JWH-" for his initials) could not be detected in urine by routine drug testing. Hence, incense products containing these compounds have been called “probationer's weed.”

2. In a recent guest blog post for Scientific American titled “Drugs from the Crucible of Nature,” you remind us that several hundred common drugs are modified natural products. What stands in the way of discovering, isolating, and testing more of these plant drugs?

Fully 25% of all pharmaceuticals can trace their roots to natural products: chemicals made by plants, bacteria, fungi, and marine creatures that possess biological effects in mammals. The first ones we recognized as humans were those which altered our perception of reality or our ability to adapt to the strenuous, pre-modern life: hallucinogens for religious purposes and stimulants to support physical activity and suppress hunger. Over time, we found other drugs that treated pain (opiates), heart failure or "dropsy" (digitalis), or cancerous lesions (podophyllin from the Penobscot Native Americans).

We know today that natural products have much greater chemical diversity than drugs made by man and are useful additions to the study of new drug targets. However, naturally-occurring drugs sometimes have major drawbacks: they are difficult to make in the laboratory or require large amounts of their natural source to be commercially viable, they can have undesired effects that may not be apparent from traditional uses, or they require chemical modifications to be safer, more resistant to metabolism, and to become patentable intellectual property.

Over the last 10-15 years, the short-term, investor- and market-driven view of pharmaceutical companies has led the big firms to eliminate their natural product research programs. Today, much of the discovery of naturally occurring drugs has been left to academic researchers and small companies where many former pharma researchers reside. Once we get compounds that may be viewed as "druggable" by the pharmaceutical industry or the National Cancer Institute (in the US), they can then move to clinical trials.

3. Psychoactive plant drugs like the poppy played a major role in the development of modern pharmacology and neurology. One school of thought says that psychoactive drugs are overprescribed, addictive, and ineffective panaceas. The other side views such drugs as targeted, effective, and increasingly sophisticated treatments for diseases once thought to be untreatable. Have we become a nation of crazed pill heads, or is this simply pharmaceutical medicine on the march?

I have a middle-of-the-road view on this topic. As you know (and my blog readers will know) my father suffered from alcoholism that was comorbid with clinical depression. Real, biochemically-based depression has been undertreated in Western societies, in part due to the stigma that admitting mental disorders is somehow viewed as compromising one's intellect. Nothing could be farther from the truth, of course. Some of the most brilliant and creative minds in all fields have suffered from depression, mania, and, sadly, ended their lives early by suicide.

So, drugs certainly have their place for those unfairly dealt a hand of bad brain biochemistry. We should not view this as any worse than getting the bad genes for hypertension or diabetes. The problem seems to be those with mild-to-moderate psychiatric disorders, many of which can be managed without drugs but that require personal effort in the form of psychotherapy, cognitive behavioral therapy, or other flavors of hard, personal work. As Americans, what do we want? The hard work or the pill? If we want to lose weight, do we want exercise, caloric restriction, or a pill? Hence, we are the ones who are complicit with pharmaceutical companies. We want the pill rather than the hard work and the companies supply that demand. Anyone who doesn't realize that we as a society facilitate what we demonize in pharmaceutical companies is just simply in denial.

4. It’s increasingly obvious that our legal and cultural approaches to addictive drugs have not been successful. What’s your take on the drug war, and on the problematic distinction between “legal” and “illegal” drugs of abuse?

My primary research field is cancer drugs, but my teaching brings me into the realm of drugs of abuse, simply because so many of those drugs are naturally-occurring. So, my views must be taken in that perspective. In the US, I think that it is morally difficult to justify the legality of addictive drugs like alcohol and tobacco while restricting other psychoactive compounds. I do not advocate for other drugs to be used recreationally. I just feel that US laws need to be consistent. Our experiment with criminalizing alcohol was an abysmal failure that fostered organized crime. Our continued experiment with criminalizing other drugs has been equally a failure. However, I am very much against a libertarian argument that society should be free to determine what they want because, frankly, many drugs impair one's decision-making ability.

But I like your question: many drugs declared illegal for recreational use are among the most useful therapeutics for pain, especially the pain associated with surgery and cancer. My greater humanistic concern is that our society's zero tolerance approach to drugs that "could" be illegal is that people who need them for their desired effect often go without. Undermanagement of pain is the major casualty of the war on drugs. No, let me fix that. People who suffer unnecessarily from pain when useful drugs could be used are the major casualties of the war on drugs.

5. What’s going on in pharmaceutical research these days that has you excited?

When I was graduating with my toxicology degree in 1985 from the Philadelphia College of Pharmacy and Science, I asked my chairman Dr. Gary Lage where I should expect new drugs to come from. His words of wisdom were that I should pay close attention—not to drug companies, but rather to major advances in physiology. Learning that the kidney played a role in red blood cell count led to the use of erythropoeitin for anemia caused by renal failure and chemotherapy.

Today, I see major drug targets in the epigenome—the part of genetics that is affected by environmental influences. We are all stuck with the static part of our inherited DNA—the exact base sequences and their polymorphisms and mutations. However, we're learning that those things can be modified by diet, environmental exposures, and, yes, drugs. The epigenome is a broad target for a multitude of diseases, never more complicated but never more promising.