Tag Archives: irritable bowel syndrome

Hallucinogenic molecules and the brain

Psychedelic drugs seems to be enjoying a ‘moment’. After decades of being vilified and  declared illegal (in many jurisdictions), psychedelic (or hallucinogenic) drugs are once again being tested for use in therapy. A Sept. 1, 2017 article by Diana Kwon for The Scientist describes some of the latest research (I’ve excerpted the section on molecules; Note: Links have been removed),

Mind-bending molecules


All the classic psychedelic drugs—psilocybin, LSD, and N,N-dimethyltryptamine (DMT), the active component in ayahuasca—activate serotonin 2A (5-HT2A) receptors, which are distributed throughout the brain. In all likelihood, this receptor plays a key role in the drugs’ effects. Krähenmann [Rainer Krähenmann, a psychiatrist and researcher at the University of Zurich]] and his colleagues in Zurich have discovered that ketanserin, a 5-HT2A receptor antagonist, blocks LSD’s hallucinogenic properties and prevents individuals from entering a dreamlike state or attributing personal relevance to the experience.12,13

Other research groups have found that, in rodent brains, 2,5-dimethoxy-4-iodoamphetamine (DOI), a highly potent and selective 5-HT2A receptor agonist, can modify the expression of brain-derived neurotrophic factor (BDNF)—a protein that, among other things, regulates neuronal survival, differentiation, and synaptic plasticity. This has led some scientists to hypothesize that, through this pathway, psychedelics may enhance neuroplasticity, the ability to form new neuronal connections in the brain.14 “We’re still working on that and trying to figure out what is so special about the receptor and where it is involved,” says Katrin Preller, a postdoc studying psychedelics at the University of Zurich. “But it seems like this combination of serotonin 2A receptors and BDNF leads to a kind of different organizational state in the brain that leads to what people experience under the influence of psychedelics.”

This serotonin receptor isn’t limited to the central nervous system. Work by Charles Nichols, a pharmacology professor at Louisiana State University, has revealed that 5-HT2A receptor agonists can reduce inflammation throughout the body. Nichols and his former postdoc Bangning Yu stumbled upon this discovery by accident, while testing the effects of DOI on smooth muscle cells from rat aortas. When they added this drug to the rodent cells in culture, it blocked the effects of tumor necrosis factor-alpha (TNF-α), a key inflammatory cytokine.

“It was completely unexpected,” Nichols recalls. The effects were so bewildering, he says, that they repeated the experiment twice to convince themselves that the results were correct. Before publishing the findings in 2008,15 they tested a few other 5-HT2A receptor agonists, including LSD, and found consistent anti-inflammatory effects, though none of the drugs’ effects were as strong as DOI’s. “Most of the psychedelics I have tested are about as potent as a corticosteroid at their target, but there’s something very unique about DOI that makes it much more potent,” Nichols says. “That’s one of the mysteries I’m trying to solve.”

After seeing the effect these drugs could have in cells, Nichols and his team moved on to whole animals. When they treated mouse models of system-wide inflammation with DOI, they found potent anti-inflammatory effects throughout the rodents’ bodies, with the strongest effects in the small intestine and a section of the main cardiac artery known as the aortic arch.16 “I think that’s really when it felt that we were onto something big, when we saw it in the whole animal,” Nichols says.

The group is now focused on testing DOI as a potential therapeutic for inflammatory diseases. In a 2015 study, they reported that DOI could block the development of asthma in a mouse model of the condition,17 and last December, the team received a patent to use DOI for four indications: asthma, Crohn’s disease, rheumatoid arthritis, and irritable bowel syndrome. They are now working to move the treatment into clinical trials. The benefit of using DOI for these conditions, Nichols says, is that because of its potency, only small amounts will be required—far below the amounts required to produce hallucinogenic effects.

In addition to opening the door to a new class of diseases that could benefit from psychedelics-inspired therapy, Nichols’s work suggests “that there may be some enduring changes that are mediated through anti-inflammatory effects,” Griffiths [Roland Griffiths, a psychiatry professor at Johns Hopkins University] says. Recent studies suggest that inflammation may play a role in a number of psychological disorders, including depression18 and addiction.19

“If somebody has neuroinflammation and that’s causing depression, and something like psilocybin makes it better through the subjective experience but the brain is still inflamed, it’s going to fall back into the depressed rut,” Nichols says. But if psilocybin is also treating the inflammation, he adds, “it won’t have that rut to fall back into.”

If it turns out that psychedelics do have anti-inflammatory effects in the brain, the drugs’ therapeutic uses could be even broader than scientists now envision. “In terms of neurodegenerative disease, every one of these disorders is mediated by inflammatory cytokines,” says Juan Sanchez-Ramos, a neuroscientist at the University of South Florida who in 2013 reported that small doses of psilocybin could promote neurogenesis in the mouse hippocampus.20 “That’s why I think, with Alzheimer’s, for example, if you attenuate the inflammation, it could help slow the progression of the disease.”

For anyone who was never exposed to the anti-hallucinogenic drug campaigns, this turn of events is mindboggling. There was a great deal of concern especially with LSD in the 1960s and it was not entirely unfounded. In my own family, a distant cousin, while under the influence of the drug, jumped off a building believing he could fly.  So, Kwon’s story opening with a story about someone being treated successfully for depression with a psychedelic drug was surprising to me . Why these drugs are being used successfully for psychiatric conditions when so much damage was apparently done under the influence in decades past may have something to do with taking the drugs in a controlled environment and, possibly, smaller dosages.

Sniffing out disease (Na-Nose)

The ‘artificial nose’ is not a newcomer to this blog. The most recent post prior to this is a March 15, 2016 piece about Disney using an artificial nose for art conservation. Today’s (Jan. 9, 2016) piece concerns itself with work from Israel and ‘sniffing out’ disease, according to a Dec. 30, 2016 news item in Sputnik News,

A team from the Israel Institute of Technology has developed a device that from a single breath can identify diseases such as multiple forms of cancer, Parkinson’s disease, and multiple sclerosis. While the machine is still in the experimental stages, it has a high degree of promise for use in non-invasive diagnoses of serious illnesses.

The international team demonstrated that a medical theory first proposed by the Greek physician Hippocrates some 2400 years ago is true, certain diseases leave a “breathprint” on the exhalations of those afflicted. The researchers created a prototype for a machine that can pick up on those diseases using the outgoing breath of a patient. The machine, called the Na-Nose, tests breath samples for the presence of trace amounts of chemicals that are indicative of 17 different illnesses.

A Dec. 22, 2016 Technion Israel Institute of Technology press release offers more detail about the work,

An international team of 56 researchers in five countries has confirmed a hypothesis first proposed by the ancient Greeks – that different diseases are characterized by different “chemical signatures” identifiable in breath samples. …

Diagnostic techniques based on breath samples have been demonstrated in the past, but until now, there has not been scientific proof of the hypothesis that different and unrelated diseases are characterized by distinct chemical breath signatures. And technologies developed to date for this type of diagnosis have been limited to detecting a small number of clinical disorders, without differentiation between unrelated diseases.

The study of more than 1,400 patients included 17 different and unrelated diseases: lung cancer, colorectal cancer, head and neck cancer, ovarian cancer, bladder cancer, prostate cancer, kidney cancer, stomach cancer, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, Parkinson’s disease (two types), multiple sclerosis, pulmonary hypertension, preeclampsia and chronic kidney disease. Samples were collected between January 2011 and June 2014 from in 14 departments at 9 medical centers in 5 countries: Israel, France, the USA, Latvia and China.

The researchers tested the chemical composition of the breath samples using an accepted analytical method (mass spectrometry), which enabled accurate quantitative detection of the chemical compounds they contained. 13 chemical components were identified, in different compositions, in all 17 of the diseases.

According to Prof. Haick, “each of these diseases is characterized by a unique fingerprint, meaning a different composition of these 13 chemical components.  Just as each of us has a unique fingerprint that distinguishes us from others, each disease has a chemical signature that distinguishes it from other diseases and from a normal state of health. These odor signatures are what enables us to identify the diseases using the technology that we developed.”

With a new technology called “artificially intelligent nanoarray,” developed by Prof. Haick, the researchers were able to corroborate the clinical efficacy of the diagnostic technology. The array enables fast and inexpensive diagnosis and classification of diseases, based on “smelling” the patient’s breath, and using artificial intelligence to analyze the data obtained from the sensors. Some of the sensors are based on layers of gold nanoscale particles and others contain a random network of carbon nanotubes coated with an organic layer for sensing and identification purposes.

The study also assessed the efficiency of the artificially intelligent nanoarray in detecting and classifying various diseases using breath signatures. To verify the reliability of the system, the team also examined the effect of various factors (such as gender, age, smoking habits and geographic location) on the sample composition, and found their effect to be negligible, and without impairment on the array’s sensitivity.

“Each of the sensors responds to a wide range of exhalation components,” explain Prof. Haick and his previous Ph.D student, Dr. Morad Nakhleh, “and integration of the information provides detailed data about the unique breath signatures characteristic of the various diseases. Our system has detected and classified various diseases with an average accuracy of 86%.

This is a new and promising direction for diagnosis and classification of diseases, which is characterized not only by considerable accuracy but also by low cost, low electricity consumption, miniaturization, comfort and the possibility of repeating the test easily.”

“Breath is an excellent raw material for diagnosis,” said Prof. Haick. “It is available without the need for invasive and unpleasant procedures, it’s not dangerous, and you can sample it again and again if necessary.”

Here’s a schematic of the study, which the researchers have made available,

Diagram: A schematic view of the study. Two breath samples were taken from each subject, one was sent for chemical mapping using mass spectrometry, and the other was analyzed in the new system, which produced a clinical diagnosis based on the chemical fingerprint of the breath sample. Courtesy: Tech;nion

There is also a video, which covers much of the same ground as the press release but also includes information about the possible use of the Na-Nose technology in the European Union’s SniffPhone project,

Here’s a link to and a citation for the paper,

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules by Morad K. Nakhleh, Haitham Amal, Raneen Jeries, Yoav Y. Broza, Manal Aboud, Alaa Gharra, Hodaya Ivgi, Salam Khatib, Shifaa Badarneh, Lior Har-Shai, Lea Glass-Marmor, Izabella Lejbkowicz, Ariel Miller, Samih Badarny, Raz Winer, John Finberg, Sylvia Cohen-Kaminsky, Frédéric Perros, David Montani, Barbara Girerd, Gilles Garcia, Gérald Simonneau, Farid Nakhoul, Shira Baram, Raed Salim, Marwan Hakim, Maayan Gruber, Ohad Ronen, Tal Marshak, Ilana Doweck, Ofer Nativ, Zaher Bahouth, Da-you Shi, Wei Zhang, Qing-ling Hua, Yue-yin Pan, Li Tao, Hu Liu, Amir Karban, Eduard Koifman, Tova Rainis, Roberts Skapars, Armands Sivins, Guntis Ancans, Inta Liepniece-Karele, Ilze Kikuste, Ieva Lasina, Ivars Tolmanis, Douglas Johnson, Stuart Z. Millstone, Jennifer Fulton, John W. Wells, Larry H. Wilf, Marc Humbert, Marcis Leja, Nir Peled, and Hossam Haick. ACS Nano, Article ASAP DOI: 10.1021/acsnano.6b04930 Publication Date (Web): December 21, 2016

Copyright © 2017 American Chemical Society

This paper appears to be open access.

As for SniffPhone, they’re hoping that Na-Nose or something like it will allow them to modify smartphones in a way that will allow diseases to be detected.

I can’t help wondering who will own the data if your smartphone detects a disease. If you think that’s an idle question, here’s an excerpt from Sue Halpern’s Dec. 22, 2016 review of two books (“Weapons of Math Destruction: How Big Data Increases Inequality and Threatens Democracy” by Cathy O’Neil and “Virtual Competition: The Promise and Perils of the Algorithm-Driven Economy” by Ariel Ezrachi and Maurice E. Stucke) for the New York Times Review of Books,

We give our data away. We give it away in drips and drops, not thinking that data brokers will collect it and sell it, let alone that it will be used against us. There are now private, unregulated DNA databases culled, in part, from DNA samples people supply to genealogical websites in pursuit of their ancestry. These samples are available online to be compared with crime scene DNA without a warrant or court order. (Police are also amassing their own DNA databases by swabbing cheeks during routine stops.) In the estimation of the Electronic Frontier Foundation, this will make it more likely that people will be implicated in crimes they did not commit.

Or consider the data from fitness trackers, like Fitbit. As reported in The Intercept:

During a 2013 FTC panel on “Connected Health and Fitness,” University of Colorado law professor Scott Peppet said, “I can paint an incredibly detailed and rich picture of who you are based on your Fitbit data,” adding, “That data is so high quality that I can do things like price insurance premiums or I could probably evaluate your credit score incredibly accurately.”

Halpern’s piece is well worth reading in its entirety.