Category Archives: drugs and the brain

A cough medicine that really worked, and it contained opium – the story of Fudge’s Firewater

Runny nose, sore throat, hacking cough? Do you run to the pharmacy for a cough medicine that may or may not help? Until 2006, in the market town of Bridport in the south west of the UK, the locals had the luxury of a cough medicine that really seemed to work. The medicine was Fudge’s Mentholated Honey Syrup, or as the locals christened it, Fudge’s Firewater. Here is the story of this potent potion, how it came about and why it is no longer available.

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Mr Fudge’s Pharmacy in the late 1950s when the road was flooded. Mr Fudge is seen standing in the shop doorway with Donald Balson from the next door butchers shop in front. Photo kindly supplied by Richard Balson.

The story begins in the 1950s when Ken Fudge moved from London to Bridport to open his pharmacy in West Allington, next door to Balsons, Britain’s oldest family butchers (est. 1515). For Mr Fudge, trained in London but born in Blandford, this was something of a return to his roots. At that time, many pharmacists devised their own remedies, often to secret recipes, and Mr Fudge was no exception. He made several nostrums, as these remedies produced and sold in a single pharmacy are called, but the most popular and enduring was his Mentholated Honey Syrup (known locally as Fudge’s Firewater). When Mr Fudge retired in 1973, the recipe transferred to the East Street Pharmacy where it was sold until 2006, for much of that time under the supervision of Mr Kevin Morrish. Even now, the mere mention of the Fudge’s name evokes a warm wave of nostalgia and longing in many Bridport people.

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One of Mr Fudge’s bottles (probably about 50 years old). Photo kindly supplied by Jamie Dibdin

The medicine
Fudge’s Firewater was an old-style cough medicine recommended for common winter ailments: coughs, colds, influenza, loss of voice, hoarseness, sore throat and catarrh. The dose was one teaspoon every four hours and the label warned ominously that each spoonful should be “taken very slowly”. It was sold “over the counter” without prescription but strictly under the control of the pharmacist. Fudge’s Firewater was immensely popular and many people have told me how much they trusted it to help their symptoms: “Brilliant cough mixture, couldn’t beat it”, “Amazing medicine for coughs and sore throats”, “Never bought anything else”, “Please, if there is a god, bring back Fudge’s Firewater”. People travelled long distances to purchase the medicine, holiday makers often went home with supplies and, during some winters, as many as 250 bottles of Firewater were sold each week at the East Street Pharmacy.

The medicine also had a formidable reputation: “It nearly blew your head off but by golly it did the trick”, “Tasted like red diesel mixed with the finest brandy, lovely”, “The menthol really took your breath away” “It was a trial to take but you knew it would make you better” and several people spoke of “the Fudge’s shudder”.

As Mr Fudge himself said: “Some do swear by it, some do swear at it”.

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A bottle of Fudge’s Mentholated Honey Syrup (Fudge’s Firewater). Photo kindly supplied Emily Hicks, Bridport Museum

Unconventional uses of Fudge’s Firewater
The medicine was also a voice-saver for some professional singers and I heard about one well-known entertainer who would regularly send a friend to buy Firewater from Mr Morrish to help lubricate her vocal cords. Similarly, Marco Rossi told me that, in the 1990s, when he was part of local band, Stocky Lamaar, performing in smoke-filled pubs around Dorset, he and Al, the other vocalist, each had a bottle of the potion by them on stage. With the occasional swig of Firewater, they could sing all evening without sounding like “Madge from Neighbours at a Bonnie Tyler tribute karaoke night”.

What was Fudge’s Firewater and how did it work?
Mr Fudge’s medicine was a dark brown syrupy liquid made by mixing menthol crystals and a little fudgy flavouring into Gee’s Linctus, itself an old-fashioned cough remedy dating from the Victorian era. Gee’s linctus, or to give it its proper name, squill linctus opiate, contains several potentially active ingredients.

First, there is tincture of opium, an alcoholic extract of opium (the resin derived from the seed capsules of opium poppies). The main active ingredient in opium is morphine, a substance with an established effect on cough, but also a well-known drug of abuse, and the linctus contains morphine at low levels. Squill, a plant extract, is another potentially active component in the linctus that, paradoxically, encourages coughing and mucus removal. The medicine also contains alcohol at similar levels to a fortified wine and this may have contributed to the Firewater experience. Mr Fudge’s masterstroke was to boost the effects of the Gee’s linctus by adding menthol, a remedy used for many years to help with symptoms of coughs and colds; menthol may also act as an oral anaesthetic helping with sore throats and may relieve nasal congestion.

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The opium poppy

(from Wikipedia, for details see Link)

Although cough medicines cannot alter the course of viral infections, they may help you feel better and Mr Fudge’s medicine attacked symptoms in several ways which is perhaps why it was so popular and so successful. It was the menthol, however, that made the potion so memorable, justifying the Firewater nickname and establishing a shared experience among those who used it, believed in it and benefitted from it.

Abuse of Fudge’s Firewater
Non-prescription medicines such as Gee’s linctus, and Fudge’s Firewater, have been abused by people trying to access even the small amounts of morphine they contain. Gee’s linctus is, for example, reported to induce a “lovely euphoria and dreaminess”, but only if you are prepared to drink 50ml or more of the medicine! Local pharmacists were aware of the problem and tried to control it: Mr Morrish monitored all sales personally and Mr Conroy (manager in the early 21st century) restricted sales to one bottle per person, with a signature.

The end of Fudge’s Firewater
Gee’s linctus gradually fell out of favour as a cough medicine because of the problem of abuse. Finding commercial sources of the linctus became more difficult and temporary interruptions to the availability of Fudge’s Firewater occurred early in the 21st century. Then, in January 2006, a notice appeared on the window of Bridport’s East Street Pharmacy (then owned by Moss/Alliance) announcing that the medicine would be discontinued owing to “problems with the supply of ingredients”. That was the official line but I suspect this was not the full story. Around this time there had also been a change in the pharmacy regulations. Nostrums containing even small amounts of morphine, like Fudge’s Firewater, now required a prescription and this change must have contributed to Moss’s decision.

That wasn’t quite the end, though, because a modified Firewater was available for a few years from the St John’s Pharmacy in Weymouth, about 20 miles south east of Bridport. A Weymouth pharmacist, Mr Dipan Shah, produced and sold a version of the potion but because of the change in pharmacy regulations, people needed to persuade their doctor to issue a private prescription if they wanted the medicine. The need for a prescription severely affected sales and by 2009 production finally ceased. The change in regulations also means that Fudge’s Firewater is very unlikely ever to reappear.

Fudge’s Firewater served Bridport well for 50 years. The medicine is now just a memory but one that should be preserved as an important part of Bridport’s history.

I should like to thank Angela Alexander, Stuart Anderson, Richard Balson, David Conroy, Richard Cooper, Margery Hookings, Diana Leake, Kevin Morrish, Caroline Morrish-Banham, Dipan Shah, Elizabeth Williamson, Joy Wingfield, The Bridport Museum and the many commenters on social media who generously helped me in preparing this article.

This article appeared in a slightly modified form in the March edition of the Marshwood Vale Magazine.

The picture at the top of this post shows Mr David Conroy, manager of the East Street Pharmacy in Bridport in the early 21st century (from the Bridport News).

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For a matter of record, I have set down the timeline of Mr Fudge’s Medicine below

The Fudge’s Firewater Timeline

1950s Mr Ken Fudge opens his pharmacy at 7 West Allington, Bridport and begins production of Mentholated Honey Syrup (Fudge’s Firewater)
1973 Mr Fudge retires and the recipe for Firewater transfers to Mr Joe Sparrow at his 24 East Street Pharmacy
1975 Mr Kevin Morrish takes over the East Street Pharmacy, together with Fudge’s Firewater
1998 Mr Morrish retires and the business is acquired by Lifestyle
2001 Moss acquires the East Street Pharmacy, Mr David Conroy is the manager until 2005
2006 Moss ceases production of Fudge’s Firewater
2006-2009 Firewater available in Weymouth (Mr Dipan Shah, St John’s Pharmacy) but only with private prescription.

The opium fields of England

A surprising picture appeared in the Guardian newspaper towards the end of June. It showed fields, near Blandford, Dorset in South West England, painted lilac with the flowers of the opium poppy. This controversial crop, associated in many people’s minds with war-torn countries like Afghanistan, is now being grown commercially in England to produce the medically-important pain killer morphine. But just how did opium poppies come to be grown across swathes of rural England?

Opium and the opium poppy

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Papaver somniferum as described in a 19th century German book (from Wikipedia, click on the picture for more details)

 

The opium poppy, or Papaver somniferum as it is more correctly called, is an imposing plant with fleshy grey-green leaves, showy pastel coloured flowers and impressive pepper pot seed heads. Standing up to a metre tall, the opium poppy brings architectural interest to the garden but it has a darker side. Within the seed head is a milky liquid containing a mixture of narcotic chemicals including morphine and codeine. If the unripe seed head is pierced, this latex seeps out and, left to dry, this is opium, prized for its extraordinary psychoactive powers.

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The unripe seed capsule of an opium poppy pierced to release the opium (from Wikipedia)

 

Humans have used opium for many thousands of years and the earliest written reference to the drug comes from the Middle East around 4000BC. The ancient Egyptian, Greek and Roman civilisations were also well acquainted with the properties of the drug using it enthusiastically. Although growth of Papaver somniferum is typically associated with warmer climates, the opium poppy has a history of cultivation in the UK. In the 18th and 19th centuries, many houses in the East Anglian Fens grew a stand of white opium poppies so that the dried seed capsules could be used to brew a tea containing small amounts of morphine. This infusion helped counter the aches and pains suffered by people living harsh lives in what was then, a remote, unhealthy part of the country. Use was not confined to the Fens as  the Dorset-writerThomas Hardy, in The Trumpet Major, refers to poppy heads and pain relief.

By the 19th century, imported opium was freely available in the UK and was used extensively at all levels of society. Opium was supplied in many forms including laudanum, a tincture of opium in wine, popularised by the Dorset-born physician Thomas Sydenham. The drug was taken to relieve pain, to induce sleep and to treat cough and diarrhoea. Its euphoriant properties were also prized and recreational use occurred with some problems of dependence. Encouraged by the drug’s popularity, attempts were made in the late 18th and early 19th centuries to grow opium poppies commercially in the UK but these were abandoned in favour of imported Turkish opium.

From opium to morphine

Morphine was isolated from opium in the 19th century and the powerful pain killing and euphoriant properties of the pure drug were quickly recognised. These come at a price as, compared to opium, morphine has potentially dangerous side effects and is highly addictive. By the 20th century, all non-medical use was banned but, to the present day, morphine is widely prescribed to relieve moderate and severe pain especially after major surgery. Diamorphine (heroin) is also used for pain relief in the UK but we hear more about its illicit use, the problems of addiction and the associated criminal activity. All morphine used clinically is still obtained from the opium poppy, extracted either from crude opium or from the dried seed heads.

The 21st century opium fields of England

Poppy heads by Jane V Adams
Opium poppies growing near Bere Regis in Dorset, UK showing the seed heads (by Jane V Adams)

 

By the end of the 20th century, the morphine used for medical purposes in the UK was extracted from opium poppies grown in Tasmania and Spain. It was tacitly assumed that the climate in the UK was unsuitable for their commercial cultivation. In 1999, however, John Manners, a seed merchant from Oxfordshire questioned this doctrine. He had seen striking pictures of purple opium poppies growing commercially in Poland, and decided to have a go at growing the plants in the UK. He set up some small trial plots and grew the poppies successfully in the southern part of the country. But did they produce morphine when grown in the UK? With the help of the Scottish pharmaceutical company, Macfarlan Smith (now a division of Johnson-Matthey), he showed that indeed they did. A full field trial the following year in Oxfordshire was also a success and, by 2002, 100 hectares of opium poppies were being grown commercially in the UK, each hectare yielding about 15 kg of morphine. More farmers were persuaded to grow the crop and nowadays, early summer sees about 2500 hectares of farmland blooming with the unselfconscious lilac flowers, mostly in the counties of Dorset, Hampshire, Lincolnshire and Oxfordshire.

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Opium poppies growing in Lincolnshire, UK (from Wikipedia)

 

Although they were initially uneasy about growing opium poppies, farmers now find it to be a lucrative break crop to prepare the land for growing cereals or oil seed rape the following season. Farmers contracted to Macfarlan Smith must prepare the seed bed and sow poppy seed supplied by the company which also advises on agronomy and pest control while the opium poppies are growing. The UK climate seems to suit the poppies well and after flowering they are left to dry before the seed capsule and about 5 cm of stem are harvested. The harvest is taken to a central processing facility where the poppy seeds in the capsule are separated leaving “poppy straw”. Poppy seeds contain little or no morphine and are sold for various culinary uses such as bread making. Poppy straw is processed in Macfarlan Smith’s Edinburgh factory where the morphine is isolated by solvent extraction and purification. About half of the UK requirement of medical morphine (~60 tons/year) is now made from poppies grown in the UK, including those grown in Dorset. So when you come across these beautiful lilac-painted fields next summer, think morphine, think pain relief, and think poppy extracts ending up in medicine cabinets in hospitals and pharmacies.

I should like to thank Marilyn Peddle (www.marilynjanephotography.co.uk) for generously providing the featured image which is of opium poppies growing in North Dorset
and Jane Adams (https://urbanextension.wordpress.com/) for generously providing the photograph of opium poppies growing near Dorchester.

This is a slightly  modified version of an article that appeared in the September edition of the Marshwood Vale Magazine.

The risks of eating poppy seed bread

Our local baker makes a very good wholemeal loaf which he garnishes liberally with poppy seeds. As I tucked in to a sandwich made from this excellent bread, I spared a thought for the governor of London’s Brixton Prison who recently suffered the exquisite embarrassment of failing a drugs test. Routine heroin tests for several inmates at the Prison had come up positive but the prisoners protested their innocence and challenged the governor to take a test himself. Generously he did and that’s when the embarrassment occurred. Eventually, the source of the “drugs” was traced to bread laced with poppy seeds. The seeds contain morphine and other opiates which register as positive in the prison-drugs test and although this story sounds like an urban myth, poppy seeds are now banned from the prison.

Poppy seeds
poppy seeds
Poppy seeds are used in many cultures as a food ingredient, for example to garnish breads and rolls, as an ingredient in cakes or ground in sauces and pastry fillings. The seeds are harvested from the dried seed capsule of the opium poppy (Papaver somniferum). The opium poppy is well known as the source of the powerful painkillers and drugs of abuse, morphine and codeine (opiates). Although the seeds themselves contain only trace amounts of the opiates, they can be contaminated by poor harvesting practices or insect damage so that commercially available poppy seeds contain varying amounts of morphine.

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But does it matter that poppy seeds contain opiates? The EU clearly thinks it does matter because in 2011 it commissioned a huge report on the public health risks of consuming opiates in poppy seeds. Consumption of the seeds in food varies considerably across the EU but some Central-Eastern European cultures use poppy seeds widely. The report contains a mass of data and found that, although some groups may be consuming morphine at active levels from poppy seeds, few side effects are reported. One person did, however, report morphine-like side effects after consuming a meal sprinkled with a massive 75g of contaminated poppy seeds.

poppy-seed-bagel
poppy seed bagel

 

Poppy seed-opiates also matter to people undergoing drug testing and there are numerous reports of failed workplace heroin tests, and lost jobs, after consumption of food containing poppy seeds. It may seem surprising but consumption of just one poppy seed bagel can lead to urinary morphine levels of 250ng/ml after three hours. Workplace heroin testing actually assesses morphine levels so that it can be difficult to distinguish between consumption of heroin (heroin is broken down to morphine) and of poppy seeds. To try to eliminate the poppy seed-false positives, the threshold for a positive test was raised from 300 ng morphine/ml to 2000 ng/ml in US Federal Workplaces in 1998. Not all employers follow this rule so that confusion can still arise. For similar reasons, US Federal Prisons forbid prisoners to eat foods containing poppy seeds and athletes undergoing routine drug testing are advised to avoid foods containing the seeds.

A better solution would be to find a heroin-specific test. Forensic scientists identified 6-monoacetylmorphine (6-MAM) as a heroin-specific metabolite found in the urine of heroin users and absent after poppy seed ingestion. In principle, this should deal with the confusion but 6-MAM is broken down fairly quickly in the body so that it can be missed. Very recently a team from King’s College, London have reported another heroin-specific metabolite, ATM4G, that they hope might provide the basis of a better test.

Some people have taken advantage of the presence of opiates in poppy seeds by steeping the seeds in water to release the active compounds. We could call this a poppy seed tea, and it should in principle produce low level opiate effects. The problem with these brews is that because the levels of morphine in the seeds are very variable so the potencies of the teas also vary in a largely unpredictable manner. Great care should be taken and there are more than a dozen reports of deaths occurring after consuming poppy seed tea owing to morphine overdose.

The poppy seed-opiate story also exposes an interesting conundrum. If someone takes morphine or even uses poppy seed tea we would call them a drug user. If another person eats poppy seeds, we would say that it’s part of their culture, even if they experience low-level morphine effects. All I know is that I shan’t stop buying my baker’s bread or his lemon and poppy seed cake!

Lock up your hydrangeas, drug thieves about!

Hydrangea hortensis smith

Plants are rich and varied sources of chemicals that change brain function, so-called psychoactive chemicals. For example, the coca plant, a shrub indigenous to the foothills of the Andes, was used for thousands of years by the local people because of the effects of the cocaine contained in the leaves. The peyote cactus has been used for millennia by the inhabitants of Mexico and Central America to experience the psychoactive effects of mescaline. In the 19th century, many families living in the Fens in the East of England grew a stand of white poppies in a corner of their garden. These were harvested to make a “poppy-head tea” containing small amounts of opium. The tea was used as a traditional remedy for the various ailments that afflicted rural life in that part of the UK.

These are just three examples but they illustrate the ingenuity of humans for finding plants that have interesting or useful properties when consumed. For every flower or plant, someone, somewhere will have tried eating it or smoking it and, if they survived, they will have reported the effects.

Hydrangea May 2012-1

I was, therefore, more than surprised when, last month, I read a Guardian leader “In praise of hydrangeas” which not only extolled the plant for its blooms but also pointed out the recent discovery of the psychoactive properties of the flowers. According to a companion piece there had been a spate of hydrangea attacks in northern France, attributed, so the article alleged, to people wishing to smoke the dried flowers and leaves because of the hallucinogenic and euphoria-inducing effects which are similar to those of cannabis. The thieves must be after the new shoots judging from the state of a hydrangea in my garden; it has plenty of new growth but the few flowers left are dry, brown and rather mangy.

I hadn’t heard of the psychoactive properties of hydrangea before and didn’t know quite what to make of the story. It sounded worthy of April Fool’s Day but in fact the craze for smoking hydrangea is not new and springtime hydrangea theft has been known in Bavaria for more than 10 years. In Romania, they are so concerned that they have stopped planting the shrub in parks.

Hydrangea does not feature in my pharmacognosy textbook suggesting that if hydrangea does possess any interesting pharmacological properties, these have been overlooked. Nevertheless, the shrub does contain some unique chemicals including the coumarins, hydrangine and hydrangenol but unfortunately no psychoactive properties have been reported for these substances. Importantly, hydrangea does not contain compounds typical of cannabis such as tetrahydrocannabinol.

So what’s going on here? It doesn’t look as though there are major psychoactive chemicals in hydrangea so how does smoking the shrub produce a high? Perhaps we can get a clue from veterinary reports on the dangers of hydrangea to pets. Apparently dogs and cats can become unwell if they eat the leaves. This is attributed to chemicals found in hydrangea called cyanogenic glycosides which can break down, when metabolised, to produce the very poisonous substance, hydrogen cyanide. Cyanogenic glycosides are found in many different plants including some apricot kernels and almonds, also apple and cherry seeds.

Hydrogen cyanide is very poisonous to humans as it inhibits energy production in cells. Some of the short term effects of cyanide are headache, dizziness and confusion. Perhaps when leaves or flowers of hydrangea are smoked, small amounts of hydrogen cyanide are released. Consumption of one hydrangea joint might, therefore, provide a little cyanide and the effect, combined with a good dose of imagination could be interpreted as cannabis-like. This would also fit with the many warnings about not smoking more than one hydrangea joint because of the significant risk of cyanide poisoning.

I have not come across any reports of hydrangea smoking in the UK but I did find a report of bloom theft in Hastings and Bexhill in 2012. Apparently, the thieves were then selling the dried blooms to flower arrangers at a boot fair. At least that’s what they said!

I should like to thank Dr Ben Whalley (University of Reading) and Prof Kurt Hostettman (University of Geneva) for helpful discussions.

Poppy head tea, laudanum and heroin: now we can “see” where they act

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In the 19th century many houses in the Fenlands of East Anglia in the UK reserved a corner of their garden for a patch of white poppies.  The plants were harvested and dried to make “poppy head tea”, a beverage containing small amounts of morphine leached from the poppies.  The tea was consumed to counter the aches, chills, agues and fevers experienced in this bleak part of the UK.  The compounds present in the poppy heads may be obtained in a more concentrated form by piercing the unripe seed head.  A milky liquid seeps out and this is dried to produce “opium” which contains up to 10 % morphine.   Opium was consumed liberally in the 19th century in the form of laudanum.  This was a concoction of opium and alcohol, and was taken for relief of pain and to reduce cough.  Laudanum contains about 1% morphine and cases of addiction were common but the preparation offered the only source of pain relief for many.  Nowadays the highly addictive morphine derivative, heroin, is considered one of the most harmful drugs available. 

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There is an urgent need to find out more about how these drugs act and new research, published in Nature last week, shows for the first time a picture of the site of action of morphine.  This is a step change in our understanding of how these drugs work and a major advance in pharmacology.

The effects of opium have been known for centuries; some of the earliest reports date back to the ancient Greeks.  Morphine is the principal “opiate” in opium and quite how the drug worked was unclear until the 1970s when morphine was shown to bind to specific sites in the brain.  It seemed odd at the time that the brain should have binding sites for a plant-derived chemical but this conundrum was soon solved when natural opiates (enkephalins and endorphins) were discovered.  The sites where morphine bound opportunistically were in fact sites where the natural opiates acted to modulate brain function. 

These sites in our brains where morphine and the natural opiates bind and affect brain function came to be called opiate receptors.  Surprisingly, the principle whereby opiates are detected by their receptors is similar to that also shown for many other signals that humans are able to detect.  Other examples are smells, tastes, vision and the myriad chemicals (neurotransmitters) in the brain and hormones in other parts of the body that influence our behaviour.  The surprising conclusion of years of work in many labs has been that signal detection in all of these examples is based on a common principle.  In each case, there is a signal and a detector protein, termed a receptor, with the ability to recognise that specific signal and react to it.  The receptor collaborates with a transducer termed a G protein (named for its ability to bind a molecule abbreviated as GTP).  The receptor and G protein together sit in the membrane of a cell providing a signalling machine.  The signal molecule from the outside of the cell attaches to the receptor and activates the G protein sending a chemical stimulus to the inside of the cell and altering its activity.

Not only do we find this common principle of signal/receptor/G protein for many signalling systems but the receptors are also the sites of action of a third or more of currently prescribed drugs including many best sellers.  For example, drugs used to treat high blood pressure, asthma, schizophrenia and Parkinson’s disease act via these kinds of receptors.   Some illegal drugs such as cannabis and, of course, morphine also target this class of receptor.   If you are still not convinced of the importance of these receptors then bear in mind that if you are drinking coffee or tea while reading this, the caffeine in these drinks is also acting via one of these receptors.

In the new work, two labs in California (Brian Kobilka at Stanford and Ray Stevens at the Scripps Institute in La Jolla), have determined the structure of opiate receptors in three dimensions using x-ray crystallography.  Many labs had spent years trying to analyse the structures of this class of receptor until about five years ago a technical breakthrough made it possible to make crystals of the proteins.  The structures of several of these receptors have now been reported (see a previous post) and the new work describes the structures of two opiate receptors.     The images contained in these new studies show the structures of the receptor together with a drug sitting in its binding site.

Just having the structure of these opiate receptors is an important milestone in the field but they also open the way to rational drug design.  It should now become possible to design new drugs based on their ability to fit in to the binding site of these receptors.  The hope is that drugs will emerge that retain the pain killing ability of opiates but lack the addictive potential.

There is another fascinating aspect of one of the new opiate receptor structures:  the receptors were found in closely linked pairs.    There has been much circumstantial evidence that these kinds of receptors functioned as pairs, rather like identical twins, but this is some of the first hard evidence of this.

Se a related post: Shedding new light on how adrenaline works

Magic mushrooms, Sigmund Freud and depression?

There’s something slightly edgy about medical research using controlled drugs and it usually provides good media fodder.  So it was towards the end of January, when there was a flurry of interest in the UK media about research on the effects of the controlled psychedelic drug psilocybin on human volunteers.    Headlines such as – Magic mushrooms “could treat depression” – were seen, none of which did justice to the real substance of the work.  The BBC even carried a description of one of their presenters, Michael Mosley taking the drug – for research purposes of course! 

Psilocybin is one of the hallucinogenic substances in “magic mushrooms”.  It has a fascinating history so I thought I would write about it.

Magic mushrooms in Green Park, London

The story starts at dawn on October 3rd 1799 when a poor man can be seen gathering field mushrooms in London’s Green Park.  When he gets home, the mushrooms are cooked with flour, water and salt to provide a morning broth for him, his wife and their four children.

A few hours later Everard Brande, a doctor, is summoned to the household where the family are experiencing strange symptoms.  The father has developed vertigo and disturbed vision whereas the rest of the family complain of poisoning and stomach cramps with their extremities becoming cold.  Their pulse and breathing oscillate between frightening highs and lows.  The family are overwhelmed with the fear of dying – all that is except eight year old Edward who is “attacked with fits of immoderate laughter”.

We know nowadays that the family must have consumed, by accident and through ignorance, some Liberty Cap mushrooms (“magic mushrooms” “shrooms”).  These grow widely in the UK and continental Europe in the autumn.  The 200-year old story of the family and these mushrooms opens the door to a fascinating scientific saga.

Some history

A group of three small, conical, yellow-brown mushrooms on spindly stems, with mixed ground-cover foliage below and in the background. A smaller fourth mushroom of the same type is visible below, in the background.

Liberty Cap mushrooms (Psilocybe semilanceata) are part of the large family of up to 200 species of Basidiomycota mushroom that contain the psychedelic drug psilocybin.  These mushrooms are found in many parts of the world with the Psilocybe genus being the major type.  Psilocybe have long been associated with ritual because of their ability to change human perception – the “psychedelic” effect.   Evidence had been found in Algeria, Mexico and Spain for their use in religious ceremonies.  The Aztecs called them teonanacatl (divine mushroom) and the mushrooms were reportedly served at the coronation of Moctezuma II in 1502.  Use of Psilocybe by the Aztecs was suppressed following the Spanish conquest but they have continued to be used covertly by native Indians in this part of America.  

Little was known about these ceremonies in the US and Europe until husband and wife team, Gordon and Valentina Wasson travelled to Mexico in the 1950s.  Their aim was to understand the culture associated with the “divine mushroom” and they made several visits to Mexico at that time.  In 1955, Gordon Wasson was one of the first westerners to participate in an indigenous mushroom ceremony.  In an article in the popular magazine “Life” in 1957, Wasson described the mushroom ceremony and the sensations he experienced.  On one visit they were also accompanied by the French mycologist, Roger Heim, who identified the mushrooms as Psilocybe mexicana.   

In order to identify the active species in the mushrooms, samples were given to Albert Hofmann at Sandoz in Basel. Hofmann (pictured above) was already well known as the chemist who had first synthesised the related psychedelic drug LSD in 1938 and who later inadvertently experienced the effects of the drug himself.   Hofmann made extracts of the Psilocybe and analysed the constituents for their psychological effects.  His work was greatly helped by his readiness to test extracts on himself.  In this way he showed that there were two principal active compounds in the mushrooms, psilocybin and psilocin.  Once ingested, psilocybin is rapidly converted to psilocin.

The effects of psilocybin and LSD

So what are the effects of psilocybin and psilocin on humans?  Psilocybin has effects rather similar to the two other principal psychedelics, mescaline and LSD, although there are differences in detail and in potency.  Sol Snyder in his book “Drugs and the Brain” describes how he took LSD to document and to understand its effects.  This is an excellent description from a respected scientist and he reports changes in sensory perception, especially visual effects.  Objects may seem distorted, change colour or even move.  Confusion between sensory modalities (synaesthesia) may also occur.  Sense of time and space are altered but it is the effect on the sense of self that is particularly striking.  “Boundaries between self and non-self evaporate, giving rise to a serene sense of being at one with the universe.”  He goes on to speculate:  “The almost predictable transcendence of ego boundaries brought on by these drugs has caused scientists to consider that there might be a neural basis for the ego.”   Others report heightened awareness, super-reality and mystical experiences after taking the drug.  Many people enjoy the effects produced by these drugs which sometimes offer insights not available in normal life.  For others it is an unpleasant experience and a minority have injured or killed themselves as a result of disorientation caused by changed perception or loss of self.   The experience may depend on the state of the individual and their environment when they take the drug (“set and setting”).  More recently a five-component scale has been devised to provide a semi-quantitative measure of the effects of these drugs. 

So, how are these curious effects on human consciousness achieved by these drugs?  In the case of psilocybin and LSD, it is thought that the drugs hijack some of the normal processes in the brain.  Brain function depends on the release of chemicals termed neurotransmitters.  These are detected by their binding to specialised proteins called receptors.  One neurotransmitter that is important for regulating a host of functions in the brain and elsewhere is serotonin.  This neurotransmitter regulates behaviour, mood, sleep, appetite and blood flow.  Psilocybin and LSD both bind to and activate receptors for serotonin so it is not surprising that they lead to widespread effects. 

Therapeutic use of psilocybin

In the 1950s it was felt that drugs such as LSD and psilocybin held promise as therapeutic agents and they were used during psychotherapy to lower psychological defences and to facilitate emotional insight.  In the 1960s the effects of psilocybin were studied by the Harvard Professor, Timothy Leary, who became notorious for his work on psychedelics.    Leary’s eventual dismissal from Harvard fuelled the growing view at the time that use of these drugs was a form of cultural rebellion.  The drugs were increasingly discussed by the media in terms of their potential for abuse and there were moves by the authorities to ban the drugs.  Now, in most countries, LSD, psilocybin and mescaline are controlled drugs.  Somewhat anomalously, the Psilocybe mushrooms were not initially controlled and even in the early years of the 21st century there were shops freely selling “shrooms” in London.  In 2005 the law in the UK was changed and the mushrooms were included in the ban, but as with other controlled drugs nowadays, it is still possible to buy the mushrooms via internet suppliers. 

When the drugs became illegal this inhibited research on their therapeutic uses almost completely.  Recently there has been a resurgence of interest and several careful studies have been performed on the effects of psilocybin on humans.

Franz Vollenweider and colleagues in Zurich have carefully catalogued the effects of psilocybin on humans, describing the psychological effects using standard rating scales.  They concluded that, although there is a small risk of a bad reaction to psilocybin which could include dysphoria, anxiety or panic, the administration of moderate doses of the drug to healthy, high functioning and well prepared subjects is associated with acceptable levels of risk providing it is done in a carefully monitored research environment.  They did state, however, that this did not apply to recreational or less controlled studies. 

Roland Griffiths and colleagues at Johns Hopkins in the US administered psilocybin to human volunteers under controlled conditions and described the acute perceptual and subjective effects.  These included a complete mystical experience for 61% of those tested and/or extreme fear and anxiety in 39% of those tested.  One month after testing, about two thirds of the participants rated the experience as having substantial personal and spiritual significance leading to positive change in attitude, mood and behaviour.  14 months later, these feelings were undiminished.   These are fascinating observations suggesting that psilocybin has considerable potential for changing human behaviour. 

Psilocybin has also been reported to have useful effects in treating obsessive-compulsive disorder, cluster headache and anxiety associated with terminal cancer.

The most recent studies

But let’s now return to the work I mentioned at the outset that caused the media flurry in the UK.  This is work performed by a group lead by David Nutt at Imperial College in London in collaboration with the Beckley Foundation.

In one study, brain imaging techniques were used to try to understand how the psychological effects of psilocybin were related to changes in brain activity.  Two indicators of brain activity (blood oxygenation and cerebral blood flow) were assessed in a small number of volunteers and it was found unexpectedly that psilocybin caused reductions in brain activity.  For one brain region the reduction in activity correlated with the psychological effects reported.  They interpreted the work in terms of an effect of psilocybin to reduce activity and connectivity in key “connector hubs” in the brain.  These “connector hubs” normally act to facilitate information transfer so the authors conclude that it is not surprising that a reduction in their activity leads to profound effects on consciousness.

In a second study, the effect of the drug to facilitate access to personal memories and emotions was tested.   There have been reports in the past that psychedelics lead to “relivings” of past memories and the Imperial College group had observed this before with one volunteer who had taken psilocybin.  In the new study, volunteers were presented with memory cues and asked to recollect autobiographical memories.  The study was performed after psilocybin administration and after placebo and participants were asked to rate the vividness of the memories evoked.   Memories were found to be more vivid and more visual under psilocybin but no “relivings” occurred.  This may have been because the cues were positive whereas in the past, negative cues had lead to “relivings” of negative memories.    Two weeks after these tests were performed participants reported significant increases in well-being related to the vividness of the memories.

These are interesting observations but it should be pointed out that Vollenweider and colleagues have also studied brain activity after psilocybin administration and find activation, in complete opposition to what was reported by the Imperial College group.  This contradiction may relate to differences in experimental technique but it certainly needs to be resolved.   Another gripe I have with the Imperial College work relates to their use of the term “trend level significance” for some correlations tested.  We all know this is a sanitised way of saying “no significance”.   Indeed, for these examples, the P values are greater than 0.05 so there is no correlation; this should have been the conclusion and it is misleading to imply otherwise.

Where does the future take us?

The underlying aim of this kind of work on brain imaging in relation to psychological testing is to try to find correlates of psychological processes in brain activity.  This is moving ahead very rapidly in a field termed neuropsychoanalysis.  One of the aims here is to find neural correlates for the Freudian concepts of Id, Ego and Super Ego.  This is discussed well on another blog but personally I wouldn’t want to go very far with these correlates until I had resolved the discrepancies between the brain responses to psilocybin measured using different techniques.

The Imperial College group have also speculated that psilocybin may be a novel antidepressant.  This is based on their observation of effects of the drug on activity in the medial prefrontal cortex.  Other antidepressant treatments have similar effects to psilocybin on this brain region leading to the speculation. 

There is a lot to think about here and much promise for the future.  It is difficult to avoid the conclusion that by banning psilocybin we may have missed out on many useful effects of this drug.