24 January, 2013, Nick Kilvert
Susan* lives at 3000 feet above sea level in the majestic Great Smoky Mountains dividing North Carolina and Tennessee; two of the United States’ more conservative southern territories. She shares a house with her husband of eight years, and gets along well with her in-laws. She has three adult children, the last of whom moved out of home a few years ago. She loves to visit her kids when she can. Viewed from outside, hers seems a good life.
Susan’s a bit on the thin side, but apart from that her appearance would not strike the casual observer as abnormal in any way. She wears a wig. She has a few close friends, but says being house bound for months at a time can place a great deal of pressure on a friendship. This year, despite her best efforts, Susan lost four more kilograms (10lbs), down to just 46. Most of her hair has fallen out, and she’s weak with fatigue.
For more than six months of the year she’s stuck at home, unable to go down the hill to pick up the groceries or visit her family. She hasn’t flown in years and stays indoors if the weather looks grim. Any drop in pressure may trigger a ‘rogue’ daytime attack; wake ‘the beast’. Usually though, she knows it will be a bit after 8 pm, sometime in September, when the first one hits. She’s afraid to fall asleep.
‘Personal accounts abound of sufferers…taking aim at the source of the pain with drills or other household weapons…’
She gets three hours rest a night, at best. Her last cluster headache cycle lasted seven months, the one before it six. When she married her husband in 2005, she had been pain-free for five years. But one year into her marriage and the attacks began again. Dr Peter Goadsby, Professor of Clinical Neurology at the University of London, describes it as “probably the worst pain that humans experience”. Four times daily the ‘octopus’ tentacles’ as she calls them, begin to stir.
She’ll rub her temple absent-mindedly at first. Soon though, a cold pain will branch across her forehead toward her ear. Her rubbing will turn to a push, before she begins gouging uncontrollably into hear earlobe, trying in vain to stop the agony as it drives deeper into her brain. Behind her weeping left eye socket, always the left, an ice-pick is being levered up and down, while another enters below her jaw. The pain moves deep into her brain in waves like a rising tide, building to a relentless crescendo that leaves her convulsing in agony, panicked and out of her mind for two to three hours on end. She says time doesn’t exist in that space. She’s exhausted after one, but knows she may have as little as fifteen minutes before the next, and that all up there’ll be at least four for the night. Desperate for a cure, she says she has finally found reason to hope. If only slightly.
Susan is a ‘cluster-head’. She’s been suffering episodic cluster headaches since she was 22, although ‘headache’ doesn’t really describe the agony she lives with. “I’m still very firmly convinced that our whole society has been very conditioned by advertising, which shows people looking [sic] miserable and down and out in black and white, then comes the product – the painkiller – in colour, and rainbows come up, the music starts, and everybody starts singing and dancing…” According to Dr Gerald Edmund, secretary general of the Australian Brain Foundation, this is the image that is conjured when we think of a headache. But ‘suicide headaches’ as clusters have come to be known, sometimes carry tragic consequences.
Accounts abound of sufferers begging family members to end their misery, bashing heads against walls or their fists, and worse, taking aim at the source of the pain with drills or other household weapons near to hand. Dr Anne MacGregor of the City of London Migraine Clinic described in a recent interview, the x-ray of one sufferer who pointed a shotgun at the offending eye socket and pulled the trigger. Despite inflicting massive brain injuries, he survived the blast. The source of his pain, located deep in the head, undoubtedly survived also.
Cluster headaches, so named because they occur in daily clumps or clusters for months on end, affect about 0.1% of men and 0.08% of women worldwide. Despite their severity, not much is known about the primary cause. Episodic cluster sufferers, those that experience an annual remission period, typically start their cluster cycle around the longest or shortest days of the year, though this predictability fades over the long-term. The attacks take on a daily rhythmicity, with the first coming at the same time of night, and recurring up to 8 times daily during peak cycle. A 2012 review published in the scientific journal Cephalalgia points out that there seems to be a relationship with the onset of an episodic attack and the REM period of sleep – the sleep state in which we experience dreams. Unfortunately for chronic cluster sufferers, they don’t go into remission at any time and no such association with the REM state has been established.
“We desperately need a legal medication for CH [cluster headache] that was developed for CH, not migraine or psychosis or nerve pain or something else. Hand-me-down meds are not working. The side effects are deadly.”
Our daily rhythms – our sleeping patterns, responses to light and dark, as well as body temperature, hunger, thirst, and fatigue are maintained by the hypothalamus, an almond sized control centre located deep in the brain at the top of the brainstem. The daily or circadian rhythmicity of cluster attacks suggests that irregularities in the hypothalamus may be a catalyst. 3-D images produced by PET (positron emission tomography) scans have shown nerve signal abnormalities in the grey matter around the hypothalamus during attacks.
The pain of cluster headaches is believed to originate with the trigeminal nerve – the largest nerve in the head, responsible for relaying sensory information from the majority of our facial extremities including the forehead and jaw, to the nervous system. Initially, it was thought that vasodilation – swelling of the blood vessels in the brain, particularly the carotid artery – was causing a pinching of nerve fibres. Artificially increasing blood pressure by giving a vasodilator such as alcohol, histamine, or dilute nitroglycerine, can stimulate an attack when a patient is already within a cluster cycle. However, PET scans have shown the same vasodilation to occur in other types of non-cluster headaches. Artificial blood vessel dilation outside a cycle does not usually induce an attack, leading researchers to believe that this may be a symptom rather than a cause. These uncertainties, alongside the relative obscurity of the disorder and lack of funding for research, mean that medication has so far been non-targeted, ineffective and marred by negative side-effects.
“We desperately need a legal medication for CH [cluster headache] that was developed for CH, not migraine or psychosis or nerve pain or something else. Hand-me-down meds are not working. The side effects are deadly”, Susan tells me as she rolls off the names of ten ‘hand-me-down’ medications she remembers taking for her cluster headaches in recent years. “Carbamazepine [for seizures], Verapamil [hypertension and chest pain], Elavil and Prozac [major depressive disorder], Lithium [for manic bi-polar]… Verapamil was the most effective, but a side effect is hyperplasia (overgrowth of gum tissue), which causes loss of your teeth. I lost two teeth and switched to another preventative. In desperation I went back to the Verap [sic] last fall, but with little effect. So I quit taking it after a month.” Many sufferers including Susan inhale pure oxygen from a pressurized canister similar to a SCUBA tank. This can prove effective in aborting an attack, but can take up to half an hour to kick in, and doesn’t reduce the severity of future clusters.
‘So why hadn’t she heard of this before? Of course there had to be a catch.’
In extreme scenarios, the condition can become completely drug resistant. In 2004, 6 patients were nominated for experimental surgery involving implantation of deep-brain electrical stimulation devices capable of delivering up to 3.28 volts to the hypothalamus. After fourteen and a half months, two patients were completely pain free and another reported only sporadic attacks. One patient was unresponsive to the treatment and another had the implantation procedure aborted after suffering panic attacks. However, the sixth patient died due to an intracerebral haemorrhage that developed post surgery. The bleed risk with this type of treatment is estimated to be around three per cent. The conclusion from the trial, published in the neurological journal Brain, is that this type of surgery is a last ditch option.
By 2010, Susan was physically and emotionally exhausted. Her doctor had run out of options and there was little hope that she would ever be cluster free. Like so many people today who find themselves sick, desperate, and afraid, Susan searched for answers online. Of course there were the usual dead-ends and quackery; ‘miracle cures’. Many web-pages lamented the lack of good treatment, or offered support for family and friends. But she was after something more, and one site offered her real hope.
The seed for ‘Cluster Busters’ was planted in 1998 when a cluster headache sufferer posted on an Internet bulletin board that he suspected he had stumbled on something that had stopped his usual cycle. Others took his advice and they too reported great results. A preliminary website was established, and by 2002 Cluster Busters was officially up and running. By the time Susan stumbled across the site in 2010, there were thousands of members testifying to the success they’d had with the ‘Busters treatment. So why hadn’t she heard of this before? Of course there had to be a catch.
‘His typical annual cluster cycles had not recurred in the three years he had been taking LSD…’
The treatment that the first ‘cluster buster’ had reported in the ‘90s was his use of a compound that is defined in chemistry by its indole-ring base. In his case it was the hallucinogenic drug lysergic acid diethylamide, more commonly referred to as LSD. His typical annual cluster cycles had not recurred in the three years he had been taking LSD, but had resumed once he stopped. Today, ‘Cluster Busters’ is more focused on another indole-ring compound, psilocybin, naturally occurring in hallucinogenic mushrooms found in temperate to tropical regions across the globe.
Since 1971, the same year that US President Richard Nixon famously declared his ‘war on drugs’, psilocybin containing mushrooms have been listed as a schedule 1 prohibited substance, and possession can result in a long jail sentence for the user. Even compounds considered to have ‘similar’ effects fall under this restriction. For Susan, a middle-aged woman with a family, living in a conservative US state, this was far from ideal. She had to be sure this was the real thing.
Scientific studies on banned substances are extremely difficult to perform and studies involving human trials are next to impossible. The costs are exorbitant and red tape crisscrosses every path. Australian PhD researcher Craig Motbey of the University of Sydney, says his team was paying up to $10,000 a gram last year to perform laboratory research on a new street drug called mephedrone. At the same time the drug was selling on the streets for around $30 a gram.
So far, scientists have only managed preliminary research on psilocybin, but their results have been impressive. A 2006 study led by Yale School of Medicine research scientist Dr Andrew Sewell, and published in Neurology, documented the results of 53 cluster headache patients who went on to use psilocybin containing mushrooms or LSD as treatment. 22 of 26 psilocybin users reported that ingestion of the mushroom aborted an attack. Even more astounding was that 52 per cent of subjects had a total cessation of their cluster period. For some, this cut short months of pending agony. A further 42 percent fell into the range of partial to total stopping of their cluster period. This was the first time any treatment had offered the hope of a cluster free life.
“The delays on this sort of research can directly cost lives…”
The problem of course, is that ‘magic mushrooms’ and LSD are strongly psychoactive drugs. However, 42 percent of the volunteers from the trial reported that they achieved their results at sub-hallucinogenic doses. Dr Sewell’s research team hypothesized that the active ingredient might be separate to the properties that cause the hallucinogenic affects. This hypothesis was tested in 2010 by a German science team led by Professor Matthias Karst and including Yale Professor Dr John Halpern, who also worked on Dr Sewell’s 2006 study. They experimented with a chemically tweaked cousin of LSD known as BOL-148, that produces zero psychotropic effects. At most, the patients in the trial reported a “flabby” or “slight drunk” feeling after taking the standard dose. All five patients in the study had become unresponsive to Verapamil – the same drug that caused Susan to lose her teeth. The results were very promising. One patient classified as a chronic sufferer reported a termination of his cluster period with ongoing remission.
Two chronic sufferers reported reduced frequency in attacks including periods of remission for a month or more and a fourth patient experienced remission for less than a month at a time. Two of these patients said that the severity of their attacks was now so weakened that they no longer needed to use abortive treatments like oxygen. However, this sample size is small to say the least.
The running hypothesis is that ergotamines contained in magic mushrooms cause a vasoconstriction or shrinking of the blood vessels in the brain, counteracting the nerve pinching effect of cluster headache. Ergotamines were originally found in fungus in the 16th century and are a precursor to LSD. However, little is known about why the ingestion of these drugs may stop a cluster period long term.
The problem now, according to Professor Karst, is the huge costs and legal restrictions associated with carrying out a phase 2 randomised controlled trial (RCT) – essentially a controlled trial on a large group of people. Frustrated, Professor Karst is quick to point out that although BOL-148 is not a hallucinogenic compound, it is still restricted under United Nations drug guidelines because it is analogous in chemical structure to LSD. University of Sydney drugs researcher Craig Motbey is similarly perplexed by current drug laws, which he says hamstring scientists while doing little to curb drug use. “The delays on this sort of research can directly cost lives…”
Earlier this year, a public letter to the United Nations opened with the following: “Fifty years after the UN single convention on narcotic drugs was launched, the global war on drugs has failed, and has had many unintended and devastating consequences worldwide.” The letter went on to concede that drugs can never be eradicated from society, and that new policies of harm reduction based on scientific evidence must be pursued. Signatories to the letter included former presidents of the United States, Mexico, Brazil, Colombia, Switzerland, and Poland, numerous Nobel Prize laureates, prominent business people and entertainers.
“This destroys lives and marriages like no other disease I know of.”
In September of this year, a report prepared by Australia21, an Australian strategic research group, also declared the war on drugs a universal failure. Their paper, titled, ‘Illicit drugs: How we can stop killing and criminalizing young Australians’, made a suite of recommendations including a complete overhaul of drugs policy, and an end to failed prohibition laws. The Australia21 group has called for a national summit on the issue for 2013. According to former John Howard Defense Secretary and Chair of Australia21, Paul Barratt AO, “The world’s been through this [prohibition] before, and it seems we’re going to have to learn the lessons again”. If the premise that prohibition is killing young people and restricting the progress of medical science is accurate, then certainly the world, with the United Nations at the helm, needs a fresh approach.
As for Susan, it seems the stigma of using an illegal drug is a bridge too far. She certainly doesn’t strike me as the type to head down the street to ‘score’. Manifestly, she isn’t. She’s a member of Cluster Busters and says she supports others’ use of psilocybin to treat their pain, but that the law is a ‘brick wall’ between herself and pain relief. The last time we spoke, Susan was down. “[Cluster headache] destroys lives and marriages like no other disease I know of”, she had commented.
We spoke yesterday after a long silence. Since September she has been back on the frontline, fighting her battle with the tentacled beast once again. But she’s sounding much more upbeat. Cluster Busters recommend a regimen of numerous natural prophylactics, not all of them illegal. She says high-flow oxygen, melatonin, and vitamin D3 have reduced this cluster period to only a few attacks so far. She admits she has her hopes up about the BOL-148 research, but knows as well as any that the law may prevent this medication ever coming to fruition. Still, she says she’s looking forward to a pain-free holiday season soon.
As for the war on drugs, the evidence and the experts all say it has failed. Prohibition is denying people like Susan her full chance at a pain free life, while making criminals out of children, and businessmen out of criminals. If a law stands in the way of ending a person’s suffering, then there is something wrong with that law. No one should be legally denied the right to happiness. Perhaps as a society it is time to do away with outdated, failed ideological wars and rhetoric and to start putting science and common sense at the helm.
*Susan is an alias used on request.
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