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Sickle Cell and Cannabis

by 420insight on June 15, 2015
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Sickle cell disease (SCD) is a hereditary condition caused by a mutation in the haemoglobin gene, which leads to symptoms of anaemia, extreme pain, and organ damage if unmanaged. Individuals suffering from SCD are far more likely to use cannabis than the general population, potentially for its analgesic properties.

What is Sickle Cell Disease?

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In SCD, a mutation in the haemoglobin gene causes red blood cells to become distorted, from the usual pliable, concave disc to a rigid, sickle-shaped form. In normal conditions, the cells temporarily deform in order to be squeezed through narrow blood vessels.

In SCD, the rigid cells are unable to pass, and can build up, blocking the blood vessels. This can lead to sickle cell ‘crisis’, an umbrella term for a set of acute conditions that may in extreme instances cause death within 1-2 hours. Loss of blood to the organs is one of the primary risks of sickle cell crisis, and usually causes cumulative damage leading to a shortened lifespan (although modern treatments have improved prognoses dramatically).

For an individual to suffer from SCD, both alleles of the haemoglobin gene must be mutated; if just one allele is mutated and one is normal, the individual will exhibit both normal and sickled red blood cells and is considered a ‘carrier’. The normal copy is able to produce over 50% of the requisite haemoglobin in carriers and symptoms are not usually experienced unless triggered. ‘Triggers’ include lack of oxygen (e.g. at high altitude) and dehydration.

Sickle Cell Trait & Malaria Resistance

SCD is mainly found in (but is not exclusive to) tropical and subtropical populations, and individuals whose ancestry derives from such locations. It is thought that the sickle cell mutation occurred spontaneously in more than one location, and that positive selection pressures allowed it to take hold and flourish.

The reason for this is that possession of one mutated copy of the haemoglobin gene (also known as the sickle cell trait) is an advantage in areas high in malaria, as it confers a degree of resistance to the disease by mitigating the severity of its symptoms.

Inheritance & Selection Pressures

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However, if two parents possess one mutated copy each, there is a 25% chance that the child will possess two mutated copies and will suffer from SCD. SCD sufferers do not share the resistance; in fact, the pain associated with malaria is a major trigger for sickle cell crisis.

Although SCD is found in the descendants of tropical and subtropical populations now living in temperate zones such as Western Europe and much of the USA, the incidence is far lower than in populations still residing in their original locales. It is thought that in areas where malaria is not endemic, possession of the sickle cell trait is not advantageous and is selected out over time.

Haemoglobin, Oxygen & Sickle Cell Disease

The mechanism of SCD is highly complex. A single-nucleotide polymorphism of the β-globin gene causes the haemoglobin (the primary constituent of red blood cells) produced to contain valine instead of glutamic acid; both substances are amino acids, but valine is hydrophobic while glutamic acid is hydrophilic.

As blood plasma is mostly water, valine’s hydrophobic nature causes the mutated haemoglobin to collapse in on itself. Eventually, the haemoglobin begins to aggregate and polymerise into rigid, fibrous, sickle-shaped structures. This process occurs rapidly in times of low oxygen concentration, but is also promoted by high acidity and dehydration (reduced volume) of the blood.

Periods of low oxygen (hypoxia) in SCD patients are often followed by periods of reoxygenation—this is known as the hypoxia/reoxygenation cycle, and is associated with severe pain (and possibly inflammation) at sites of haemoglobin aggregation (often areas rich in capillary blood vessels such as the lungs and genitals).

Haemoglobin is responsible for carrying oxygen to the organs of the body; in SCD sufferers, ischemia of the organs can result due to mutated blood cells building up and preventing healthy, oxygenated haemoglobin to pass.

How is Sickle Cell Disease Treated?

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There are several ways to manage and control the various symptoms of SCD. Infants born with SCD are given folic acid, which is continued into adulthood and often supplemented with penicillin in early childhood. In malarial countries, anti-malaria prophylaxis is often maintained for life, due to SCD sufferers’ increased susceptibility.

In acute cases, blood transfusions can be performed, which increase the count of healthy red blood cells; the only known cure for SCD is bone marrow transplant, which is only known to be effective in children. The only currently-approved severe pain medications for SCD sufferers are opioids, many of which are dependence-forming and have significant side-effects, particularly impacting the blood vessels and kidneys (which are already at risk due to the disease itself).

SCD Sufferers More Likely to Use Cannabis

It has been repeatedly observed that SCD sufferers use cannabis at higher rates than the general population, and sufferers have self-reported that cannabis use brings subjective feelings of pain relief, as well as reducing anxiety and depression.

In Jamaica (where cannabis is illegal, but use is widespread and socially accepted), SCD sufferers were found to use cannabis at almost twice the rate of the general population (women: 19% compared to 10%; men: 65% against 37%), despite there being no expectation of ameliorated symptoms (only 6% of the sample associated cannabis use with management of symptoms).

The researchers noted that there appeared to be negligible difference in pain profile and number of pain events in their sample—however, the sample was small (just 145 people) and may not be indicative of trends on a larger scale.

Can Medical Cannabis Help to Cure SCD?

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In 2010, researchers at the University of Minnesota found that the synthetic THC analogue CP 55,940 was as effective as morphine sulphate in treating SCD-related severe pain in transgenic mice expressing human sickle haemoglobin, and that it was effective at smaller doses than the opioid.

In 2011, a further paper submitted by the same researchers to Blood (the Journal of the American Association of Hematology) indicated that CP 55,940 ameliorated severe pain associated with the hypoxia/reoxygenation cycle. CP 55,940 is a full agonist of both CB receptors, and is thought to act as an antagonist at the GPR55 receptor.

As well as this, cannabis has been repeatedly shown to act as a vasodilator, which could in itself assist in easing the blockages caused by build-up of sickle cells. Conversely, there is some indication that cannabis may act as a vasoconstrictor in certain circumstances, particularly in the peripheral circulatory system (the capillaries), and that its use may even contribute to ischemic stroke (caused by obstruction of blood vessels leading to the brain). However, most studies drawing this conclusion investigated cannabis smokers who also used tobacco, a known vasoconstrictor.

Is Medical Cannabis Preferable to Opioids?

The answer is usually yes, if it can be shown to be as effective. The evidence for this being the case is not complete, but is striking. Patients report far less incapacitation as a result of cannabis consumption compared to that experienced with opioids.

Sister Somayah Kambui, a medical cannabis patient and activist based in Los Angeles, California until her death in 2008, extolled the benefits of medical cannabis for SCD for many years—stating that morphine turned sufferers into ‘U.S. government junkies’ due to its hypnotic, soporific effects.

She had entirely replaced opioid use with that of cannabis and hemp oil, and managed her symptoms without incident, save for several occasions upon which her premises were raided and her cannabis confiscated. On one such occasion, a flare-up of symptoms resulted in hospitalisation and a return to the hated morphine.

More Research is Needed

Sickle-cell disease caused approximately 29,000 deaths worldwide in 2010; it is believed that at least 2 million people worldwide possess both copies of the mutated allele and are symptomatic.
Rates of SCD are on the increase: using trend data from the World Health Organisation, authors of an article submitted to PLOS Medicine calculated that the number of newborns born with SCD would increase to just over 400,000 by 2050 from just over 300,000 in 2010. Around 300 million people worldwide carry the sickle-cell trait.

SCD is a painful and debilitating disease, and the overall inefficacy of opioid treatments and resultant poor quality of life for many sufferers is an indication that our approach to it is far from perfect. If cannabis is a good candidate to replace opioids, it should be implemented forthwith to prevent ongoing suffering for existing patients.

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