Cannabis is infamous for causing ravenous hunger. This is so well-known that it is an integral aspect of the mainstream media’s “stoner stereotype”—the red-eyed, indolent (and usually male) twenty-something who plays video games all day and is never without a bag of Cheetos. Here, we attempt to explain this complex phenomenon.
Cannabis is infamous for causing ravenous hunger. This is so well-known that it is an integral aspect of the mainstream media’s “stoner stereotype”—the red-eyed, indolent (and usually male) twenty-something who plays video games all day and is never without a bag of Cheetos. Here, we attempt to explain this complex phenomenon.
How the brain produces sensations of hunger
When hunger is experienced, it is in response to a complex system of nerve signals between the gastrointestinal (GI) tract and the brain. The vagus nerves of the peripheral nervous system that surrounds the GI tract sense the levels of macronutrients present in the stomach and bowel, and send signals to the brain if nutrients are low. The specific area of the brain responsible for causing sensations of hunger is the lateral hypothalamus, which is often simply known as the “hunger centre”.
The vagus nerves themselves are stimulated by a neuropeptide known as ghrelin, which is produced in the GI tract when the stomach is empty. Presence of ghrelin stimulates the ghrelin receptors of the vagus nerves, which send signals to the lateral hypothalamus, which in turn creates the motivational state of hunger—as well as increasing gastric acid secretions and intestinal mobility in anticipation of food being consumed.
How THC tricks the body into wanting more food
The metabolic processes at work when hunger is stimulated by use of cannabis are not fully understood, but it is known that an enzyme—AMP-activated protein kinase (AMPK), produced in the hypothalamus—has a fundamental role to play. The enzyme is crucial to the metabolic processes that regulate energy homeostasis (energy balance) in the body, and is produced in response to ghrelin-induced stimulation of the GHS-R1a receptors of the vagus nerves.
Various studies have shown that THC can effectively do the job of ghrelin by activating the GHS-R1a receptors and directly stimulating the brain to produce AMPK and resultant sensations of hunger. Thus, even if the stomach is not empty, use of cannabis can cause powerful sensations of hunger. Further studies have demonstrated that the cannabinoid receptors themselves also have a role to play.
A 2008 study showed that the CB1-receptor assists in the regulation of ghrelin-induced appetite stimulation—in mice that had been genetically modified to lack CB1-receptors, ghrelin did not cause an orexigenic (appetite-stimulating) effect; as well as this, the effect of ghrelin on levels of AMPK in the hypothalamus was inhibited both in CB1-knockout mice and in wild-type mice administered with rimonabant, an inverse agonist of the CB1-receptors. The presence of ghrelin was also found to increase endocannabinoid levels in the hypothalamus of wild-type mice, an effect that was inhibited by administering rimonabant. This effect of ghrelin was not seen in CB1-knockout mice.
Ghrelin, cannabinoids and metabolic function
An interesting and little-known effect of the interaction between cannabinoids, ghrelin and AMPK is that of ischemic heart protection. Cannabinoids have a range of effects on heart function, and in a very small subset of predisposed individuals ingestion of exogenous cannabinoids may even trigger acute myocardial infarction (heart attack). However, outside of this small subset, it appears that the effects of increasing cannabinoid levels in the heart have several beneficial effects.
Both ghrelin and cannabinoids increase AMPK activity in the heart as well as in the hypothalamus; the effect of cannabinoids on AMPK activity is thought to reduce infarct size (area of tissue necrosis) in the myocardium following a heart attack, limiting damage to the heart and circulatory system, as well as provide a generally positive effect on blood flow in cases of ischemia.
Another interesting point is that as well as increasing AMPK activity in the heart, ghrelin and cannabinoids both exhibited the ability to inhibit its activity in the liver and adipose (fatty) tissue, which has a range of effects on expression of glucose and insulin in the blood. This is thought to play an important part in maintenance of weight and body fat in cannabis users, who have been shown on in several studies to possess smaller waist circumferences than non-users.
Thus, even if succumbing to the temptation of the munchies, most cannabis users can feel safe in the knowledge that they are providing their bodies with a significant level of protection against possible negative repercussions of over-indulging on unhealthy food, both by protecting the heart and limiting the deposition of body fat.
Cannabis, blood sugar, and hunger
Cannabis use is well-known to have an effect on blood sugar levels; for inexperienced users, this effect can be dramatic, and can result in a drop in blood sugar levels that may lead to weakness, sickness or even temporary unconsciousness. It may also increase feelings of hunger acutely, as the body reacts both to the cannabis’ own appetite-stimulating effects and to the effect of low blood sugar itself.
If symptoms of low blood sugar are experienced immediately following consumption of cannabis, providing a sugary drink or snack is a quick and effective remedy. Even if loss of consciousness occurs, this typically lasts just a few seconds, and unless injury has been sustained (such as by falling), the individual should experience no long-term ill effects. The affected individual should be helped into a sitting position and provided with a sugary drink or snack, and should remain seated until any feelings of shakiness or dizziness have passed. Providing more substantial food within an hour of such episodes will also help to maintain blood sugar.
The ability of cannabis to improve the symptoms of glaucoma has been demonstrated in various studies, but doubts still remain over its efficacy and consistency within patient populations. Despite this, many medical cannabis patients utilize cannabis for glaucoma, and report subjective improvements in various symptoms.
Reduces intraocular pressure
Increased intraocular pressure (ocular hypertension) is the risk factor in the majority of glaucoma cases, although it is absent in certain populations in almost 50% of individuals suffering from open-angle glaucoma (OAG)—the most common type, comprising around 90% of all cases. Intraocular pressure is determined by the production of aqueous humour in the eye coupled with the rate of drainage of the aqueous humour via the trabecular meshwork, a spongy tissue located at the base of the cornea. Consistently high intraocular pressure can cause progressive damage to the optic nerve and the retinal ganglion cells that contain light-sensitive photoreceptors. If damage is severe enough, total blindness can result.
During his decades-long tenure at the University of the West Indies, the respected pharmacologist Professor Manley West conducted landmark research into cannabis as a potential treatment for glaucoma alongside the noted ophthalmologist Dr. Albert Lockhart. As a result of their work, which began in 1964 and investigated traditional cannabis use in Jamaican communities, they developed cannabis-based eye-drops and gained approval to market their product in Jamaica under the name “Canasol”, in 1987. Professor West sadly died in 2012, and will be much missed by the medical cannabis community in Jamaica and beyond.
Canasol has been demonstrated to be effective in lowering intraocular pressure, and has also been shown to potentiate the effectiveness of other widely-used glaucoma drugs such as Timolol. Recently, a new and improved drug was developed by the same research team; this drug is known as Cantimol, and contains Canasol and Timolol, but has not yet been approval for market. Canasol contains no psychoactive cannabinoids and has also been widely prescribed by physicians in the USA and Canada—and has apparently been used by patients in the UK and Australia too, despite not having market approval or a legal precedent for use.
A common phenomenon found in glaucoma patients is mydriasis, in which the pupil becomes dilated. In fact, it is thought that extreme mydriasis may actually cause the characteristic bulging-out of the iris in attacks of closed-angle glaucoma—in order for the pupil to dilate, muscle tissue in the iris (known as the dilator pupillae) must contract. When muscle tissue contracts, it bulges, and in extreme cases this bulging tissue can expand into the anterior chamber (the fluid-filled space between the iris and cornea) and press up against the cornea, totally preventing escape of aqueous humour via the anterior chamber and into the trabecular meshwork.
The opposite of mydriasis is miosis (not to be confused with the form of cell division known as meiosis). Miotic drugs are highly useful in glaucoma treatment, not only CAG, as constriction of the pupil allows increased drainage of aqueous humour into the trabecular meshwork. Cannabis has been shown to possess miotic properties on various occasions, including one notable case of apparent acute cannabis poisoningin a 20-month-old infant.
While the majority of glaucoma cases are painless, the rarer form of the disease (known as closed-angle glaucoma or CAG) is characterized by sharp, stabbing pains in the eyeball and rapid loss of vision, which may be permanent if not given medical attention. Closed angle glaucoma differs from the more common form in that it produces acute symptoms instead of chronic (and generally painless) symptoms. An attack of CAG is considered a medical emergency, and occurs due to a total blockage of the trabecular network (rather than a progressively reduced ability to drain aqueous humour, as with OAG) caused by a sudden bulging forward of the iris.
Although not specifically tested as an analgesic in glaucoma cases, cannabis’ wide-spectrum efficacy as an analgesic, mood-enhancer and muscle relaxant may provide subjective relief to individuals suffering from acute attacks of closed-angle glaucoma.
On the basis of recent research, some medical professionals are beginning to suspect that persistent, low-level inflammation in the trabecular meshwork may have an important role to play in the progressive, chronic form of glaucoma, OAG. As well as this, a further type of glaucoma that is often found in patients suffering from uveitis (inflammation of the uvea, the area of the eye that contains the iris and the ciliary body) is known as inflammatory glaucoma as it has been proven that inflammation of the trabecular meshwork is to blame. In most respects, inflammatory glaucoma resembles OAG, but is characterized as occurring as a secondary symptom of uveitis.
Cannabis has been proven time and time again to be a useful and effective anti-inflammatory for a range of different conditions, although no formal studies have been conducted on the potential of cannabis to reduced glaucoma-related inflammation. As understanding of the role inflammation has to play in the progression of the disease increases, it may well prove to be the case that cannabis also provides relief to glaucoma patients due to its anti-inflammatory properties.
Attacks of closed-angle glaucoma are often accompanied by secondary symptoms of nausea and vomiting, which is believed to arise as a result of a phenomenon known as the oculoemetic reflex. Various past studies have shown an association with ophthalmic surgery and post-operative vomiting (particularly squint surgery, which causes vomiting in 41% of patients), which gave rise to the possibility of the oculoemetic reflex existing.
It is believed that noxious (painful or unpleasant) stimulation of the orbital nervesthat surround the eye sends signals to the area postrema of the medulla oblongata, the section of the brain that is often simply known as the vomiting centre. The brain then sends signals to the gastrointestinal tract via the vagus nerve (a fundamental part of the parasympathetic nervous system, which controls cardiac and gastrointestinal function), which in turn causes the vomiting reflex by stimulating retroperistalsis (backward/upward movement of GI tract contents).
It is not known what precise role the endocannabinoid system has to play in regulation of vomiting, but it has been shown that cannabinoid receptor agonists such as THC appear to directly suppress vomiting and nausea by agonizing the CB1-receptor –while antagonists of the CB receptors such as CBD are neutral, and inverse agonists actually cause nausea.
Alzheimer’s is a progressive neurodegenerative disease that typically presents in adults over the age of 65. The disease causes symptoms such as dementia; as it progresses, it renders the sufferer increasingly unable to care for themselves. There is no cure for Alzheimer’s, but medications such as cannabis may slow its progression.
The biochemistry of human neural networks is vastly complex and as yet not fully understood. However, it is thought that maintaining healthy brain tissue throughout one’s life can significantly reduce the chances of developing neurodegenerative diseases such as Alzheimer’s in old age, or at least slow the onset of such diseases by reducing the rate of cognitive decline. Regular physical and mental exercise is believed to be vitally important to maintaining neural health, and is arguably the most healthy and effective method of doing so; however, the balance of chemicals in the brain may also be improved by utilizing certain exogenous compounds such as those contained within cannabis.
Cannabis contains various compounds known as cannabinoids, which are structurally similar and have varying effects on brain function and metabolism. Of these, arguably the most important are THC and CBD, which have a range of physiological effects relevant to Alzheimer’s—they can reduce inflammation, act as antioxidants and neuroprotectants, and even stimulate the growth of new neural tissue—and if taken regularly, there is evidence that they can not only slow the progression of existing Alzheimer’s cases but also slow the onset of new cases. Indeed, based on earlier work on animals, researcher Gary Wenk believes that young adults and the middle-aged could stave off dementia by taking “a puff of marijuana every day”.
Decreases beta amyloid production
The term ‘amyloid beta’ refers to peptides created by the enzymatic fragmentation of amyloid precursor protein, a substance that is thought to be fundamentally involved in the regulation of synapse formation and neural plasticity. The precise primary function of amyloid precursor protein (APP) is unknown, and our comprehension of the normal functions of amyloid beta is in its infancy. However, it is clear that in individuals suffering from Alzheimer’s, excess amyloid beta accumulates in the brain and aggregates to form amyloid plaques, which are toxic to neural tissue.
A study published in 2014 by researchers at the University of South Florida, USA investigated the relationship between the endocannabinoid system and the process of plaque production, and demonstrated that APP cells incubated with THC at very low doses produced amyloid beta at a slower than normal rate; THC also directly interacted with beta amyloid peptide and inhibited its aggregation into plaques.
The study also demonstrated that THC at low doses also reduced levels of glycogen synthase kinase 3 beta (GSK3ß), an enzyme that is normally involved in energy metabolism and neuronal cell development but is also responsible for the development of neurofibrillary tangles in the brains of Alzheimer’s patients. These neurofibrillary tangles are comprised of tau proteins, particularly paired helical filament tau (PHF-Tau); GSK3ß is believed to be responsible for the production of PHF-Tau.
Cannabis is anti-inflammatory
Inflammation of neural tissue is increasingly thought to play a major role in the development of Alzheimer’s and other neurodegenerative diseases such as multiple sclerosis and Parkinson’s disease. It is thought that acute inflammation that initially occurs as a defense mechanism may lead to an uncontrolled chain reaction resulting in chronic inflammation and neuronal deterioration. Thus, various anti-inflammatory drugs have been investigated as possible treatments for conditions such as Alzheimer’s.
Several recent studies have investigated the relationship between the endocannabinoid system and the regulation of neuroinflammation. A study published in 2009 found that the brains of deceased Alzheimer’s patients show noticeable alterations to components of the endocannabinoid system, including increased expression of cannabinoid receptors type I & II in the microglia (the principle immune cells of the central nervous system). This suggests either that a dysfunctional EC system has a role to play in the development of Alzheimer’s or that the progression of Alzheimer’s causes the EC system to become altered.
It appears that in Alzheimer’s, the microglia surround the amyloid plaques in an attempt to destroy amyloid beta clusters through phagocytosis (“eating” the unwanted tissue). However, the rapid production of amyloid beta overwhelms the microglia, keeping them in a constant state of activation that causes them to produce excess inflammatory compounds such as interleukin. Exactly what modulatory role the cannabinoid receptors play in this scenario is yet to be ascertained, and determining the precise mechanism will enable the development of treatments that target the microglial receptors and control inflammation at its source.
Cannabis is antioxidant/neuroprotectant
Oxidative stress and the release of reactive oxygen species is a key component of diseases such as Alzheimer’s, and is inherently associated with immune inflammation—when inflammation occurs, it induces oxidative stress, reduces the antioxidant capacity of cells, and causes the production of free radicals such as reactive oxygen species, which in turn react with fatty acids and proteins in the cell membranes. The presence of amyloid beta also causes an increase in reactive oxygen species in surrounding cells through interactions with the cell membranes. Ultimately, this contributes to loss of neurons and synapses in the brain, leading to impaired memory and a range of other neurological symptoms.
Again, the role of the EC system in modulating the processes of oxidative stress is not fully understood, but it has been demonstrated repeatedly that administration of cannabinoids can help to reduce its effects and can provide a neuroprotective effect on the neurons, slowing the rate of oxidative cell death. In 2004, a study demonstrated that exposing cells to amyloid beta caused a significant decline in cell survival, but that treating the cells with cannabidiol prior to amyloid beta exposure caused a notable increase in cell survival.
As well as reducing inflammation and mediating the effects of oxidative stress, cannabidiol is also thought to promote the growth of new neural tissue (a process known as neurogenesis). In Alzheimer’s, the rapid destruction of neural tissue causes devastating neurological effects, and the normal processes of neurogenesis are interrupted by the presence of amyloid beta. Developing therapies that can stimulate neurogenesis may therefore slow the progression of the disease or even reverse its symptoms to some extent.
A 2011 study on Alzheimer’s demonstrated that cannabidiol exerted its anti-inflammatory and antioxidant effects via a mechanism that is independent of the EC system, instead working on a receptor known as the peroxisome proliferator-activated receptor-? (PPAR?). By working on the PPAR?, cannabidiol was not only able to reduce inflammation and production of reactive oxygen species to protect existing cells, but was also able to induce neurogenesis in the hippocampus (a region of the brain that is heavily affected by Alzheimer’s) by directly blocking the action of amyloid beta.
We still have much to learn of the complex processes that cause Alzheimer’s and related neurodegenerative conditions. However, there is abundant evidence that the endocannabinoid system has an integral role to play in the maintenance of neural health, and that administration of exogenous cannabinoids such as THC and CBD can provide a range of preventative and curative benefits to individuals at risk of, or already suffering from debilitating diseases like Alzheimer’s.
Cannabis preparations have been repeatedly shown to alleviate the symptoms of chronic skin conditions such as eczema and psoriasis, and the endocannabinoid system appears to play an important role in the regulation of various key processes involved in inflammation. Imbalance of the EC system may even be a major underlying cause.
What causes chronic skin conditions?
Chronic skin complaints such as psoriasis or eczema (formally known as atopic dermatitis) may occur due to genetic, environmental or lifestyle influences, or a combination of the three. Psoriasis may also afflict individuals taking certain prescription medications (including beta blockers, NSAIDS and lithium), or those with severely weakened immune systems—such as HIV sufferers. Prevalence of psoriasis varies widely between countries, and is estimated at around 2-4% in Western countries.
Lifestyle influences on occurrence and severity of common skin conditions include obesity, smoking, stress, general ill-health, poor diet, and alcohol consumption. Environmental causes include changes in season or climate, particularly those involving dramatic changes in humidity. For eczema, it is postulated that overly sterile human environments may contribute to development of allergies in children; as well as this, it is suggested that dust mite allergy is strongly associated with the condition. Eczema is estimated to affect around 10% of all humans, to varying degrees of severity; in some areas, lifetime prevalence is thought to be as high as one-third of the population, and appears to be rising over time.
Symptoms of dermatitis
There are several forms of dermatitis, with the two most common forms being atopic or chronic dermatitis (eczema) and contact or acute dermatitis (which is caused by direct contact with an allergen or irritant, and is often mistaken for eczema). The symptoms generally range from red skin and bumpy rashes to severe blistering and lesions in severe cases. Blisters and lesions may weep or ooze and may ultimately lead to unsightly scarring.
Dry, itchy skin is the most common symptom; areas most commonly affected include the cubital and popliteal fossa (the inner fold of the elbow and knee, respectively), the wrists, hands and face. Eczema can be extremely debilitating, but is not fatal; however, resultant infections gaining a foothold through broken skin have occasionally been known to cause fatalities. Infection by staphylococcal or streptococcal bacteria is very common in eczema; rarely, this can lead to widespread infection and septicaemia. As well as this, the herpes simplex virus can infect eczema-damaged skin and cause an extreme condition known as eczema herpeticum, which can in turn lead to systemic bacterial ‘superinfection’ and even death.
Symptoms of psoriasis
Psoriasis also comes in various forms. The most common form is known as psoriasis vulgaris or plaque psoriasis. The ‘plaques’ this terminology refers to are raised, inflamed (often roughly circular) patches of skin covered with a silvery, scaly, plaque-like substance. These plaques usually appear on the elbows, knees, scalp, and back. Psoriasis vulgaris affects up to 90% of psoriasis sufferers; other forms include pustular psoriasis, which causes raised, pus-filled bumps or pustules accompanied by severe itching and tenderness. Pustules usually appear on the hands and feet, or randomly across the body.
A rare, potentially-fatal form of the condition is known as erythrodermic psoriasis; this debilitating disease can lead to inflammation and exfoliation of the majority of the sufferer’s skin. The severity of the inflammation and skin loss can be such that normal temperature regulation and barrier function control is irreparably disrupted and death can result.
Genetic influences on eczema and psoriasis
Eczema sufferers have been found to exhibit variations in the FLG gene that encodes expression of a protein known as filaggrin, which is crucial to regulation of the stratum corneum, the outermost layer of the epidermis. Filaggrin binds to free strands of keratin and causes it to form a matrix within the keratinocyte cells of the epidermis. This tough, impermeable matrix is the foundation of the waterproof ‘barrier’ that makes up the outer layer of human skin; it keeps the skin hydrated both by preventing evaporation and by absorbing water. Variations in the FLG gene have also been implicated in another debilitating skin condition, ichthyosis vulgaris, which causes the skin to take on a scaly appearance due to over-production of keratinocytes.
Psoriasis, which also involves over-production of keratinocytes, has a strong genetic association; around one-third of sufferers report family history of the condition. It is thought that several genes interact to determine occurrence of psoriasis in ways that are not fully understood; around thirty-six different loci that correspond to psoriasis susceptibility have been found on the chromosomes. The genes found within these loci are involved in inflammatory response, and several have been implicated in other autoimmune diseases as well as psoriasis.
Chronic skin conditions and immune response
Both eczema and psoriasis involve an atypical immune response. Psoriasis is considered to be autoimmune in nature, as it does not occur due to any external allergen but due to a malfunction of the immune system that causes it to attack formerly healthy tissue. Eczema is a generalised response to the presence of external allergens, and is not an autoimmune disease—although it is often present in individuals suffering from other autoimmune diseases, and certain other forms of dermatitis have an autoimmune component.
Specifically, eczema and psoriasis are conditions that are caused by atypical inflammatory response. The inflammatory response is a fundamental part of the immune system: upon initial exposure to a pathogen (or perceived pathogen in the case of an autoimmune disease such as psoriasis), increased levels of blood plasma and white blood cells (particularly granulocytes) are then brought via the bloodstream to the affected tissues. These fluids then accumulate, causing the characteristic swelling; the increase in blood flow in the affected area causes reddening and the sensation of heat, and itching and pain occur due to release of compounds that stimulate the nerve endings.
Hemp seed oil and skin complaints
Application of several different oils and emollients, such as petroleum jelly, beeswax, almond oil, olive oil, and various synthetic preparations, have been shown to reduce symptoms of psoriasis and dermatitis. As these conditions are characterised by overly dry skin, products which can moisturise the skin while avoiding further irritation are fundamental to their treatment. In eczema and psoriasis, dry skin occurs due to excessive transepidermal water loss, as persistent inflammation compromises the skin’s ability to act as a barrier and regulate diffusion and evaporation.
Beyond directly providing moisture, compounds contained within some of these products may be the key to controlling the imbalance that underlies the condition; with hemp seed oil and several other natural oils, high concentration of polyunsaturated fatty acids (PUFAs) is believed to reduce itching and inflammation better than moisturisers that are low in PUFAs. Linoleic acid in particular is thought to be of interest, although other PUFAs are also being investigated.
Dietary PUFAs and skin moisture
PUFAs are typically incorporated in the diet, and there is evidence to suggest that dietary hemp seed oil can raise levels in the epidermis and render them more comparable to the fatty acid profile found in ‘normal’ skin. In a Finnish studypublished in 2005, researchers compared hemp seed oil with olive oil, and found that the former exhibited far more significant signs of efficacy against eczema. Dietary hemp seed oil increased endogenous levels of two essential fatty acids (EFAs), linoleic acid (omega-6) and a-linolenic acid (omega-3), as well as boosting levels of the non-essential PUFA, ?-linolenic acid (omega-6). As well as this, transepidermal water loss decreased, subjective levels of skin dryness and itchiness improved, and perceived need for medication among patients diminished.
Although no hemp-specific studies have apparently been performed on psoriasis, plenty of anecdotal evidence exists, and there have been several studies which attest to the potential for PUFAs to be of use in this condition too. A link between low rates of psoriasis and high consumption of PUFAs from fish oil in certain populations (such as Eskimos) has been established for some time, although in this case it is thought that two non-essential PUFAs, eicosapentaenoic acid and dihomo-?-linolenic acid, are of particular potential in reducing symptoms; hemp seed oil is mostly comprised of linoleic acid and a-linolenic acid. Conversely, the non-essential PUFA arachidonic acid is thought to be involved in the development of psoriasis.
Ratio of hemp seed oil composition
As our understanding of the mechanisms underlying chronic inflammation grows, we are finding that diseases that affect the skin (one of the primary anatomical barriers involved in the immune response), such as eczema and psoriasis, are closely linked to another major barrier, the gastrointestinal tract. Thus, it may be that underlying problems with dietary PUFA absorption or utilisation in the GI tract also play a part in the development of chronic skin conditions.
It has been observed that fatty acid profiles of hemp seed oil vary according to cultivar, with linoleic acid making up 50-70% and linolenic acid (both a- and ?-) making up 15-25% of total volume; ?-linolenic acid content may be as much as 2.46% or as little as 0.80%. As we gain more insight into the complexities of PUFA levels and dermal health, different cultivars may be of use in different conditions, or specific cultivars may even be bred for the purpose.
Cannabinoids and dermal health
It has been relatively well established that eczema and psoriasis respond well to PUFA-rich treatments; however, PUFAs are extremely widespread and can be obtained from multiple sources (although hemp seed oil is an abundant source, with a generally favourable ratio). Cannabinoids, on the other hand, are almost exclusively found in cannabis, and they too have been demonstrated to have significant effect on chronic skin conditions. Cannabinoids are well-known to have a role to play in regulating inflammation, and it appears that this may be the key to their ability to treat eczema and psoriasis.
It is well-documented that the gastrointestinal tract (which, like the skin, is one of the primary physical barriers of the immune system) has abundant cannabinoid receptor sites. Now, recent research has indicated that the skin also has an endocannabinoid system of its own, which helps to regulate the production of various hormones and proteins (including cytokine, which is also involved in immune response), as well as various cellular process including proliferation, differentiation, and apoptosis (cell death). Thus, imbalance of this system may also be responsible for the occurrence of chronic skin conditions such as psoriasis and eczema, and developing targeted cannabinoid therapies may help to control them.
A study published in 2007 demonstrated that THC, CBD, CBN, CBG and anandamideall demonstrated some level of effectiveness in inhibiting keratinocyte production in the epidermis; as over-production of keratinocytes is involved in psoriasis, these results support further investigation into cannabinoid therapies to treat it. Cannabinoid receptors have been found in even the smallest nerve fibres controlling hair follicles; keratinocytes have also been shown to bind and metabolise anandamide, the most prolific endocannabinoid.
Diabetes is the term for a group of related metabolic disorders characterized by prolonged high blood glucose levels. Diabetes affects almost 400 million people worldwide, resulting in up to five million deaths per year–and its prevalence is rising. Substantial evidence indicates that cannabis may prevent and treat the disease.
Diabetes is associated with high levels of fasting insulin and insulin resistance, as well as low levels of high-density lipoprotein cholesterol (HDL-C). In 2013, the results of a five-year study into the effects of cannabis on fasting insulin and insulin resistance were published in the American Journal of Medicine. Of the 4,657 respondents, 2,554 had used cannabis in their lifetime (579 were current users and 1,975 were past users) and 2,103 had never used the drug.
The researchers found that current users of cannabis had 16% lower fasting insulin levels than respondents who had never used cannabis, as well as having 17% lower levels of insulin resistance and higher levels of HDL-C. Respondents who had used cannabis in their lifetime but were not current users showed similar but less pronounced associations, indicating that the protective effect of cannabis fades with time.
The researchers also ran analyses on the data that excluded individuals diagnosed with diabetes. Even after excluding diabetics, current cannabis users were found to exhibit reduced fasting insulin and insulin resistance levels, indicating that cannabis can help prevent the occurrence of diabetes as well as controlling symptoms in diagnosed cases.
Lowers insulin resistance
Insulin resistance (IR) is a condition that causes cells to reject the normal mechanism of insulin, a hormone that is produced by the pancreas and is fundamental to the regulation of glucose metabolism. IR is associated with type 2 diabetes; in type 1 diabetes, the body is unable to produce insulin, while in type 2, insulin production is unaffected but the cells are unable to process it. When cells become insulin-resistant, they are unable to absorb the glucose needed to supply them with energy, and the unused glucose builds up in the bloodstream–leading to hyperglycemia.
The authors of the 2013 study found that current users of cannabis had a mean IR of 1.8, compared to 2.2 for past users and 2.5 for those that had never used cannabis. Current cannabis users were also found to have lower levels of blood glucose compared to past users and non-users. Current users had mean blood glucose levels of 99.7 mg/dL, compared with 100.6 mg/dL for past users and 103.5 mg/dL for non-users. However, the precise mechanism via which cannabinoids exert their effects on IR has thus far not been determined.
Helps to prevent obesity
Obesity, high body mass index (BMI) and large waist circumference are all linked to diabetes risk. Various studies have been conducted on the relationship between cannabis use and BMI, with conflicting results. A 2005 study on young adults found that cannabis use was not associated with changes in BMI, whereas two large national surveys found lower BMI and decreased levels of obesity in cannabis users despite higher-than-average daily consumption of calories. The 2013 study found that current cannabis use was associated with smaller waist circumferences than in past or non-users.
While the mechanism underlying the complex relationship between the endocannabinoid system, obesity and diabetes has not been fully established, a 2012 study demonstrated that obese rats lost significant weight and experienced an increase in pancreas weight after exposure to organic cannabis extract. The increase in the weight of the pancreas indicates that the beta cells of the pancreas (which are responsible for the production of insulin) are protected by the presence of cannabinoids–in type 1 diabetes, the beta cells are destroyed by an autoimmune response, so providing protection to them may help to control the disease.
May treat diabetes-induced neuropathy
People with diabetes often experience nerve disorders as a result of their disease. Nerve damage often affects the peripheries such as the hands and feet, but may occur in any organ or region of the body. The damage may be symptomless, but in many cases, pain, tingling and numbness accompany the disorder. As with many f0rms of nerve pain, diabetic neuropathy can be hard to treat with conventional analgesics; however, there is evidence to indicate that cannabis may have a role to play here too.
A study published in 2009 investigated the antinociceptive (pain-reducing) effects of cannabidiol extract in cases of diabetes-induced neuropathy in rats. The authors found that repeated administration of CBD extract “significantly relieved” mechanical allodynia (painful response to non-painful stimuli) and restored normal perception of pain without inducing hyperglycemia. The treatment was also found to protect the liver against oxidative stress (which is believed to be a major contributing factor to developing neuropathy) and increase levels of nerve growth factor to normal levels.
However, studies on humans have thus far yielded less positive results. Also in 2009, a randomized controlled trial investigated the ability of GW Pharmaceuticals’ Sativex spray to ameliorate the symptoms of diabetes-induced peripheral neuropathy. 30 subjects were administered with either Sativex or placebo; pain scores improved significantly across the board, but the effect of Sativex was not found to be significantly greater than that of the placebo.
May treat diabetic retinopathy
Up to 80% of diabetes patients that have had the disease for over a decade acquire a complication known as diabetic retinopathy (DRP), in which the cells of the retina are progressively damaged. This condition is responsible for approximately 12% of new cases of blindness each year in the USA.
DRP is associated with glucose-induced breakdown of the blood-retinal barrier, a network of tightly-packed cells that prevent unwanted substances in the blood from entering retinal tissue. This breakdown causes neural tissue to be exposed to neurotoxins, as well as increasing the chance of bleeding within the retina.
It is thought that the pro-inflammatory immune response and oxidative stress processes have a key role to play in the breakdown of retinal cells–and there is evidence that cannabidiol, with its known ability to combat both oxidative stress and inflammation, may be useful in treating the disorder. In a 2006 study published in the American Journal of Pathology, diabetic rats were administered with CBD and tested to determine the rate of retinal cell death. It was shown that treatment with CBD significantly reduced oxidative stress and neurotoxicity–including levels of tumor necrosis factor-a, a substance that is known to be involved in the inflammatory response–and protected against retinal cell death and the breakdown of the blood-retinal barrier.
HIV/AIDS refers to a group of conditions caused by the human immunodeficiency virus (HIV). Around 35 million people worldwide are infected with the HIV virus, and since the 1980s, AIDS has caused approximately 36 million deaths. Cannabis has been shown to be extremely effective at treating several important symptoms of HIV/AIDS.
Furthermore, eating occasions averaged 404 kcal across the board, but dronabinol and cannabis caused a significant shift in distribution of nutrient intake–when given placebo, patients derived 51% of their nutrients from carbohydrates, 36% from fat, and 13% from protein; when given dronabinol, fat consumption increased to 40% and carbohydrate consumption decreased, and when given cannabis, protein consumption dropped to 11% while fat consumption tended to increase.
When given high doses of cannabis and dronabinol, patients experienced significant increases in body weight. Under placebo conditions, the respondents’ mean weight was 77.5 kg; after four days of cannabis, patients gained 1.1 kg, and after four days of dronabinol, patients gained 1.2 kg.
Nausea is a common symptom of HIV infection, and as the disease progresses, the causes of the nausea can become increasingly complex. Nausea may arise due to gastrointestinal issues, hepatorenal dysfunction, central nervous system disorders, or as a result of treatments used to treat the disease.
The ability of cannabinoids and certain synthetic analogues to counter the symptoms of nausea in HIV/AIDS patients is well-known; indeed, the THC analogue dronabinol is approved by the US Food & Drug Administration for the treatment of nausea and appetite loss associated with cancer and HIV. An early study into the dronabinol as a treatment for AIDS-induced appetite loss was published in 1995, and found that patients experienced an average 20% improvement in nausea.
The previously-mentioned 2005 patient survey found that 93% of HIV-positive cannabis users reported subjective improvements in nausea after smoking. Another 2005 study found that among HIV-positive patients experiencing nausea, those who used cannabis were more likely to adhere to their anti-retroviral therapies than non-users. Patients not suffering from nausea did not experience significant improvements in adherence if they used cannabis, indicating that adherence was increased by improving symptoms of nausea.
Anxiety, depression and mood disorders are a common feature of HIV/AIDS, and can arise due to a combination of negative physiological, psychological and social pressures. The 2005 patient survey found that 93% of respondents experienced relief of anxiety after using cannabis, while 86% reported an improvement in depression too.
The above-mentioned 2007 double-blind study into cannabis and dronabinol found that both substances improved respondents’ mood and caused a “good drug effect” that increased feelings of friendliness, stimulation and self-confidence. Interestingly, lower doses of THC seemed to provoke higher rates of anxiety in the subjects than higher doses of THC, or dronabinol at any dose.
HIV/AIDS can cause severe and debilitating pain that arises from various complex sources, including joint, nerve, and muscle pain. A 2011 cross-sectional study on 296 socioeconomically disadvantaged patients found that 53.7% had severe pain, 38.1% had moderate pain, and 8.2% had mild pain; over half the subjects had a prescription for an opioid analgesic. More severe pain was also found to correlate with incidence of depression.
The 2005 patient survey found that 94% of respondents experienced relief from muscle pain as a result of using cannabis; 90% also reported improvement in neuropathy (nerve pain) and 85% in paresthesia (burning, tingling and prickling sensations). The fact that cannabis can provide significant long-term subjective relief of chronic pain in HIV/AIDS sufferers is noteworthy; safer and potentially-cheaper medications that could replace use of opioids in disadvantaged groups could have several positive ramifications, including a decline in opioid-related deaths and increased availability of medicine to those in need.
Reduces peripheral neuropathy
A specific and particularly common form of pain associated with HIV/AIDS is peripheral neuropathy, in which one or more nerves of the peripheral nervous system (any part of the nervous system outside the brain and spinal cord) become damaged and lead to pain, twitching, paresthesia, muscle loss and impaired coordination. It has been shown that cannabis can help improve symptoms of peripheral neuropathy in HIV/AIDS, as well as in other conditions in which it appears, such as diabetes.
Beyond the above-mentioned subjective reports of reduced nerve pain and paresthesia, several other studies have assessed the ability of cannabis to improve peripheral neuropathy in HIV/AIDS patients. In 2007, a patient survey conducted in the U.S., Puerto Rico, Colombia and Taiwan found that 67 of 450 patients with peripheral neuropathy reported use of cannabis to improve their symptoms.
A randomized placebo-controlled trial also published in 2007 found that pain was reduced by over 30% in 52% of the cannabis-using group and by just 24% of the control group, and that there were no serious adverse effects. The first joint smoked by the cannabis-using patients reduced chronic pain by a median of 72% compared to 15% in the placebo group.
In 2009, a double-blind, placebo-controlled, crossover trial into the effectiveness of cannabis in reducing peripheral neuropathy found that of 28 subjects, neuropathy was reduced by over 30% in 46% of the cannabis-using group and 18% of the control group, and that mood and general functioning were improved by a similar degree throughout the course of the study.
Epidermolysis bullosa (EB) refers to a group of rare, potentially-lethal inherited conditions characterized by extremely fragile skin, which blisters and forms sores easily in response to minor trauma. EB shares similarities with other skin conditions such as dermatitis and psoriasis, which cannabis is known to benefit.
1. Analgesic – Pain reducing
Due to the rarity of EB, there is little existing research into the potential for cannabisto improve its symptoms. However, substantial anecdotal evidence in recent years has led to increasing interest within the medical community. One almost-universal symptom of EB that cannabis may help to improve is chronic pain due to blistered and broken skin (as well as later complications such as loss, deformity, or fusion of fingers or toes). Various patient reports online testify as to cannabis’ effectiveness in managing EB-related pain, and numerous physicians and dispensaries list EB pain as treatable with cannabis.
U.S. medical cannabis patient Miguel Garcia, who suffers from EB, has documented his use of cannabis to manage his symptoms, and in a video uploaded to YouTube remarked that cannabis helped him to “physically numb the pain” and meant that he did not need to use opioid painkillers such as hydrocodone or oxycodone.
2. Antipruritic or anti-itch
Pruritus (itching) is another almost universal symptom of EB. There is a relatively wide selection of articles and papers available that attest to the fact that cannabis and certain synthetic cannabinoid analogues can act as antipruritics in cases of EB and several related conditions.
It is thought that inflammatory immune responses are the cause of blistering in many cases of EB. Cannabis has been shown to be effective against inflammation of the skin in numerous related conditions, and there are plenty of anecdotal reports of its effectiveness to be found online. The presence of dermal cannabinoid receptors is now thought to be crucial to the regulation of various immune responses, including regulation of oxidative stress and programmed cell death as well as itching and inflammation.
The mechanism via which cannabis exerts its anti-inflammatory effects is complex and not fully understood. It is thought that both THC and CBD have anti-inflammatory properties, and that while the cannabinoid receptors are involved in the process, other mechanisms independent of the CB-receptors also have a part to play.
Thus, the precise relationship between endocannabinoids, the CB-receptors, and immune inflammatory responses in the skin is unclear, and gaining a clearer understanding of the mechanisms at work will allow us to develop targeted therapies to treat EB and numerous related conditions.
A common complication of EB is infection due to exposure of broken skin to pathogens present in the natural environment. As well as causing pain to the patient, infected wounds prevent healing, may become necrotic, and ultimately contribute to all-round ill-health (as well as causing failure to thrive in children). The most common wound-colonizing bacteria in individuals with EB are staphylococcus, streptococcus, diptheroids, pseudomonas, and candida.
Again, no specific research has been conducted on the ability of cannabis to combat bacterial infections in EB patients, but there is abundant evidence indicating that it can exert a significant antibacterial effect in vitro and in vivo against various common bacteria and in the treatment of several important diseases.
Cannabis medications have been used as antimicrobials since the days of antiquity. In the late 19th and early 20th centuries, modern researchers began to document traditional folk uses of cannabis, and in many cases, demonstrate their veracity with new empirical methods. In 1960, a landmark paper was published demonstrating the ability of cannabis extract to destroy several species of staphylococcus and streptococcus bacteria; since then, various other papers have found that cannabis can also kill pseudomonas and candida bacteria.
Some forms of EB dramatically increase the risk of skin cancer in affected individuals, particularly a rare form of cancer known as squamous cell carcinoma (SCC). Again, no specific research into the potential for cannabinoids to treat EB-related SCC exists, but there are various anecdotal reports of individuals afflicted with SCC who have successfully treated their condition with high doses of cannabis oil.
An American medical cannabis patient, Michael McShane was diagnosed with HIV in the late 1980s, and a few years later developed SCC, perhaps as a complication of his HIV. After undergoing several surgical procedures to remove tumour growth that repeatedly grew back, he began to use cannabis oil and rapidly experienced improvements, ultimately becoming cancer-free after around four months. According to his website, he remains cancer-free.
It is clear that much work remains before we will have a complete understanding of the various ways in which cannabis can help this understudied disease. However, the existing evidence strongly suggests that cannabis treatments could improve the symptoms of EB in several key ways, and that further research is needed.
Research into CBD does however back up the therapeutic benefits of CBD products. These can be safely used to contribute to a healthy lifestyle, without the high effects of THC.
Asthma is a chronic respiratory disease that currently affects up to 300 million people worldwide, and was responsible for approximately 250,000 deaths in 2011. Cannabis has been used as a means of treating the symptoms of asthma for millennia, in various medicinal traditions including those of ancient India and China.
1. Analgesic / cannabis to relieve pain
Although pain is not necessarily considered to be a primary symptom of an acute episode of asthma, studies have shown that up to 76% of patients experience chest pain during an attack. Generally, asthma-related pain is characterized by a deep ache or sharp stabbing sensation that develops gradually over the first few hours of the attack, and slowly dissipates as the attack recedes.
While there are no studies that specifically investigate the ability of cannabis to treat asthma-related pain, several studies into the general effect of cannabis on asthma have noted subjective improvements in pain. The known bronchodilatory and analgesic effects of certain cannabinoids suggest that they could be useful in managing asthma-related pain both by reducing pressure and constriction in the lungs, and by acting directly at the nociceptors (pain-sensing nerve cells) themselves.
2. Cannabis as an Antibiotic
Although asthma is generally thought to have some genetic basis, there is increasing evidence for the fact that the disease may be triggered or caused by bacterial or viral infections in early childhood, which due to their effect on the immune system, leave sufferers susceptible to various allergens and irritants.
An emerging body of research is currently looking into the potential for antibiotics to treat both the short- and long-term symptoms of asthma, and thus far, several studies have pointed to the potential for common antibiotics such as erythromycin and azithromycin to ease the acute symptoms of asthma.
Cannabinoids including THC, CBD, and CBG have been shown to have a broad-spectrum bactericidal effect against many common and infectious pathogens. One group of bacterial agents suspected of being a potential underlying cause of asthma is the Streptococcus genus, which includes S. pneumoniae and S. aureae, has been shown in several studies to succumb to the bactericidal effect of cannabinoids.
Asthma is considered to be a chronic inflammatory condition, as persistent, low-level inflammation has been found to occur in the bronchi and bronchioles even during non-attack circumstances. During an attack, levels of inflammation increase, exacerbating the levels of constriction caused by muscular contractions of the bronchial tissue. Asthma-related inflammation is generally thought to be an immune response to the presence of allergens, although the immune response has not been definitively ascertained and may differ greatly between individuals.
Generally, acute episodes of asthma are treated using bronchodilators as a first line of defence, but in severe cases it is also likely that some form of anti-inflammatory drugs such as steroids or NSAIDs (non-steroidal anti-inflammatory drugs) will be administered.
Cannabinoids are well-known for their anti-inflammatory effects, and while most studies thus far into cannabis and asthma have focused primarily on the bronchodilatory effect, some have also observed a reduction in bronchial inflammation. Furthermore, cannabis is currently being investigated for its ability to produce targeted therapies for immune-modulated inflammatory diseases.
Cannabinoid receptors have been found in human lung tissue, although in relatively low concentrations, and are thought to play a vital role in the regulation of inflammation, muscular contractions and dilations, and various metabolic processes. However, research into the immune-modulated inflammatory response (and how cannabis may assist it) is in its infancy.
The ability of cannabis to act as a bronchodilator is perhaps its most significant property in terms of the treatment of asthma. During an asthma attack, the bronchioles (the branching network of tubes that carry oxygen to the alveoli) become constricted, causing the rate of oxygen flow to drastically reduce.
Generally, the extent of bronchoconstriction during an attack is determined by peak expiratory flow measurements, which are taken from patients and compared to readings taken in normal circumstances. The difference between the normal rate of airflow and the limited airflow during an attack can thus be determined.
Several studies have shown that administration of cannabis in various forms can significantly improve bronchoconstriction both during an asthma attack and in normal circumstances (sufferers of severe asthma often have lower-than-average airflow compared to non-asthmatics even when an attack is not occurring).
In the early 1970s, a spate of studies were published investigating the bronchodilatory effects of cannabis for asthmatics. A study in 1973 observed that cannabis smoke—unlike that of tobacco—caused a bronchodilatory effect; a 1974study found that while the bronchodilatory effect of cannabis was weaker than that of isoproterenol, its effects lasted longer, and a 1976 study found that cannabis was as equally effective as salbutamol, although the latter achieved maximal bronchodilation somewhat more rapidly.
As with much of cannabinoid science, there are complicating factors. For example, a recent study found that the endogenous cannabinoid anandamide could actually exert a biphasic (two-stage) effect on lung tissue: it strongly inhibits bronchial constriction in the presence of an allergen or irritant (in this case capsaicin) but causes bronchial constriction in normal circumstances, i.e. when no irritant is present. Indeed, some patients administered with THC have reported experiencing bronchial constriction. Thus, further research is needed to determine exactly how cannabinoid treatments should be used across the board.
It is thought that cannabis can exert a bronchodilatory effect mostly through its ability to reduce inflammation. However, it is also thought that cannabis’ ability to reduce muscular spasms (involuntary contractions) plays a significant role in the management of bronchoconstriction during an asthma attack. The bronchi and bronchioles are composed of smooth muscle, and during an attack, they contract and narrow as well as becoming inflamed.
In a study published in 2014, researchers took bronchial lung tissue from 88 human patients and subjected it to electrical field stimulation to cause the muscle tissue to contract. They then administered THC, the endogenous cannabinoid 2-AG, and various synthetic agonists of CB-receptors type I & II. They found that certain agonists of the CB1-receptor, including THC, reduced muscle contractions in a dose-dependent manner. Furthermore, it was observed that the endogenous cannabinoid 2-AG had no effect.
The ability of cannabis to act as an expectorant is somewhat controversial. It has been used as such for thousands of years, and appears in the ancient pharmacopoeiae of China and India, but modern research has been sparse and has thus far yielded only ambiguous results.
Countless people throughout the world report an expectorant effect after smoking or vaporizing cannabis. If it were noted only in smokers of cannabis, it could easily be dismissed as a result of the irritation caused by smoke particles ; the fact that an effect is experienced even when inhaling vapour suggests that an active substance in cannabis is causing it.
However, most existing research actually points to the propensity of cannabis to cause production of mucus. For example, a study published in 2014 observed increased mucus secretions in habitual cannabis smokers, along with damage to the tissues of the airways. Thus, further research into the expectorant and decongestant effects of cannabis could be advantageous.
Cannabis has been used to treat topical wounds such as cuts and burns for millennia. Now, modern research is investigating the science behind cannabis’ ability to treat topical injuries, and is discovering exactly how vast a role the endocannabinoid system plays in the maintenance of healthy skin and wound healing.
Cannabis and wound healing in history
The historical medical texts of various different cultures mention the use of cannabis in topical preparations to treat cuts, scrapes and burns. Egyptian papyri note the use of topical antiseptic preparations thought to be made from cannabis mixed with fat; Greek writers from the 1st century BCE record the use of cannabis to treat horsessuffering from wounds and sores, as well as to treat nosebleed in humans.
The medieval French herbalist Ruellius recorded in his 1536 treatise De Natura Stirpium that cannabis extract could be used to treat wounds and ulcers; a few decades later, the renowned German botanist Tabernaemontanus recommended a mixture of butter and cannabis leaves to be applied to burns.
In 1649, the eminent British herbalist Nicholas Culpeper recorded that cannabis could be used to treat burns and bleeding, due to its antiseptic properties. In 1751, British herbalist Thomas Short wrote in his Medicina Britannica that a preparation of cannabis could be used to treat burns, wounds, insect bites and ulcers.
Modern research into wound healing & cannabis
In the modern era, researchers have investigated the ability of cannabis and cannabis preparations to reduce pain, swelling and bleeding associated with cuts and burns, and to aid in the repair of epidermal tissue.
Research conducted thus far has provided ample evidence that cannabis has a strong analgesic, anti-inflammatory and antiseptic effect. Indeed, it appears that the endocannabinoid system is fundamentally involved with the process of healing itself, and has a vital role to play in the formation of scar tissue.
Wound healing & the endocannabinoid system
The endocannabinoid system plays a major role throughout the entire process of wound healing. Immediately after an injury occurs, levels of anandamide in the affected tissues rise, and provide an analgesic effect by acting on the CB1-receptors present in the peripheral nerves.
A 2010 study conducted at the University of California found that if a synthetic compound known as URB937 was administered to rats and mice with peripheral injuries, levels of anandamide increased and the analgesic effect became stronger. URB937 exerts this effect by inhibiting the fatty acid amide hydrolase (FAAH) enzyme, which is responsible for the degradation of anandamide.
Another 2010 study conducted at the China Medical University found that in mice inflicted with skin incisions, the number of cells expressing CB1-receptors increased at the injury site. The increase in CB1-expressing cells began six hours after injury occurred, peaked at five days post-injury, and reduced to baseline levels by fourteen days post-injury.
At first, the majority of new CB1-expressing cells at the injury site were mononuclear cells (such as red blood cells and specialized immune cells known as monocytes) that are known to mediate inflammation and the immune response; after several days, fibroblastic cells (which are vital to wound healing and scar formation) began to dominate. While it is not clear exactly what mechanisms are at work, it is evident that anandamide and the CB1-receptors are involved in the process.
Cannabis & wound healing in the internal organs
As well as wounds affecting the epidermis and cutaneous tissue, the endocannabinoid system has a role to play in the healing of injuries to the internal organs, particularly to the epithelium (the smooth layer of cells lining the surface of organs and other bodily structures).
In the human colon, the epithelial tissue expresses both CB1 and CB2-receptors. In normal tissue, CB1-receptors are more commonly expressed, and in abnormal conditions (such as in individuals with inflammatory bowel disease) CB2-receptors begin to dominate. The CB1-receptors are routinely involved in the closure of wounds to the colonic epithelium; if damage is chronic, CB2-receptors become crucial to ensuring that excess scarring does not occur.
In the corneas, injury to the epithelial tissue causes the local release of endogenous cannabinoid and vanilloid receptor agonists that are believed to assist in the process of wound-healing. In a 2010 study, researchers treated human corneal epithelial cells in vitro with WIN55,212-2 and capsaicin—a CB1-receptor and a vanilloid-receptor agonist—to determine the role each receptor played. They found that activating either receptor led to the transactivation of the epidermal growth factor receptor, which is vitally important for the regeneration of damaged epidermal and epithelial tissue.
In periodontal tissue, an upsurge in cells expressing CB-receptors was also observed immediately subsequent to injury. As well as this, an increase in anandamide levels in patients who had just undergone periodontal surgery was noted. Administration of AM251 and AM630, synthetic selective antagonists of the CB1 and CB2-receptors respectively, was observed to cause significant reductions in fibroblast numbers—suggesting that agonists of the CB-receptors promote fibroblast survival and therefore expedite wound-healing.
Cannabinoids & cirrhosis of the liver
In the liver, chronic tissue damage and inflammation (such as that caused by alcoholism or hepatitis) promotes the wound-healing response, causing fibroblast cells to migrate to the damaged area and begin the process of fibrosis (scar formation). Over time, the overproduction of fibrous connective tissue causes cirrhosis, and inhibits the liver’s ability to function normally.
In this instance, presence of anandamide in high levels could increase the rate of fibrosis and therefore the severity of cirrhosis. Anandamide is an agonist of the CB-receptors; conversely, presence of a antagonist such as cannabidiol could block the effect and slow the rate of fibrosis.
A 2006 study on mice published in Nature Medicine demonstrated that administration of a synthetic CB1-receptor antagonist, SR141716A, inhibited the wound-healing response to acute hepatic injury, and slowed progression of cirrhosis in three types of chronic injury—supporting the idea that CBD and similar antagonists can help to treat cirrhosis.
The CB2-receptor & hepatic wound healing
Interestingly, the CB2-receptor has its own unique role to play in the onset and progression of fibrosis in the liver. Usually present in lower concentrations than CB1-receptors, their numbers increase dramatically during fibrogenesis (production of fibrous tissue) and after injury.
A 2007 study on mice showed that for mice genetically modified to lack CB2-receptors, fibrosis was significantly worsened—indicating that presence of CB2-receptors in typical mice inhibits fibrogenesis. It is thought that the CB2-receptors exert this effect by causing apoptosis (programmed cell death) of the fibroblasts; when CB2-receptors are limited in number or absent, the fibroblasts can accumulate and fibrous tissue can thus build up more rapidly .
Hemp seed oil for wound healing
Although hemp seed contains no cannabinoids (except residual traces from the production process), it may be useful in treating burns, cuts and other external wounds due to its unique balance of omega-3 and -6 essential fatty acids, which are present in optimum levels for human health.
Although very few formal studies have been done into the ability of hemp seed itself to treat topical injuries, there have been multiple papers written on the ability to improve wound-healing of essential fatty acids in general. There has also been one clinical trial into the uses of topically-applied hemp seed oil, which concluded that it had a good ability to heal mucosal skin wounds after eye, nose and throat surgery.
Thus, cuts, burns, lacerations and other similar injuries may be treatable both with hemp seed oil and with cannabinoid-rich cannabis preparations. For those looking for a safe way to use CBD, Sensi Seeds has a couple of CBD-products on offer. One of them is CBD oil: a food supplement that contains different phytocannabinoids. The most well-known being CBD, CBC (cannabichromene), CBG (cannabigerol), and CBN (cannabinol).
For injuries to the internal tissues or organs, cannabinoids have a definite role to play, but further investigation is required so that targeted therapies can be developed. With such a complex and finely-tuned system, incorrect dosages or cannabinoid ratios could cause the opposite effect to the intended one.
There is a growing body of evidence to suggest that the endocannaboid system has a fundamental role to play in various aspects of the aging process, both mental and somatic. Furthermore, regular use of cannabis itself may assist in slowing down this process, although the precise mechanism of action has not been ascertained.
Brain ageing & the endocannabinoid system
The ageing of the brain, and the resultant neurodegeneration associated with it, cause increasing levels of debilitation and cognitive decline as they progress. Common features of typical age-related neurodegeneration include memory loss, difficulty with orientation, and difficulty paying attention (although research suggests that the latter may be more closely related to impairment of hearing and vision rather than directly due to cognitive decline).
Abnormal brain ageing is also a significant concern to health authorities worldwide-increasingly so, as the global population ages and age-related health problems become more prevalent. Conditions that cause the brain to age or decline prematurely or too rapidly include Alzheimer’s, Parkinson’s, Huntington’s, and amyotrophic lateral sclerosis (ALS).
There have been various studies into the potential for cannabis and cannabinoid therapies to slow or even reverse the symptoms of neurodegeneration in diseases such as Alzheimer’s, as well as a significant amount of research into the possibility that normal brain ageing could be slowed by cannabis use.
Research into normal brain ageing and cannabis
The ageing process is determined by the balance between detrimental and defensive biological processes, such as oxidative stress and antioxidation; the bulk of research suggests that the endocannabinoid system (ECS) is more closely associated with the latter camp than the former.
On a cellular level, the ECS regulates expression of the important neurotransmitter, brain-derived neurotrophic factor (for example, chronic exposure to THC induces upregulation of BDNF in rats), an important protein responsible for the development and maintenance of healthy neurons, which underlies its ability to assist in neurogenesis (growth of new neurons).
Pathological brain ageing and the ECS
In terms of ageing that is non-typical or pathological (i.e. that caused by disease), the ECS has been widely implicated in the suppression of neuroinflammation (for example, mice bred to lack CB1-receptors exhibit significantly higher levels of neuroinflammation), which can lead to the development of neurodegenerative diseases and early-onset age-related cognitive decline.
Thus, it is clear that the ECS (particularly with regards to the CB1-receptors and their agonists) has a vital role in the onset and progression of the ageing process. The two best-known endogenous cannabinoids, anandamide and 2-AG, are both agonists of the CB1-receptor; it is not known with certainty which of the two is more deeply involved in the anti-ageing process.
However, preliminary research indicates that low levels of fatty acid amide hydrolase (FAAH; the enzyme responsible for the degradation of anandamide) are associated with delayed brain ageing, suggesting that high levels of anandamide are likely to have a beneficial effect. Thus, FAAH inhibitors would make an ideal candidate for further research.
Ageing of skin & the endocannabinoid system
The other major aspect of ageing aside from the mental is obviously the physical, and this aspect is primarily characterized by changes to the epidermis, dermis and hypodermis (the layer of fat, fibroblasts, and macrophage cells that lies just beneath the dermis).
Exposure to UVA and UVB rays causes thinning of the dermal layer, meaning that as skin ages, it becomes less elastic and begins to sag, causing the epidermis to droop and become wrinkled. The skin also becomes prone to blemishes such as liver spots, which are thought to arise due to an accumulation of aged basal cells that can no longer be removed by the body’s natural waste-clearing mechanisms.
It is now known that the endocannabinoid system is involved in the maintenance of healthy skin in various ways, and that dysfunction of the ECS could be behind various neurodegenerative diseases. A 2012 study published in the journal Neurobiology of Aging observed that in mice bred to lack CB1-receptors, not only did the subject animals exhibit early onset of neurodegeneration, they also demonstrated histological changes in skin elasticity resembling those found in typical ageing. However, the researchers noted that no other signs of ageing were seen to be associated with the deletion of the CB1-receptors.
Furthermore, a 2010 study demonstrated that anandamide was integral to the processes of basal cell proliferation and death. Basal cells are the primary constituent of the epidermis, making up approximately 90% of all cells present, and it is well-known that maintenance of healthy skin requires their effective proliferation, growth and eventual death.
Senescence, cell death & the endocannabinoid system
The process of programmed cell death is involved in the process of ageing in various key ways, and there is a growing body of evidence suggesting that the ECS has an integral role to play.
While there have been no studies specifically investigating the role of the ECS in cell death related to the normal ageing process, there are abundant studies documenting the ability of both CBD and THC to cause it in general terms.
For example, it has been shown that that leukaemia and glioma (a tumour of the glial tissue of the brain) cells are sensitive to cannabidiol-induced apoptosis(apoptosis is a primary form of programmed cell death), but that primary monocytes and glial cells are relatively insensitive. THC has been shown to induce apoptosis in human prostate cancer cells, although it is thought that this effect may be mediated by some other means that via the cannabinoid receptors, as other agonists such as WIN55,212-2 had no effect.
A 2008 study also showed that the cannabinoid acid and precursor to THC, THCA, is responsible for the regulation of cell death in the leaves of cannabis plants. The study showed that THCA is injected into leaf tissues, where it causes mitochondrial dysfunction within leaf tissues, and ultimately leads to necrosis (another important type of cell death).
Other ways that cannabis & hemp can help
As well as anandamide, THC, and CBD, there are other phyto- and endocannabinoids that may have a role to play in the maintenance of healthy skin. For example, the endogenous CB2-receptor agonist n-palmitoylethanolamine has been shown to reduce pruritus (itching of the skin) reported in patients with atopic dermatitis and related diseases; although pruritus can affect individuals of any age, its occurrence becomes far more prevalent with age.
Furthemore, the unique combination of omega-3 and omega-6 oils found in hemp seed may also have distinct benefits on the process of skin ageing. A 2012 study on mice concluded that the sample group administered with hemp oil demonstrated significant improvements in dermal thickness, along with improved collagen fibre texture, and increased numbers of hair follicles (reduction in hair follicle count leading to balding is another common sign of ageing).
Could cannabis sometimes speed the rate of ageing?
Although it seems that cannabis use is generally advantageous in terms of delaying the ageing process, there may be certain circumstances in which it can have a deleterious effect.
Smoking as a delivery method may negate the potential benefits of cannabinoids as an anti-ageing treatment, and may even contribute to accelerated skin ageing. This is due to the fact that cannabis smoke contains many of the same hydrocarbons as tobacco smoke.
Overall, it appears that the likelihood of cannabis use speeding the process of ageing is small, and that regular use (although preferably via a means other than smoking) could in fact slow or even reverse clinical signs of ageing seen in the brain and the tissues of the epidermis and dermis.