This follows on from herbal remedies and covers substances that are not herbs but they occur naturally and are thought to have medicinal properties.
This will cover the following topics:
- Glucosamine and Chondroitin
- Cod Liver Oil
- Medicinal Cannabis
- Further Resources
- Site Index
If you wish to go directly to any of the above headings, click on the title in blue.
The use of vitamins and other supplements has been moved to the chapter on Supplements in the section on nutrition. There may be some overlap of interest with this chapter and the one on supplements as well as the other sections on nutrition.
Glucosamine and Chondroitin
Both these substances are involved in the synthesis of cartilage in the body. They are promoted either individually or together to aid osteoarthritis which is fundamentally a disease of cartilage. It is a disease that affects us all with advancing years and with an aging population it is becoming more important. The usual treatment is painkillers of a class called non-steroidal anti-inflammatory drugs (NSAIDs) and they are not entirely satisfactory. Their greatest problem is a tendency to cause bleeding from the upper gut. This can be pernicious and cause anaemia or it can be acute with severe haemorrhage. They may just cause pain and indigestion. They do not prevent the natural progress of the disease.
In view of the demand for something safer but effective it is unsurprising that this has such a great market. However, there are a number of questions to answer:
- Does it relieve pain?
- Does it slow the natural progression of the disease?
- What are the side-effects?
A PubMed search for “glucosamine and osteoarthritis” produced 646 results of which 181 were reviews. For simplicity, I turned to the reviews. Often chondroitin is included too. Osteoarthritis is a disease of cartilage in joints. A typical feature on x-rays of affected joints is a narrowing of the joint space as the cartilage is eroded.
The trials were of variable quality. Some of the reviews were reluctant to give their conclusions without access to a website that required payment. A meta-analysis from the BMJ gave free access, suggesting that they think the topic is important.1Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee It examined 10 trials for osteoarthritis of the hip or knee, each of more than 200 patients, involving 3,803 patients in total who received either glucosamine, chondroitin, both or placebo. The main outcome to be examined was effect on pain. The secondary outcome was joint space narrowing. As so often occurs, the trials that were funded by the industry tended to have more positive results than those that were not. They concluded that glucosamine, chondroitin and the two in combination do not reduce joint pain or have an impact on narrowing of joint space compared with placebo.
I then turned to the systematic review that is seen as the gold standard. This was an updated Cochrane review of 25 studies with 4,963 patients.2Glucosamine for osteoarthritis The results were slightly different depending upon whether a not a brand called Rotta was used. The Rotta brand seemed to give slight improvement in pain compared with placebo but it was not very impressive. The other brands were no better than placebo. Narrowing of cartilage was not considered but side effects were. They were generally no more than with placebo.
A recent study from the USA had 201 subjects with mild to moderate pain from osteoarthritis in one or both knees.3The effect of oral glucosamine on joint structure They were randomised to either 1,500mg of glucosamine daily given in lemonade or just lemonade for 24 weeks. The knees were assessed by MRI scans and urinary excretion of CTX-II was measured. This is a measure of degradation of cartilage. There was no significant difference between the two groups.
In conclusion, glucosamine and chondroitin are part of the building blocks of cartilage but taking daily doses of them does not seem to have any significant benefit in osteoarthritis of the hip or knee. It does not ease pain, nor does it seem to slow the process of erosion of cartilage. However, at least side effects do not appear to be a problem.
Cod Liver Oil
Again, this is not a herbal product but it is a natural product that is claimed by many to be beneficial for arthritis. Cod liver oil is very rich in the fat soluble vitamins A and D. Vitamin A is important for night vision and vitamin D is important for the absorption of calcium from the gut.
There are three diseases or groups of diseases that should not be confused. Osteomalacia is a deficiency of calcium in the bone. This will occur if vitamin D levels are inadequate. In children it causes rickets with distortion of bones. Osteoporosis is different and due to a shortage of the matrix of the bone that supports the calcium and minerals. It is usually seen in older women although it can occur younger and 15% occurs in men. Arthritis is different again. It is a disease of joints, not bone. The most common form is osteoarthritis that is often seen as wear and tear. It is a disease of the cartilage in the joint. There are several other types of arthritis including rheumatoid arthritis and gout. There is no theoretical reason why cod liver oil, rich in vitamin D so that it enhances calcium absorption, should benefit arthritis which is not due to calcium deficiency.
A PubMed search for “cod liver oil” produced 848 results but I wished to be more specific so I changed the search to “cod liver oil for arthritis”. This produced just 15 results of which 4 were reviews. Many of the results were for rheumatoid rather than osteoarthritis. Several were not in English language journals. Of the four reviews, two were in foreign languages.
One review in English states that “This article reviews the use of nutraceuticals as alternative treatments for pathological manifestations of arthritic disease. The efficacy of fish oils (eg cod liver oil) in the diet has been demonstrated in several clinical trials, animal feeding experiments and in vitro models that mimic cartilage destruction in arthritic disease. In addition, there is some evidence for beneficial effects of other nutraceuticals, such as green tea, herbal extracts, chondroitin sulphate and glucosamine. However, in most cases, there is little scientific evidence at the cellular and molecular levels to explain their mechanisms of action.”4Biological basis for the benefit of nutraceutical supplementation in arthritis This looks very promising although the Cochrane review and others had concluded that chondroitin sulphate and glucosamine are not helpful in arthritis.
The other review was from 1988 which is really rather a long time ago. It is surprising that there have been no more recent reviews if the treatment is promising. It was rather reticent about benefits and looked forward to more and better trials.5Do diets rich in polyunsaturated fatty acids affect disease activity in rheumatoid arthritis?
If there is benefit from cod liver oil, it may be due to an anti-inflammatory effect. This would also account for its greater value in rheumatoid arthritis which is an inflammatory condition. It seems that cod liver oil can reduce the amount of non-steroidal anti-inflammatory drugs (NSAID) used in rheumatoid arthritis.6Cod liver oil (n-3 fatty acids) as an non-steroidal anti-inflammatory drug sparing agent in rheumatoid arthritis
A paper from Germany, where they are very keen on complementary therapies, found that cod liver oil was effective in rheumatoid arthritis at reducing morning stiffness, painful and swollen joints.7Effect of cod liver oil on symptoms of rheumatoid arthritis
A paper from back in 1992 was called 8Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. This compared 10ml of cod liver oil with olive oil as a placebo within a general practice setting. Assessment of pain and interference with daily activities was made. This treatment was to supplement their regular NSAID. There was no significant difference between the two groups.
Rheumatoid arthritis is an inflammatory disease. Note the considerable damage to the knuckle joints and how the fingers are deviated away from the thumb.
For something that is as widely used as cod liver oil there is remarkably little evidence about its efficacy. It may well have a slight anti-inflammatory effect which accounts for its greater value in rheumatoid arthritis than osteoarthritis. The conclusion has to be that it may be beneficial rather than it definitely helps or does not. Most people find that the oil tastes unpleasant but capsules may provide an inadequate dose compared with two teaspoons (10ml) daily. Complications of treatment are unlikely to be a problem provided that the dose is not excessive. Some people think that if a little of something is good then a lot is even better. The fat soluble vitamins A and D can be taken to excess and cause toxicity. The water soluble ones such as the B complex and vitamin C are excreted in the urine but vitamins A and D can build up and have unpleasant effects.
Honey has often had almost magical powers ascribed to it with a great many health claims. Its use goes back to antiquity. Honey comes in many forms but the one which has the most claims is manuka honey. It usually comes from New Zealand where the manuka bush is native but it can be made where manuka bushes are cultivated elsewhere including the UK. Manuka honey is very expensive.
A PubMed search for manuka honey gives 146 papers going back only as far as 1991 suggesting that interest is fairly recent. All honeys have some antibacterial effect. A drop of honey on an agar plate with bacterial colonies growing on it will produce a ring around itself in which the bacteria will not grow. This is rather like the rings when antibiotics are dropped on such plates to test antibiotic sensitivities of bacteria. Manuka honey is said to be better than the others in that the effect is more long lasting. An important component is methylglyoxal which is about 100 times more concentrated in manuka than other honeys. The papers on PubMed are mostly about the use of topical manuka honey in dressings of wounds including burns, to prevent bacterial infection.
The evidence of the effectiveness of honey seems good. They produce hydrogen peroxide and this can help to overcome bacterial contamination in various skin diseases and to kill some fungal infections.9Honey in dermatology and skin care Manuka honey appears to be even better. It is sometimes used in dressings to kill bacteria including MRSA and it seems very promising. However, before spreading honey from the jar on an open wound, beware that these dressings contain medical quality honey. Ordinary honey contains bacteria and it has to be specially treated before it is fit for medical use. Honey contains a large amount of sugar and it can raise the blood glucose. However, a single paper on the use of manuka honey in diabetic ulcers suggested that it was beneficial.10Manuka honey-impregnated dressings in the treatment of neuropathic diabetic foot ulcers
Beware of the many other claims that are made for honey. There is a paper about intravenous manuka honey inhibiting tumour growth in a mouse with melanoma. However, to extrapolate this to state that eating honey helps to prevent or cure cancer is a step too far and I would certainly not recommend intravenous honey. Beware of claims related to animal models or in vitro studies when there is no experience in humans. Honey may help with some of the adverse effects of cancer treatment.
There is no evidence that honey has any effect in preventing or curing the common cold.
Vitamin and mineral supplements are an enormous market, but for most people they should be totally unnecessary if they eat a balanced and varied diet. Growing children have a high demand, but this should be met by a proper diet containing very little processed, fast and take-away food. In pregnancy, most women would suffice without supplements, but iron and folic acid are given to all, as prevention is more satisfactory than treatment of deficiency. Some diseases may limit diet or lead to poor absorption whilst others put an increased demand on nutrients. These do require supplements. For the majority of the population, we need a good and varied diet with plenty of fresh fruit and vegetables and try to have as many colours as possible to cover the range of trace minerals. Even vegetarians or those who do not eat red meat, can get enough iron from the correct amount of green vegetables.
Bacteria are all around us and inside us. The gut contains around 1014 bacteria, especially in the large intestine and they are important for health. They weigh about a kilogram. The skin has normal bacteria as does the mouth. The vagina is heavily colonised with bacteria, especially lactobacilli. They are so called because they were first isolated from bad milk and they produce lactic acid. This makes the vagina more acid and the low pH discourages less desirable flora. Just as Penicillium and Streptomyces produce antibiotics to kill the competition, lactobacilli produce acid to impede the competition. A course of antibiotics may kill many of the bacteria and permit other organisms to thrive such as Candida albicans, also known as thrush.
Antibiotics can upset the normal bacteria of the gut and result in diarrhoea. A particularly nasty bacterium that may remain after antibiotics is called Clostridium difficile. We must not think of all bacteria as being bad.
From this comes the concept that putting desirable bacteria into the right place may be beneficial. Such organisms are called probiotics. This has been examined for many conditions, especially diseases of the gut. Only live or natural yoghurt can help the flora of the gut and most yoghurt on sale is pasteurised. However, “live” or “natural” yoghurt is available. It has been suggested to treat or prevent vaginal candida. This has usually meant applying yoghurt directly. However, a trial comparing live yoghurt with pasteurised yoghurt by mouth found that the live yoghurt increased the colonisation of both the rectum and vagina with lactobacillus.11Ingestion of yogurt containing Lactobacillus acidophilus compared with pasteurized yogurt as prophylaxis for recurrent candida vaginitis and bacterial vaginosis Presumably the bacteria are transferred from the anus to the vagina. Faecal bacteria are the commonest cause of bacterial vaginosis as well as urinary tract infection.
High levels of glucose are helpful to the candida and I have seen diabetes presenting with a very heavy candida infection. The environment must be kept in balance.
Probiotics should be avoided in patients who are immunologically compromised, such as those with AIDS, malignancies of the immune system or transplant patients.
With so many papers about probiotics the obvious place to turn is the Cochrane Library where experts have already assessed the evidence.
- For patients with Clostridium difficile infection, the short-term use of probiotics appears to be safe and effective when used along with antibiotics.12For patients with Clostridium difficile infection, the short-term use of probiotics appears to be safe and effective when used along with antibiotics
- There is inadequate evidence of effectiveness in acute ulcerative colitis or in preventing relapse.13Probiotics for the treatment of active ulcerative colitis
- In Crohn’s disease there is inadequate evidence for treating active disease14Probiotics for treatment of active Crohn’s disease or preventing further attacks.15Probiotics for maintenance of remission in ulcerative colitis
- Probiotics are of no use to treat eczema.16Probiotics for treating eczema
- A Cochrane review for irritable bowel syndrome was underway at the time of writing but another systematic review found that probiotics were useful but the extent of their value was uncertain.17The efficacy of probiotics in the treatment of irritable bowel syndrome
There were many other Cochrane reviews. Some were underway. Many had inadequate evidence of good quality to make any conclusions. Subjects included preventing allergy in children, vaginal thrush, preventing urinary tract infection and preventing early labour. The general tone of papers and reviews seems to be that there is enthusiasm for the potential of these substances but very poor quality research to support them. This may imply that the people who produce the papers are more enthusiastic than objective.
A problem that seems to be ignored is the question of which organisms are being used. There are many different species and they are not all equal. One may be useful in a specific condition but not in other diseases. Where probiotics help there may be only one or two species that do help. Sometimes it is not just the species that matters but even he correct strain. This is a major problem that does not seem to have been addressed even by the Cochrane authors. You may suffer from irritable bowel disease and find that a certain species of probiotic is helpful in that condition. You then have to find which proprietary product has the correct organisms. Some organisms are available in the USA but not the UK. No one would simply talk about antibiotics as if they are all the same, but probiotics seem to be bundled together.
Antibiotics are prescription only medicines and so claims have to be validated and a doctor has to sign the prescription. Probiotics have no such limitations and so marketing can play fast and loose. An Irish review of the market potential for probiotics concluded that “The long-term exploitation of probiotics as health promoters is dependent on several factors, including sound, scientifically proven clinical evidence of health-promoting activity; accurate consumer information; effective marketing strategies; and, above all, a quality product that fulfils consumer expectations.”18Market potential for probiotics The suggestion that the success of these products depends on good science and accurate consumer information seems naïve.
An American review compared and contrasted regulations in the USA and UK. It stated that many claims are made for probiotics on the basis of poor and underpowered trials.19Health claim regulation of probiotics in the USA and the EU It said, “On one end of the spectrum regulators may take a limited approach to regulation relying primarily on the marketplace that respects individual autonomy and assumes a sophisticated consumer and honest sellers; alternatively they may choose substantial regulation based on a belief that consumers need protection from profit-seeking manufacturers.” There are a great many advertisements that claim that probiotics will give a general improvement in health in a non-specific way. This is similar to the groundless claims for vitamin supplements for healthy people.
Publications from the American Gastroenterological Association in 2020 showed that probiotics have not been shown to be safe and effective for most gastrointestinal conditions. As one expert put it, “Aside from offering probiotics to premature newborns, there is no good evidence to support their use in any situation.” Probiotics are regulated in the USA as foods or dietary supplements and so are not required to specify on their product labels the strains or the number of live microbes of each strain that the product delivers through to the end of its shelf life. If manufacturers want to claim that their probiotic can be used to diagnose, treat, mitigate, cure, or prevent disease, the products are treated as drugs and require clinical trials. This is costly and can take more than a decade to complete. There is no probiotic strain on the market that has been approved by the U.S. Food and Drug Administration to treat a disease.20Probiotics Lack Supporting Evidence for Most GI Conditions.
No one would perform a drug trial without reporting possible adverse effects. However, very few trials adequately report adverse effects and so their safety cannot be assumed.21Harms Reporting in Randomized Controlled Trials of Interventions Aimed at Modifying Microbiota: A Systematic Review
The nature and variety of bacteria in our guts is an interesting and advancing field. It affects our health and even how easy it is to achieve and sustain a good weight. We eat many micro-organisms each day. Many are killed by the acid in the stomach but food, especially the diary proteins, act as a buffer to the acid. Cheese, especially a rich, blue cheese, is a good source of bacteria. Other cheeses are also good, but not processed cheese. Conversely, a course of antibiotics can have an adverse effect on gut flora. Even without ingesting live bacteria, our diet can have a marked affect on gut flora. Fibre and slow starch offer a good medium for friendly bacteria whilst sugary and “junk” food is bad. Nuts also offer fibre in a friendly form.
The concept of probiotics has been around for more than 100 years but it is only in recent decades that they have received great attention. It is a matter that may be of great value and is worth pursuing.22Use of probiotics in gastrointestinal disorders At present evidence is mixed. If you want to find evidence about probiotics in other conditions, go to the Cochrane website at http://www.cochrane.org/ and type in “probiotics for..” whatever you choose. The failure to find definitive results may be due to many poor trials but failure to discriminate between different organisms for a specific condition is a major problem. In the meantime probiotics are marketed to a gullible population in Europe, America and much of the world with unsubstantiated claims.
I had not originally intended to include anything about cannabis as I saw it as largely a recreational drug that remains illegal in most countries including the UK. However, medicinal cannabis has hit the headlines, with much misunderstanding and misinterpretation. I have put it in the section on Other Natural Products rather than Herbal Remedies, partly because the latter is so full and partly because the ingredients from cannabis that are used in medicines are so refined that they are not like traditional herbal remedies.
The Cannabis plant has many uses. The plant fibres can be converted into cloth. Cannabis produces large amounts of tetrahydrocannabinol (THC) which produces euphoric and intoxicating effects, making it popular as a recreational drug. It can be eaten but is usually smoked, often mixed with tobacco. It has been used for centuries, more so in some cultures. It was popular amongst jazz musicians in the 1920s who thought that it helped them to play better. However, as with alcohol, what it really did was to impede self-criticism and anyone who was not intoxicated realised that they were really playing worse.
Cannabis became part of the hippy culture in the 1960s and remains popular with all age groups from teenagers to the pretentious aging who really ought to know better. It always struck me as ironic that whilst young people in the 1960s and 1970s would advocate boycotting products from South Africa in apartheid days or from Israel, they were quite happy to buy illegal drugs that helped to fund the mafia, the IRA or notorious gangs such as the Krays and the Richardsons.
I have often heard people say that cannabis is completely safe to use and safer than alcohol. At least we know what we have with alcohol and the concentration. Illegal substances can vary from dangerously potent to such a low level that it is impossible to prosecute for possession because the amount in it is not detectable. There may also be adulteration with other drugs or undesirable substances. However, there is very little research about illicit cannabis as it is difficult to do, and lack of evidence of toxicity is not the same as evidence of safety. Even back in the 1960s and 1970s, I was convinced that heavy and habitual users have psychological changes. There is now much evidence that heavy and regular use of cannabis can produce psychiatric disturbance including psychosis.
A more recent change has been a form of cannabis called skunk which is said to be about 40 times more potent than the usual form. To draw an analogy with alcohol, this is like the difference between half a pint of beer and a bottle of whiskey. However, others say that the amount of THC in normal cannabis is around 4% compared with between 14% and 23% for skunk. This is still about 4 to 6 times as much and very significant. Skunk smells different from ordinary cannabis. With this increase in potency, descriptions of cannabis-induced psychosis have become more common.23Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis It has been noticed that psychosis is more prevalent in young men of Afro-Caribbean origin, and this has been attributed to skunk. In London, about 95% of the cannabis seized is skunk.
I do not intend to delve into the argument about whether or not recreational cannabis should be legalised but instead to look at medicinal cannabis. This is a very different matter, just as the medical use of morphine or similar drugs is totally different from heroin abuse. The substances used in medicinal cannabis are highly refined and it is not like taking the product sold by your local drug dealer. For a start, the dose will be reliable.
There are two main chemicals in cannabis which can be of medicinal value. One is tetrahydrocannabinol (THC) that has already been mentioned. The other is called cannabidiol (CBD). THC is the substance which is largely responsible for the effects most often associated with cannabis use, including relaxation, euphoria and possible psychosis. Even for a given dose of THC, CBD can have a marked modifying effect, alleviating paranoia, and probably reducing the risk of psychosis. It is possible to buy products with CBD over the counter in pharmacies and health food shops, but the concentration is much lower than in medicinal preparations and there is no evidence of benefit in any condition. There are receptors in the brain for substances called endocannabinoids.24Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?
The conditions in which it is said that cannabis may be useful include25Clinicians’ Guide to Cannabidiol and Hemp Oils:
- Multiple sclerosis
- Alzheimer’s disease
- Arthritis although there are several different forms that are very different
- Chronic pain
- Crohn’s disease
- Severe Epilepsy
In July 2018, it was announced that medicinal cannabis would be moved out of Schedule 1 drugs, which by definition means that they have little or no therapeutic potential.26Cannabis Scheduling Review However, in keeping with most academic reviews in the field, the report was not effusive about the value of medicinal cannabis, saying that the volume and quality of the evidence was poor. Nevertheless, the field would seem to be quite promising but, in keeping with good practice, it is important to gather enough evidence first before allowing its use. A drug that was initially held to be very safe is thalidomide.
To turn to NICE, a publication in August 2019 called for much more research into medicinal cannabis, especially since the reclassification of products in 2018, to allow specialist doctors to prescribe them where the clinical needs of patients cannot be met by licensed medicines.27NICE draft guidance and NHS England review highlight need for more research on cannabis-based medicinal products It seems to be a problem throughout the world that whilst there is much pressure to bring cannabis-based products into the medical world, the quality and quantity of evidence is very poor.
A more substantial review was produced in November 2019 and updated in 2021. Specialist medical practitioners are now able to initiate the prescription for some cannabis-based drugs for specific conditions.28Cannabis-based medicinal products NICE guideline [NG144]
- Delta-9-tetrahydrocannibinol (THC) combined with cannabidiol (CBD) (Sativex) for treating spasticity in patients with multiple sclerosis (MS)
- Cannabidiol (Epidyolex) combined with clobazam as a treatment option for people aged 2 years or older with severe treatment-resistant epilepsy in Dravet syndrome or Lennox-Gastaut syndrome
- The synthetic cannabinoid nabilone as an add-on treatment for adults with intractable chemotherapy-induced nausea and vomiting
However, NICE ruled out prescribing nabilone, dronabinol (a synthetic THC preparation), THC alone or the combination of CBD with THC to treat chronic pain.
I turned to Cochrane for more.
A review called 29Cannabis for schizophrenia did not find any benefit.
A review of cannabis oil for Crohn’s Disease found the evidence too poor to draw conclusions about the effectiveness of side-effects of cannabis and cannabis oil for the condition. It called for much more research including various does and the effect whilst in remission.30Cannabis and cannabis oil for the treatment of Crohn’s disease The same group formed an almost identical opinion about its use for ulcerative colitis.31Cannabis and cannabis oil for the treatment of ulcerative colitis
A similar result came for the treatment of neuropathic pain (pain from nerves).32Cannabis products for adults with chronic neuropathic pain.
With regard to nausea and vomiting from cancer chemotherapy, they found that the trials were of generally of low to moderate quality and reflected chemotherapy treatments and anti-sickness medicines that were around in the 1980s and 1990s. There have been great improvements since then. They were unsure about how well the anti-sickness medicines worked, and further research reflecting modern treatment approaches is important. Nevertheless, they concluded that cannabis-based medicines may be useful for treating chemotherapy-induced nausea and vomiting that responds poorly to commonly used anti-sickness medicines.33Cannabis-based medicine for nausea and vomiting in people treated with chemotherapy for cancer
The use of cannabis (marijuana), its active ingredient or synthetic forms such as dronabinol, has been advocated in patients with HIV/AIDS, to improve the appetite, promote weight gain and lift mood. Dronabinol has been registered for the treatment of AIDS-associated anorexia (poor appetite) in some countries. However, the evidence for positive effects in patients with HIV/AIDS is limited, and some of that which exists may be subject to the effects of bias. Those studies that have been performed have included small numbers of participants and have focused on short-term effects. Longer-term data, and data showing a benefit in terms of survival, are lacking. There are insufficient data available at present to justify wide-ranging changes to the current regulatory status of cannabis or synthetic cannabinoids.34Medical use of cannabis in patients with HIV/AIDS
A review for fibromyalgia, compared nabilone, a synthetic (man-made) cannabis product with placebo or amitriptyline (an antidepressant frequently used in the treatment of fibromyalgia). Nabilone did not convincingly relieve fibromyalgia symptoms (pain, sleep, fatigue) better than placebo or amitriptyline. The tolerability of nabilone was low in people with fibromyalgia. It cannot be recommended.35Cannabis products for people with fibromyalgia
I looked for evidence about cannabis products for asthma and all I found was reports of asthma attacks following cannabis use.
Laboratory studies have indicated that cannabinoids may regulate some of the processes that lead to degeneration of the brain. Hence, cannabinoids could be useful in the treatment of neurodegenerative dementias such as Alzheimer’s disease. So far, only one small randomized controlled trial has assessed the efficacy of cannabinoids in the treatment of dementia. This study had poorly presented results and did not provide sufficient data to draw any useful conclusions.36No evidence that cannabinoids are effective in the improvement of disturbed behaviour in dementia or in the treatment of other symptoms of dementia
No reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy. The dose of 200 to 300 mg daily of cannabidiol was safely administered to small numbers of patients generally for short periods of time, and so the safety of long term cannabidiol treatment cannot be reliably assessed.37Cannabinoids for epilepsy There have been some very impressive anecdotes about cannabinoids in resistant childhood epilepsy but it may take six weeks to notice any difference. It may be only a minority who benefit but they get the publicity. It is very expensive. Cannabinoids for childhood epilepsy can be prescribed with caution by specialists such as paediatric neurologists but there is great demand and it is not a panacea.
There is currently weak evidence that oral nefopam (a cannabis-based product), topical capsaicin (a gel derived from chillies that depletes nerve endings) and oromucosal cannabis (absorbed through the wall of the mouth) are all superior to placebo in reducing pain in patients with rheumatoid arthritis. However, each agent has significant side effects. There were difficulties due to lack of blinding in trials, the small numbers of participants involved and the lack of data on adverse events. The review gave some backing to capsaicin but not oral nefopam and oromucosal cannabis because of more significant side effects and the potential harms seem to outweigh any modest benefit achieved.38Neuromodulators for pain management in rheumatoid arthritis
A Cochrane review found no evidence of benefit from cannabis products in multiple sclerosis (MS).39The use of different treatment for incoordination of limb movement (ataxia) or tremor in people with multiple sclerosis It did not help incoordination of movement or tremor (shaking).
Another major problem with MS is spasticity, which is great stiffness and difficulty moving. To date, Sativex is the only commercially available formulation containing cannabinoids used as add-on therapy for treatment of spasticity in adult MS patients who are not responding to conventional therapies. It is an oromucosal spray containing tetrahydrocannabinol and cannabidiol in approximately 1:1 ratio. A review from Italy found that it did offer benefit 40Sativex in the management of multiple sclerosis-related spasticity: An overview of the last decade of clinical evaluation but NICE recommends not offering it as it is not a cost-effective treatment.41NICE Multiple Sclerosis in Adults These highly refined forms of cannabis at reliable doses, appear to be very expensive. Sativex costs around £175 a bottle. Hopefully their prices will fall significantly in the near future.
Raised pressure inside the eyeball causes glaucoma. The evidence about marijuana and its effect on intraocular pressure has not changed since the research in the 1970s and 1980s. Marijuana is effective at reducing pressure in the eyeball but cardiovascular and neurological effects are observed at the same dose. It may theoretically reduce the beneficial effect of lowering intraocular pressure by reducing blood flow to the eye. 42Cannabinoids for treatment of glaucoma
There is no evidence that cannabinoids are of benefit in athletic training. THC does not enhance aerobic exercise or strength.43Exercise performance and sport
A number of people with advanced cancer causing severe pain acquire illegal cannabis to try to augment the effect of the opiate painkillers that they are prescribed. However, a systematic review and meta-analysis, published in 2020, concluded that “Studies with a low risk of bias showed that for adults with advanced cancer, the addition of cannabinoids to opioids did not reduce cancer pain.”44Cannabinoids for adult cancer-related pain: systematic review and meta-analysis Once again, cannabis has failed the objective test.
Despite the enthusiasm from pressure groups, there seems to be very little good, objective evidence for the use of cannabis products, either THC or CBD. They have been used in Israel for a few decades. They are used to treat nausea and poor appetite after chemotherapy and THC, at the rather high dose of 18%, is used for pain in the elderly. They claim that it reduces the number of falls, probably because less morphine and benzodiazepines are used. However, their research seems to be mainly descriptive and uncontrolled trials rather than proper RCTs.
As well as the lack of objective evidence of efficacy, another problem with THC and CBD is the price. I have seen reports of people going to the Netherlands to buy cannabis oil which appears to have a remarkable effect on their child’s epilepsy but they complain that it costs them £3,000 a month and they want the NHS to pay the £36,000 a year. As we have seen in Basic Maths in Medical Research and Decision Making, NICE requires the cost of treatment to be under a certain price per quality added life year (QALY). Money that is spent in one direction by the NHS is not available elsewhere and so they have to set priorities. Even if a child goes from multiple fits per day to fit free, the improvement would be less than 1.0 QALY and the limit per QALY is around £25,000 to £30,000. I would think that the NHS should be able to negotiate a much better price than individual consumers, but we need both good evidence and a price that matches the benefits.
- Supplements. Who needs them? A behind the headlines report. NHS Choices. June 2011
http://www.nhs.uk/news/2011/05May/Documents/BtH_supplements.pdfExplanation of a recent report from 2011 which showed that supplements of vitamins and minerals are no use to the normal person with a balanced diet.
- Vitamin Supplements in pregnancy. NHS Choices.
https://www.nhs.uk/conditions/pregnancy-and-baby/vitamins-minerals-supplements-pregnant/Pregnancy is a different time. Although it is not a disease there are greater requirement and this shows what is helpful, what is useless and what may even be harmful from supplements.
- Are you fooled by super-foods? BBC.
- NHS England. Cannabis-based products for medicinal use: Frequently Asked Questions
A lot of sound facts and advice with the authority of the NHS
- Wandel S, Jüni P, Tendal B, Nüesch E, Villiger PM, Welton NJ, Reichenbach S, Trelle S. Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis.
BMJ. 2010 Sep 16;341:c4675. doi: 10.1136/bmj.c4675. [full text]
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This website is now completed, although I shall continue to do updates. The following list shows the sections or chapters. Just click on the topic in blue to go to that part of the site.