Sep 6, 2019

Cannabis, CBD and health – benefits?

Screen Shot 2018-07-03 at 12.59.05Hemp, CBD oils and marijuana are separate varieties of the same plant cannabis sativa. If the oil is extracted by cold pressing, it contains 80% polyunsaturated omega 3 and 6 fatty acids such as Linoleic acid (LA) and linolenic acid (LNA). It is rich in the oil soluble vitamin E and other phytochemicals which have numerous reported health benefits but scientists are particularly interested in biologically active components called cannabinoids and these are driving the interest the health benefits of cannabis. There are over a 100 known cannabinoids in cannabis but the two most well characterized pharmacologically are the cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) the later having the psychotropic (high) effects responsible for the plant’s popularity. So far, it has be discovered that THC has analgesic, anti-spasmodic, anti-tremor, anti-inflammatory, appetite stimulant and anti-emetic properties, whilst CBD has anti-inflammatory, anti-convulsant, anti-psychotic, anti-oxidant, neuroprotective and immunomodulatory effects. CBD is not intoxicating and indeed it has been postulated that the presence of CBD in cannabis may alleviate some of the potentially unwanted side-effects of THC. There is currently limited scientific information on the pharmacology and toxicology of the other cannabinoids.

Cannabinoids can be made synthetically or extracted from the plant, in which case they are referred to as phytocannabaloids. The concentrations of different ingredients depend on the varieties of plant, sex of the plant, the growing conditions and what part of the plant is used for the extract. The THC is found in the resin secreted by glands located around the reproductive organs (flowering buds). The CBD is found in the seeds, leaves and stems. The dried buds, seeds and leaves of cannabis have been used in herbal remedies and recreation for centuries but more recently they have been developed as a nutritional supplement and from 2018, medicinal products.


dnaMedicinal cannabis

A clear definition of what constitutes a cannabis derived medicinal product has been developed by the Department for Health and Social Care for England and the UK Medicines and Health Products Regulatory Agency (MHRA), and only products meeting this definition have been rescheduled under the UK’s misuse of drugs legislation – otherwise the director of these companies will have ended up in jail. Synthetic cannabis has had medical licence 1982, phytocannabinoids gained a licence in the autumn of 2018 largely due to the research and development efforts of the UK pharmaceutic company GWpharma. All other THC containing products remain illegal in the UK and many other countries.There are numerous ongoing studies in progress which may gain medical licences in the future but the indications for medicinal product so far include:

Nausea: Dronavinol and nabilone both containing man-made delta-9-THC, are approved for cancer related nausea. A Cochrane meta-analysis of 23 subsequent randomized RCTs reviewed studies showed that, either as on their own or in combination with other anti-emetics, individuals were more likely to report complete absence of nausea and vomiting when they received these cannabinoids compared with placebo. Participants were, however, more likely to withdraw from the studies because of an adverse event such as sedation, or drowsiness, dizziness, dysphoria or depression, hallucinations, paranoia or hypotension. Since these studies newer very effective anti-emetics are available such as ondansetron and aprepitant which have less side effects. Their role is now only relevant if these medications fail.

Multiple sclerosis.Sativex is an oromucosal spray of extract of the cannabis sativa plant that contains the principal cannabinoids delta-9-tetrahydrocannibinol (THC) and cannabidiol (CBD) in a 1:1 ratio as well as specific minor cannabinoids and other non-cannabinoid components. It is administered as an oromucosal spray, and has received regulatory approval in 21 countries to help relievemuscle spasticity, spasms, bladder dysfunction and pain symptoms associated with multiple sclerosis.

Epilepsy:Epidiolex, gained a medical licence for the treatment of some rare epilepsies associated with Lennox-Gastaut syndrome or Dravet syndrome in patients 2 years of age and older. It contains a mixture of THC and CBD.


Conditions under investigation (not yet licenced)

Appetite stimulation: Small studies have shown cannabis increased appetite in patients with AIDs compared to placebo. Three other studies have showed it was slightly inferior to progesterone called megestrol another appetite stimulator but did not have the fluid retention properties. Trials conducted in the 1980s involved healthy control subjects, inhaling cannabis and reported an increased caloric intake although they did not educate or prepare participants so most of these calories were via sweet and fatty foods.

Analgesia, anxiety and sleep disorders: One small study reported that cannabinoids were associated with substantial analgesic effects, with antiemetic effects, relaxation benefits and appetite stimulation. In a follow up study, 10 mg doses of delta-9-THC produced analgesic effects for 7 hours comparable to 60 mg doses of codeine. Another study reported that patients who used nabilone experienced improved management of pain, nausea, anxiety, increased quality of sleep and relaxation when compared with untreated patients, resulting in decreased use of opioids, anti-inflammatory drugs, anti-depressants, gabapentin and anti-sickness drugs.  Patients often experience mood elevation after exposure to cannabis and depending on their previous experience could be positive or negative. A small study of inhaled cannabis reported that patients who self-administered Cannabis had improved mood, improved sense of well-being, better sleep patterns and less anxiety.

Peripheral neuropathy (neuropathic pain): Two RCTs of inhaled cannabis in patients with peripheral neuropathy or neuropathic pain of various aetiologies found that pain was reduced compared with those who received placebo. Two additional trials of inhaled cannabis have also demonstrated a benefit over placebo in HIV-associated neuropathic pain.


labThe evidence for cannabis and cancer management:

There is enormous interest in the anti-cancer properties of cannalabinoids in the media and within advocacy groups. Most of this interest is based on laboratory studies and anecdotal reports of responses and cures but there are very few well conducted clinical studies substantiating its anti-cancer effect. There are a number of possible reasons for this:

First, its illegal status has thrown substantial bureaucratic barriers to designing trials evaluating an anti-cancer effect. Second, as a plant product, it is difficult to circumnavigate the rules of licencing organisations such as the MHRA and FDA who require precise levels of active ingredients. For most plant based products sources from various farms across the World it is difficult to achieve this. Companies such as GWpharma, who have conducted the trials on multiple sclerosis and epilepsy grow their crops in heavily guarded hermetically sealed biospheres; the seeds, soil, nutrients, water and light have to be identical for each crop and even then, they have to measure the levels of THC and CBD and only select the plants within a strict concentration band – This level of technology is outside the abilities of most companies. The final and probably most important point. Cannabis itself cannot be patented or intellectually protected so that pharmaceutic companies are reluctant to invest millions of dollars in trial development when the results could just be copied the product made by rival companies.

Despite these drawbacks there are some studies which provide interesting data and suggest a justification to invest time and money in definitive studies.

Cannabis and cancer – is there an increased risk?

Screen Shot 2018-11-20 at 16.57.46A number of studies have yielded conflicting evidence regarding the risks of various cancers associated with cannabis smoking but most have concluded there is no increased risk if the influence of tobacco was excluded. For example, the large, cohort study of 64,855 men from the United States found that cannabis use was not associated with tobacco-related cancers. Another population-based study of lung cancer patients revealed that chronic exposure was not associated with an increased risk of oral, pharyngeal, laryngeal, lung or oesophagus cancer when adjusting for several confounders. A systematic review of observational studies failed to demonstrate a statistically significant association between cannabis inhalation and lung cancer and finally a meta-analysis from the National Academies of Sciences, Engineering, and Medicine report concluded that there was no statistical association between Cannabis smoking and lung cancer.

Chronic marijuana use does have effects on the endocrine and reproductive system which explains why three population-based case-control studies reported an association between cannabis use and slightly elevated risk of germ cell or testicular cancers. This was confirmed in a study of 49,343 Swedish men enrolled in the military then followed up for 42 years. Although it did not affect infrequent users heavy cannabis use (more than 50 times in a lifetime) was associated with a 2.5-fold increased risk.

Cannabis and cancer – evidence for a treatment effect 

The California Men’s Health Study followed 84,170 participants for 16 years and found that cannabis users developed a small but statistically significantly lower number of bladder cancer compared to non-users. In animal studies, cannabis extracts, have demonstrated anticancer properties of THC and other cannabinoid agonists. The mechanism of action included activation of pathways that leads to the stimulation of apoptosis; inhibition of VEGF leading to inhibit tumour angiogenesis; and decrease cancer cell migration reducing invasion into adjacent tissues and metastasis. Two major endocannabinoid-specific receptors have been identified andandamine and 2-arachidonoyllglycerol (2-AG) These are over-expressed in several types of tumours including glioblastoma multiforme (GBM), and higher grade prostate and colon cancers.  Researchers are suggesting that future studies measure these receptors levels and give cannabolids only to people who tumours over express them. In this design, any response in these subgroups will be evident.

Despite these promising laboratory studies, there is little evidence, so far, for a significant, benefit in humans.  One small pilot study gave intratumour injections of delta-9-THC in patients with recurrent but there was no significant clinical benefit. A number of other ongoing trials are giving oral cannabidiol (CBD) to patients with recurrent solid tumours on its own, in combination with chemotherapy but at the time of writing this section they had been recruiting slowly and have not been reported. In view of the synergy with a chemotherapy for brain tumours (temozolomide) seen in animal studies, there is particular interest in the investigation of nabiximols (with a 1:1 ratio of THC:CBD) in conjunction with temozolomide in patients with recurrent glioblastoma multiforme and these trials are still underway. Some case studies have been published reporting good responses for topical application of cannabis oil for a type of skin cancer called basal cell carcinoma but further long term randomised studies are required before this becomes confirmed and added to routine management.

Cannabinoids are known to potentially interact with the liver enzyme cytochrome P450 but in one small study, patients treated with irinotecan or taxotere, addition of cannabis tea did not significantly influence exposure to and clearance of the chemotherapy.

Non-medicinal cannabis use.

Outside clinical studies and the licenced indications mentioned above the two main situations where cannabis plant produces are used are recreation use or nutritional supplements. Both these situations will not be discussed:

Recreational cannabis

This goes by many names, including marijuana, pot, grass, cannabis, weed, hemp, hash, ganja, and dozens of others. Although in some parts of the World it’s recreational use is legal is the most widely used illegal drug. When whole cannabis is eaten between 6%-20% of the cannabinoids become bioavailable with 1-6 hours but can stay in the blood stream for up to 30 hours. Inhaled cannabis has a peak serum level within 2-30mins declining rapidly within an hour and has less generation of the psychoactive metabolites. The reported pleasant and detrimental effects of cannabis vary from person to person.

Possible pleasant effects:

  • being chilled out, relaxed and happy
  • some people get the giggles or become more talkative
  • hunger pangs (“the munchies”) are common
  • colours may look more intense and music may sound better
  • time may feel like it’s slowing down

Possible negative effects:

  • unaccustomed users may feel faint or sick
  • it can make users sleepy and lethargic
  • it can affect memory
  • it makes some people feel confused, anxious or paranoid,
  • some experience panic attacks and hallucinations
  • it interferes with the ability to drive safely
  • regular users, may get uninterested in education or work.
  • long-term use can affect the ability to learn and concentrate.
  • about 10% get addicted, mainly if using from their teens
  • it may encourage people to stronger more harmful drugs
  • withdrawal lead to insomnia, irritability and restlessness.
  • smoking cannabis risks bronchitis, coronary heart disease.
  • regular and early cannabis use increases the risk as schizophrenia.
  • regular use reduces sperm count in men and ovulation in women

Cannabis as a food supplement

Screen Shot 2018-11-21 at 16.12.33Oils and extracts can be legally sold as nutritional supplements in most countries and do not require a medical licence as long as they do contain >0.2% THC. The two most commonly sold supplements include Hemp oil and cannabinoid (CBD) oils.

 Difference between CBD oils, hemp oil and THC containing oils

These are all natural component of the cannabis, marijuana or hemp plant. Hemp oil is rich in short chain omega 3, omega 6 and vitamin E but has no THC and very little CBD. It is usually a side product from industrial hemp production grown for many commercial and industrial products including rope, clothes, food, paper, textiles, plastics, insulation and biofuel. The seeds are then crushed and the oil extracted biofuel or supplement use. CBD oil is found in the seeds, leaves and stems of plants which have been grown specifically to enhance their CBD levels. As mentioned above THC oils include extracts from the flower and resin from the adjacent glands.

There has been an enormous interest in CBD oils in cancer management as they have potent anti-inflammatory, immunomodulation and anti-oxidant properties and have exhibited direct anti-cancer mechanism as already highlighted above. They don’t have the psychotrophic and sedation properties THC which on a day to day basis are usually unwelcomed.  As they are legal in most countries they are seen, by many, as a safe way to benefit from the potential attributes of the plant without the negative effects. They usually come in an oil containing 5-12% cannabinoids which is dropped into the mouth, under the tongue. They are generally regarded as safe with few drug interactions.

The best CHD oils are derived from organically grown plants. This ensures they are free from pesticides and herbicides and are made from plants specifically grown for CBD produce rather than a side product for hemp products which are rarely organic. It is also important to buy from a reputable source as the supplement industry is not as well-regulated as the pharmaceutical industry. Reports of bogus product with contaminants and inadequate levels of CBD are rife. Finally, the law allows a small amount of THC which many supplements do not include or even measure. This small amount will not cause the negative psychotrophic effects but is very likely to add to the potential beneficial effects. A good supplement will ensure levels of TCH up the legal limit. The product recommended on the website satisfied these criteria.

In conclusion

Cannabinoids have a useful role in cancer management if used wisely and patients are monitored closely. There is reasonable evidence of a benefit for neuropathic pain, other pains, appetite stimulation and nausea but some patients have troublesome side effects. There are laboratory data to suggest anti-cancer benefits and one population study linking a lower risk of bladder cancer. Evidence for a direct anticancer benefit in humans, outside anecdotal reports, is lacking although studies are ongoing. CBD oils are safe but should be bought from reputable long established companies with a high quality assurance, be extracted form organic plants and contain the full legal quota of THC.

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