Cancer and cannabis – is there a role?
Cannabis sativa plant has been used traditional herbal medicine for years. Of the many biologically active components, called cannabinoids, the two most studied are the chemicals and cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) the later having the psychotropic (high) effects responsible for its popularity. As a natural plant based product it also contains numerous other polyphenols and phytochemicals which as a group have numerous reported health benefits [Thomas].
When cannabis is taken orally about 10% of the cannabidiols become bioavailable with 1- 6 hour but can stay in the blood stream for up to 30 hours. Inhaled cannabis great has a peak serum level within 2-30 mins declining rapidly within an hour and has less generation of the psychoactive metabolite [Adams, Agurell].
There is enormous interest in the media and within advocacy group blogs based on anecdotal reports of miraculous responses for cancer and cannabis. Most of which are unsubstantiated, exaggerated or failed to mention concomitant medical treatments which were likely to have the main influence on the responses. That said, there are very few well conducted studies evaluating its anti-cancer effect and there are a number of possible reasons for this.
Why is there a lack of medical trials on cancer and cannabis:
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 barriers, there are some published studies, particularly looking at its benefit as a supportive agent to help symptoms of disease and treatments.
Published studies of links between cancer and cannabis:
1. Increased lung cancer Risk:
A 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 [Berthiller]. For example, the large, study of 64,855 men from the United States found that cannabis use was not associated with tobacco-related cancers [Sidney]. Most conclusively, a meta-analysis the National Academies of Sciences, Engineering, and Medicine report concluded that there was no statistical association between Cannabis smoking and lung cancer [National].
2. Increased testicular cancer risk
Chronic use does use produces affects on the endocrine and reproductive. Three population-based case-control studies reported an association between cannabis use and slightly elevated risk of germ cell or testicular cancers [Daling, Trabert, Lacson]. 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 [Callaghan].
3. Decreased cancer risk
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 [Thomas].
4.Cancer and cannabis – clinical studies:
Despite these promising laboratory studies, there is little evidence, so far, for a significant, benefit in humans. One small pilot study gave intra cancer injections of delta-9-THC in patients with recurrent but there was no significant clinical benefit [Guzmán]. 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. 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.
Why could cannabis have an anti-cancer effect:
In animal studies, anticancer properties of THC and other cannabinoid agonists have been demonstrated. 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-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 [Guzman, Velasco, Pisanti]. Cannabis also has an anti-inflammatory effect which can help reduce the risk of chronic inflammation – a drive of cancer but also for amyloid, a precursor for Alkzeimer’s dementia.
Potential negative issues with cannabis use:
- 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 demotivated and uninterested in education or work.
- long-term use can affect the ability to learn and concentrate.
- about 10% can get addicted particularly if users start using it in their teens
- it may encourage users to chance the euphoric effect with stronger more harmful drugs
- withdrawal can lead to insomnia, mood swings 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
- 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 [Engels].
Evidence for positive health benefits
1.Anti-sickness (Antiemetic) effects
Dronavinol and Nabilone both containing synthetic delta-9-THC, are approved for cancer related nausea since 1982 [Sutton]. A Cochrane meta-analysis of 23 subsequent randomized RCTs reviewed studies showed that, either as on their own (monotherapy) or in combination with other antiemetics, individuals were more likely to report complete absence of nausea and vomiting when they received cannabinoids compared with placebo, although they were more likely to withdraw from the study because of an adverse event such as sedation, or drowsiness, dizziness, dysphoria or depression, hallucinations, paranoia or hypotension [Ahmedzai, Smith]. Since these studies newer very effective anti-emetics are available such as ondansetron and aprepitant with less side effected making the role of cannabaloids are less relevant.
2. Appetite Stimulation
Small studies have shown THC increased appetite in patients with AIDs compared to placebo [Biel]. Three other studies have showed it was slightly inferior to progesterone called megestrol another appetite stimulator [Jatoi]. In trials conducted in the 1980s that involved volunteer, inhaling cannabis increase in calorie although mainly in the form of between-meal snacks, with increased intakes of fatty and sweet foods [Strasser, Foltin]. Published studies, to date, have explored the effect of inhaled cannabis on appetite in cancer patients.
3. Analgesia, anxiety and sleep
One small study reported that cannabinoid delta-9-THC was associated with substantial analgesic effects, with antiemetic effects, relaxation benefits and appetite stimulation [Abrams]. In one study, 10 mg doses of delta-9-THC produced analgesic effects for 7 hours comparable to 60 mg doses of codeine, and 20 mg doses of delta-9-THC induced effects equivalent to 120 mg doses of codeine [Wilsey]. 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 [Wilsey]. Patients often experience mood elevation after exposure to cannabis and depending on their previous experience could be positive or negative. A five-patient series of inhaled Cannabis reported that patients who self-administered Cannabis had improved mood, improved sense of well-being, and less anxiety[Noyes].
4. Peripheral neuropathy (neuropathic pain)
Two RCTs of inhaled cannabis in patients with neuropathic pain of various aetiologies found that pain was reduced compared with those who received placebo [Hohnsom, Lynch]. Two additional trials of inhaled cannabis have also demonstrated a benefit over placebo in HIV-associated neuropathic pain [Maida, Wilsey].
Cannalaboids have a useful role in cancer management if used wisely and patients 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.
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