- Cannabis-based medicines are whole-plant extracts from Cannabis sativa L. or isolated substances found in C. sativa.
- The antiemetic effect of cannabis-based medicines in chemotherapy-induced nausea and vomiting, but only when compared to the standard antiemetics in use before 5-HT3 antagonists had been developed, has been established in a meta-analysis.
- At present, there is insufficient evidence to recommend the routine use of cannabis-based medicines for the symptomatic treatment of anorexia in patients with cancer cachexia.
- Cannabis-based medicines seem to have an analgesic effect comparable to weak opioids according to a systematic review; the use of these medicines for pain that is insufficiently relieved by opioids is still being investigated.
- The main limitation of cannabis-based medicines appears to be their side-effects on the central nervous system.
The term medical cannabis denotes extracts or preparations taken from the herb Cannabis sativa L. (hemp), used for medical purposes. The term cannabinoids covers the natural or synthetized substances (delta-9-tetrahydrocannabinol (THC), cannabidiol and others) that are found in C. sativaand that interact with the endocannabinoid system in the human body.
Medical cannabis and cannabinoids (i.e. cannabis-based medicines) are claimed to have an antiemetic effect in patients receiving chemo-/radiotherapy and in patients with advanced cancer who have nausea of various origins. They are also recommended for the stimulation of appetite and food intake in advanced cancer patients with cachexia. Furthermore, there have been claims that cannabis-based medicines have an analgesic effect in cancer patients. In experimental settings, the potential of cannabis-based medicines for anti-tumour activity (e.g. glioblastoma) has been suggested. However, at present there are no clinical data to support their use as anticancer agents.
The antiemetic efficacy of the cannabinoid dronabinol (THC), when compared to standard antiemetics that were in use before the development of 5-HT3 antagonists for chemotherapy-induced nausea and vomiting, has been established in a meta-analysis. The question of whether cannabis-based medicines have a place in the era of modern antiemetic medication, e.g. for patients with refractory nausea and vomiting despite antiemetic prophylaxis according to current standards, remains uncertain but warrants further research. Limited evidence is available to support the use of cannabis-based medicines in the therapy of radiotherapy-related nausea and multifactorial nausea in advanced cancer patients.
The use of cannabis-based medicines for appetite loss and other symptoms associated with cancer cachexia is still unclear at present, since trial results have not only varied widely but also been criticised for the methodology employed (including diversity in stages of cachexia in the patients included and possibly too a low dose of THC/medical cannabis).
For cancer pain, several randomised controlled trials of cannabis-based medicines in cancer patients with various pain syndromes have indicated an analgesic effect comparable to weak opioids. The role of cannabinoid medicines as add-on medication for pain that is insufficiently relieved by strong opioids is currently being investigated in several clinical studies and has shown some promising results so far.
The main limitation of cannabis-based medicines seems to be adverse effects on the central nervous system. Known contraindications and pharmacological interactions should be considered. In addition, cannabis-based medicines are subject to country-specific prohibitory legislation.
Although not seen as first-line drugs for the claimed indications, cannabis-based medicines might be beneficial in individual cases as adjuncts to other antiemetic or analgesic medication, or in patients with cancer cachexia to help improve taste and smell perception and/or appetite when standard treatment fails in control symptoms. The toxicity profile should be considered, however.
Fully revised and updated by Natalie Magaya-Kalbermatten in December 2015.
Last updated in November 2011 by Gabriele Dennert.
Fully updated and revised in November 2009 by Gabriele Dennert.
Summary first published in November 2005, authored by Gabriele Dennert.
Natalie Magaya-Kalbermatten, CAM-Cancer Consortium. Cannabis and cannabinoids [online document]. January 19, 2016.
The term medical cannabis is used to denote whole-plant extracts from Cannabis sativa L. (hemp), usually with standardized concentrations of the phytocannabinoids delta-9-tetrahydrocannabinol (THC) and/or cannabidiol. The term cannabinoids covers a heterogeneous group of molecules that demonstrate activity upon cannabinoid receptors and are either endogenous cannabinoids, phytocannabinoids or synthetic cannabinoids.
In C. sativa about 500 different substances have been identified so far, around 70 of which are cannabinoids1,2. The most important phytocannabinoids are THC, cannabidiol (CBD), cannabigerol and cannabichromen.
Currently available cannabis-based medicines
Various whole-plant cannabis extracts with standardized concentrations of THC (and partially also of cannabidiol) are available for medicinal use. Nabiximols (Sativex®) is the name for a fixed combination of a THC-rich and a CBD-rich whole-plant cannabis extract.
Isolated THC or THC derivatives are currently available as dronabinol (Marinol®), which is half-synthetic THC, and nabilone (Cesamet®), Nabilon®), a synthetic THC derivate.
Another synthetic THC analogue, levonantradol, has been investigated in clinical trials but serious side-effects have limited its use3.
Application and dosage
Cannabis-based medicines are usually taken orally in an oily or alcoholic solution, in capsules or via the application of a sublingual spray; less commonly they are inhaled using a mechanical device.
For clinical use, individual dose titration is usually recommended. Generally, for pain and symptoms associated with cachexia, lower doses than for chemotherapy-induced nausea and vomiting are recommended.
For oral whole-plant extracts and synthetic THC (dronabinol), a typical starting dose is 2–3×2.5 mg THC/day, which is then gradually uptitrated until a recommended maximum daily dose of 50 mg THC/day has been reached4. For nabiximols (sublingual application containing 2.7 mg THC and 2.5 mg cannabidiol per spray) the recommended starting dose is one spray/day; the number of sprays might be increased to a recommended maximum of 12 sprays/day. The recommended dose increase for all mentioned preparations is typically around 2.5 mg THC every 1–2 days. For the synthetic THC derivate nabilone, a daily dose of 1–4 (–6) mg is usually recommended.
The medical use of cannabis in different regions and medical systems around the world has been a long-established tradition over several thousand years5. Therapeutic use is documented in traditional Chinese and Indian (Ayurvedic) medicine as well as in mediaeval European healing systems. Modern Western medicine rediscovered the therapeutic potential of cannabis in the 19th century, and by the beginning of the 20th century the use of cannabis products as prescribed medicines was widespread in several Western countries. With the rise in popularity of cannabis as a recreational drug, many countries have instigated prohibitory legislation which has in turn lead to a gradual, but almost complete, elimination of cannabis plant products for medicinal purposes. Debate is still ongoing regarding the potential and therapeutic use of cannabis-based medicines in diseases where available treatment is not satisfactory. Current clinical research and usage is concentrated around multiple sclerosis, AIDS and cancer.
Claims of efficacy and alleged indications
Cannabis-based medicines are claimed to have an antiemetic effect in patients receiving chemo-/radiotherapy and in advanced cancer patients with nausea of various origins. They are also recommended for the stimulation of appetite and food intake, and the consequent stabilisation or weight increase in patients with advanced cancer and weight loss (cancer cachexia). Furthermore, cannabis-based medicines have been claimed to have an analgesic effect in cancer patients.
Mechanisms of action
Two types of cell-surface receptors for cannabinoids have been identified in human tissue (CB1 and CB2)6–9. Derivates of arachidonic acid, so-called endogenous cannabinoids, work as physiological ligands for both receptor subtypes. The CB1 receptor is predominantly found in tissues of the central, peripheral and autonomous nervous system, with the highest density occurring in the basal ganglia of the brain. The main effect of CB1 receptor stimulation is via a decrease in the release of neurotransmitters, such as dopamine, norepinephrine and serotonin. This receptor subtype mediates the central effects of cannabinoids, such as antiemesis and the alteration of cognitive processes, movement, appetite and pain regulation. The CB2 receptor subtype is mainly expressed in tissue with immunologic function, including peripheral blood leucocytes, bone marrow, spleen, thymus, tonsils, macrophages and mast cells. CB2 receptors mediate the immunomodulative effects of cannabinoids.
A high density of cannabinoid receptors has been found in the nucleus solitary tract, which is important for the control of emesis. Evidence has been found that an activation of the CB1 receptor in the central nervous system also inhibits chemically induced vomiting in animals7. The appetite-stimulating effect of cannabis products has regularly been reported by recreational users of cannabis drugs and has been confirmed in controlled studies in which healthy male volunteers used both smoked cannabis and oral THC.10 The alteration of appetite and food intake has been attributed to the effects cannabinoids have on the central control of food intake, especially in the hypothalamus6. The analgesic effects may be produced by both central and peripheral mechanisms including modulation of central neuronal activity, anti-nociceptive effects in descending pain pathways, and anti-inflammatory properties by acting through prostaglandin synthesis inhibition11.
The action of THC on cannabinoid receptors is responsible for a substantial part of the therapeutic, but also of the typical psychotropic effects of cannabis-based medicines. However, cannabinoids are probably activated by a number of other mechanisms. The major non-psychotropic cannabinoid, cannabidiol, has no direct affinity to CB receptors11, but does have anti-psychotic, anxiolytic, anti-inflammatory and immune-modulatory effects, partially, but not exclusively, via modulation of the endocannabinoid system1,12,13. Cannabidiol and other cannabinoids modulate effects of THC through a variety of mechanisms, as has been shown in a number of experimental and clinical studies12,14,15. This is the so-called ‘entourage effect’ and has been shown to contribute to therapeutic effects as well as to the reduction of side-effects.
Pharmacokinetics have been intensively investigated3,16. Absorption in the gastrointestinal tract is high (90–95%) but, because of hepatic first-pass metabolism, the range of oral bioavailability is only 5–20%1. Systemic bioavailability is slightly higher after inhalation, with considerable inter-individual variation (~20% ±10%). Peak plasma concentrations are seen within minutes if administered either intravenously or via inhalation, and 2–4 hours after oral intake. In plasma, THC is strongly bound to plasma lipoproteins (95–99%) and less so to albumin. As a lipophilic compound THC is rapidly eliminated from plasma via distribution to highly vascularised tissue and is also able to cross the blood–brain barrier. Subsequently, redistribution to, and accumulation in, body fat can be observed. Peak effects are seen with a lag of 15–60 minutes after peak plasma concentration; pharmacologic effects are not correlated with maximum plasma levels3,16. Plasma half-life ranges from 28–57 hours owing to inter-individual differences in redistribution from fat tissue. Cannabinoids are metabolised by cytochrome P450 subsystems in the liver and metabolites are excreted in bile and urine over several days, with extensive enterohepatic circulation.
Prevalence of use
Data on the prevalence of cannabis-based substances for medical use are not available for countries in Europe. However, several surveys have been conducted, with convenience samples, of self-selected users of cannabinoids and cannabis products for medical purposes. Survey participants in different European countries have most commonly reported the use of cannabis-based medicines for neurological diseases such as multiple sclerosis and chronic pain. In a UK survey, less than 1% used cannabis for cancer17, while in a Dutch survey 14% reported use for a malignant disease18.
Legal issues and providers
Trading cannabis-based medicines is internationally restricted and there are differing legal regulations between countries for the medical use of cannabis. Special legal requirements have to be met in order to substantiate an import claim19.
The legal situation concerning non-licensed whole-plant cannabis extracts (e.g. produced by individual pharmacies), and consequently their availability, differs between countries. Nabiximols has been licensed in Europe for use against the spasticity associated with multiple sclerosis. Dronabinol is licensed as an antiemetic in the USA for the treatment of chemotherapy-induced nausea and stimulation of appetite in AIDS patients. It is also marketed by a German pharmaceutical company. Nabilone is manufactured in the UK and licensed for chemotherapy induced nausea and vomiting. All products may be imported via an international pharmacy.
Cost and expenditures
The cost of cannabis-based medicines ranges from €1–5/mg depending on the provider. Whole-plant extracts are generally cheaper than synthetic cannabinoids. A patient’s monthly expenses for the minimum daily dose can add up to anything between €150 and €750. Some health insurance companies reimburse these expenses, but regulations and practices vary between European countries and also between health insurance companies.
Medical cannabis (whole plant-extracts) or isolated cannabinoids?
In appraising the evidence for the effectiveness of cannabis-based medicines, it is important to distinguish between the different preparations and substances available (i.e. different whole-plant extracts, synthetic delta-9-tetrahydrocannabinol (THC) and THC derivates, isolated cannabidiol). Evidence regarding isolated THC, for example on the high frequency of side-effects on the central nervous system, cannot be transferred directly to other cannabis-based medicines, and vice versa. As mentioned earlier, previous research has shown that cannabidiol, but also other cannabinoids, may reduce undesirable effects on the central nervous system (both psychoactive and anxiogenic), as well as on the cardiac system; they may also contribute other therapeutic effects12,14. It seems that these facts should be taken into consideration when exploring the full potential of cannabis-based medicines; research should not focus solely on THC (or other isolated substances)12,14,15,20.
1. Do cannabis-based medicines work for nausea and emesis in cancer patients?
Nausea and emesis induced by chemotherapy
A systematic review, and also a meta-analysis, are available establishing the efficacy of cannabis-based medicines against acute chemotherapy-induced nausea and vomiting (CINV)21,22. The meta-analysis included trials investigating oral dronabinol (30–40 mg), oral nabilone and intramuscular levonantradol compared with placebo and with antiemetics available in the 1980s (prochlorperazine, metoclopramide, haloperidol, domperidone and others). Dronabinol (but not nabilone and levonantradol) showed significantly better control (in terms of remission) of acute CINV than the control medication in medium emetogenic chemotherapies, but side-effects occurred more often (dizziness, hallucinations, dysphoria, hypotension). The cannabinoids were preferred for future chemotherapy cycles by the majority of patients in crossover trials. Since all included trials were done before the development of modern forms of antiemetic prophylaxis (5-HT3 antagonists, NK1-receptor antagonists and drug combinations including glucocorticoids), no statement about the potential benefit of the investigated cannabis-based medicines, as compared to or in addition to these modern forms, could be made by the authors. They concluded that, owing to other mechanisms of action, benefiting from cannabis-based medicines in the new era of antiemetics is still plausible (e.g. as add-on medication for patient with refractory nausea) but needs further research.
A systematic review on antiemetic medication for the prevention and treatment of CINV in children identified four randomised controlled trials investigating cannabis-based medicines, which were not meta-analysed because of study heterogeneity23. The authors concluded that cannabis-based medicines ‘are probably effective but produce high levels of side effects’ and no clear route, schedule or dose recommendation could be identified from the included studies.
Table 1 summarises the results of controlled clinical trials for CINV. One randomised, placebo-controlled trial investigated the efficacy of dronabinol alone or when combined with ondansetron for the prevention of delayed CINV24. Sixty-four participants receiving moderate to high emetogenic chemotherapy were randomised to one of four intervention groups. All participants received dexamethasone plus ondansetron before chemotherapy, the three active intervention groups received additional dronabinol on the day of chemotherapy and either dronabinol (individual dose titration), ondansetron or both on the following four days after chemotherapy. The primary endpoint total response was not different between placebo and all the active groups. Dronabinol and ondansetron were equally effective as were the combination of both for the total control of nausea and the intensity of nausea on a visual analogue scale (secondary endpoints). Acute CINV on the first day of chemotherapy was reduced in the three groups receiving additive dronabinol compared to the standard treatment alone (dexamethasone + ondansetron). The incidence of adverse events was not different in the active groups, which the authors hypothesise might be because of the lower dose of THC (maximum 20 mg) than in the studies included in the above-mentioned meta-analysis (30-40 mg)22. However, this trial failed to recruit the necessary number of participants for a valid evaluation and findings need to be replicated in a larger study to further elucidate the potential benefits of additive dronabinol.
Another randomised controlled trial, this time a pilot phase II trial, tested the whole-plant extract preparation nabiximols (individual dose titration), against placebo, as an add-on to standard prophylaxis (not defined, but mostly dexamethasone and 5-HT-3-antagonists) and treatment of delayed CINV25. In all,16 patients receiving moderately emetogenic chemotherapy, that had experienced delayed CINV despite standard prophylaxis in the previous chemotherapy cycle, were included. They were advised to administer a maximal dose, defined by toxicity, until 2 hours after the application of the chemotherapy, and thereafter if nausea occurred, until day 4 after administration of the chemotherapy. Cancer types were not equally distributed in the two groups. The primary endpoint total remission was significantly more often observed in the nabiximols group. More mild or moderate neuropsychiatric adverse events were experienced in the nabiximols group. Further larger studies with fully defined standard CINV prophylaxis and equally distributed populations are needed to confirm this findings.
Nausea and emesis induced by radiotherapy
One double-blind randomised crossover trial compared the THC derivate nabilone and metoclopramide for the prevention of radiotherapy-induced nausea in 40 patients26. Findings suggested no difference in the antiemetic effect of 2 mg nabilone compared to 30 mg metoclopramide, but more patients in the nabilone group had adverse reactions (dizziness, disorientation, dry mouth, fatigue).
Multifactorial nausea and emesis in advanced cancer patients
For multifactorial nausea and vomiting that often occurs in patients with advanced incurable cancer (‘palliative care patients’), only case reports and one uncontrolled observational study have been published27. Over the course of 30 days, 112 advanced cancer patients were observed in a specialist palliative care centre, 47 receiving nabilone, 65 not. Propensity-score adjusted improvement of nausea (and pain) was significantly better in the patients receiving nabilone. No information on safety is available. Owing to the fact that the patients were not randomised, no causality can be inferred from this study.
In conclusion, isolated THC seems to be more effective, but also have more side-effects, than ‘old’ standard antiemetics. Only one underpowered study25 has compared isolated THC directly with a 5-HT3-anagonist showing no difference between the groups - a result, however, that needs confirmation. There might be a clinical potential for the use of cannabis-based medicine as add-on therapy for patients with refractory CINV, despite modern antiemetics, but more research is needed to confirm this indication.
2. Do cannabis-based medicines have beneficial effects in advanced cancer patients suffering from cancer cachexia?
Table 2 summarises results from controlled clinical trials of cannabis-based medicines for symptoms associated with cancer cachexia. Jatoi et al. tested oral dronabinol plus placebo versus the progesterone derivate megestrol (plus placebo) versus both agents28. Altogether 469 patients with advanced cancer and weight loss participated in this double-blind randomised trial. Megestrol acetate had better outcomes (appetite, food intake, body weight) than dronabinol, while the combination was not more effective than megestrol alone.
The Cannabis-In-Cachexia-Study-Group et al. conducted a randomised placebo-controlled phase III trial comparing oral THC with an oral cannabis extract and placebo for patients with cancer cachexia-related anorexia29. In all, 243 adults with advanced cancer were randomly assigned to the cannabis extract, THC alone or placebo orally daily for 6 weeks. The results showed no benefit of cannabis-based medicines over placebo on appetite or overall quality of life (primary study end points), or mood or nausea (secondary end points). Cannabis extract and THC was well tolerated. Recruitment for this study was terminated early because of insufficient differences between study arms.
Brisbois et al. investigated THC (individual dose titration) or placebo in a randomised pilot trial in 46 patients with advanced cancer with altered taste and smell (chemosensory) perceptions, which are common in patients with cancer cachexia30. Per-protocol analyses of 21 patients found increased appetite and improved taste perception in the THC group; THC was well tolerated. These findings need to be confirmed in a larger study.
In conclusion, based on these studies, the clinical potential of cannabis-based medicines for symptoms associated with cancer cachexia is still unclear.
Doses were fixed except in the most recent study30, where individual dose titration was used. This approach was also successfully used in the newer promising studies on CINV25 and pain20,31. Incidentally, the dosage of 5-7.5 mg for THC seems rather low. It was probably chosen because of concerns about potential dose-dependent severe adverse effects, which seem not have been a major problem in the above-mentioned studies for the other indications using a whole-plant based preparation in individual dose titration.
It is important to note that stages of cachexia were heterogeneous in both earlier trials because, at the time when the studies were undertaken, the different stages of cachexia had not yet been defined32. This diversity might have affected outcomes, since response to treatments mostly depend which stage of cachexia has been reached32.
3. Do cannabis-based medicines work for pain in patients with cancer?
A systematic review of randomised clinical trials has investigated the efficacy of cannabis-based medicines in the management of pain (cancer pain, chronic non-cancer pain and postoperative pain)33. The five studies on cancer pain included a total of 128 cancer patients comparing oral THC, nabilone, levonantradol or a THC congener (benzopyranopyridine) to placebo, codeine or a barbiturate. The pain syndromes were not further classified. The first three cannabinoids investigated were found to be more effective than placebo, and as effective as codeine (dose for THC: 5-20 mg). Studies were rather small (n=10-37) and dose-limiting adverse effects were common. Reviewers concluded that there is insufficient evidence to support the introduction of cannabis-based medicines for widespread clinical use as analgesics.
Table 3 summarises results from controlled clinical trials of cannabis-based medicines for cancer pain. Johnson et al. conducted a randomised controlled trial comparing two cannabis extracts (nabiximols and a THC-rich whole-plant extract, individual dose titration) versus placebo for pain control on top of opioids in 177 patients with cancer pain insufficiently relieved by opioids31. Pain syndromes, as well as previous cannabis experience, were variable but equally distributed between the groups. A significant improvement in average pain as compared to baseline was seen for nabiximols compared to the THC-rich extract and placebo. Mild to moderate adverse events (somnolence, dizziness, confusion) were seen in both active groups. This trial was followed by an open-label extension study with some of the study patients to evaluate long-term efficacy and tolerability34.
Portenoy et al. conducted a randomised controlled trial comparing three dose ranges of nabiximols and placebo in 360 patients with cancer pain insufficiently relieved by opioids20. Pain syndromes were classified, but not equally distributed between the groups. Previous cannabis experience was more frequent in the active groups than in the placebo group (which could have affected blinding). The proportion of responders (reduction of average pain score per day) was significantly higher in the lower- and middle-dose groups compared to placebo, but not in the high-dose group. Only the high-dose group had significantly more adverse events than placebo.
Lynch et al. compared nabiximols (individual dose titration) versus placebo in 18 patients with chemotherapy-induced neuropathic pain in a pilot crossover randomised controlled trial35. The analysis of the whole group showed no statistically significant difference between active treatment and placebo. Five of the patients, however, were considered as responders (two or more points reduction in the numeric rating scale) from which the authors concluded that further research is warranted. Nabiximols was well tolerated and, in the extension phase with 10 patients, some reported further improvement of pain.
In conclusion, medical cannabis seems to have clinical potential for a variety of cancer pain mechanisms insufficiently relieved by opioids. However, more high-quality research on pain syndrome specific indications and optimal (individual) doses are needed to define the role of cannabis-based medicines for the treatment of cancer patients with pain.
A number of adverse events have been observed after the intake of medical cannabis and cannabinoids. Some may be welcome, such as mood enhancement or sedation.
Commonly reported adverse effects on the central nervous system comprise alteration of mood (euphoria as well as dysphoria), depression, anxiety and paranoia, sensation of depersonalisation, hallucinations, memory impairment, blurred vision and dizziness.1 Cardiovascular adverse effects are hypotension and tachycardia. In addition, patients frequently complain of dry mouth.
A systematic review investigated the adverse events of cannabis-based medicines in 23 randomised controlled trials36. The cannabis-based preparations examined were nabiximols, oral whole-plant extracts and isolated delta-9-tetrahydrocannabinol (THC). The rate of non-serious adverse events was higher among participants assigned to the cannabis-based medicine groups than to the control, but not for serious adverse events. The most commonly reported adverse event in the active groups was dizziness (15.5%).
Patients who intake cannabis-based medicines over the long term may develop tolerance, not only for the psychoactive but also for the cardiovascular side-effects. Long-term intake of cannabis-based medicines should therefore not be stopped abruptly1. The overall risk for physical and psychic dependency seems to be low in comparison with opioids, tobacco, alcohol and benzodiazepines1.
Cannabinoids can change DNA synthesis and cell reproduction in vitro, but there is no evidence of mutagenic effects or of long-term carcinogenicity of orally administered cannabinoids37.
Pharmacokinetic interactions from medical cannabis and cannabinoids may occur because of interference with metabolism at the cytochrome P450 subsystem in the liver (Cyt P450 3A4), and may theoretically lead to delayed elimination of, for example, fentanyl. Interactions are also possible with known inhibitors (ritanovir, estradiol etc.) or inductors of Cyt P450 3A4 (rifampicin, phenytoin, carbamazepin, St John’s wort)11.
There is evidence that cannabinoids interact pharmacodynamically with levodopa and similar anti-Parkinson drugs38. Currently, the use of anti-Parkinson drugs is a contraindication for cannabis-based medicines.
Little is known so far about possible interactions with other centrally active drugs, especially psychiatric medication or with herbal products.
Epidemiologic data have shown an association between heavy adolescent use of smoked cannabis with the development of psychotic disorders39. Even though no causality between use of cannabis and psychotic disorders has been shown, a history or family history of psychotic disorders is generally seen as contraindication for the use of cannabis-based medicines.
The placental barrier is crossed by THC, and also accumulates in breast milk. Controversy exists regarding findings for the effects of cannabinoids on male reproduction, although there is some evidence that cannabinoids decreases sperm count and motility40. Therefore, pregnant and breast-feeding women, and women and men who wish to have children, must not use cannabinoid products.
Some medical cannabis or cannabinoid preparations contain additives, e.g. sesame oil, which are contraindicated in people who may be allergic to these substances41.
The use of cannabis-based medicines might impair the ability to drive a car, especially during any phases during which a dosage is being increased.
- Grotenhermen F (2003). Pharmacokinetics and pharmacodynamics of cannabinoids. Clin Pharmacokinet; 42:327-360.
- Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004.
- Walsh D, Nelson KA, Mahmoud FA (2003). Established and potential therapeutic applications of cannabinoids in oncology. Support Care Cancer; 11:137-143.
- Mutschler E, Geisslinger G, Kroemer HK, Schäfer-Korting M (Eds). Mutschler Arzneimittelwirkungen. Lehrbuch der Pharmakologie und Toxikologie. Stuttgart: Wissenschaftliche Verlagsgesellschaft, 2001.
- Russo E. History of cannabis as a medicine. In: Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004; pp. 1-16.
- Cota D, Marsicano G, Lutz B, Vicennati V, Stalla GK, Pasquali R et al. Endogenous cannabinoid system as a modulator of food intake. Int J Obesity 2003; 27:289-301.
- Martin BR, Wiley JL. Mechanism of action of cannabinoids: how it may lead to treatment of cachexia, emesis, and pain. J Support Oncol 2004; 2(4):305-314.
- Townsend DW 4th, Thayer SA, Brown DR. Cannabinoids throw up a conundrum. Br J Pharmacol 2002; 137(5):575-577.
- Brenneisen R. Pharmakokinetik. In: Grotenhermen F (Ed). Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potenzial. Bern: Hans Huber Verlag, 2001; pp. 87-92.
- Robson PJ, Guy GW. Clinical studies of cannabis-based medicines. In: Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids, London: Pharmaceutical Press, 2004; pp. 229-269.
- Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013; 33(2):195-209.
- Russo E, Guy GW. A tale of two cannabinoids: the therapeutic rationale for combining tetrahydrocannabinol and cannabidiol. Med Hypotheses 2006; 66(2):234-246.
- Campos AC, Moreira FA, Gomes FV, Del Bel EA, Guimarães FS. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos Trans R Soc Lond B Biol Sci. 2012; 367(1607):3364-3378.
- Wagner H, Ulrich-Merzenich G. Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 2009; 16(2-3):97-110.
- Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA. Cannabidiol interferes with the effects of delta 9-tetrahydrocannabinol in man. Eur J Pharmacol 1974; 28(1):172-177.
- Grotenhermen F (Ed). Cannabis und Cannabinoide. Pharmakologie, Toxikologie und therapeutisches Potenzial. Bern: Hans Huber Verlag, 2001.
- Ware MA, Adams H, Guy GW. The medicinal use of cannabis in the UK: results of a nationwide survey. Int J Clin Pract 2005; 59:291-295.
- Gorter RW, Butorac M, Cobian EP, van der Sluis W. Medical use of cannabis in the Netherlands. Neurology 2005; 64(5):917-919.
- International Association for Cannabinoid Medicines website. Available online. Accessed 21st October 2011.
- Portenoy RK, Ganae-Motan ED, Allende S, Yanagihara R, Shaiova L, Weinstein S et al. Nabiximols for opioid-treated cancer patients with poorly-controlled chronic pain: a randomized, placebo-controlled, graded-dose trial. J Pain 2012; 13(5):438-449.
- Tramer MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. BMJ 2001; 323(7303):16-21.
- Machado Rocha FC, Stéfano SC, de Cássia Haiek R, Rosa Oliviera LMQ, da Silveira DX. Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis. Eur J Cancer Care (Engl) 2008; 17(5):431-443.
- Phillips RS, Gopaul S, Gibson F, Houghton E, Craig JV, Light K et al. Antiemetic medication for prevention and treatment of chemotherapy induced nausea and vomiting in childhood. Cochrane Database Syst Rev 2010; 9: CD007786. doi: 10.1002/14651858.CD007786.pub2
- Meiri E, Jhangiani H, Vredenburg JJ, Barbato LM, Carter FJ, Yang HM et al. Efficacy of dronabinol alone and in combination with ondansetron versus ondansetron alone for delayed chemotherapy-induced nausea and vomiting. Curr Med Res Opin 2007; 23(3):533-543.
- Duran M, Pérez E, Abanades S, Vidal X, Saura C, Majem M et al. Preliminary efficacy and safety of an oromucosal standardized cannabis extract in chemotherapy-induced nausea and vomiting. Br J Clin Pharmacol 2010; 70(5):656-663.
- Priestman SG, Priestman TJ, Canney PA. A double-blind randomised cross-over comparison of nabilone and metoclopramide in the control of radiation-induced nausea. Clinical Radiol 1987; 38(5):543-544.
- Maida V, Ennis M, Irani S, Corbo M, Dolzhykov M. Adjunctive nabilone in cancer pain and symptom management: a prospective observational study using propensity scoring. J Support Oncol 2008; 6(3):119-124.
- Jatoi A, Windschitl HE, Loprinzi CL, Sloan JA, Dakhil SR, Mailliard JA et al. Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol 2002; 20(2):567-573.
- Cannabis-In-Cachexia-Study-Group, Strasser F, Lueftner D, Possinger K, Ernst G, Ruhstaller T et al. Comparison of orally administered cannabis extract with and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J Clin Oncol 2006; 24(2):3394-3400.
- Brisbois TD, de Kock IH, Watanabe SM, Mirhosseinie M, Kamoureux DC, Chasen M et al. Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo controlled pilot trial. Ann Oncol 2011; 22(9):2086-2093.
- Johnson JR, Burnell-Nugent M, Lossignol D, Ganae-Motan ED, Potts R, Fallon MT. Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain. J Pain Symptom Manage 2010; 39(2):167-179.
- Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol 2011; 12(5):489-95.
- Campbell FA, Tramèr MR, Carroll D, Reynolds DJ, Moore RA, McQuay HJ. Are cannabinoids an effective and safe treatment option in the management of pain? A qualitative systematic review. BMJ 2001; 323(3703):13-16.
- Johnson JR, Lossignol D, Burnell-Nugent M, Fallon MT. An open-label extension study to investigate the long-term safety and tolerability of THC/CBD oromucosal spray and oromucosal THC spray in patients with terminal cancer-related pain refractory to strong opioid analgesics. J Pain Symptom Manage 2013; 46(2):207-218.
- Lynch ME, Cesar-Rittenberg P, Hohmann AG. A double-blind, placebo-controlled, crossover pilot trial with extension using an oral mucosal cannabinoid extract for treatment of chemotherapy-induced neuropathic pain. J Pain Symptom Manage 2014; 47(1):166-73.
- Wang T, Collet JP, Shapiro S, Ware MA. Adverse effects of medical cannabinoids: a systematic review. CMAJ 2008; 178(13):1669-1678.
- Hall W, Christie M, Currow D. Cannabinoids and cancer: causation, remediation, and palliation. Lancet Oncol 2005; 6(1):35-42.
- Notcutt W. Cannabis in the treatment of chronic pain. In: Guy GW, Whittle BA, Robson PJ (Eds). The Medicinal Uses of Cannabis and Cannabinoids. London: Pharmaceutical Press, 2004; pp. 271-299.
- Moore TH, Zammit S, Lingford-Hughes A, Barnes TR, Jones PB, Burke M et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007; 370(9584):319-328.
- Rossato M, Ion PF, Ferigo M, Clari G, Foresta C. Human sperm express cannabinoid receptor Cb1, the activation of which inhibits motility, acrosome reaction, and mitochondrial function. J Clin Endocrinol Metab 2005; 90(2):984-991.
- Slatkin NE. Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis. J Support Oncol 2007; 5(Suppl. 3): 1-9.