Cannabinoids offer new directions for prostate cancer treatment. THC and CBD , discourage the formation of tumor blood vessels pain relief and nausea) rather than the efficacy of the cannabis oil to shrink cancer tumors. If you ask any man who has used cannabis oil for prostate cancer and had his The THC in cannabis is known to relieve pain, control nausea and There are studies that suggest that cannabis oil or hemp oil can shrink. In our hospital we notice the popular use of cannabis oil in prostate cancer (PCa) contain a higher THC and lower CBD ratio than cannabis for medicinal use. However, the effect of cannabinoids in chronic neuropathic pain was clearly.
cancer for prostate cbd pain dosage
Most—if not all—of these were short-term studies that were conducted in a limited number of subjects who had these chemicals administered via a different route than inhalation and at doses that contain higher amounts of CBD and THC than those found in most marijuana ointments sold online. Some patients believe that applying these ointments directly on the tumor site is unlikely to cause the psychiatric problems seen in marijuana smokers.
Numerous animal studies have shown that CBD, THC, or their combination inhibit tumor growth and reduce the risk of cancer cells spreading to distant organs. To my knowledge, none of the data to support these claims were obtained in animals that received these chemicals by topical application or inhalation. Rather, most preclinical studies conducted in mice administer cannabinoids via injections.
I would go so far as to argue that it is dangerous to think that applying marijuana cream or oil on tumors would be of any benefit in reducing chronic pain or inhibiting tumor growth. Aymen Idris on his campaign to raise awareness of the medicinal benefits and harm of marijuana among the general public and to influence politicians to support medical use of cannabis. Marijuana as a mainstream treatment for cancer has a long way to go, but research on its medicinal benefits has been growing within the scientific community.
Many companies and research laboratories, mine included, are currently testing existing and new preparations of marijuana that may one day be used in the clinic to treat cancer pain with fewer side effects than smoking or vaping marijuana. A recent clinical trial has found Sativex to be a useful treatment for chronic pain in advanced cancer patients who take opioids. Although patients who received Sativex alone did not show any improvement over a placebo, the results of this trial suggest that Sativex can benefit cancer patients who have failed to respond to prescription painkillers.
It has already been approved in the U. Another promising development is drugs that mimic the action of natural marijuana in the human body or stop its breakdown. For example, a number of elegant articles have recently reported that increasing the level of naturally occurring cannabis-like substances in the body reduced the growth and progression of tumors in experimental models of cancer.
Subsequent studies carried out in our laboratories at the University of Edinburgh and the University of Sheffield have revealed a direct link between MAGL and late-stage prostate, breast, and primary bone cancers. Our initial experiments demonstrated that these agents inhibited tumor growth and the spread of cancer cells to other parts of the body, such as the lungs, in preclinical models of bone cancer.
Moreover, a paradigm shift, fueled by an almost exponential expansion of basic scientific and clinical research since the end of the 20th century, is showing that cannabinoids have beneficial effects beyond pain and symptom management and could be entering into the domain of disease modulation 1. Starting in the early s, Canada was one of the first of a growing number of countries to legalize botanical Cannabis for medical purposes 5.
Medical cannabis in Canada is cultivated under quality-controlled conditions and contains reproducible levels of the main cannabinoid and non-cannabinoid substances. Moreover, the composition of medical cannabis can be tailored to meet the particular needs of the patient. The Cannabis genus has two main species—namely, Cannabis sativa and Cannabis indica 1 — 4.
The Cannabis plant generates more than chemical compounds, of which approximately 80 are cannabinoid compounds and more than are non-cannabinoid compounds 1 — 4. From a health care perspective, the most clinically relevant compounds include the cannabinoid agents thc and cbd , and the non-cannabinoid terpenoids and flavonoids 1 — 4. Medical cannabis can be dispensed in a dried botanical format that might be smoked, vaporized, brewed as tea, or cooked as edible food products 1 — 4.
More recently in Canada, medical cannabis extracts compounded in organic edible oils can be orally ingested, administered through vaporization, or applied topically 7. Anecdotally, experienced users say that, compared with C. That difference might be attributable to different thc: However, the purported differences between the two plants might also be a result of different levels of other components such as terpenes and flavonoids 1 — 4. The endogenous opioid and cannabinoid systems are the only chemical systems in the human body that have survived more than million years of human evolution 1 — 4.
Interestingly, the endogenous cannabinoid system might have evolved millions of years before the evolution of the Cannabis plant itself 1. The endogenous cannabinoid system is composed of all cannabinoid receptors, endogenous ligands endocannabinoids , second messengers, and endocannabinoid degradation pathways, most notably the fatty acid amide hydrolase system 1 — 4 , 7 — Although an understanding of the endogenous cannabinoid system is far from complete, two human receptors, cb 1 and cb 2, have currently been defined and cloned 1 — 4 , 8 — A third putative human cannabinoid receptor, gpr 55, is currently in the process of being characterized 8 — Cannabinoid receptors are ubiquitous and have an estimated to-1 preponderance over opioid receptors in humans 1 — 4.
Furthermore, unlike opioid receptors, which are located only extracellularly, cannabinoid receptors are also expressed on intracellular organelles such as mitochondria, the Golgi apparatus, and nuclei The cannabinoid receptors that are located on cell membranes are functionally coupled with G proteins 1 — 4 , 8 — The cb 1 receptors are located mostly on neural tissue within the central nervous system and afferent nociceptors.
The cb 2 receptors, although located mostly in immune system tissues such as spleen, tonsils, lymph nodes, mast cells, macrophages, and lymphocytes, are also expressed within the central nervous system through their presence on microglia.
Generally speaking, cb 1 signalling mediates neuromodulatory activities, and cb 2 signalling mostly mediates immunomodulatory activities. Thus, cannabinoid signalling is intrinsically involved in multiple physiologic and homeostatic systems as well as in pathophysiologic mechanisms 1 — 4 , 8 — The main human endocannabinoids are N- arachidonylethanolamide and 2-arachidonlyglycerol. Those two molecules activate cb 1, cb 2, gpr 55, and transient receptor potential ion channels such as trpv 1 1 — 4 , 8 — Endocannabinoids, acting as retrograde synaptic messengers at neural synapses, are short-lived because they are degraded by fatty acid amide hydrolase.
Exogenous cannabinoids, whether pharmaceutical or botanically sourced, mimic and potentiate signalling by the endocannabinoids 1 — 4 , 8 — Exogenous cannabinoids such as botanically derived thc and pharmaceuticals such as nabilone and dronabinol are agonists of both cb 1 and cb 2 1 — 4 , 8 — Cannabidiol functions as an activator of trpv 1, an inhibitor of both cyclooxygenase and lipoxygenases, and reduces N- methyl- d -aspartate toxicity. The activity of cbd as a negative allosteric inhibitor of cb 1 helps to reduce the cb 1-mediated psychotomimetic effects of thc , thereby increasing its therapeutic potential 11 , 13 , In Canada, more than strains of medical cannabis are available from licensed producers 5.
Given the heterogeneity of both the cannabinoid and non-cannabinoid components of those multiple strains, it is not surprising that their complete pharmacologic profiles have not been fully elucidated. Although much is known about botanically sourced thc and cbd , and the pharmaceutical cannabinoid agents, little clinical data on the pharmacology of terpenoids and flavonoids have been published. Adverse outcomes such as psychotomimetic reactions and hypotension are more likely to occur with recreational cannabis because it tends to be preponderant in thc.
The Cannabis plant yields inactive acidic forms of thc and cbd , namely thc - a and cbd - a. The process of decarboxylation, which occurs through thermal treatment heating or combustion , generates the pharmacologically active formats 15 , Although dried botanical cannabis from licensed producers for medical use is not thermally treated, medical cannabis oils contain cannabinoids that have undergone decarboxylation Tweed Inc. Personal communication, 18 September Generally speaking, higher bioavailability levels are achieved with smoking and vaporization than with oral ingestion.
Peak serum concentrations occur within 2—10 minutes. Absorption of both thc and cbd from the gastrointestinal tract is good, but both molecules undergo extensive first-pass metabolism. Table i summarizes the pharmacokinetic profiles of the various forms of cannabinoid therapies 5 , 17 — As summarized in Table ii , thc and cbd are both processed through the cytochrome P cyp system in the liver 5 , 17 — The effect of cyp 2C9 on thc metabolism is significantly affected by genetic polymorphisms; compared with individuals carrying high-functioning variants, those who carried genetic variants with diminished function experienced a doubling or tripling in thc exposure Furthermore, higher levels of thc and cbd can be observed with concomitant use of strong cyp 3A4 inhibitors.
Although neither thc nor cbd are inducers of cyp enzymes, both are inhibitors of a number of those enzymes, most notably 3A4, the enzyme that has the largest number of commonly used medical drugs as substrates Smoked cannabis has been noted to induce cyp 1A2 Being highly lipophilic, thc and cbd both have a large volume of distribution.
They are also highly bound by serum proteins. Although, theoretically, a high incidence of drug—drug interaction by displacement from protein binding sites might be expected, only one case report to date has described the occurrence of an increased normalized ratio and bleeding complications in a patient who smoked recreational cannabis Although the assessment and treatment of pain and other symptoms in patients with advanced cancers has become a standard of care, many patients still have incomplete symptom control That situation persists despite a plethora of pharmaceutical therapies, including opioid analgesics and adjuvant or targeted therapies for example, antiepileptic and antidepressant therapies.
Many oncology physicians are unaware of the potential medical benefits of cannabis 28 and are unwilling or unable to authorize their use. A selective review of the best-supported treatments follows.
Cannabinoids, including herbal cannabis and extracts, have been used for the treatment of pain for centuries. There is evidence in historical texts and ancient pharmacopeia of treatment for various pain syndromes—from menstrual cramps to childbirth to headaches 1 — 3.
In terms of cannabinoid use in the modern era, an emerging literature includes systematic reviews that are showing benefit in several areas, including non-cancer pain 34 , Early studies using dronabinol, nabilone, and levonantradol demonstrated benefit, but their methodologies were not as rigorous as in more recent trials, and so the benefits might have been overestimated The few trials using cannabinoids in acute pain have shown essentially no benefit, and present recommendations are against cannabinoid use in the postoperative setting 37 — Cannabinoid treatments for cancer pain have been studied in a few randomized trials, but the evidence has been less than convincing.
Earlier studies published before , as reviewed by Campbell et al. Comparators such as codeine and secobarbital are not commonly used in patients with severe cancer pain, and so it is difficult to extrapolate the results.
More recently, two placebo-controlled trials using a cannabis extract nabiximols did show modest benefit when used in addition to opioids and other adjuvant pain medications in patients with chronic cancer pain 40 , Chronic neuropathic pain has received the most focus, with studies looking at the use of pharmaceutical cannabinoids and cannabis and its extracts in a variety of settings posttraumatic neuropathies, diabetic neuropathy, aids -related neuropathic pain, and so on.
Two recent publications confirmed the benefit of cannabinoid use, with twenty-nine randomized studies having been examined and included in separate systematic analyses 34 , Cannabinoids were found to be safe, modestly effective, and a reasonable option for treating chronic neuropathic pain. Those data have contributed to the revision, by the Canadian Pain Society, of their consensus statement on the treatment of chronic neuropathic pain to include cannabinoids as third-level therapy Inhaled or vaporized cannabis has also been studied, but, again, few randomized trials have been conducted.
A recently published meta-analysis demonstrated that 1 in 5—6 patients would benefit from the use of inhaled cannabis treatments for neuropathic pain Controlling nausea and vomiting was one of the initial uses of cannabinoids documented in the modern scientific literature.
In , Sallan et al. Since then, several larger-scale studies—including placebo-controlled randomized studies using dronabinol, nabilone, and cannabis extracts—have been completed. At least two systematic reviews on the topic have shown benefit with the use of cannabinoids, especially pharmaceutical cannabinoids, in patients undergoing chemotherapy 45 , When looking at the use of cannabis or extracts to control nausea and emesis, the picture is not quite as clear.
Many of the published studies were observational or uncontrolled, and certainly randomized controlled trial data for cannabis use are in short supply 47 , Preclinical research has established animal models for nausea mouse, shrew , which have shown benefit with the use of cbd That benefit has been especially evident in a model of anticipatory nausea, a condition that has been difficult to treat for patients undergoing longer-term chemotherapy Anecdotal reports to us from patients who routinely smoke or vaporize cannabis containing varying amounts of thc and cbd before chemotherapy confirm improvement in their quality of life as measured by the Edmonton Symptom Assessment System and subsequent appetite and food intake.
Although treatment of some specific body areas abdomen, chest, whole brain with radiotherapy can induce nausea, very few reports of cannabinoid use in those situations have been published, and the reports that exist have used mainly pharmaceutical cannabinoids A recently published placebo-controlled study demonstrated that quality of life for patients with head-and-neck cancers undergoing radiotherapy is not improved with the use of nabilone The authors postulated that nabilone on its own is not potent enough to affect symptoms.
Another recently published study surveyed 15 patients with previously treated head-and-neck cancer about their use of medical cannabis, and all respondents endorsed the benefits of cannabis in the treatment of the long-term residual effects of radiation The data supporting cannabis and cannabinoid use in appetite stimulation is less conclusive than it is in pain or nausea.
When used in cancer patients with cachexia, cannabinoids appear to be only modestly effective. A study from the North Central Cancer Trial Group compared the use of an oral cannabinoid dronabinol with oral megestrol acetate and with the two drugs together. Final results did not show any statistical improvement in weight with dronabinol, either alone or in combination A Swiss-led study using cannabis extract in cancer patients also did not show benefit in terms of appetite or weight gain, and the trial was closed early after a mandated review A small Canadian study using oral dronabinol in advanced cancer patients demonstrated improved sense of taste and subsequent increased protein consumption.
That change did not translate to weight gain, but patients did express improvement in quality of life measurements More promising results were seen in studies of the non-cancer population. A study of response to smoked cannabis, dronabinol, or placebo in patients with aids demonstrated that the patients using smoked cannabis experienced the greatest weight gain 3.
An earlier study in patients with dementia treated with either dronabinol or placebo documented an increase in appetite, increased weight gain, and modulated aggressive behaviour Although the main use of cannabinoids in patients with cancer and palliative patients has been symptom management, there could be other roles for these molecules in the treatment of malignancies.
In one of the first reports of cannabinoids having antitumour effects, extracts of cannabis were shown to inhibit the growth of lung adenocarcinoma cells in vitro An in vivo mouse model produced similar results.
Preclinical studies have investigated cannabinoid activity in several malignancies lung, glioma, thyroid, lymphoma, skin, pancreas, endometrium, breast, prostate 59 — 61 , demonstrating antiproliferative, anti-metastatic, antiangiogenic, and proapoptotic effects reviewed by Velasco et al. Cannabis has not been studied clinically as a treatment for malignancy. The only clinical study published to date that used cannabinoids enrolled patients with glioblastoma multiforme and was based on extensive preclinical work by the same investigators Their small study 9 patients showed the safety of intracranial administration of thc and demonstrated antiproliferative effects in some of the patients.
All patients eventually progressed and died, but not because of any effects of the extract. The investigators are actively continuing their clinical and research work, focusing on tumours of the central nervous system Oncologists might be concerned that cannabinoids could reduce the effectiveness of established chemotherapy agents. Several authors have investigated cannabis extracts used in tandem with a variety of chemotherapy agents in vitro and in animal models, showing synergism in reducing cell numbers, and no negative effect on anticancer function.
Cell cultures from pancreatic 64 , glioma 65 , gastric 66 , lung 67 , and colon 68 cancers have been investigated using a range of antineoplastic agents, including gemcitabine, temozolomide, paclitaxel, and 5-fluorouracil. Synergism in inducing cancer cell death is a common finding, which bodes well for the possibility of human clinical trials in future Despite the emerging evidence of antineoplastic activity, some older in vitro studies demonstrated cancer cell proliferation and loss of immune-mediated cancer suppressor activity after treatment with cannabinoid preparations 58 , Some studies have even shown discordant results depending on the concentration of cannabinoids: Thus, conflicting evidence points to the need for sober second thought before outright recommendations of cannabinoids for cancer patients can be made.
But again, mice and rats are not people, and what is observed in vitro does not necessarily translate into clinical medicine. The preclinical evidence that cannabinoids might have direct anticancer activity is provocative as well, but more research is warranted.
Currently, several clinical studies using cannabinoids in cancer therapy are registered at http: When a patient is referred to our outpatient clinic with a request for medical cannabis, several questions come to mind:. Most of our patients have either tried medical cannabis or read about its role in symptom control. Those who have tried it recreationally or for medical purposes can accurately reflect on the benefits or the adverse effects experienced, which makes the discussion somewhat easier.
Those who have little knowledge and less experience require a complete discussion with respect to the benefits, the possible adverse effects, the process of application and authorization, and the cost which is borne by the patient, because it is not covered by provincial or private medical insurance. Table iii lists our contraindications to authorization, which are similar to those published by Health Canada 70 , the College of Family Physicians of Canada 71 , and the Canadian Medical Protective Association It should be noted that no special license or additional certification is necessary to authorize the use of medical cannabis, but a working knowledge of cannabis as already presented is helpful for oncology professionals who are considering a patient request.
Once the decision is made to support authorization, the choice of which licensed producer and product to use can be somewhat difficult for some patients. The more than 30 licensed producers list more than products for sale, which can be a problem for those who do not have experience with cannabis or patients who might be elderly or excessively fatigued.
We do not advise that patients smoke the dried product; rather, they should vaporize, which is likely safer in the long run We also advise neophytes to choose a product that has a balanced thc: Cannabinoid proportions can be guided by available efficacy data summarized in Table iv.
Once patients have started to use the product and document the effects, the thc: Conditions potentially responding to cannabinoid therapies 74 — Titration of dose should follow the effect on the symptom in question for example, pain reduction, nausea control.
Follow-up with patients is essential to determine benefits and any adverse effects, questions about use or strain selection, and outcomes. Certainly, if the adverse effects are not tolerable, then an alternative therapy should be considered. If the patient is not getting the desired symptom control, then some dose modification might be necessary. Discontinuation of cannabis should be considered if an adequate trial does not result in the desired outcome as determined by the treating team or the patient.
Inter-professional collaboration is the new paradigm under which modern health care operates Research has demonstrated that inter-professional collaboration is enabled and promoted by inter-professional education, especially at the undergraduate level 79 , Although physicians ultimately authorize and prescribe cannabinoid therapies, valuable insights and inputs about achieving optimal patient outcomes can be derived from other members of the health care team, including nurses, social workers, rehabilitation therapists, and pharmacists.
Furthermore, pharmacies are designed to ensure proper storage and security of medical products. Pharmacists are also well positioned to comprehensively counsel patients and caregivers on the optimal methods of opioid and by extension, cannabis storage and disposal so as to limit diversion and unintentional exposure Moreover, given the emergence of cannabinoids as a novel therapeutic class, cannabinoid education for medical professionals as well as for patients and caregivers should be conducted per the principles of inter-professional education Industrialized countries are experiencing exponential increases in the utilization of opioids 84 , Major public health issues are emerging as a result, not the least of which relate to drug diversion, opioid addiction, and death from opioid overdose 84 , Currently, opioids remain the mainstay of cancer pain management, and increased cancer survival translates into patients using opioids for longer periods of time High-dose and long-term opioid therapy in cancer patients is becoming a concern, given observed risks such as poly-endocrinopathy, osteoporosis, and immunosup-pression Preclinical studies have demonstrated that certain opioids—such as codeine, morphine, methadone, and remifentanil—are associated with increased morbidity and mortality attributable to worsening of cancer and infections Opioid-induced hyperalgesia syndrome is also being reported with increased incidence, especially in patients with advanced cancer and escalating pain Thus, it behooves physicians to explore options that will allow for improved overall pain relief while curbing the overuse of opioids.
Opinion: Do Not Believe the Hype
CBD Oil Dosage: General Tips to Assess How Much CBD to Take Loss of Appetite in Cancer Patients: mg of THC (orally), with or without 1mg . The following is a chart of illnesses/conditions that whose symptoms may be relieved by CBD: .. My husband would like to use cbd capsules he has prostate cancer he has.  The presence of pain in men with advanced prostate cancer is an WIN- 55, results in a significant dose- and time-dependent decrease in cell viability  Cannabidiol (CBD), another major constituent of the Cannabis sativa plant. The Cannabis plant yields inactive acidic forms of thc and cbd, namely thc-a and cbd-a. . Cannabinoid treatments for cancer pain have been studied in a few demonstrated mild benefits, with adverse effects limiting the dose used. . thyroid , lymphoma, skin, pancreas, endometrium, breast, prostate)–.