[SOUND] Hi, thanks for joining us once again. As you've seen so far, unraveling the mysteries of cannabis is a real adventure and we are gradually completing the puzzle. So far, you have learned the essentials about pain, its types, physiology, and treatments. You have also heard about the cannabis plant, its history, its botanics, and the way in which it interacts with the body. We are now ready and very excited to finally explore the effectiveness as an emerging pain therapy. As a pain specialist, I treat many patients who experience different types of pain. One of the frequent questions I get from patients is to what degree I expect the prescribed treatment to be effective. This is not an easy question to answer as the term effectiveness is subjective and difficult to quantify. So what does effective mean? Let's look at the study on the use of medical cannabis for neuropathic pain. In a recent American study published in the Journal of Pain, researchers concluded quote, medical cannabis may be effective at ameliorating neuropathic pain. This group of researchers recruited 39 patients with different types of neuropathic pain. All of whom had been exposed to cannabis prior to the study. They excluded patients with uncontrolled blood pressure, heart disease, chronic lung disease, and severe depression. Participants were invited to a laboratory for three visits, with a minimum of three days between visits. During each visit, they were asked to smoke a different cigarette. One cigarette contains 7% THC, [SOUND] a relatively high concentration. Another, [SOUND] with a lower concentration of 3.5% of THC [SOUND], and the third consisted of a plant from which THC had been excluded, essentially a placebo. The cigarettes were given in a random order, and through a double blind test procedure, so that neither administrator no patient was aware of what was smoked at a given session. In medicine, this approach is termed a randomized controlled trial and is regarded as the most reliable means of conducting medical research. Patients in this study were instructed to take 9 puffs and then observed over a 3-hour period. Spontaneous and evoked pain in response to light touch was tested in the two hours after the last two puffs were inhaled. Results showed that smoke, both the low and high medical cannabis concentrations reduced pain intensity when compared to the placebo. On an intensity scale of 0 to 100, pain evaluated at 55 at baseline dropped to about 40 with the placebo and other 35 with medical cannabis. No difference and the effect was reported between the two concentration of THC. No effect on allodynia or hypersensitivity due to pain could be demonstrated. Now let me ask you a question, assume for a moment that you suffer from chronic neuropathic pain. Based on what we have seen in the American study, can we conclude that medical cannabis is indeed effective as a long-tern treatment for neuropathic pain? So how do doctors determine the effectiveness of any given treatment anyways? Well, effectiveness is largely determined based on clinical trials. Meaning studies that had been performed on patients and evaluated. These studies can be conducted in many different ways. Some are more reliable than others. And the degree of certainty depends not only on results but more importantly [SOUND] on the process used to obtain these results. Let's look at a few examples. In some fields of medicine, such as rare diseases, there are no clinical trials on with to base our evaluation. When a decision needs to be made as to whether or not a specific treatment should be administered, it relies purely on expert opinion. Basically, a team of experts reach a consensus based on their experience, but without any supporting evidence drawn from clinical studies. Although the term expert opinion sounds convincing it clearly represents the lowest level of scientific evidence. Another type of evidence comes from case reports or case theories. Case reports are descriptions of patients whose response to a certain treatment is interesting and worthwhile reporting. A higher level of evidence emerges from retrospective studies. So whenever there is a gap in knowledge that needs to be filled quickly, retrospective studies are used. This method takes a retrospective look at charts of patients who received a certain treatment for a given medical condition. Let's assume that a doctor has treated 100 patients with back pain using three different medications. One of the three drugs is considerably more expensive than the two others and the doctor is asked if that medication is more efficacious and merits its price. In order to answer this question, the doctor needs to compare pain intensity reports before and after treatment for his group of patients. Only once he has reviewed the group's medical charts can he say if one medication is more effective that it to others. The problem with this type of study comes from lack of uniformity in processes. Our doctor may have noted that in one patient pain dropped from 7 to 4 on a scale of 0 to 10. And in another patient, a 30% reduction in pain was observed. In a third patient, he may have requoted pain intervention from very severe to moderate. He may also discover that he gave one medicine to 20 patients, a second medication to 30 patients, and a third to 50 patients. So this type of research, even when conducted properly, can only be used to roughly estimate effectiveness as the scientific value of such data remains limited at best. So what are the alternatives? Prospective studies are more reliable. A prospective trial is a treatment that is administered to a select group of patients, who are observed in a structured fashion for a determined period of time. Most of these trials involves small group of selected patients, and are typically aimed at proving a concept. These studies do not have a control group or a control treatment. And they are therefore called, open labeled studies. The scientific value is greater than that of retrospective studies but still is not ideal. The following two categories of prospective studies provide the best scientific evidence of effectiveness, of treatment, and should be regarded as complimentary to each other. One group is turned randomized control trials, such as the American study I mentioned earlier. And the other is called large scale prospective studies or registries. Each category has advantages and disadvantages. Typically, the advantages of one are the disadvantages of the other. Randomized controlled trials, or RCT's are aimed at comparing one treatment to another or to a placebo in a highly selected group of patients. So if we say that there is a strong evidence that treatment A is better than treatment B for patients with shingles, this is typically based on one or more RCT's. The principles of RCT's are, one, they include the most homogenous patient base possible. Two, administered treatments resemble each other. Three, patients are randomly assigned to receive one treatment or the other. Four, the number of participant is sufficient to draw sound clinical outcomes. And five, study outcome is extremely well defined. While these principles produce high quality scientific evidence, they also have some shortcomings. One, RCT's are expensive. And to reduce costs RCT's usually include the minimal number of patients needed for the required statistical analysis, and the duration of the study is usually short, rarely exceeding three months for pain trials. Two, they may vary in quality. Let's look back at the study I presented to you at the beginning of this talk on the small cannabis cigarettes for neuropathic pain. The study included only 39 patients, a relatively small number. And follow up lasted just three hours, a very short time. And all patients had various forms of neuropathic pain. So they were not really homogenous. Overall, the study cannot be considered as high quality as it is. Three, eligibility. One of the problems with RCT's is, that they strive for patient homogeneity. Hence, only selected patients enter such studies after meeting strict inclusion criteria. In the study we just referred to, patients were included only if they had neuropathic pain and excluded if they had elevated blood pressure, lung disease, depression and so forth. Four, narrow focus. RCT's focus on a very specific condition like neuropathic pain related to shingles or neuropathic pain related to post-traumatic nerve injury. So, if we wish to come to a broad understanding of the effectiveness of medical cannabis, relative to other existing treatments, we need many, many RCTs. In some fields, numerous RCT's are conducted, and yield consistent results. While in others, results can be conflicting, and even diametrically opposed. This may confuse doctors who cannot tell if a tested treatment is indeed effective. The solution to this problem comes from meta analysis, a sophisticated way of recalculating the effect of a given treatment, based on extraction of raw data from all relevant studies. Registries which refer to large-scale open label, prospective studies, overcome some our cities-related problems. In registries, all patients receiving treatment are included in the study and are observe in the most structured way possible over a long period of time. This long term studies last many month and sometimes even years. Since patients are not excluded from these studies, they are better at reflecting real life conditions than are RCT's in which exclusion is central. By the end of the study, researchers can determine which condition responds better to a treatment, which factors predict the response to the treatment, and how safe the treatment is. Such studies are required in areas where large gaps in knowledge exist. This seems to be particularly relevant to medical cannabis. This brings our lesson to its conclusion. Now, that we understand the types of evidence, and the methods available to us, we can start analyzing the effectiveness of medical cannabis for various pain conditions.
