[SOUND] Cannabis can be consumed in many different ways. For clarity, we make a distinction between natural herbal cannabis and cannabinoid based medications. The principal difference is that herbal cannabis has over 500 constituents which vary in concentration and biological effects. While cannabinoid medications have precise doses of one or more defined molecules. Natural herbal cannabis is consumed through the respiratory system, sublingually, orally, or by topical application. Cannabinoid based medications are either swallowed as pills or capsules or sprayed onto the oral mucosa. So let's start with natural herbal cannabis. Cannabis is most commonly smoked as a cigarette. And while some prefer smoking pure cannabis flowers, others mix cannabis and tobacco. When smoked, cannabis is actually burned at high temperature and inhaled into the respiratory tract. Despite the potential harm associated with smoking, which will be discussed later in our course, many people prefer this method of consumption due to the rapid onset of effect which generally occurs within minutes. The main reason for this swift onset of action is that smoked cannabis is transformed rapidly from the lungs to the bloodstream. And from there it reaches the brain very quickly. Numerous factors determine the speed and magnitude of the effect of smoked cannabis. These include the quantity ingested and the concentration of the active constituents. The relative tobacco cannabis contents. The number and depths of inhalations. And the duration smoke is held in the lungs. All these factors contribute to the large variability of clinical effect noted when comparing different cannabis smokers and sometimes even different smoking sessions for the same patient. An alternative to smoking is the use of water pipes or vaporizers. In the case of water pipes, smoke passes through a water chamber prior to being inhaled. With vaporizer, the plant material is heated to a temperature at which THC is released but smoke is not generated. Vaporizers and water pipes may be safer consumption methods since they reduce the quantity of combustion products in the inhalant. At the same time, these methods may be less effective than smoking cannabis. A company called Syqe has developed a device, now in clinical testing, which provides metered doses of vaporized cannabis. Once approved, the device will dramatically reduce the viability of inhaled THC. Medical cannabis can also be consumed using sublingual tinctures, which typically come in the form of oil based drops. Patient keeps the drops under the tongue for a few minutes, allowing the tincture to be absorbed through the oral mucosa and into the bloodstream for a quick onset of effect. Although a formal comparison is not available, the onset of effect in sublingual consumption appears to be slower than that of smoking. This may, to some extent, be explained by the fact that some of the oil is actually swallowed. Non-smokers may prefer edibles, such as cannabis cookies or cannabis tea. Although easy to consume, digested cannabis is often inconsistently absorbed from the gut and has to pass through the liver before being introduced into the bloodstream. This takes time, and the resulting magnitude and onset of effect are usually unpredictable, with delayed response reaching 90 minutes. Some people may not wait long enough before eating another cookie or drinking some more tea and risk overdose. What's more, if cannabis edibles find a way into the home, they may put others, like children, at risk and have serious consequences. Finally, natural herbal cannabis may be applied topically using drops or ointments. Since cannabinoids are highly oil-soluble, they may be absorbed into the body and produce a local and even a systemic effect. So far, the effectiveness of topical cannabinoids has not been studied and cannot be estimated. We'll now switch to cannabinoid-based medications. FDA-approved oral cannabinoid-based medications are available in a number of countries. Dronabinol and Nabilone are systemic molecules similar to THC and are sold as pills. Those drugs were released some 30 years ago and are indicated for the treatment of chemotherapy-induced nausea and wasting caused by AIDS. Data regarding the ability of these drugs to relieve pain is limited. A positive outcome was reported in one clinical trial in which Nabilone reduced neuropathic pain in patents with diabetic neuropathy. In recent years, an oral mucosal spray combining THC and CBD in a 1 to 1 proportion has been commercialized as Sativex. It is approved for the use of chronic neuropathic pain and spasticity induced by multiple sclerosis, an immune disease of the central nervous system. It is also approved in some countries for intractable cancer pain. Sativex is intended to be absorbed from the oral mucosa. But studies have shown delayed concentrations in the plasma indicated that at least some of it is swallowed and absorbed in the gut. So the way in which medical cannabis is consumed is one of the determining factors in understanding its clinical effects.