Cannabis and Cannabinoid Research (Dr. Daniele Piomelli: CCR) : I would like to start with a few questions that should not be too controversial. First of all, what is the geographic origin of the cannabis plant?
Dr. Russo : Cannabis is native to Central Asia and possibly the foothills of the Himalayas. There are converging lines of evidence, including a center of biological diversity there, and biochemical data that supports it. There is no record of its presence in the Western Hemisphere before the 16th century.
CCR : What are the main chemicals responsible for the psychoactive effects of cannabis? Δ9-tetrahydrocannabinol, cannabidiol or others?
Dr. Russo : Δ9-tetrahydrocannabinol is, of course, the main psychoactive component of cannabis. Δ8-tetrahydrocannabinol, a more heat-stable component, is probably slightly less psychoactive, but is present only in trace amounts or as an artifact of laboratory analysis. Cannabinol is the non-enzymatic oxidative breakdown product of tetrahydrocannabinol (THC), seen in aged cannabis, and is approximately 25% of the potency of THC. Tetrahydrocannabivarin (THCV) is a neutral CB1 antagonist at low doses, but an agonist at high doses, and is certainly psychoactive, but rarely seen at high levels in commonly available cannabis strains. Finally, although cannabidiol (CBD) is not intoxicating, it certainly has anxiolytic, antipsychotic, and even antidepressant effects, so they should be considered psychoactive with these qualifications.
CCR : What about the plant’s other medicinal properties? For example, the local anti-inflammatory actions praised by certain ancient writers?
Dr. Russo : CBD is a versatile anti-inflammatory analgesic through many distinct mechanisms, and various other minor cannabinoids and terpenes in cannabis can certainly contribute notably to the therapeutic profile of cannabis. Extensive basic science and even clinical trial data support the concept of herbaceous synergy in cannabis beyond the effects of individual components. We are only seeing the beginnings of the therapeutic potential of this plant!
CCR : Can you explain what the entourage effect means as it relates to cannabis?
Dr. Russo : This concept was first stated by Drs. Mechoulam and Ben-Shabat more than 15 years ago to explain how certain components of the endocannabinoid system enhance the therapeutic effects of its main players, anandamide and 2-arachidonylglycerol. So, it is like a symphony, in which many musicians support and harmonize the melody provided by the soloists. The same analogy applies well to the synergistic phenomena observed in cannabis, whose various components reinforce and complement those of its best-known components, THC and CBD.
CCR : People have been breeding cannabis strains for some time now. Human selection might be expected to have substantial effects on the psychoactive and medicinal properties of cannabis. Is it true ?
Dr. Russo : Absolutely ! While there have always been some very potent cannabis strains, they are certainly more commonly available today thanks to breeding and growing techniques that produce ganja or sinsemilla, i.e. unfertilized female flowers. The plant puts all of its energy into producing cannabinoids and cannabis terpenes instead of producing seeds. Unfortunately, until recently, almost all breeding efforts have been directed toward more potent THC strains rather than mixed or predominant CBD strains, which are safer and perhaps much more therapeutically versatile. Breeding for medicinal efficacy is a relatively new phenomenon that is now accelerating.
CCR : Now let's move on to something more controversial. Here is a statement that can be found on the web: “It is widely accepted that marijuana has two different species: Cannabis indica and Cannabis sativa. » This was of course also the opinion of the great 18th century naturalist, Jean-Baptiste Lamarck, but would academic botanists agree with this statement today?
Dr. Russo : Botanical taxonomists never agree on anything for very long! To paraphrase and expropriate an old Yiddish expression: 12 botanical taxonomists, 25 different opinions. Many classical botanists would argue for cannabis as a polymorphic species based on the ability of all of its types to interbreed. However, if this were true, hundreds of neotropical gesneriaceae (Gesneriaceae, members of the African violet family) would all be a single species since they readily interbreed and produce fertile offspring. It is clear that there are many cannabis chemotypes: THC-dominant, CBD-dominant and mixed types. This is a good basic classification, but it was also possible to select other chemotypes expressing high levels of THCV, cannabidivarin, cannabichromene and even those producing 100% of their cannabinoids in the form of cannabigerol, or others without any cannabinoids. The debate continues. Some argue for cannabis as a single species, while others describe as many as four: Cannabis sativa, Cannabis indica, Cannabis ruderalis and Cannabis Afghanica (or kafiristanica).
CCR : Some users describe the psychoactive effects of Cannabis indica and sativa as distinct or even opposing. But are they really? Beyond user self-reports, is there concrete evidence for the existence of pharmacologically different cannabis species?
Dr. Russo : There are biochemically distinct strains of cannabis, but the sativa/indica distinction as commonly applied in popular literature is completely absurd and a waste of time. There is no way to guess the biochemical content of a given cannabis plant based on its height, branching, or leaf morphology. The degree of crossing/hybridization is such that only a biochemical test tells a potential consumer or scientist what is actually in the plant. It is essential that future commerce enables comprehensive and accurate cannabinoid and terpene profiles.
CCR : Sativa is often described as stimulating and energizing, while indica is described as relaxing and calming. Can you speculate on what might be causing these perceived differences?
Dr. Russo : We would all prefer simple explanations for complex systems, but this is futile and even potentially dangerous in the context of a psychoactive drug like cannabis. Again, it is necessary to quantify the biochemical components of a given cannabis strain and correlate them with the effects observed in real patients. Beyond the growing number of CBD-dominant strains in recent years, almost all cannabis on the market comes from high-THC strains. The differences in effects observed in cannabis are therefore due to their terpene content, which is rarely tested, and even less reported to potential consumers. The sedation of so-called indica strains is falsely attributed to CBD content when in fact, CBD is stimulating in low and medium doses! Rather, the sedation in most common cannabis strains is attributable to their myrcene content, a monoterpene with a strongly sedative "couch-lock" effect that resembles a narcotic. In contrast, a high content of limonene (common in citrus peels) will be mood-boosting, while the presence of the relatively rare terpene in cannabis, alpha-pinene, can effectively reduce or eliminate loss of short-term memory classically induced by THC.
CCR : How do you think we could approach the sativa/indica dichotomy in a scientifically sound way?
Dr. Russo : Since taxonomists cannot agree, I would strongly encourage the scientific community, press, and public to abandon the sativa/indica nomenclature and instead insist on accurate biochemical testing of cannabinoid and terpene profiles are available for cannabis in the medical and recreational markets. Scientific precision and public health demand nothing less.
CCR : Thank you, Dr. Russo. We appreciate all your clarification on this controversial, complex and very important topic.
Source: HERE