Phytocanabinoids•THC and other marijuana chemicals

Our bodies make a variety of marijuana-like chemicals called “endocannabinoids” that activate many brain, pain receptor, and other endocannabinoid receptors distributed throughout the tissues and organs of our bodies. As you would expect, the activation of these endocannabinoid receptors affects and regulates the chemical processes of our bodies—pain, inflammation, immune response, cardiovascular function, gastrointestinal function, etc.
 
How necessary to our health are these cannabinoid systems? Recall the European diet drug Rimonabant™. Rimonabant blocked endocannabinoid receptors and was a fabulously effective diet drug. Unfortunately, Rimonabant so effectively blocked cannabinoid receptors that it caused such severe depression that patients taking Rimonabant committed ѕυιcιdє and the drug had to be pulled from the market. Activation of cannabinoid receptors is essential to mental health and life itself.

THC and the other unique chemicals of the marijuana plant, cannabis, are categorized as “phytocannabinoids,” namely, “plant cannabinoids.” THC and other phytocannabinoids mimic our own endocannabinoids because, in three dimensions, the phytocannabinoids are shaped like our endocannabinoids. Because of their similar shape, phytocannabinoids activate our endocannabinoid receptors. It is no surprise then that marijuana’s chemicals cause a multiplicity of pleasant and beneficial effects, enhancing physical and mental health. Recall too that, quite unlike the medical and recreational drugs marijuana replaces, marijuana has never caused a fatality. In a 1997 New England Journal of Medicine article “Reefer Madness–The Federal Response to California's Medical-Marijuana Law” (N Engl J Med. 1997 Aug 7; 337(6): 435-9.), George Annas calculated that one would have to smoke “nearly 1500 pounds of marijuana within about fifteen minutes to induce a lethal response,” a death by asphyxiation, not drug toxicity. Unless a 1-ton bale of marijuana falls on your head, marijuana cannot kill you. You cannot say the same for aspirin, oxycodone, or even alcohol.

In 1964 THC was the first of marijuana’s unique chemicals to be isolated, but discovery of CBD and numerous other cannabinoids quickly followed. Marijuana has other unique cannabinoids, “terpenophenolic” chemicals that, besides giving marijuana strains their unique scent and flavor properties, are being discovered to have medical benefits. Let’s focus on the two most-studied cannabinoids, THC and CBD.

THC

THC, short for ∆9-tetrahydrocannabinol, read “delta-9-tetrahydrocannabinol,” is marketed commercially as “dronabinol” or Marinol™ and is the most psychoactive of marijuana’s chemicals. THC partially activates CB1 and CB2 receptors about equally (see https://www.cathinfo.com/health-and-nutrition/the-endocannabinoid-systemwhazzat/). THC mimics the endocannabinoid anandamide and so eases pain and is thought to account for the neuroprotective effects of marijuana (e.g., the decreases in the damaging demyelination of multiple sclerosis, amyloid deposition and neurofibrillatory tangles of Alzheimer’s Disease, and even regression of the aggressive “GBM” brain cancer, glioblastoma multiforme).

THC and other cannabinoids dissolve poorly in water, but dissolve well in fats, glycerine, and alcohol. Their relative insolubility in water explains why the cannabinoids resin-making cells of marijuana, the “trichomes,” can be separated by cold-water extraction methods to make bubble hash without the trichomes’ active ingredients simply dissolving into a soupy tea in your hash bags. Because some of the characteristic chemicals of marijuana do dissolve in water, some compounds are washed away by the cold-water method and so connoisseurs do note a blandness of bubble hash in comparison with hash made by traditional methods. On the other hand, the non-traditional methods of extraction do provide the “full melt” characteristic that lends so well to vaporization. Qualified patients who wish to study these methods in depth should consult the 2010 second edition of Robert Connell Clarke’s book Hashish.

Too, THC’s excellent solubility in fats, glycerine, and alcohol explains why butter, oils, glycerine, and liquor make such effective extracts and tinctures.

CBD

CBD, short for “cannabidiol,” acts by influencing endocannabinoids, phytocannabinoids, and serotonin. While there is evidence that CBD directly activates CB1 or CB2 receptors, CBD’s indirect actions chemically competing with THC and other cannabinoids may also be important. CBD has also been shown to activate a certain subset of serotonin receptors, the 5-HT1A receptors (receptors related to commonly prescribed anti-depressants such as Prozac and Zoloft).

It is often, but inaccurately, said that CBD is not psychoactive. CBD does moderate the cerebral “high” of THC. Strains of marijuana high in CBD are less psychoactive than the percentage of THC would otherwise suggest, but CBD does display its own subtle psychoactivity. Paradoxically, some CBD research has shown that CBD can be sedating while other research shows CBD increases alertness. Interest in CBD, however, does not center on its subtle psychoactive properties. Instead CBD is receiving increasing attention for its remarkable anti-epilepsy, anti-inflammatory, anti-anxiety, anti-nausea, and even anti-cancer benefits. CBD inhibits cancer cell growth through a combination of actions (CB2 receptor, TrpV1 capsaicin-receptor, down-regulation of the ID1 oncogene, and induction of oxidative stress) that force “apoptosis,” forcing the programmed cell death from which cancers escape.

To reap these benefits of CBD, breeders have developed high-CBD strains of marijuana. Currently the Society of Cannabis Clinicians defines high-CBD strains as those with greater than 4% CBD by weight or greater than 2.5% CBD if CBD exceeds THC content. Typical medical grade cannabis may have only 0.5-1% CBD, but 14-18% THC. Among the better known high-CBD strains (percentages vary greatly depending on drying, curing and storage, but are reported here as tested by Steep Hill Lab, Oakland CA): Cannatonic 6% CBD/6% THC (Resin Seeds, Barcelona, Spain), Harlequin 8-9% CBD/5.5-6% THC (Cornerstone Research Collective, Los Angeles CA), Women’s Collective Stinky Purple 9.7% CBD/1.2% THC, and the champion, outdoor-grown “True Blueberry x OG Kush” 13.9% CBD/6-7% THC (Full Spectrum Genetics, Yreka CA).

Patient preferences and needs vary. Some prefer and need more THC; others prefer and need more CBD. Besides choice of strains, patients have another method to adjust their relative THC and CBD dosages, vaporizing their medicine. Vaporizing or “vaping” involves heating the medicine to a temperature below the combustion temperature, the temperature at which the marijuana actually burns, approximately 200°C. (392°F.). This allows the inhalation of the vaporized medicine without inhaling actual smoke.

THC and CBD vaporize (turn from a solid into a gas) at different temperatures. THC vaporizes at 157°C. (315°F.) and CBD at 188°C. (370°F.). By adjusting the temperature of a quality vaporizer like the Storz and Bickel Volcano® (http://www.storz-bickel.com), patients may selectively inhale medicine that is THC-rich or CBD-rich.

To obtain THC-rich medicine, simply set the vaporizer for 160°C. and titrate your inhalation of the collected vapor.

To obtain CBD-rich medicine, set the vaporizer for 160°C., allow all the THC to be vaporized without collecting it (or collect it to be used by another patient that prefers the THC-rich fraction). After all the THC has vaporized, turn up the vaporizer temperature to 190°C. and titrate your inhalation of the now CBD-enriched vapor.

For the history and to follow promising developments in the study of CBD, I refer readers to http://www.projectCBD.com.

“Et cetera, et cetera, et cetera”

This is, of course, a short and simplified overview. Approximately 100 phytocannabinoids have been isolated from marijuana, so stay tuned. Much more remains to be known about other common cannabinoids: CBG (Cannabigerol), CBC (Cannabichromene), CBL (Cannabicyclol), CBV (Cannabivarin), THCV (Tetrahydrocannabivarin), CBDV (Cannabidivarin), CBCV (Cannabichromevarin), CBGV (Cannabigerovarin), and CBGM (Cannabigerol Monoethyl Ether).



In 2003 the US government awarded itself US patent #6630507 for cannabinoids as antioxidants and neuroprotectants. No, you are not confused; that is the same federal government that classifies marijuana as a Schedule 1 drug because it supposedly has no medical usefulness. Go figure.

Underscoring “our” government’s hypocrisy regarding inexpensive and easily-grown marijuana is the recognition that besides endocannabinoids and phytocannabinoids, there is a third class of cannabinoids, synthetic cannabinoids, the drugs that Big Pharma is patenting to sell you. Wanna bet whether the feds will classify those expensive synthetic drugs as Schedule 1 having “no medical benefit”? Follow the money.





It is worth mentioning that marijuana is not the only plant with phytocannabinoids.