Alphabet Soup
As a followup to yesterdays discussion about terminology and the correct use of cannabis referring to the plant and its herb products. The plant contains a lot of chemicals including the gold star, “delta 9 tetra hydro cannabinol, or THC for short. THC is found as an inactive precursor THCA in the plant and requires heat to convert to THC. This is historically accomplished by combustion and inhalation through the lungs. Two related chemicals as suggested by the alphabet soup names THC and THCA but with two entirely different effects in the body.
Quick point of emphasis: Your dog eats a ziplock baggie full of dry cannabis bud also called flower. Should you worry, no, not really. The herb is non-toxic, there is no dose that has ever been found to be lethal. The dog won’t even get high, as the chemical transformation from THCA to THC has not yet occurred. Let us contrast this example for one less benign. The food in question is now brownies, special edibles in which herb is extracted with oil and heat activated. If your dog ate a plate full of special brownies, the first concern is chocolate. Due to a difference in metabolism, a chemical called theobromine/ a cousin of caffeine, builds up to dangerous levels in dogs when fed chocolate. Science has a morbid language to describe this danger, LD50. My understanding of the term LD50, is that is the dose in which 50% of the subjects die. For dogs the LD50 for chocolate is near one pound (of milk chocolate/dark chocolate more toxic), meaning only 50/50 chance of survival, not to mention the long term effect of the poisoning. In contrast to the theobromine concern from the chocolate poisoning which does require immediate medical attention, THC is safe. The dog ingested THC will be absorbed by the dog and get it “stoned”. Will the effect be pleasant?, don’t know, how long will it last?, don’t know, will it be toxic? definitely not. To repeat, while intoxication with THC may led to poor judgments which are harmful (car crash), the drug itself does not appear significantly toxic.
So how does THC work? Good question but first a sidetrack into why and how our understanding of cannabis was slowed. Back around the time I first began my teenage experimentation with cannabis in the 70’s, the government of Richard Nixon was busy twisting the system. The controlled substance Act of 1970, seems helpful on the surface. Establishing powers for the FDA and DEA to regulate drugs especially those with increased risk for abuse and/or addiction. A reasonable outline has been made into four categories of risk: High, Medium, Moderate, Lowest. As opposed to making these the groups or classes 1 to 4, a fifth group was added to the top of the list and the above became classes 2 to 5 (lower class higher risk). The unique class one category was carved out for those “hated” drugs that have no medical indication. The members are few but include: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote. Licensed practitioners such as myself only get DEA licenses for classes/schedule 2 through 5 drugs. So any drug placed in the group of schedule 1, is off limits for use or research. You see the Catch-22, it will stay in schedule 1 until there is medical evidence but collecting evidence in illegal, so progress or change will be avoided. The current obstacle appears to reside in the executive branch, with the DEA under the President. Too numerous to count expert panels have been asked to address the abuse/addiction potential of the drug and not only have they found the risk low, it is much lower than drugs that are not even on the schedule list including nicotine and alcohol. Older panels have cited lack of supporting evidence that cannabis has therapeutic medical use, but current data is overwhelming. It appears that the current stalemate is more a product of drug policy leading to mass incarceration and social injustice in which no one wants to acknowledge the mistake and consequences.
Back to the science. For many drugs, their action appears to involve binding to a receptor with a lock and key like functional model in which the unlocked receptor has a changed function. Nicotine is a common drug that works via this mechanism, it hijacks a receptor in the body which normally binds to acetylcholine. Both the nicotine and acetylcholine are called ligands because they bind to the receptor. The acetylcholine comes from within and is the endo-ligand and the nicotine comes from outside and is the exo-ligand.
Scientists have now discovered a new receptor which binds selectively to THC which has been named the cannabanoid receptor. In fact they have found two different locks to which the THC key unlocks, named receptors subtype CB1 & CB2. THC is the exo-ligand, but our knowledge about the endo-ligands like AEA and 2-AG, is is still evolving. A whole field of science has opened up involving the endocannabinoid system and the natural chemical transmitters the endocannabinoids. Effects that are commonly seen include changes in appetite/nausea (munchies), euphoria/ mental uplifting (high), vasodilation (blood shot eyes), changes in autonomic tone (dry mouth, +/- anxiety), alterations in conscious perception altered sense of time (spaced out), short term memory loss and inactivity (stoned).
While THC has risen to stardom, it is part of a family of chemicals (100 or so) which share similar chemical structures and have the letter “C” in their abbreviation , CBD CBN CBG etc. CBD is the second most common cannabinoid by weight, but does not bind to the CB2 receptor as some authors suggest. Outside the limited medical indication of suppressing seizures in young children with rare seizure disorders, CBD has much less science to support its use. Widespread promotion of CBD as health supplement, is premature, and should only be considered experimental. Terpenes represent a different class of chemicals within cannabis (their volatile nature is behind smells like citrus, berry, mint, pine, skunk, and cheese). Sometimes represented as essential oils, the terpenes are still poorly understood. The reality is that cannabis has a mixed chemical profile, that will vary plant to plant and be affected by route of administration.
To illustrate my feelings about cannabinoids and other cannabis chemicals, let me use a stock portfolio comparison. The only chemical/stock that I would give a “buy” rating is THC. However I think a portfolio should be diversified and only owning the blue-chip stock THC, will likely under perform compared with a THC+ portfolio. The other stocks to own remain uncertain at this point due to market volatility “pun intended”.
Precursors changed by heat, decarboxylation, in which the carboxyl group (-COOH or acid) is removed and CO2 released. Of the four keys shown, only THC is the key which fits the discovered locks. The mechanism of CBD remains to be fully understood, ?lock yet to be discovered. My personal impression is that it may be a co-factor, which has much less effect on its own, but much greater additive co-effect.
