Debunking Previous CBD -> THC Conversion Research

Earlier in the year, we published an article about CBD converting to small amounts of THC in the stomach, based on a 2016 study lead by John Merrick, “Identification of Psychoactive Degradants of Cannabidiol in Simulated Gastric and Physiological Fluid”. This study found that cannabidiol, when immersed in a bath of acid similar to stomach acid, produces a significant amount of THC in the same acid bath. Researchers hypothesized that this was because THC and CBD, despite having wildly different effects, actually start as the same pre-cursor chemical (cannabigerolic acid). Different enzymes then convert this chemical to destination chemicals THC or CBD, depending on plant genetics and environmental factors. However, strangely enough, in the year following the study, we have not seen the results confirmed. Were this a less significant finding, we might expect such delay. However, the finding is especially relevant to cannabis/cannabinoid research because it undermines CBD as a therapeutic drug. If part of the drug is converting to THC in stomach acid, this effect might preclude its use in situations where THC must be avoided. However, despite the lack of confirmation, outstanding questions loom, such as, if edible CBD converts to THC, why are CBD users not noticing psychedelic effects? How did such a large, obvious conclusion fly below the radar? Apparently because it’s false. As far as we can determine at this point in time, there is no reason to believe CBD converts to THC in the human stomach. Spearheading the commentary refuting this article, Franjo…

Genetics Modify Response to Cannabis: A Look at the COMT Gene

Last week we talked about the need for genetic testing of both the cannabis plant itself and of patients. Speaking in broad terms, we noted that slight alterations in human DNA can lead to noticeable differences in reactions to cannabis. This is something medical cannabis patients can attest to when comparing strains with other medical users. A strain that makes one person feel tired may have little impact on the energy level of another. Today we can introduce one specific mechanism that seems to influence genetic variation in response to cannabis. Interestingly enough, researchers at Warneford Hospital in the UK actually approached this discovery while searching for causes of psychosis (when thought and emotions are so impaired, patients suffer a disconnect from reality). One of the most debated questions in the scientific community is whether cannabis contributes to the development of psychosis. Believers cite that while many people consume cannabis with no lingering health issue, some develop psychotic symptoms immediately after first exposure. Critics do not necessarily disagree with this observation but believe that many different substances and environmental factors can trigger psychotic illness. Regardless, the data would suggest that if only some patients develop symptoms, the cause might be genetic. What gene is causing this? Researchers have identified catechol-o-methyltransferase (COMT) as a gene that regulates dopamine in the cortex of the brain. Studies show that cognitive function is improved in animals “with reduced COMT activity”. This pattern implies that the gene is some sort of limiter, perhaps designed to…

Cannabigerol, Making Food Appetizing for Cancer Patients

For all of the states that initially passed medical cannabis legislation, cancer was not only an approved condition but also a major data point supporting such legislation. Specifically, cancer patients, forced to undergo exhausting chemotherapy treatments, lose appetite. This drastic, prolonged loss of appetite, similar to anorexia, decreases body weight and in turn, decreases overall health. Cannabis has long been observed to increase appetite in humans (we’ve written several Cornerstone blog posts on the “munchies”), with the most active ingredient identified as THC, the psychoactive component of cannabis. Unfortunately, not all patients enjoy or can tolerate this psychoactivity. Originally, this posed a serious downside to treatment with cannabis. However, with the discovery of the endocannabinoid system, researchers realized that the effects of THC might be achieved, without psychoactivity, via other cannabinoids. Additionally, research has confirmed that cannabis containing no THC can still restore appetite. In line with this thinking, one paper, published last month in the medical research journal, Psychopharmacology, tested a molecule known as cannabigerol (CBG) on rodents to observe changes in feeding patterns. Readers may be surprised to learn that cannabigerol, unlike many other cannabinoids, found mostly in the resin of medicinal plants, exists in higher concentrations in plain hemp. Most medicinal strains, in fact, have concentrations lower than 1%. CBG also binds to the CB1 receptor at a much lower rate than THC and may even serve to temporarily disable the receptor. However, CBG has also been shown to be a 5-HT1A receptor agonist and an alpha2-adrenergic…

Vaping To Relieve Pain, Does It Really Work?

One of the most popular recurring topics on the Cornerstone blog is pain management, and for good reason; currently available pain treatment options may go a long way toward reducing pain, but most individuals with chronic pain still report unmet treatment needs. One relevant issue is that multiple sources contribute to pain, and therefore, a single “magic bullet” pain medication does not exist that is capable of treating all sources. As medical science advances, part of researchers’ collective job is elucidating what other pain treatments might be effective and worth adding to the rotation of commonly used painkillers. As readers know, researchers have identified both THC and CBD as potential pain treatments, with CBD’s anti-inflammatory effects making it an especially good candidate for pain stemming from inflammation (such as in arthritis). Cannabinoids such as CBD represent a great treatment option because abuse potential is relatively non-existent. Opiate-based medicines on the other hand, such as morphine, must be carefully controlled. Doctors are frequently put in the position of evaluating a patient’s pain and choosing whether to prescribe opiates or to withhold that medication to prevent abuse, addiction, and drug trading. That decision can be difficult, and the more non-abusable drugs in a doctor’s arsenal, the more likely pain will be treated effectively. Lately, as medical research delves deeper into the world of cannabinoids and the body’s own endocannabinoid system, the emerging consensus is that new cannabinoids could be created that are even more effective at reducing pain than cannabis itself. For…

Is Cannabis Addictive?

One of the early concerns that dominated the medical cannabis discussion was over both the addictive potential and long-term effects of cannabis. For decades, it has generally been understood by the medical community that cannabis is not physically addictive but can be psychologically addictive. To differentiate, individuals addicted to alcohol cannot suddenly end consumption without risk of death or serious health consequences, because their bodies have learned to literally need alcohol. In contrast, even a frequent cannabis consumer can end consumption immediately without serious health risk. However, this transition might be severely uncomfortable due to the psychological dependence of cannabis use. Some anti-cannabis advocates and researchers alike have pushed for the notion that this dependence is life-long. Researchers from Geneva, Switzerland recently pressed one step forward to directly answer this question by observing changes in brain chemistry during and after chronic cannabis use. To back up, what is addiction and what causes addiction? As researchers note, “the addictive effects of virtually all drugs…are thought to be mediated through activation of mesolimbic dopamine projections to the nucleus accumbens.” Essentially, a neurotransmitter, dopamine, is activated to a greater degree than normal, causing an increased interaction with the part of the brain that deals with decision making, risk, and reward. Dopamine is responsible for a multitude of signaling tasks, but perhaps the most known and most important job is signaling reward. When a user consumes a drug, dopamine is released in the brain, essentially rewarding the user for consuming the drug and teaching…

Schizophrenia, Cannabis, and the AKT1 Gene

We’ve written several articles on the Cornerstone blog about cannabis and schizophrenia. The association between the two is one of the most fascinating puzzles of cannabis science. What we know is that people suffering from schizophrenia are more likely to use cannabis than non-users, and daily cannabis users have a small but doubled risk of developing a psychiatric disorder. Like all psychoactive substances, medical or recreational, cannabis is not for everyone. What makes someone more susceptible to an adverse reaction to cannabis? Or any substance for that matter? What increases someone’s likelihood of being a daily user? At the turn of the century, the idea that anyone could be predisposed to a particular psychoactive reaction was largely disregarded. In fact, many physicians did not accept alcoholism as a valid illness when it was originally added to the Diagnostic and Statistical Manual of Mental Disorders. However, genetic research has changed so much of our understanding of psychiatric health. Rather than imagining everyone to have the same psychological operating system, we know that genes dictate large differences from person to person. Even within an individual, genes can be activated and deactivated throughout a person’s lifetime due to environmental factors and stress. Readers may be able to identify with having a friend who cannot or does not smoke cannabis due to repeatedly unpleasant experiences. “It just doesn’t sit well with me.” Such people are unknowingly referring to their genetic make up and general neurological condition. Of course, knowing that there is a genetic…

Cannabis and Motor Coordination

As cannabis rounds the bend in many states toward legalization, one of the biggest questions on society’s mind is how to ensure that it is safe and does not impair potential life threatening activities. Since the founding of MADD in 1980, we’ve grown more aware of the danger of drunk driving, which kills close to 28 people a day in America and is a heart-breaking drain on society. Since cannabis can also have mind-altering effects, as a society, we’re equally wary about the danger of driving under the influence of cannabis or any psychoactive substance for that matter. In fact, this fear is constantly cited as reason for not passing medical cannabis legislation. This concern has led states that have already approved medical cannabis to pass regulations specifying levels acceptable for operating vehicles. At first glance, this all seems acceptable. In the same way that patients with allergies should not take Benadryl before operating machinery, medical cannabis patients must be careful about actions that can jeopardize their safety or the safety of others. However, some of these legal driving limits are unbelievably low. In Washington State, for example, the legal limit is 5 nanograms THC-COOH per milliliter of blood in a blood test. To put that in perspective, this amount could actually exist in a medical cannabis patient 24 hours after consuming cannabis. But is a patient realistically an inhibited driver 24 hours after medication? Of course not. Anyone with a proper medical cannabis experience knows that. However, that’s just…

Cannabinoids as Weight Loss Drugs Part II

The association between cannabis and appetite is well known both in the scientific world and pop culture. As many of our longtime blog readers already know, this association ultimately led to the development of one of the most horrific weight loss drugs of the past century, known as Rimonabant. Researchers at the Sanofi-Aventis pharmaceutical company, noticing the role of THC (and more generally, activation of the CB1 cannabinoid receptor) in increasing appetite, guessed correctly that the reverse would also be true – that deactivating the CB1 receptor would decrease appetite and therefore allow weight loss. Of course, that was before scientists understood how essential the endocannabinoid system is to our healthy functioning; as numerous reports came flooding in of increased suicide rates and depression in individuals with no previous history of mental illness, the drug was quickly pulled from the market. Needless to say, plans for all similar CB1 blockers (CB1 antagonists) were nixed at competing pharmaceutical companies, and researchers have since been hesitant to touch cannabinoids as weight loss drugs, for good reason. However, as we’ve expressed in previous articles, the endocannabinoid system is not a simple system compromised of only two light switches (in this case, two receptors that can merely be turned off or on). In fact, the endocannabinoid system can be activated through non-standard receptor binding sites, and endocannabinoids themselves can also activate other chemical pathways throughout the body. Unfortunately, due to a lack of research, many of the specific effects of manipulating the endocannabinoid system…

Anandamide

Up to this point, we haven’t spoken much of the body’s own endocannabinoids. As a quick refresher, the endocannabinoid system consists of receptors and enzymes that metabolize any cannabinoids bonding to those receptors. However, our cannabinoid receptors do not exist for the purpose of consuming externally produced cannabinoids like those found in cannabis. These receptors exist because our bodies produce their own cannabinoids (endocannabinoids), which are used to signal and control various functions. Of all our naturally produced cannabinoids, one of the most important is anandamide (AN). Anandamide, like our other endocannabinoids, is produced on the spot, where needed. It primarily bonds to CB1 receptors, giving it an effect profile similar to THC, the well-known psychoactive ingredient of cannabis. FAAH (fatty acid amide hydrolase) then metabolizes the anandamide, clearing the receptor for re-activation. Because anandamide is produced locally where needed, while external cannabinoids, like THC, are supplied to any tissue, comparing effect differences may be comparing apples to oranges. However, an oversimplification would be that ananadmide is the body’s own THC with a shorter effect endurance. In fact, the name “anadamide” is actually based on the Sanskrit word “ananda”, meaning “joy” or “bliss”. Rimonabant, the failed weight-loss drug we often reference on the blog, blocked CB1 receptors from being activated by anandamide. From known research, we can now safely guess that many of the negative psychological effects of Rimonabant resulted from preventing the body from using its own anandamide. In other words, anandamide seems to hold at least one key…

Inhibiting Re-Uptake To Enable Treatment: The Endocannabinoid System and New Medicines

In popular culture, we like to think of an inventor as someone who notices a problem, thinks really hard about a solution, and solves that problem with a novel device or approach. Oftentimes however, discovery proceeds in reverse: first a solution is found and then a clever inventor looks for a problem that the solution might apply to. For instance, the invention of the Post-it Note® occurred when a scientist attempting to develop a better superglue accidentally developed a glue with low adhesion but high re-usability. Although that scientist attempted to promote the glue, the company that had financed the research tossed it to the side, chalking it up as a failure. After all it was not the superglue they wanted. Six years later a colleague managed to develop a use outside of the company; he noticed he could apply it to the back of a bookmark to keep it from falling out without developing a permanent bond that would tear the page. Thus the Post-it Note® was born and subsequently became one of 3M’s most successful products. Drug development, as Christopher Fowler argues, might also proceed more effectively this way. Fowler, a clinical neuroscience researcher at Umea Unversity of Sweden, recently reviewed studies involving inhibitors of cannabinoid metabolism. Metabolism, whether specific to nutrients or in this case chemicals in general, simply means how something is broken back down to be disposed of or recycled by the body. The idea is that rather than supplying the brain with more cannabinoids,…

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