Drug interactions are a significant consideration in modern medicine. Over fifty percent of U.S. adults regularly take prescription meds and at least 75 % of Americans take at least one over the counter drug. Many people, including most seniors (the fastest growing demographic of cannabis users), take multiple drugs, and those compounds can interact and affect the metabolism of each other.
Cannabis is probably the most widely consumed substances in the United States and throughout the world, and a large number of cannabis users also consume pharmaceutical products. Due to the increasing acceptance and prevalence of cannabis being a therapeutic option, it’s necessary for physicians and patients to know how various cannabis components, including cannabidiol (CBD) and tetrahydrocannabinol (THC), the main phytocannabinoids, may interact with commonly consumed pharmaceuticals.
But pertinent details about cannabinoid-drug interactions is difficult to acquire due to marijuana prohibition and consequent restrictions on clinically relevant research. Hence the need for Project CBD’s primer, which had been written not just to help health care professionals and patients anticipate and steer clear of problematic outcomes but also to take advantage of situations where cannabis and pharmaceuticals can act synergistically in a positive way.
“It’s a complicated issue,” says research chemist Adrian Devitt-Lee, the author of the Project CBD primer. “Although drug interactions are rarely so dangerous regarding entirely preclude utilizing a medication, they can have serious impacts on a patient’s treatment and wellbeing.”
The Project CBD primer includes a discussion of varied “substrates” or drugs which are metabolized by cytochrome P450, a sizable family of non-specific enzymes that take part in breaking down an estimated 60 to eighty percent of pharmaceuticals. Cytochrome P450 enzymes could be inhibited or amplified by CBD, THC and other plant cannabinoids, thereby reducing or prolonging the activity of another drug.
By suppressing or inducing specific cytochrome P450 enzymes, CBD and THC can alter how one metabolizes an array of substances. Much depends on the particular substrate active in the drug interaction. Some pharmaceuticals, referred to as “prodrugs,” don’t become functional until they are metabolized into an energetic component. If CBD or THC inhibits the breakdown of a prodrug, the second will stay inactive – whereas inhibiting your metabolism of any regular drug can lead to higher blood amounts of the active substance.
Several variables make precise predictions about drug interactions difficult, even for practiced physicians. “It is much easier to gauge whether drug interactions are most likely rather than predict their exact effect,” the Project CBD primer asserts.
To date, according to observations with regards to the widespread usage of raw cannabis flower and full-spectrum cannabis oil, it will not appear that there has been many problems due to cannabinoid-drug interactions. The clinical utilization of Sativex (a 1:1 CBD:THC sublingual tincture) and Marinol (a pure, synthetic THC pill) has resulted in few, if any, reported adverse events attributable specifically to interactions with pharmaceuticals.
To the extent that there has been problematic drug interactions with cannabinoids, these have involved high doses of nearly pure CBD isolates, not cannabis in general. Despite the fact that THC is definitely an intoxicant and CBD is not really, the reality that people tend to use much higher doses of pure CBD can make it a significantly riskier player in metabolic drug interactions.
Take into account the numbers: Ten milligrams of THC in a cannabis product is a hefty dose for a naive patient and sufficiently psychoactive for your occasional recreational user. Ten mgs of THC along with the same level of CBD in a Sativex tincture hit the analgesic sweet spot in clinical trials. These are generally moderate doses compared to the quantity of single-molecule CBD administered to epileptic children in clinical studies – as much as 50 mg per kilogram – with CBD doses up to 2000 mg not uncommon among patients who obtain CBD isolates from internet storefronts and other unregulated sources.
THC has its own built in guard rails – consume a lot of and you’ll know you’ve hit your limit. With CBD, there are no guard rails, no dysphoric feedback loop which says you’ve had enough. CBD is intrinsically safe, however when obtained from the plant and concentrated being an isolate, high doses are necessary for therapeutic efficacy – unlike whole plant CBD-rich extracts, which have a broader therapeutic window and therefore are effective at lower doses than single-molecule CBD.
Drug interactions are much more likely with high dose CBD therapy than other types of cannabis consumption. Physicians and patients needs to be worried about this, considering the fact that the present regulatory regime privileges CBD isolates over artisanal, plant-derived, multicomponent formulations.
The way in which cannabinoids are administered (smoking, eating, etc.) even offers a significant effect on whether drug interactions occur. Interactions are much more likely when both drugs are taken orally and processed by the liver prior to being distributed with the body. Cannabinoids are absorbed more if ingested on a full stomach. Ingested cannabinoids will have higher peak liver concentrations than inhaled cannabinoids, so ingested cannabinoids must have more potent drug interactions.
The Project CBD primer notes that the sequence and also the route of administering cannabidiol may influence how another drug is metabolized. One study disclosed that CBD has a stronger inhibitory effect on a certain cytochrome P450 enzyme if it’s administered twenty minutes prior to the second drug.
CBD also interacts with THC. By taking CBD and THC together, individuals could find that this results of THC are tempered but prolonged slightly. It is known that 11-OH-THC, a THC breakdown component, is a lot more potent than THC in the CB1 cannabinoid receptor, which mediates psychoactivity. 11-COOH-THC, another THC metabolite, has anti-inflammatory effects without creating a high.
Some individuals can hardly tolerate any THC. The wide range of reactions to THC-rich cannabis might be influenced by genetic tkqkzu factors. A typical polymorphism (or variant) of any gene that encodes a certain cytochrome P450 enzyme alters how one metabolizes THC so that it fails slower and stays active longer, causing hypersensitivity to THC’s psychoactive effects.
That may be one of the reasons why many people find THC-rich cannabis to get unpleasant, while hundreds of millions smoke it to chill out. This genetic variant exists among 20% in European & Middle Eastern populations, meaning one in five Caucasians are THC-averse. Less than 10% of Africans have this genetic variant and among Asians it’s under 5%.