What effect will modafinil plus alprazolam have?

CBD could become dangerous if you take other medications

"Lollipops? Yes. CBD cannabis flowers? NO!" Such a post that the Berlin police shared on Facebook at the beginning of the year. That means: Products that contain CBD, i.e. the cannabis active ingredient cannabidiol, are legal as long as they are not real grass flowers.

Cannabidiol is not intoxicating. Instead, it can reduce inflammation, nausea and epilepsy, and help with mental health problems ranging from schizophrenia to anxiety. For many consumers, these positive effects are worth the slight side effects: some feel a little dull, their appetite can change, or diarrhea occasionally occurs. According to the current state of research, however, CBD is harmless, at least in the short and medium term.

But even if CBD has an overall benign effect, it does not have to stay that way in interaction with other drugs. As soon as we mix two substances in our body, they may affect each other. Even simple foods like black pepper can affect the absorption and effects of other drugs, explains Donald Abrams, a medical professor specializing in medical cannabis at the University of California, San Francisco. As previous research shows, CBD could interact with numerous other agents, but little is known about which doses of which drugs could cause significant problems.

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Because there is still no systematic research on CBD interactions. The only scientific record of such effects comes from studies on Epidiolex, a remedy for some rare forms of epilepsy that consists largely of cannabidiol. It has already been approved in the USA, and approval in the UK and the rest of Europe is expected by mid-2019. The Epidiolex studies show that particularly high doses of CBD increased levels of other epilepsy drugs in the blood of some patients - including clobazam, Zebinix, Inovelon, Topamax, valproic acid, and zonisamide.

With clobazam, the interaction resulted in a particularly sedative, i.e. dampening, effect. With valproic acid, the liver was stimulated in a way that in the long term could lead to a toxic effect. A case study also found that patients who took the blood thinner warfarin and CBD had even thinner blood than expected. Not many such interactions have been documented so far, so it is possible that there is no great danger for the average patient.

CBD interacts with liver enzymes that alprazolam and diazepam also interact with

However, we do know quite a bit about what happens in our body while we are processing CBD. As the researcher Carola Rong from the University of Toronto has found, cannabidiol interacts particularly strongly with an enzyme system in the liver. Simply put, CBD could prevent other drugs from getting to these enzymes so they don't break down and build up in the bloodstream. In addition, this effect could prevent some of these drugs from working in a timely manner.

The liver enzymes affected do not only interact with one type of drug, but, according to Rong, with around 60 percent of all pharmaceuticals on the market, including common psychoactive agents. Such as with Alprazolam - known in the USA and Switzerland under the sales name Xanax, in Germany under the name Tafil. Or the sedative diazepam, also known as Valium, as well as a long line of antihistamines, antiretrovirals, and steroids.

Fortunately, the mere presence of CBD does not mean that the other drugs have a completely different effect on the body. As Rong explains, however, we do not know which CBD dosages trigger a significant interaction with which drug.

Dave Bearman, a general practitioner who has treated more than 3,000 patients with medical marijuana, rarely hears complaints from them that may indicate an interaction with other drugs

Adrian Devitt-Lee is a cannabinoid researcher and works for the Project CBD research initiative. He points out another factor that should be considered: You don't know for how long CBD works on liver enzymes. There are also interactions at lower doses, but Devitt-Lee assumes that there can be significant effects from one gram of CBD per day.

Dave Bearman is a general practitioner in California and has worked with medical marijuana for nearly 20 years. He has treated more than 3,000 patients with it. Bearman says he rarely hears any complaints from them that may indicate an interaction with other drugs. Devitt-Lee also emphasizes that he only knows of a few cases in which CBD has interacted with blood thinners. Most CBD products also contain much lower concentrations of the active ingredient than the epilepsy drug Epidiolex, which has caused problems in certain doses. This is confirmed by Timothy Welty, a pharmacologist at Drake University in the US state of Iowa.

For cancer patients, the interaction of their drugs with CBD is unpredictable

Some experts have expressed concern that people who regularly take high doses of CBD could inadvertently overdose on tranquilizers. Devitt-Lee explains that most drugs are so safe that they still help and at most cause a few minor side effects, even if they build up in the blood. The researcher is more concerned about drug interactions that are only effective in a small dose window - that is, a little less and they have no effect, a little more and they become toxic. CBD could "switch" such agents from therapeutic to toxic if the cannabidiol causes them not to be broken down properly.

The fact that we do not know in which drugs CBD interactions are particularly pronounced is a major problem. Because it is often precisely the people who are already taking medication who want to treat themselves with CBD. If CBD has an impact on the processing of chemotherapy, for example, it could be dangerous, according to Devitt-Lee: Doctors often give cancer patients the highest tolerable dose at the beginning. If the chemo is not broken down normally, it could poison sick people.

The fact that we do not know in which drugs CBD interactions are particularly pronounced is a major problem. Because it is often precisely the people who are already taking medication who want to treat themselves with CBD.

It is impossible to systematically research which agents become dangerous when interacting with CBD. This is partly because there is very limited funding for cannabis research. However, there are also practical and ethical limits. "You're not going to give hundreds of different doses of CBD to people who interact with their chemotherapy just to get data," said cannabis medic Donald Abrams.

Even if we could collect such data, it would not be a perfect indicator of the possible risks. Researcher Rong emphasizes that people metabolize substances at different rates. Unfortunately, we also do not know how such differences affect tolerances and interactions.

For now, one thing is particularly important for people who take CBD and other medications at the same time: caution. According to Devitt-Lee, particular attention should be paid to people who are undergoing chemotherapy or who are taking the blood thinner warfarin. Here the side effects could be very serious. Carol Rong calls on health professionals to be extra careful which drugs they prescribe to patients who consume CBD products.

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