Eating a high-fat diet can help with the absorption of oral CBD for those with epilepsy

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While oral cannabidiol (CBD) capsules were approved by the U.S. Food and Drug Administration (FDA) for use in patients with seizures in 2018, very little was known about the effect of food on CBD absorption.

A University of Minnesota study, published in Epilepsia, examined whether eating high-fat foods after taking CBD increased the body’s absorption of CBD. The study tested whether fasting or a high fat meal has an effect when cannabidiol oral capsules were taken by patients.

To find out what effect a fatty meal would have on CBD absorption, the research group measured CBD concentrations in epilepsy patients at the MINCEP Epilepsy Care clinic who were taking 99 percent pure CBD capsules.

Concentrations from patients who took CBD on an empty stomach and a standardized fatty breakfast (i.e. breakfast burrito) were compared.

“The type of food can make a large difference in the amount of CBD that gets absorbed into the body.

Although fatty foods can increase the absorption of CBD, it can also increase the variability as not all meals contain the same amount of fat,” said Angela Birnbaum, a professor in the College of Pharmacy and study co-author.

“Increases in the amount of the CBD dose being absorbed into the body can also lead to lower medication costs,” said Ilo Leppik, study co-author, a professor in the College of Pharmacy and an adjunct professor at the Medical School.

The study found:

  • CBD exposure is vastly increased when CBD is taken with high fatty foods;
  • when compared to fasting, taking CBD with food increased the amount of CBD in the body by four-times and the maximum amount recorded in the participants’ blood by 14-times;
  • no cognitive differences were identified, which is consistent with previous studies.
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Concentrations from patients who took CBD on an empty stomach and a standardized fatty breakfast (i.e. breakfast burrito) were compared. The image is in the public domain.

“For epilepsy patients, a goal is to maintain consistent blood concentrations of drug,” said Birnbaum. “This study shows that CBD concentrations could vary significantly if patients take it differently, sometimes with or without food. Variations in blood concentrations could leave a patient more susceptible to seizures.”


Cannabis sativa, commonly called hemp, has thousands of years-long history of medical use.

Cannabis extracts were widely used in Europe and North America for their therapeutic value as sedatives, hypnotics, analgesics, muscle relaxants, and anticonvulsant agents [13].

However, cannabis was removed from British and American Pharmacopoeias in 20th century, partially due to politic bias [4].

Although prohibited, many patients were nevertheless self-medicating to obtain therapeutic benefits from cannabis for various conditions, including AIDS wasting syndrome, multiple sclerosis (MS) and spinal injuries [1,4].

More recently, a growing interest in the therapeutic effects of cannabis has developed following the isolation of cannabinoids, the principal chemical compounds of cannabis, as well as the discovery of endocannabinoids and their cognate receptors in humans [57].

These advances supported legalisation and wide-spread use of cannabis for therapeutic purposes in many countries. Currently, the use of cannabis for medicinal purposes is legalised in 23 states of the US, as well as in Canada, the Netherlands, and Israel.

In addition, the legalisation is currently under consideration in some other US states, as well as in Australia and New Zealand [8]. In Canada, the number of patients enrolled in the federal cannabis for therapeutic purposes program (28,115, as per Dec 2012) represents fewer than 5% of the estimated total users of medical cannabis in the country [9]. In the US, it is estimated that there are currently more than one million legal medicinal cannabis users; the number of non-registered users, however, could be significantly higher (http://medicalmarijuana.procon.org/).

Cannabis is typically consumed by either smoking or oral ingestion. For many people, smoking is the preferred way of consuming medical cannabis as it allows tailoring of the dose to achieve rapid therapeutic effects [1].

However, this method of delivery is not appropriate in considerable number of patients due to the irritant effects of some components in the smoke, the difficulty of consuming cannabis in smoke-free places, and other potential risks and difficulties associated with the smoking process [10].

Oral ingestion of cannabis or cannabis-based medicines is therefore the preferred route of administration in many cases [1,11].

When patients self-medicate with cannabis, it is frequently added to cookies or cakes. The vast majority of cannabis-cooking recipes involve the use of dietary lipids (whole milk, butter, or vegetable oil) for the preparation of these cannabis-containing foods.

This was attributed to the fact that therapeutically-active cannabinoids are lipid-soluble and therefore easily extracted from cannabis upon preparation with dietary fats [12]. It has also been proposed that the longer the fatty-acid chains in the lipids, the more potent cannabis-effect is expected following oral administration [12,13].

The two main natural cannabinoids, the psychoactive Δ9-tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD), have been the focus of research over the last few decades for their potential multiple therapeutic effects [14]. Both cannabinoids are currently available as pharmaceutical formulations. Nabiximols (Sativex®) is a commercially available oromucosal spray that contains a mixture of THC and CBD. It is used to alleviate spasticity in MS patients [15].

Dronabinol (Marinol®), the first oral preparation of synthetic THC, is approved to treat nausea and vomiting associated with cancer chemotherapy and to enhance appetite in AIDS patients suffering from weight loss. In addition, the FDA has recently approved Epidiolex® (an oral solution of CBD) as an orphan antiepileptic drug in the treatment of Dravet syndrome in children [16].

Oral formulations of THC and CBD (Marinol® and Epidiolex®, respectively) contain sesame oil, which is mostly composed of long-chain triglycerides (LCT). It has been stated that the rationale for adding sesame oil to the formulations is to dissolve the lipid-soluble cannabinoids, THC and CBD [1,17]. Moreover, many clinical trials have also reported the use of vegetable oils as vehicles to prepare capsules containing cannabis extracts [1821].

Thus, the available evidence suggests that the use of dietary fats and pharmaceutical lipid-based excipients is common practice in the preparation of cannabis-containing foods and cannabis-based medicinal formulations.

However, despite the widespread use of lipids in cannabis formulations, to our knowledge the effect of lipid excipients on the exposure of patients to orally administered cannabis or cannabinoids has not been investigated.

Therefore, the aim of this study is to elucidate the effect of oral co-administration of lipids on the exposure to the main cannabinoids, and hence on the therapeutic effect or potential toxicity of cannabis-based treatments.

The possible mechanisms underlying the impact of lipids on the systemic exposure to orally administered cannabinoids have also been investigated in this work.


Funding: This research was funded by the Epilepsy Foundation of America, the Patricia L. Nangle Fund, and a gift from a grateful family. Additional U of M study authors include Susan Marino, College of Pharmacy, Masonic Cancer Center; Christopher Barkley, College of Pharmacy; Rory Remmel, College of Pharmacy, Masonic Cancer Center; Michaela Roslawski, College of Pharmacy; U of M Twin Cities student Ashwin Karanam; and Aden Gramling, University of Minnesota Physicians.



Source:
University of Minnesota
Media Contacts: 
Katrinna Dodge – University of Minnesota
Image Source:
The image is in the public domain.

Original Research: Closed access
“Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy”. Angela K. Birnbaum, Ashwin Karanam, Susan E. Marino, Christopher M. Barkley, Rory P. Remmel, Michaela Roslawski, Mary Gramling‐Aden, Ilo E. Leppik.
Epilepsia. doi:10.1111/epi.16093

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