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ROGER M. BRAUNINGER, Biosafety Program Manager, A2LA

Anyone coming of age in the ’70s and ’80s and having a “certain inclination” could have learned about cooking with cannabis from the European editions of a cookbook by literary maven Alice B. Toklas. The Alice B. Toklas Cookbook, first published in 1954, was a collection of traditional French recipes including what might have been one of the earliest instructions for “haschich fudge” (“which anyone could whip up on a rainy day”):

“Take one teaspoon black peppercorns, one whole nutmeg, four average sticks of cinnamon, one teaspoon coriander. These should all be pulverized in a mortar. About a handful each of stoned dates, dried figs, shelled almonds and peanuts: chop these and mix them together. A bunch of Cannabis sativa can be pulverized. This along with the spices should be dusted over the mixed fruit and nuts, kneaded together. About a cup of sugar dissolved in a big pat of butter. Rolled into a cake and cut into pieces or made into balls about the size of a walnut, it should be eaten with care. Two pieces are quite sufficient.”

Today the inclusion of cannabinoids into foods and beverages, in states where adult use of cannabis has been legalized, ranges from cannabis butters and oils to cannabis-infused wine and seemingly everything in between. It has even gone upscale with restaurant chefs creating tasting menus of all sorts of foods crafted with cannabis — although no chefs worth their herbs and spices would consider recommending that raw cannabis be added to baked goods as Toklas’s recipe suggests. Brownies however are acceptable.

Brownies are good delivery devices because they are baked. The main psychoactive ingredient in cannabis is THC (delta-9-tetrahydrocannabinol), which naturally occurs only in very small amounts in the plant. The form that predominates is Tetrahydrocannabinolic acid (THCA) or THC-Acid. THC-Acid has little binding affinity at the body’s endogenous CB1 and CB2 endocannabinoid receptors, so it has little psychoactive effect. The neutral, decarboxylated form does, but it needs to be “toasted” at about 250°F to decarboxylate the material to make it available for receptor binding.

Cannabis consists of more than 420 components and at least 60 pharmacologically active cannabinoids with the two best-described cannabinoids being THC and cannabidiol (CBD). Many may have valuable medicinal properties, and medical research in these areas is proving promising for a number of disorders, but most of the other compounds are not yet well understood, and their physical effects are largely unknown. CBD does not produce any of THC’s psychoactive responses and actually appears to block some of the effects of THC by acting as an antagonist at the CB1 and CB2 receptors.

The body reacts to ingested cannabis differently than smoked. With edibles, the onset of effects is delayed and peak concentrations in the bloodstream are lower, but the duration of pharmacokinetic effects (the high) are extended. This is due to the phenomenon, first-pass metabolism: for there to be an effect, the cannabis needs to go through the GI tract, then be shunted to the liver where it is modified for excretion and gradually absorbed into the bloodstream. This results in a smaller fraction of the ingested cannabis extracts that circulates to the brain. But both the GI tract and liver contain certain drug-metabolizing enzymes and some have an interesting effect. As one is digesting the cannabis-containing food, some of the drug-metabolizing enzymes are creating another potent psychoactive metabolite of THC called 11-OH-?9-tetrahydrocannabinol (11-OH-THC), which has a longer half-life than THC. Because both it and the remaining THC circulating in the bloodstream are psychoactive, the two, together, may significantly add to the level of effect.

In contrast, when smoked, THC is absorbed directly through the lungs bypassing the liver, so virtually no metabolism takes place before it reaches the bloodstream and brain. The THC then quickly distributes to other body tissues and only a small fraction of it remains in the bloodstream to be converted to 11-OH-THC and other metabolites.

Because THC is fat soluble (highly lipophilic), the duration of effect also can be impacted by the fat content, whether the food is saturated or unsaturated, and whether the individual has an empty stomach. Thus, the effect can be prolonged and can last for several hours as it is slowly metabolized. Edibles also create other safety concerns. Many pesticides and extraction solvent residues are fat soluble, so they, too, linger longer. Because of this most, states mandate that raw materials, extracts, and finished edible products undergo laboratory testing for pesticides, heavy metals, and microbial contaminants, as well as appropriate THC concentration. This brings a wrinkle into the laboratory where additional extraction and analytical methods must be devised to be able to test for these materials in the presence of fats and carbohydrates which can mask or otherwise impede analysis.

Thus, food producers, chefs — and the edibles consumer — need to keep in mind that judging the duration and peak effect of edibles is complicated, as it is impacted by not only the amount of THC but also the fat content of the food. And whether or not required by state law, testing is important, as other unwanted chemical compounds can remain throughout processing that may have negative impacts.