Beyond the Smoke: Suppositories — An Innovative Delivery System

CRx has covered a lot of innovative cannabis administration methods, from metered-dose inhalers to topical creams and salves, and here’s another one: suppositories. Both rectal and vaginal suppositories containing CBD only or a combination of CBD and THC are available in certain markets. And while market share of this segment of the industry isn’t yet included in reports, the segment must be growing, because the number of products and brands available is on the rise. Cannabis suppositories are being marketed as a sexual aid to increase sensitivity and stimulation and for pain relief from other health issues. However, research is limited, and how and to what extent they work isn’t clear.

The cannabis market’s interest in suppositories may be ahead of its time when compared with mainstream pharmaceutical companies’ apparent disregard for the ancient method of administration. In fact, one researcher involved in the development of a novel anti-HIV drug noted that “virtually no rational pharmaceutical development of antiviral suppositories has been performed,” which he attributed to the lack of user acceptability.1 As with so many other advances that have emerged from the cannabis industry, this may open the eyes of medicine developers and patients alike.

The Basic Suppository: Rectal and Vaginal
Suppositories have been used to deliver medicine to patients for thousands of years. Some research has traced the first suppositories back to Ancient Babylonian culture, when healers used suppositories to treat hemorrhoids and other GI problems.2 Today, manufacturers of cannabis suppositories market them as powerful topicals that are applied internally.

Commercially available suppositories are characterized by a “bullet” or “torpedo” shape, a size of about 2 g, and base ingredients that may be cocoa butter, coconut oil, glycerinated gelatin, hydrogenated vegetable oils and hard fats, polyethylene glycols, and fatty acid esters of polyethylene glycols.1 Active ingredients such as cannabinoid distillates are added to create the final product.

Suppositories fall into two types: lipophilic and hydrophilic. Lipophilic suppositories melt at body temperature to release the drug into the body and are commonly used in rectal delivery. Hydrophilic, or water-based suppositories, are unaffected by body temperature and require water to dissolve and release the drug, which makes them more appropriate for vaginal delivery.1

Benefits of Cannabis Suppositories
While research in humans is lacking, anecdotal accounts from people using suppositories generally have been positive and consistent in reporting the lack of psychoactive activity or intoxication that’s typically caused by smoking or other cannabis administration methods. Users claim that even after insertion and absorption, they still feel clear-headed. This suggests that the suppository acts more like a topical with a local effect rather than providing a systemic dose as do transdermal patches or edibles. However, other patients report having a similar “head high” experiences akin to those when smoking or taking edible cannabis preparations. Therefore, it’s important for patients to experiment with suppositories at a time when the psychoactive effects of cannabis won’t interfere with their daily activities.

This unique administration method makes suppositories a viable alternative to medication delivery for patients who are experiencing severe nausea and/or vomiting, compromised esophageal or gastrointestinal tracts, and other conditions that make oral administration difficult.

Clinicians are also using suppositories to conquer common women’s health issues such as endometriosis, severe dysmenorrhea, cramps, pelvic pain, and even premenstrual syndrome. The root cause of many of these women’s health issues is thought to be inflammation, thus cannabinoids, especially CBD, may be used as an effective treatment. In addition, because the pelvic region houses a matrix of nerves that travel to the legs, spine, and colon, which all express concentrated cannabinoid receptors (CB1 and CB2) on which THC and CBD can exert their effects, suppositories may deliver the active ingredient closer to the source of pain.

Research
Clinical research on cannabis is lacking in general, but even more so in the novel preparation of suppositories. The earliest studies of cannabis suppositories were done to determine the bioavailability of cannabinoids in rectal administration. One study in 1985 found no circulating levels of THC in blood plasma after rectal administration of THC in rhesus monkeys, giving credence to the belief that suppositories that contain THC may not have a psychoactive effect.3

Much of the “research” into cannabinoid suppositories is being done behind closed doors with suppositories made at home and effects reported anecdotally. These patients aren’t necessarily worried about bioavailability of CBD or THC, or whether or how either enters the bloodstream; they are reporting that these products alleviate pain and discomfort in the lower body and enhance sexual pleasure.

Cannabis suppository leader Foria has a number of different products aimed at various conditions. The THC:CBD rectal suppository is marketed to help relax the anal sphincter before sex and minimize pain. In addition, patients are experimenting with these suppositories to relieve other lower-body issues such as cramping and pelvic discomfort, with reported good results. According to the Foria website, THC-rich suppositories (both anal and vaginal) yield better pain relief results than do CBD-rich products. Recently, Foria forged a partnership with Harvard neuroscientist Staci Gruber, PhD, to conduct a study intended to track women’s responses to CBD suppositories.4

Quite a bit of the cannabinoid suppository research has been done with a synthetic molecule called THC-hemisuccinate (THS-HS). THC-HS is readily absorbed into rectal mucosa and enters circulation as THC but avoids first-pass liver metabolism, which means it doesn’t convert into the more psychoactive THC metabolite 11-hydroxy-THC.3 One study determined that THC-HS from a suppository is 70% to 80% bioavailable, yet there were no reports of intoxication by test subjects.5 Further studies of THC-HS show that when rectally administered, it could improve symptoms of spasticity, rigidity, and pain while producing no measurable signs of intoxication.6 However, THC-HS is a patented molecule and can only be prepared with a license from the University of Mississippi.

How to Use Suppositories
The most important question to ask before recommending a suppository is “are you willing to try a rectal or vaginal suppository?” Not only is this a novel method of cannabinoid delivery but many patients also may not be comfortable with any medication delivered in this manner. Directions on how to insert suppositories correctly are easily found on the internet if patients want to do some investigation on their own. The second most critical message to patients who are willing to try suppositories is to ask plenty of questions before making a purchase. Common questions include the following:

• Is it to be used rectally or vaginally? While some products are interchangeable, some are formulated to work in one physiologic environment or another, but not both.
• What are the inactive ingredients?
• Are there different sizes?
• What is the cannabinoid profile?
• How should they be stored?
• Can they be cut in pieces?
• How long must the user wait after discharge before administering again?

As with any medical cannabis recommendations, it’s best to start low and go slow. If suppositories can be cut into pieces, start with something in the range of 30 mg of cannabinoids and work up from there. Effects can be felt within 10 to 15 minutes and last four to eight hours. One of the benefits of suppositories is the lack of intoxicating effects in most people, so the dose can be increased by 30 mg at a time over the course of a few hours to experience relief.

As with any suppository, there are drawbacks. Discharge is common due to the ingredients used to administer suppositories such as cocoa butter, which can be messy. They may also cause irritation, abdominal pain, swelling, and loose stools. Instruct patients to be aware of these potential side effects and stop using suppositories if they occur. Often these symptoms are caused by an inactive ingredient, so trying another brand may be the key.

Conclusion
Clinical studies suggest that THC isn’t bioavailable when administered rectally. Thus, it’s assumed that any effects reported by users are delivered through local, topical pathways. As with so much about cannabis medicine, far more research is needed to understand how cannabinoid suppositories work. To that end, because the majority of patients using suppositories do not report the intoxicating effects associated with other methods of administration, this may be a remarkable alternative.

— Bonnie Johnson, MS, RDN, HCP, is a registered dietitian nutritionist, food industry consultant, speaker, and certified cannabis consultant. She spends much of her volunteer time educating a variety of audiences about the benefits and potential risks of using cannabis to treat chronic pain, anxiety, insomnia, and other ailments. As a consultant, she works with the food and cannabis industries to bring science-based education to health care professionals and category-changing products to market.

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