Cannabis suppository bioavailability: YES or NO?
Finding the ideal method of taking cannabis preparations is essential in every patient’s protocol and it varies depending on a lot of factors (type and location of disease, preparation accessibility, patient’s personal preferences, patient’s tolerability/sensitivity/endocannabinoid tone…).
The use of cannabis suppositories has lately seen an increase, especially in some parts of Europe. In recent months, there has been a debate on the internet, about the efficacy of cannabis suppositories.
There have been several online articles claiming that taking cannabis the rectal way was a good option, due to its high bioavailability and lack of unwanted side effects (1,2). The reasoning behind these claims was that cannabinoids in suppositories, if inserted correctly, bypassed the first-pass metabolism of the liver and went directly into the bloodstream.
I also followed interested this theory and wrote an article on this topic : “Cannabis suppositories: Taking your medicine down under” , which I am willing to update with this in-depth report.
Suppositories
Suppositories are defined as solid dosage forms intended for insertion into body orifices (rectum, vagina, urethra) where they melt, soften or dissolve and exert a systemic effect.
Rectal suppositories are conically shaped, 2-3 centimeters in length and weight 2 grams. They are placed into the rectum (the last 15-20 cm of the gastrointestinal tract) where they can be absorbed by 3 separate veins; the lower, middle and upper rectal (haemorrhoidal) veins. The lower and middle rectal veins drain directly into the general circulation, while the upper drains into the portal vein which flows to the liver.
Figure 1: The lower (inferior), middle and upper rectal (superior) veins
Several physiological (quantity of available fluid, properties of rectal fluid, contents of the rectum, circulation route) and physicochemical drug factors (drug solubility in the vehicle, particle size, nature of the base, spreading capacity) have an effect on rectal absorption.
As an example, regarding drug solubility in vehicle, substances that are highly soluble in the vehicle (like THC in lipid bases) tend to have a slow release rate into the rectal fluid.
The research
When we evaluate a certain method of taking medicine, one of the important parameters is absorption effecting the systemic bioavailability; how much of the drug is actually getting into our bodies.
It is usually measured in the blood as a percentage of the taken drug. Different drugs/molecules have different properties, affecting their absorption rates and bioavailability.
Most of the studies on cannabinoid rectal absorption were done on delta-9-trans-tetrahydrocanabinol (Δ-9-THC) or other tetrahydrocannabinol (THC) derivatives.
Δ-9-THC, as most cannabinoids, is highly lipophilic (“likes” fats) and essentially water-insoluble (3). A study published in the mid 80’s, done on monkeys, has shown that Δ-9-THC taken via suppositories (in a lipophilic or hydrophilic base) was not detected in the blood leading to the conclusion, that it was not absorbed via the rectal route (4).
This has led to the search of more appropriate derivatives of Δ-9-THC, that would have better bioavailability. At the beginning of the 90’s, El Sohly’s team found that Δ-9-THC hemisuccinate (Δ-9-THC-HS) had 13,5% bioavailability in suppositories administered to monkeys (5). Δ-9-THC hemisuccinate, a prodrug hemiester of Δ-9-THC, is prepared in laboratory and it is not present in cannabis or cannabis extracts.
The same team also tested different types of Δ-9-THC esters (hemisuccinate, N-formyl alaninate, N-methyl carbamate and methoxy acetate) in different suppository bases, this time on monkeys and dogs. The results showed that Δ-9-THC-HS had the highest absorption rate and the bioavailability for each base was found to range from 52-61% and 13,5%, in dogs and monkeys respectively.
Δ-9-THC-HS was then tested on humans (3 females) and compared to an oral formulation of Δ-9-THC in sesame oil (Marinol ®). The results showed that “areas under the curves for plasma THC were more than 30-fold higher than after oral dosing” (6).
A pilot study done on two patients evaluating the effects of oral (Marinol ®) or rectal (Δ-9-THC-HS) administration of cannabinoids concluded that the bioavailability of the rectal route was approximately twice that of the oral route due to higher absorption and lower first-pass metabolism (7).
An animal study showed analgesic and reinforcing properties in adjuvant-arthritic rats suggesting that “Δ-9-THC-HS has therapeutic potential and is unlikely to possess an abuse liability when used in the context of chronic pain” (8).
Figure 2: Δ-9-THC (left) and Δ-9-THC-HS (right) structure comparison
Several studies have been published on methods of stabilizing (9,10,11,12) and enhancing (13) Δ-9-THC-HS prodrug which led to a number of patents over the years (14,15).
A 2014 study, looking at the release rate of cannabinoids from suppositories, using plant extract in theobroma oil (cocoa butter) as the suppository base with different percentages of polysorbate 85, found that “release profile of marijuana from the suppository bases was generally low” ranging from 0.0030 to 0.065 % at 150 min. It should be noted, that the extract was prepared using fresh cannabis leaves and was done in a laboratory setting (16).
If we look at review studies of cannabinoid pharmacokinetics, under rectal administration, they all cite studies and bioavailability of Δ-9-THC-HS (17,18).
Patient cases and anecdotal evidence
We have had some very interesting results with suppositories in different types of health problems. Whole plant cannabis extract suppositories, with different ratios of THC and CBD, have been very efficient in localized anal or vaginal health problems.
Regarding the bioavailability, we have had some reports of some patients experiencing classical THC side effects. A particular case of a cancer patient comes to mind, where she took one suppository and was high for 3 consecutive days. This is an extreme case, where we have to account the patient’s high sensitivity to THC, but it shows that there definitely was absorption into the blood.
What are suppositories good for?
Here are a few examples of efficacy with cannabinoid suppository use I came across during my practice:
- Haemorrhoids – with protocol of only a few suppositories we have seen very good results in haemorrhoids, with patients reporting that they were completely free from any symptoms. Even patients with chronic haemorrhoids, who have tried all the classical treatments and had undergone surgery, without any results, cannabinoid suppositories were effective and got rid of the problems.
- Inflammatory bowel disease – a patient had a colonoscopy and the doctor diagnosed it as Crohn’s disease. After taking 10 suppositories he had another colonoscopy and the doctor could not find any signs of the disease. In other cases of IBD this method has been very successful, due to the fact of applying cannabinoids right were the problem occurs.
- Cancer – in 2 cases, patients using suppositories have had positive results with negative CT scans of existing tumors. In both cases however, they were also using oral/sublingual extracts so it is hard to make any conclusions.
- Vaginal suppository – while this article focuses mainly on the rectal route of administration, vaginal suppositories are also showing positive results. They are very effective in alleviating pain, such as menstrual cramps, inflammation and have an antibacterial effect. Women with hormonal imbalance problems, such as lack of regular menstruation, have also had great results in reinstating a normal balance.
Conclusions
The topic of cannabis suppositories is a hot one, with patients and caregivers who swear by them and others who are not so convinced.
The truth is that we don’t have any real studies, done with natural cannabis extracts in suppositories, evaluating all the variables (different cannabinoids, different suppository bases, different cannabinoid concentrations, different rectal insertion lengths…) measuring the systematic bioavailability of cannabinoids in the blood.
This does not mean that patients shouldn’t use them, especially if they have good results with this method. Suppositories for localized problems are extremely effective and have shown very good results in practice.
On the other hand, using only suppositories as an efficient systemic absorption method is at least questionable if not irresponsible. In diseases such as cancer, where usually higher doses of cannabinoids are needed, cannabis suppositories should always be used in conjunction with other more proven methods, such as sublingual drops.
This is a great time for cannabis research and the number of studies on cannabis/cannabinoids/endocannabinoid system is bound to surpass 3000 for 2016 – that’s 8 new studies per day!
We can also learn a lot from patients/doctors/caregivers experiences with treating specific ailments with different methods of cannabinoid intake.
So what are your experiences with cannabis suppositories? Have you ever tried a cannabis suppository? If you have any, I’d invite you to share them with us in the comments section.
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References:
1. Backdoor Medicine: How Cannabis Suppositories Can Save Lives http://cannabisdigest.ca/cannatory/
2. Cannabis Suppositories: Is the Posterior Superior?
14. Stable suppository formulations effecting bioavailability of Δ9 -THC. US 5508037 A
15. Method for effecting systemic delivery of delta-9-tetrahydrocannabinol US 4933363 A
18. Huestis, M. A. 2007. Human Cannabinoid Pharmacokinetics. Chemistry & Biodiversity, 4(8), 1770–1804
Well this was a plain as mud. So I still don’t know if I should be using the suppositories or not. I have used them for several months because I heard of two people who seem to have been cured of cancer using them. My blood pressure got much better and my heart rate came down to where it should be. However I was also using a bit sublingually.
Hi Fran,
This article does not attempt to substitute your physician in taking the decision over the best administration form of cannabinoids for treating your condition. The aim of this article is discussing the role of rectal administration as “locally acting” rather than “systemic”.
I hope this helps!
Viola
“Exceptional content quality and corroboration!”
Thank your for leaving us a feedback Geoffrey, we truly appreciate it!
I used 50/50 THC/CBD 1/2 gram suppositories once daily for 2 1/2 months along with a strict vegan diet – I took none orally – I have prostate cancer and my PSA still went up. I don’t think they worked for me.
Thanks a lot for sharing your experience with other readers- Have you decided to switch to another way of administration?
Using THC and CBD at the exact same time is probably counterproductive. Mara Gordon has been treating cancer patients and collecting data for over a decade. AuntZelda) She notes in many of her seminars that CBD counteracts THC and advises to dose THC and CBD at least 2 hours apart from each other. It may very well be that you had inadvertently cancelled the effects by taking them together. Of course, it may also still be that that rectal absorption is inefficient.
“On the other hand, using only suppositories as an efficient systemic absorption method is at least questionable if not irresponsible. In diseases such as cancer, where usually higher doses of cannabinoids are needed, cannabis suppositories should always be used”
This statement is contradictory to all the info presented in the rest of the article. What is the basis for the ‘questionable if not irresponsible’ statement?
I have prostate cancer; been taking 1g/day RSO both orally and rectally for the last 2.5 months as of Jan 17 I switched from oral to rectal so that I could function better. This article has my wife panicking and I need better data. Can you help?
Hello David,
Thanks for writing in. First of all let me clarify that the most important voice in each specific patient’s treatment is that of his or her MD. So I am confident that your doctor switched you to only 1 method of administration for specific reasons.
What the author meant is that there is not enough scientific evidence for rectal administration to be considered efficient for systemic absorption.
Cannabis is used both locally and systemically, and this article is clarifying that in the case of cannabis suppositories they are to be considered as locally acting.
I hope this clarifies your doubts, I wish you and your wife all the best.
Viola