Weekly Dose: cannabis has been used medicinally for millennia, why is legalising it taking so long?
Senior Lecturer, University of Sydney
Betty Chaar does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.
University of Sydney provides funding as a member of The Conversation AU.
The Conversation UK receives funding from these organisations
Cannabis has a long history, and its misuse hangs over it like a dark shadow.
Cannabis is used recreationally for its euphoriant effects. But it also has the potential for effective therapeutic use. With mounting evidence for its medicinal benefits, there have been increasing calls for its decriminalisation and legalisation.
Used for centuries across various ancient cultures both medicinally and recreationally, cannabis has its roots in Central and South East Asia from as early as the third millennium BCE.
The use of cannabis for purposes of healing predates recorded history. The earliest written reference is found in the 15th century BC Chinese medicine list, the “Rh-Ya”.
Cannabis pollen was found on the mummy of Ramesses II, who died in 1213 BC. Prescriptions for cannabis in Ancient Egypt included treatment for the eyes (glaucoma), inflammation, as well as administering enemas.
In ancient Greece, cannabis was used as a remedy for earache, swelling, and inflammation. The history of mankind has a plethora of evidence for the use of medicinal cannabis dating back centuries.
It was used recreationally by the ancient Chinese and by Hindus of India in religious celebrations of the God Shiva. Around this era, the use of cannabis also expanded in ancient Egyptian ceremonies and swept throughout the Middle East as its psychoactive effects became popular.
Cannabis began to appear in conventional Western medicine in the 19th century, when its plant-derived formulations were believed to relieve pain, inflammation, spasms, and convulsions.
Today, evidence relating to medicinal benefits of cannabis in many patients is still more anecdotal than evidence-based, but there is mounting clinical evidence to support the claim that cannabis has significant beneficial effects on various conditions.
How it works
Marijuana or cannabis are general terms used interchangeably to describe preparations of the cannabis plant. Cannabinoids are the active constituents of cannabis, with at least 60 of these constituents believed to have some pharmacological activity. The main psychoactive component is 9-tetrahydrocannabinol (THC).
Other more promising components include the non-psychoactive, anti-anxiety agent and antispasmodic cannabidiol (CBD), as well as cannabinol (CBN), which has non-psychoactive, anti-inflammatory effects.
THC acts on the CB1 cannabinoid receptors in the central nervous system, and is known to cause sedation, amnesia and appetite stimulation. It affects memory, motivation and pleasure. CBN is known to act on CB2 cannabinoid receptors, which influence our immune system and inflammatory activity, while CBD’s mechanism of action is still not fully understood.
Relatively few studies have investigated the evidence behind the medicinal use of cannabis. In a recent review of the literature a total of 27 studies, all conducted after January 2000, were found. The reviewed articles explored cannabis use for the treatment of various symptoms, including pain, nausea and vomiting, anorexia, sleep, muscle spasm, urinary tract symptoms and inflammatory bowel disease symptoms. The majority of the studies found medicinal cannabis improved symptoms.
What it’s used for
Medicinal applications of cannabis include pain relief, treatment of multiple sclerosis, inflammatory bowel disease, cachexia (weakness from chronic illness), cancer-induced nausea and vomiting, Parkinson’s disease and potentially, sleep apnoea. Submissions for further investigation have been made and clinical trials are currently being undertaken to investigate the benefits of medicinal cannabis for epilepsy in both adults and children as well as terminal illnesses.
Recreationally, cannabis use or abuse is grounded on the psychoactive effects of the THC component, which cause euphoria, paranoia, sedation, cognitive impairment, and feelings of light-headedness, giddiness and relaxation.
Other more brief side effects include blurred vision, sedation, increased heart rate, and bloodshot eyes. Cannabis is also known to stimulate eating by activating sections of the brain that regulate food intake (the hypothalamus), and make food seem more palatable (the limbic system). It also instigates hunger from within the stomach and intestinal tissue.
Because of the relatively low number of cannabinoid receptors in the brain, overdosing on cannabis is virtually impossible and its potential to be addictive is based on the presence of THC. THC affects the reward centre of the brain, leading to a surge of dopamine – the pleasure chemical.
When using CBD or CBN extracts, these side effects on cognition and addiction are absent. Finding a standardised formulation that optimises the medicinal effect while minimising adverse effects is a difficult quest in the manufacturing and development of all medications.
The Australian Crime Commission estimates the street price of a gram of cannabis ranges between A$12 and A$50.
The projected costs in pharmacies are unclear, but based on pharmacoeconomics and calculations for currently registered products such as nabixamols (mouth sprays for treatment of spasticity in multiple sclerosis), it would cost A$15,000 to A$45,000 for a year of effective treatment.
If it was subsidised by the Pharmaceutical Benefits Scheme, the net cost per year is estimated to be A$10 million to $30 million, while the average cost to a patient is estimated to be around A$500 to A$800 a month.
These projections, however, are likely to be exaggerated, with current compassionate access schemes and clinical trials providing products with no charge. As awareness increases and legislative procedures made clearer, the pricing is also likely to drop.
In Australia, the Therapeutic Goods Administration has approved the man-made Dronabinol (for the treatment of anorexia in HIV/AIDS and chemotherapy-induced nausea and vomiting), Nabilone (also for chemo-induced vomiting) and Nabixamols.
Countries including the United Kingdom, Denmark, Czech Republic, Austria, Sweden, Germany, and Spain, as well as 23 US states, have all formally approved the use of cannabis-based products, thereby decriminalising its therapeutic use. However, cannabinoids generally remain illegal everywhere else in the world.
Earlier this year, the Victorian government passed the Access to Medicinal Cannabis Bill 2015 as a plan to have medicinal cannabis available by 2017. Victoria, along with Queensland, joined NSW’s clinical trials into the cannabis-based drug Epidolex, with a focus on children with epilepsy, as well as a trial for the terminally ill taking place in Newcastle’s Calvary Master Hospital.
In February, the Australian Federal Parliament passed national legislation to allow the cultivation of cannabis in Australia for medical or scientific purposes, described by the health minister as:
paving the way for the use of medicinal cannabis by people with painful and chronic illness.
As of July 2016 the Therapeutic Goods Administration rescheduled cannabis from a prohibited substance (schedule nine) to a controlled drug (schedule eight), and cannabidiol became a prescribed substance (schedule four).
The greatest change occurred almost overnight in New South Wales, when The Poisons and Therapeutic Goods Amendment Regulation 2016 was implemented on August 1, 2016, allowing NSW doctors to apply for an authority to prescribe unregistered cannabis-based products for patients with unmanageable conditions who have exhausted all commercially available treatments.
Cautious progress has been made in making medicinal cannabis available and accessible in Australia; however, it is still a confusing tangle of state and federal legislation.
Pharmacy honours graduate Sami Isaac also contributed to this article.
* The graphic has been updated since publication to better relfect the classification of cannabidiol.Cannabis has a long history, and its misuse hangs over it like a dark shadow.
Recreational Rectal Use of Cannabis (Or, What I Did for Science)
The scientific and anecdotal reports on rectal cannabis use are surprisingly conflicting. Sometimes, the best way to research something is to do it yourself. For science, for Sensi Seeds, for journalistic integrity, and for pure fun, I tried a cannabis suppository and wrote about the results.
Recreational rectal use of cannabis is not a subject I’ve ever heard discussed. Vocal proponents of every other kind of cannabis ingestion can be found everywhere, from internet forums and international hemp fairs to coffeeshops and any given living room on a Friday night. The subject of savouring a potent high by inserting suppositories, however, has not been broached (at least with me). Is rectal cannabis the last taboo of recreational use? Does it even work? There was only one way to find out.
I’d never put cannabis, nor indeed any drug, in my nether regions before. I am familiar with the concept, but I’ve never been moved to try it.
When I was a joint smoker I enjoyed the ritual of making the perfect, tasty, smooth-burning cone. I imagine there’s an element of ritual in rectal cannabis use if one does it frequently enough. However, it’s unlikely to be the sort of thing you can take 20 minutes over in a roomful of friends whilst drinking tea.
Luckily, some friends are closer than others, and I was able to enlist a lab partner for my first foray into this brave new world.
Step one: Get some suppositories for recreational rectal cannabis use
Cannabis suppositories are not a product that you can buy in a coffeeshop, nor a pharmacy, even in Amsterdam. Luckily I was able to obtain some (from a source who wishes to remain anonymous). They were made from butane-extracted whole plant concentrate in a base of coconut oil, giving them a pleasant, almost chocolatey smell, rather like spacecakes. They weighed two grams each.
I had them tested and the results showed 16% THC and 1% CBD, which would definitely give a psychoactive effect if taken in any way that I was familiar with.
Having procured cannabis suppositories, our preparations were twofold: the classic ‘set and setting’. The former consisted of research. I found practical tips, including ‘lie on your side and bend one leg to make insertion easier’ and ‘don’t pass wind for at least 15 minutes afterwards’.
I found anecdotal reports: “For me, music starts playing in my head about 1 minute after “dosing”,”; “Within minutes I could feel a warm, pleasant sensation washing over my entire pelvic region”.
And I found science which said maybe it shouldn’t work at all.
What is the science behind using cannabis rectally?
According to Allan Frankel, MD, who has researched and written about rectal absorption of cannabis, nothing was felt by his test patients when they tried cannabis oil in cocoa butter. Analysis of their plasma revealed negligible THC and CBD levels. According to “Practical Pharmaceutics: An International Guideline for the Preparation, Care and Use of Medicinal Products”, the rectum does not absorb fats efficiently.
Any active substance in a suppository must first dissolve into the aqueous mucus that lines the rectum, and then pass into the bloodstream. It cannot be absorbed directly by the membrane without traversing the aqueous mucus layer.
Therefore active substances that are themselves lipophilic (such as cannabinoids) should not be combined with a fatty or oily carrier if they are intended for rectal use, as this will reduce their overall absorption. Since virtually every cannabis suppository I found mentioned online was in a fatty base (as was mine), this should have impaired their efficacy.
Where Did 420 Come From, And Where Is It Going?
The rectal veins – superior, middle and inferior
Assuming that some of the cannabinoid content makes it through the mucus, it then circulates either via the inferior and middle rectal veins into the inferior vena cava, bypassing the liver; or via the superior rectal vein to the liver where it is ‘first pass’ metabolized.
It was thought that the lack of psychoactivity resulted from THC missing the liver and therefore not metabolizing into 11 hydroxy delta-9 THC (11-OH-THC). This metabolite is more potent, and stays in the system for longer, than THC. It also crosses the blood-brain barrier more easily. Interestingly, the effect of many drugs is reduced by first pass metabolism, but not cannabis!
Large amounts of 11-OH-THC are produced when cannabis is eaten (although the unmetabolised THC has a low absorption rate), so this metabolic process determines much of the strength of the same dose when ingested in different ways. In other words, exactly the same dose of cannabis will produce different effects depending on whether you vape it, smoke it, eat it, or insert it into your rectum.
The most recent scientific research on the rectal absorption of THC was published in 1991, and used crab-eating macaque monkeys. (People to whom I’ve told this have said “poor monkeys!”, to which the reply is, have you seen what else they do to monkeys? These monkeys are the lucky ones.)
Results showed no rectal bioavailability of THC, but when the cannabinoid was processed to create a combination with the molecule ester hemisuccinate (THC-HS), the bioavailability shot up to 13.5% and the mean residence time of THC in the blood was 5.8 hours. THC-HS is water-soluble, which is why it dissolves into the aqueous mucus.
Back to my personal rectal cannabis experience
What all my theoretical research came down to was basically “anecdotes say something might happen, science says nothing should happen”. This being as far as I could get with ‘set’, I moved onto ‘setting’.
We put mattresses on the living room floor and made sure there were enough drinks and munchies on hand. I had music, films, and interesting picture books to stimulate us if needed. I considered lighting some candles, figuring I should make it as nice an experience as possible after subjecting my lab partner to descriptions of animal experiments and rectal aqueous mucus, but fire and altered states don’t mix so I just turned the lights down.
To give an accurate report as possible, we had abstained from any other drugs (including the legal ones) and I set my phone to beep at half-hour intervals so I could chart the experience.
We toasted each other with the large, slippery, dark green bullets. First lesson: insert them as soon after removal from the fridge as possible, because fingertip heat alone is enough to start them melting. However, this means they are basically self-lubricating, which isn’t a bad thing. We lay down, me on my back and my lab partner on his side, and waited.
After half an hour, I felt quite giggly. This could have been the beginnings of a high, or the incongruity of live-tweeting rectal cannabis use as part of my job. In response to a tweet asking me how it was going, I attempted to analyse what I was experiencing.
There was a mild tingling sensation, not unpleasant, around the ground zero area of application. I wasn’t able to say for sure if there was any psychoactive effect. My lab partner had fallen asleep, but he had travelled overnight from London to Amsterdam and arrived that morning. The data was inconclusive thus far.
6 Differences Between Medicinal and Recreational Cannabis
One hour into the experiment: getting high
My lab partner was still fast asleep and I was explaining to people on Twitter that I didn’t have IBS or IBD, this experiment was purely for research. A feeling of deep relaxation suffused me, especially my legs and pelvic area. I believe the use of suppositories to ease menstrual cramps could be very effective, based on this. I felt extremely tranquil, but not sleepy, and decided to finally get up and go to the kitchen for a change of scenery and to see if any psychoactive effects made themselves known.
They did. Once in the kitchen, the munchies kicked in with a vengeance and I noticed that colours and patterns were enhanced. I heated up some soup; flavours were enhanced too. I giggled to myself thinking about the great Dr Lester Grinspoon’s realisation that he was having his first cannabis experience when the pizza he was eating became the best he’d ever tasted.
Despite being a clearly recognisable cannabis high, what I was experiencing was unlike what I’ve felt when eating, smoking or vaporising it. My head felt clear and I felt peaceful yet alert; a sativa type of high without the soaring headrush or potential confusion.
It was extremely enjoyable and not at all overpowering, yet I was definitely in an altered state. The dragon trees in my living room looked fascinating. Getting back under the duvet was lovely. I felt no need for additional entertainment. There was an opiate-like quality to the contentment and relaxation, but no nausea or feelings of disassociation.
An hour and a half in: definitely high
I was still feeling the same effects, which seemed to have hit a plateau rather than fading or intensifying. My lab partner woke up and said he wasn’t sure if he was feeling anything apart from very relaxed, but he definitely felt like eating something. He just wasn’t sure what. (In retrospect, this was a total giveaway that he was experiencing the effects!) The following conversation took place:
“Is it chocolate?”
“Is it oatcakes with vegan cream cheese?”
“Is it… (I am having trouble remembering what else there is to eat) …is it tomatoes?”
“I don’t think so.”
“Ooh, is it pineapple soy yogurt?”
“YES. Yes, it is. Oh yes.”
“We are definitely high.”
We devoured a litre of said yogurt in under three minutes. It tasted fantastic. Then we lay back down and discussed the high. It was strong but not psychedelic, and deeply physically relaxing. The best analogy is that of lying in a warm bath that you don’t want to get out of. All muscle tension was dissolved.
Alert, talkative, and surprisingly fragrant
We felt warm and heavy but not sleepy, and the effect seemed to end at the upper neck – literally as though lying in a bath with only your head out of the water. However, it was not a ‘couchlock’ stone. We remained alert and talkative. Although the effect was powerful, it was not at all disorienting or overwhelming.
(There was one additional fact that I was not expecting. I hadn’t read about it anywhere during literally hours of research. So, dear reader, I will share it with you. After eating, the digestive system starts up. This can lead to passing wind. And if you’re experimenting with rectal use of cannabis, this causes your wind to smell like a growroom of strong sativas just before harvest. You’re welcome.)
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The following day: Still high
It was also very, very long-lasting. Neither of us use cannabis regularly anymore and consequently we both have low tolerance; even so, I was not expecting to still be high the next morning. After I left for work, my lab partner had a large breakfast and went back to bed.
By the time he texted me at 15:00 to say he had just woken up and could I get some more pineapple yogurt, the effects I had felt had almost completely worn off. It took him several more hours to feel completely back to normal. This makes rectal use of cannabis by far the most economical method I’ve tried.
More research is needed on the rectal use of cannabis
Based on my research, what conclusions can be drawn? Firstly, there is no way that we were experiencing a placebo effect. I’ve used enough cannabis to know the difference. Secondly, although I had no way of measuring THC in our blood plasma, I can assure you that there was plenty sloshing around our endocannabinoid systems.
So how did it get there? It’s fairly safe to assume that at least some THC entered the superior rectal vein and achieved first pass metabolism into 11-OH-THC. I was aiming for this to happen, so I literally aimed for it (unlike medicinal users who would presumably keep the suppository lower in the rectum to avoid it).
It might be possible that the effect was so long-lasting because any THC missing the first pass when it initially entered the bloodstream via the inferior and middle rectal veins would eventually reach the liver. If this is so, a second phase of metabolism into 11-OH-THC could have taken place long after the initial dose.
However, for the THC to get to any of the rectal veins, it still needs to traverse the aqueous mucus layer. As previously stated, this shouldn’t be possible without the presence of the hemisuccinate ester. Could it be that some part of the process of making the butane-extracted concentrate creates THC-HS, or a similar enough ester or analogue to permit absorption to occur?
The experiments on the macaque monkeys used THC only, not whole plant extract. Could the presence of other cannabinoids, the ‘entourage effect’, make the crucial difference? However, Dr Frankel’s studies used full spectrum cannabis oil in cocoa butter, and that did not seem to work. The doctor himself concludes that more research is needed in order to take full advantage of this delivery method.
Benefits of rectal cannabis use
Having tried it, I can think of various benefits for both medicinal and recreational rectal cannabis use. There’s the long-lasting deep relaxation, which would definitely relieve pain and muscle tension. The extended ‘munchies’ effect would doubtless aid anyone who needed to gain weight, plus the delivery method means that there is no risk of vomiting up oral appetite stimulants. The amount needed for an effective dose is small, and the dosage is easy to control.
There is also the advantage over edibles (such as cake or sweets) of it being highly unlikely that someone will accidentally insert a cannabis suppository thinking it is a harmless treat. There are numerous tales of people eating ‘medibles’ by accident, and they seldom end well. However, in all my years of psychonautics, I have never heard of anyone casually inserting a random suppository they found lying around.
Work the following day was a little more challenging than usual, but by no means impossible. I would not have wanted to drive or operate heavy machinery, but the clarity of the high was fine for writing, interacting with colleagues, going to the shops, and cooking dinner. For people who need effective pain relief without being incapacitated, this would be ideal.For science, for Sensi Seeds, for journalistic integrity, and for fun, I tried a cannabis suppository and wrote about the experience. ]]>