Grow Life 420: Across the Synapse - Special to Cannabis Culture

Across the Synapse - Special to Cannabis Culture

Medical Cannabis in Scotland

January 14, 2021

#KahliBuds #MMJ #CBD #THC

CANNABIS CULTURE – A look back to the mid 19th Century when cannabis extract (AKA ‘Rick Simpson Oil’) was being administered in the Edinburgh Royal Infirmary.

Scotland is making a return to growing cannabis, with medical production starting at Hilltop Leaf Ltd in Dumfries and Galloway, and the developments of farmers in Angus and Aberdeenshire working alongside the Scottish Hemp Association , Rowett Institute , SAOS and Rural Innovation Support Services to start growing hemp in 2021, this article takes a look back to the early days of cannabis being used as a medicine in Scotland. While evidence exists of cannabis being grown for industrial purposes in Scotland from around the 11th Century, the records of medicinal use start in the mid 19th Century, with the West being introduced to cannabis extract by Dr. O’Shaughnessys 1839 publication ‘On the preparations of the Indian Hemp, or ‘Gunjah’ (Cannabis indica), their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases’. At the time Doctors had no idea what the active constituents of cannabis were, but that didn’t prevent cannabis being used successfully as a therapeutic. Knowledge was built up through case reports, collated user experience and self-experimentation. It is striking how many things were ‘known’ about cannabis a century and a half ago but which have only been ‘proven’ in recent years.

To understand how cannabis was being dosed, we will look at all the relevant data, put observations in context, and try to get an idea of just how much cannabinoids were being administered to patients in Scotland in the mid 19th Century. We’ll take a look at documents from Dr. Christison, M.D, President of the Royal College of physicians, and Professor of Materia Medica in the University of Edinburgh, his 1850 Inaugural Dissertation, ‘On the Natural History, Action and Uses of Indian Hemp’, which was awarded a prize by the Medical Facility of the University of Edinburgh, and case reports.

For reader context, ‘Indian Hemp’ was the description for all cannabis coming from India, its not referring to hemp plants such as less than 0.2% THC ‘European hemp’ varieties, for example.

What quantity of cannabinoids were being administered to patients?

Here, we need to pull together a wide range of data points to make a reasonable assessment of the likely composition of these extracts. Dr. O Shaughnessy describes the process of making the preparations in 1839, of the same type that were used in Scottish hospitals.

“The resinous extract is prepared by boiling the rich adhesive tops of the dried gunjah in spirit, until all the reason is dissolved. The tincture thus obtained is evaporated to dryness in a vessel placed over a pot of boiling water. The tincture is prepared by dissolving three grains of the extract in one drachm of proof spirit.”

1 grains = 64.79mg (3 grains = 194.39mg)

1 drachm = 3.69ml

= 52.68mg of extract per 1ml of spirit

= 526.80mg of extract per 10ml (to use 10ml as a point of reference for a tincture. ‘Just over half a gram of extract per 10ml’)

Starting with 2 personal accounts of Dr. Christisons own self-experiments, the 1st of which he consumed ‘4 grains of Dr. Robertsons extract’ (just over a 1/4 gram of extract) around 3am which produced ‘cessation of pain, a pleasant numbness in the limbs, giddiness, a rapid succession of unassociated ideas, and impossibility to follow a train of thought, frequent intervals of sleep, and slight increase in the force of the pulse; at the same time felt no pain.’ He went on to describe feeling a bit lethargic until around 2pm the next day and that the symptoms ‘ceased entirely in a few minutes after drinking lemonade.’

In the second case report of self-experimentation from Dr. Christison, he consumed only 1/4 of his original dose, ‘1 grain of the same extract, dissolved in spirit’ a short time later, “I laughed heartily several times, answered questions incoherently, and immediately forgot what they were about, and what I had answered. Delightful reveries came over me, and whatever I look at became lost, as it were, in a maze: the lamp appear to be slowly turning around: and when I lost sight of this, the red lines on the paper of the room appeared to intertwine in a most beautiful manner. The most remarkable effect was the constant succession of new ideas, each of which was almost instantly forgotten. When roused to tea, I ate ravenously, without feeling satisfied. I slept soundly at night afterwards; and next day was stupid and forgetful, but was much improved by drinking lemon juice.”

It was noted amongst doctors at the time that there were a wide range of effects and therapeutic outcomes in patients. While some didn’t suffer any side-effects even at high doses, other case reports described profound effects produced by only a single grain of extract. In December 1845 in the Edinburgh Royal infirmary, a Highland Porter suffering from chronic asthma and bronchitis was give a single grain of extract under the care of Dr. Robertson. Around one hour later the patient called the nurse, as was noted, ‘he seemed to have awaked suddenly, and stared wildly about him… He informed them “that he had been transported to heaven”, and his language, usually commonplace, was quite enthusiastic.’

So, we can safely assume there was THC present in these extracts. With case reports using doses of 65mg of extract producing such results, there were clearly decent ratios of THC present. These effects do not match with case reports of using CBD dominant extracts in such doses.

In a letter dated 17th August 1849 sent to Dr. Christison, Mr Jameson, Director of the Botanic Gardens at Saharunpore gave an account of hemp growing in India, “In Kimaon and Gurwhal cannabis is grown in large quantities, partly in order to obtain its resinoid secretion, and partly for its bark, from which a strong coarse cloth, called ‘bungila’, is manufactured, for the dress of the poorer inhabitants, particularly through Gurwhal.” Also that “In October, in crossing the Himalayas from Almora to Mussuri, I have passed through dozens of villages 6000 to 8000 feet above the level of the sea, and seen hundreds of men, women, and children, all employed in making churrus. The plant grows to a height of from 10 to 14 feet.”

The Gurwhal region in North India has a long history of using cannabis as a multi-use crop for food, clothing and medicine, while the varieties in the South of India were primarily evolved for medicinal/drug use with consistently higher cannabinoid content and consistently higher THC:CBD ratios.

Mr Jameson is known to have sent various batches of ‘churrus’ to Dr. Christison in Edinburgh for experimentation, including a block from Yarkand, Thibet, ‘as big as two fists’.

By the geographical and morphological descriptions, we can rule out these plants being of the short Indica ‘Afghanica’ variety, typical of Afghanistan and Pakistan. We also know that European hemp varieties are not found growing wild in that region, and if the plant was grown for multi-purpose use including food and clothing then its metabolic potential wouldn’t solely be focused on cannabinoid production. We can therefore narrow the likely variety of cannabis being extracted down to the recently classified Cannabis sativa ssp. Indica var. Himalayensis. Formerly known as Cannabis sativa ssp. indica var. Kafiristanica, or Cannabis ssp. indica feral biotype. The new classification likely doesn’t go far enough to differentiate between ‘wild type mountain cannabis’ var. Himalayensis which was harvested for textiles, ‘bhang’, and ‘jungli’, a lower grade of charas, and the domesticated cultivars which are known to be higher yielding, can be even taller, and produce a superior grade of charas than their wild relatives. These varieties likely represent the ancestral source of what became cultivated Cannabis sativa ssp. indica var. indica, Southern Indian high THC/low CBD ‘drug varieties’, commonly referred to as ‘sativas’.

Wild-growing Cannabis sativa ssp. indica var. Himalayensis, Northern Pakistan, 2019. Photograph courtesy of Landrace Genetics.

A 2004 study of 157 Cannabis accessions from around the world found that the typical Cannabis var. Himalayensis/C.Indica feral biotype, contained 0.3-6% THC and 0.0-7.9% CBD.

A study in 2020 found the THC content in var. Himalayensis ranged from 0.06% to 9.3%, with varying ratios of THC/CBD being found.

Averaging the known data, we’ll use 6% total cannabinoid content in the biomass for calculations. Across the various studies of THC:CBD ratios there are a few things to consider, the 2020 study noted a typical ratio of 7:1 THC:CBD, and while some specimens have been found with up to 100:1 THC:CBD ratio, others have contained less than 0.3% THC total with a 1.28 – 1.56 THC:CBD ratio. The lower THC content, but still ‘THC dominant plants’ likely represent reacquired wild-type traits of East-Asian fibrous varieties. Asian hemp fibre varieties are often THC dominant, the opposite of European hemp.

Narrowing down the contents of the extract and tinctures being administered.

Various extraction methods, refinement techniques, and trials of extracts from different sources of plants were well understood at the time.

Notes from an extraction method developed by Dr. Robertson in Calcutta, India, and described by Dr. Christison state:

‘From a hundred weight of gunjah he obtained 8 pounds of extract’

A hundred weight = 50.8kg

8 pounds = 3.62kg

= 7.12% yield of extract

Dr. Christison commented in his 1850 dissertation on Indian Hemp, “the finest extract I have seen, is one prepared by Mr Robertson, professor of chemistry at Calcutta, which, however, is not in the market.” He went on

“the preparing of it cost him much time and trouble… he abandoned the attempt to manufacture it this way. Specimens, however, were sent for experiment to various parts of Europe, and, among others, to Edinburgh, for Dr. Christison; – This is now 4 years old, yields a beautiful green texture with rectified spirit, retains all its energy, and is more effective than the extracts of the shops generally seem to be.” He went on to document further issues he had with the texture and consistency of ‘the new extracts of the shops’ and concluded “probably feeble, if not inert”.

To read comments from 1849 that the new extracts in the shops are not up to the quality of an extract received in 1845, is quite the flash back for 2021 as shops in the UK are being pushed towards selling products containing only isolated ‘white powder’ CBD. A move away from the whole-plant only hemp extract market that existed 4 years ago, before CBD isolate dropped in price and started to dominate the supply chain.

When Dr. Christison extracted cannabis biomass in Edinburgh, he documented a 10% yield using the original method as described by Dr. O’Shaughnessy. Dr. Robertsons extraction method was noted to be superior, but with the lower yield and economics being the deciding factor, the finest extract was not made commercially available.

Dr. Christison was very familiar with the range of extracts available, as he noted of M. de Courtive of Paris experiments, that ‘6 grains of Paris grown ‘Indian hemp’ produced the desired effect, whereas ‘French hemp’ required 8 to 16 grains.’

In 1846, The Messrs Smith of Edinburgh, a Scottish based Pharmaceutical research company founded in 1815 and now one of the worlds leading manufacturer of opiate alkaloids, attempted to concentrate the cannabis extract down to its ‘active compound’, of which they assigned the name ‘Cannabin’, only with a query. The end result, after a somewhat “complex process”, was a 7-8% yield of extract, the same as Dr. Robertsons, and despite various processes to purify and concentrate the active compounds further, Dr. Christison described the results as “not appeared to me to make any material difference in the preparation… there is little advantage in substituting a well-prepared extract the resin obtained by a so operose a method as that of the Messrs Smith.”

Estimating cannabinoid content:

To start with we have Dr. O’Shaughnessys decription of the extract that it “hardens at 90° (32C); softens at higher temperatures and fuses readily”. “the extract softens at a gentle heat, and can be made into pills without any addition.”

Then we have Dr. Christisons description that

“good extract thus prepared, like all other good extracts that I have seen, has a dark greenish-black colour, a firm consistence… it softens in the hand, and adheres with great obstinacy to the fingers; it is not at all miscible with water. It forms a beautiful deep green tincture with rectified spirit, in which it is easily soluble.”

Hardens at 32C, firm consistence, softens in the hand…. These extracts were clearly not at the higher end of the potential cannabinoid concentration obtained by alcohol extraction. Higher concentrations, 70-80%+ cannabinoids in alcohol extractions would not be described in this way. A 70-80% cannabinoid purity extract dissolved into rectified spirit would not turn it deep green, but rather golden. Without access to freezers for extraction, and not filtering down to as small a micron as would be common place nowadays, and being described as ‘firm and dark green’, clearly some of the weight was made up with excess plant material. Going by the descriptions ‘adheres with great obstinacy to the fingers’ and being ‘easily soluble in rectified spirit’, we can also assume these extracts also could not be under 30% cannabinoids to fit these descriptors. Anything in the 20% range would have too much ‘other’ plant material present to be described this way, a resin in that cannabinoid concentration range would not be ‘easily soluble’ in rectified spirit. All considered, a reasonable assessment of the evidence would put these extracts in the 30-60% cannabinoid range. For calculations we’ll use 50% cannabinoid concentration as a working number.

If the reader thinks this range is unworkable for historical reference of therapeutic use, it is worth noting that now, in 2021 with Medical Cannabis being available once again on prescription in the UK, with (some of) the active ingredients being known and quantified, and that “every batch is exactly the same”, well, it is a plant and a wide range of analysis can be found online for what is actually contained in these products, so lets have a look.

Bedrocan, the first cannabis flower to be prescribed in the UK for vaping is labelled as ‘approx 22% THC’, with a previous batch coming in at only 17.6% THC, and another recent batch testing at 24.8% THC.

17.6% THC, Bedrocan sativa, batch number: 18H06EY18H28

24.8% THC, Bedrocan sativa, batch number: 20CO2EY20D01

Thats a difference of 72mg THC per gram, which in a 5g product container comes to a difference of 360mg THC content in a prescribed medical product, where every batch is ‘exactly the same’… Its worth noting these batches did pass all checks in the medical system for compliance of content and labelling. To give some consumer context to 360mg of THC, recent studies that propose to set a ‘standard THC unit’ say

‘On the basis of experimental and ecological data, public health considerations and existing policy, we propose that a ‘standard THC unit’ should be fixed at 5 mg THC for all cannabis products and methods of administration.’

While there are no end of problems with the proposed idea of setting a standard THC unit across all cannabis products; isolates, cannabinoid-rich/terpene-free distillates, and whole plant full-spectrum extracts, the example given of 360mg THC variability per product would equal ’72 standard units of THC’ difference in total content.

Another example would be the approx 14% THC Bedica indica, also prescribed in the UK, with a recent batch analysis testing at 16.5% THC.

16.5% THC, Bedica indica, batch number: 19J28FP19L17

UK medical cannabis patients have recently shared photographs on social media after receiving Medical Cannabis flowers with a package stating 20% THC, 4% CBD on the label, but a batch analysis showing it to actually be 21.3% THC and less than 0.1% CBD. Quite a variability of expected content to labelling.

Photographs courtesy of @Matthew420Ross

When a patients records are updated with the positive feedback, if they have been consuming a 213:1 THC:CBD ratio product, there’s little benefit in writing down the product was a 5:1 THC:CBD ratio as it said on the label, if it wasn’t that. Which just proves how herbal cannabis, and its extracts, can be used therapeutically even when batches have variability. Regardless what the label says, although that is a starting point, the user feedback loop is what guides the next step forward.

So all things considered, the estimated range of cannabinoids present in the extracts hypothesised in this article are clearly not unworkable…

Oils that are being made currently by mixing isolates of THC and CBD will be able to consistently hit an accurate milligram content every time on the label, other producers are likely reading this and would like to draw attention to their ‘spot on’ cannabinoid analysis, but all isolate blenders should take note; long before the (main) active ingredients of THC and CBD were discovered in cannabis, it was well understood that different extracts had different therapeutic properties. Some extracts were clearly superior to others with climatic region, soil content, and altitude all significantly influencing a plants cannabinoid and terpene production, and subsequent downstream therapeutic potential.

In a letter to the British medical journal dated June 1883, Dr. G.C. Wallich noted that “the fact which came to light was, that the therapeutic efficiency of the (cannabis) plant grown in the plains is very markedly inferior to that of the plant when produced in the hill districts.” Commenting that he had these discussions with Dr. W.L. McGregor in 1841 and 1842.

Just an observation at the time, but also proven in a recent study:

‘A mountain environment, with condition of UV length exposure and critical conditions, deeply influences the quantity of the inflorescence compounds, favoring the production of CBDA and cannaflavins. Information regarding the differences in industrial hemp inflorescences phytochemical profile supports hemp cultivation in mountain areas as a source of pharmacologically active cannabinoids, terpenes and cannaflavones that are considered also as promising nutraceuticals. Metabolomics approaches delineated this crop as resourceful and highly adaptable to the variation of climate/geographical conditions.’

Another thing we have to consider is that these extracts would not have been fully decarboxylated. All of the production descriptions involve soaking plant material in alcohol and using boiling water to remove the alcohol. Due to the lower temperatures involved in this process, we have to assume that these extracts could not have been fully decarboxylated, and would likely have only been around half-way decarboxylated, at most, meaning the majority of the cannabinoids present would be in their neutral acidic form as THCA, or CBDA. A 2013 study by Arno Hazekamp comparing the extraction properties of different solvents showed that ‘Most extracts contained only a small proportion of THC (5-10% of total THCA + THC content), as a result of the relatively low heat of max. 100°C applied during the evaporation, or extraction.’

As the extracts were not subjected to high enough temperatures to fully decarboxylate, but also factoring in various factors such as the handling of cannabis in India, transportation to Scotland, the opportunity for oxidisation that would otherwise be minimised in a modern lab experiment, the time required to boil off all the alcohol etc, we can safely assume the Indian Hemp extracts would be more than 10% decarboxylated, but still not fully ‘active’. We’ll hypothesis the extract was around half way decarboxylated for further calculations, with 50% of its THCA content being activated into THC, likewise with CBDA and CBD.

The above study also explains Rick Simpson’s original well-intentioned, but misguided advice about using the petrochemical solvent naphtha for extraction, which is worth covering here. Rick originally stated naphtha was the best solvent for extraction. Compared to other solvents ‘the naphtha extracted 3x times more THC’, based on seizures by local authorities. This only makes sense when you also look at the THCA content and realise its active THC content that’s being referred to. As the 2013 study discovered, the higher level of active THC in the naphtha extract, over 3x more than when extracted with ethanol extract, and 2x more than that of olive oil, was caused by reactions with other unknown chemicals and contaminants present in the naphtha. Most likely stabilisers present, acting as chemical catalysts causing decarboxylation at the lower temperature. Otherwise the ‘rice cooker’ method described by Rick, being under 100C will not achieve full decarboxylation. While most have moved on since then to using the oven method to decarboxlyate the plant material prior to extraction, it is always at the expense of terpenes in the trade off. Comparisons of different extractions in the same study show a significant loss of terpenes when achieving full decarboxylation.

Now to understand the context of just how much cannabis extract was being administered to patients in Scottish hospitals. To get a working number, the summary of this analysis so far comes to assume the extracts contained around 50% cannabinoids, with 50% of the cannabinoids present were likely still in their acidic form. Evidence suggests the plants used for the extracts were of mixed cannabinoid ratios, some 1:1, some CBD dominant, but typically THC dominant overall with 7:1 THC:CBD being a common ratio as noted in the 2020 study, so we’ll calculate it as 2 possibilities, 7:1 THC:CBD, and a less likely 1:1 THC:CBD ratio.

At 7:1 THC:CBD ratio, 1 grain weighing 64.79mg, extracted from var. Himalayensis, containing 50% cannabinoids, half way decarboxylated, would likely contain:

13.88mg THCA

13.88mg THC

2.31mg CBDA

2.31mg CBD

Or 1 grain at a (less likely) 1:1 THC:CBD ratio, would contain:

8.10mg THCA

8.10mg THC

8.10mg CBDA

8.10mg CBD

Start low and go slow?

Not according to Dr. Christison, as he stated “an error is, I believe, often committed in giving small doses.”

In November 1844, Dr. Lawrie of Glasgow wrote in to the “Monthly Journal” and described several cases where “alarming symptoms presented themselves… The individuals so affected were invariably females.” Professor Millar also made similar observations.

From a 2017 review of published studies, ‘These sex-dependent physiological effects may, in part, be attributed to sex differences in cannabinoid metabolism… but it is unclear what neurobiological sex differences contribute to this phenomenon and more studies are necessary.’

As Dr. Christison commented in 1850 “but perhaps enough has been said on this subject to prevent anyone from being taken by surprise by such occurrences.” He went on,

“it will not do, however, as a means of avoiding such consequences, to administer small doses. It appears to be much better to give full narcotic doses at once, by which means this stage of excitement will be as much as possible avoided.”

Patients were frequently treated with cannabis extracts for tetanus, with notes of using ’10 grain doses’, and “Another patient consumed 134 grains of the extract, and was ultimately discharged from the hospital cured.”

Case reports document a girl age 7 being given extract every 30 minutes, “and sometimes many hours in succession, doses of hemp sufficient to narcotise an adult… the most remarkable effect observed, was the tolerance of the remedy.”

In other patients, doses were continually increased until there was improvement, or when dosing reached the point there was clearly no reason to continue as it wasn’t working with that patient. Tincture was given to some patients building up to 100 drop doses, and dosed every half hour for several hours until they fell asleep.

In other cases of tetanus that were not successfully treated, Dr. Christison commented “the doses at first were evidently too small.”

Dr. J Russell Reynolds, physician to Queen Victoria, documented his experience after over 30 years experience administering cannabis to patients with comments of its wide reaching benefits ranging from “most markedly valuable results are obtained in certain mental conditions,” “in painful maladies it is very useful,” to “an attack of violent convulsions in an over-fed man, who has had a heavy supper, maybe stopped by a full dose of Hemp.”

When Dr. Ethan Russo publish his groundbreaking paper “Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects” in 2011, it was the first time the modern medical establishment took the concept of the entourage effect seriously, pending more data to be proven…

According to Dr. Christison in 1850, “Lemon juice is stated by various authors to have great influence in modifying the action. For my own observations, I am persuaded that it possesses this property to a high degree – that will arrest the action entirely in many cases, but not during the intensity of the effects, – and that, when it does not arrest it, great modification will be produced.”

It is clear these Doctors had a very practical understanding of the therapeutic application of cannabis extract, and a surprise to many how it was being dosed in Scottish hospitals, 170 years ago, for a variety of conditions. The fact that it was used very successfully while the contents were completely unknown, and is once again being used successfully by patients even if the labelling to contents have a 400x swing range on certain cannabinoids.

Cannabis is an amazingly versatile plant, and one that has had a long-standing, co-evolutionary, symbiotic relationship with mankind. This is just a continuation of that story, patients achieving therapeutic benefit when all other medicines have previously failed.