Day: October 7, 2026

Open a pharmacy reference from 1918 and look up the dose of cannabis tincture. Here is what you find: “Dose, ten to thirty minims (0.6–1.8 mils), to be gradually increased until some effects are experienced.” Read that again, because two things are wrong with it as a dose. The first is the range. Ten to thirty minims is a threefold spread. Imagine a paracetamol box telling you to take between one tablet and three. The second is the instruction that follows. Gradually increased until some effects are experienced. That is not a dose at all. It is an admission, politely worded, that nobody knew the dose — and an instruction to find it by trial, on the patient. Eli Lilly’s own handbook for physicians used almost identical language for its cannabis preparations: start low, and increase until the desired effect is produced. This wasn’t carelessness. It followed inevitably from a problem we covered in our article on what was actually in a bottle of cannabis medicine: until 1940 nobody could measure what was in it. And if you cannot know a batch’s strength, you cannot print a number. The only honest thing left to say is work it out as you go. What follows is how the profession lived with that for a hundred years — and what, exactly, changed. 1. The Instruction, in Four Versions The titration instruction shows up wherever cannabis was dosed, phrased slightly differently each time. The 1918 United States Dispensatory on the fluid extract advised starting with one or two minims and increasing daily until some effect was obtained. On the tincture, ten to thirty minims, gradually increased. In Dublin in 1851, Michael Donovan of the Apothecaries’ Hall put it more fully than anyone: “The most prudent mode of proceeding is to begin with a small dose, and slowly increase it night, noon and morning, until the pain give way, or until it be proved that it will not give way, even when the sensorium becomes affected.” That’s a complete clinical protocol in one sentence. Start small. Increase on a fixed schedule. Stop when the pain goes — or when it’s clear it won’t, and the patient is getting woolly instead. And in Ohio in 1860, a state medical committee collected prescribing habits from physicians across the country. Dr Buckingham gave one or two grains every hour until the pain was relieved. Dr Dalton started patients at twenty drops of tincture three times daily and worked up to a hundred. Twenty drops to a hundred drops. A fivefold range, inside one doctor’s practice. 2. Why They Had No Choice The reason is in that Ohio report too, stated more bluntly than most period sources manage. The committee’s chairman, Dr R. R. McMeens, wrote: “To the impurity of the hemp, is to be attributed the diversity of opinion as to its operation and benefit in disease.” In other words: doctors disagreed about whether cannabis worked because they were not all using the same thing. One physician’s success and another’s failure might both be accurate reports — of two different substances sharing a label. Buckingham put the same point in practical terms. The activity of the medicine, he said, depended very much upon the parcel from which it was taken. The parcel. Not the plant, not the preparation, not the dose — the particular batch that happened to arrive. This is the thread running through this whole series. The 1918 Dispensatory, writing sixty years later, had not moved on: commercial samples varied so greatly in power, it said, that it was impossible to assign the proper dose. The closest thing to a strength test anyone had was the dog assay, which the profession itself admitted was inadequate. 3. Dublin Got There First The Irish contribution to this story is bigger than it looks, and it is almost entirely forgotten. William Brooke O’Shaughnessy, born in Limerick, published his Calcutta cannabis research in 1839. Within six years it had reached Dublin, and Dublin did something useful with it: it identified the dosing problem and proposed the solution still in use today. Sir Dominic Corrigan, writing in the Dublin Hospital Gazette in 1845, was explicit about where the difficulty lay: “While the Indian hemp has much to recommend it, there are circumstances connected with it that require to be well borne in mind. The first of these is its very variable effects on different individuals.” Note what Corrigan is describing. Not batch variability — person variability. The same preparation, the same dose, different people, different results. That is a separate problem from the one McMeens identified, and it is the one that has never gone away. Donovan, meanwhile, had run into batch variability directly. He tested hemp available locally in Ireland and found it weak; his clinical results improved markedly once he was working with material supplied by O’Shaughnessy himself. He also experimented on himself, treating his own leg pain, and left one of the more memorable descriptions in the literature — walking without much consciousness of the motion of his legs, feeling as though they did not belong to him. So by 1851, Dublin had established three things: preparations differ, people differ, and the only safe response is to start small and climb slowly. There is more on Ireland’s long and strange relationship with this plant here. The measurement problem would take another ninety years to solve. The dosing advice was already right. 4. When the Standard Itself Moved Here is the detail that makes the whole picture clear. The US Dispensatory, describing the official tincture, notes almost in passing that the strength of the current preparation is about 33 per cent less than the 1890 tincture. Sit with that for a second. Not a bad batch. Not a dodgy supplier. The official standard definition of tincture of cannabis — the one every pharmacy in the country was meant to dispense against — had shifted by a third between editions of the reference book. A doctor who learned