INNOVATION  

It’s the dose that counts

An ancient med­i­c­inal plant is making a come­back. Although its recre­ational use is con­tro­ver­sial, the med­ical use of cannabis can help many severely ill patients. The key to symptom alle­vi­a­tion without serious side effects is pre­cise dosage.

The evi­dence for the ther­a­peutic ben­e­fits of cannabis is aston­ishing. Its active sub­stances, par­tic­u­larly the cannabi­noids THC and CBD, ease chronic pain and side effects of chemotherapy, and reduce spas­ticity and inflam­ma­tion. Despite this, for decades the plant was never used as med­ica­tion or only when all other drugs had failed, as it was clas­si­fied in most coun­tries around the globe as a nar­cotic drug and was illegal.

Even­tu­ally the thinking began to change. Increasing num­bers of physi­cians value the ther­a­peutic poten­tial of the ­flowers of the plant, the leaves of which resemble a hand with the ­fin­gers out­stretched. As of spring 2017, cannabis can be pre­scribed by physi­cians in Ger­many and obtained from phar­ma­cies in dried form or as a ready-to-use prepa­ra­tion. A sep­a­rate au­thority within the German Fed­eral Insti­tute for Drugs and Med­ical Devices (BfArM), the Cannabis Agency, mon­i­tors the import, quality, dis­pen­sa­tion, and in the future the cul­ti­va­tion of canna­bis as well. Other coun­tries, such as Canada and 28 states in the United States of America, approved cannabis for med­ical use and in some cases even for recre­ational use much earlier. 

The founder of Syqe, Perry Davidson, banks on the admin­is­tra­tion of cannabis in a med­ically con­trol­lable dosage. The first inhaler series and its ver­sion for hos­pital use are from the 3D printer.

Among the pio­neers is Israel, where Pro­fessor Raphael ­Mechoulam and the sci­en­tists working with him were the first to iden­tify the most impor­tant sub­stances in cannabis and also dis­cov­ered the human system of cannabi­noid recep­tors. Today, well over 25,000 Israelis legally receive med­ical cannabis, and the research is sup­ported by the health min­istry. This is man­i­fested in the com­mit­ment of Perry Davidson, founder and CEO of the start-up Syqe Med­ical from Tel Aviv, who is ded­i­cated to increasing accep­tance of cannabis as a med­ical treat­ment both in the gen­eral public and among patients. He aimed at deliv­ering to patients the lowest pos­sible, repro­ducibly pre­cise and med­ically con­trol­lable dosage, without adverse psy­choac­tive effects wher­ever possible.

Effec­tive inhalation

The most effi­cient admin­is­tra­tion route for medi­cinal cannabis is inhala­tion. Studies have shown that the quan­tity of THC released with the Syqe inhaler is three times higher than during smoking.

Cannabis and its effects

The cannabis plant (Cannabis indica or sativa), a form of hemp, is rich in ingre­di­ents, including more than 100 cannabi­noids. The most impor­tant of these are delta-9-tetrahy­dro­cannabinol (THC, dron­abinol) and cannabidiol (CBD), the con­tent of which may be as high as 20 per­cent, depending on the variety. Hemp grown for fiber and commer­cial uses have only traces of these sub­stances. THC acts on the ner­vous system via the body’s own recep­tors, changing the per­ception and sen­si­tivity to pain. The non-­psy­chotropic CBD can, among other things, stim­u­late appetite and inhibit tumor growth. Only the female plants supply the raw mate­rial for the drug known as cannabis. Dried flowers are also known as mar­i­juana, while the oily resin is also called hashish, or hash. In the plant, the cannabi­noids THC and CBD are present as acids, which are con­verted into the phar­ma­co­log­i­cally active forms only when heated. Cannabis extracts as well as syn­thet­i­cally pro­duced THC and CBD are also avail­able as ready-to-use phar­ma­ceu­tical prepa­ra­tions (drops, oral spray, capsules).

Smart metered-dose inhaler

Syqe Med­ical there­fore devel­oped an intel­li­gent aerosol inhaler that is capable of elec­tron­i­cally con­trol­ling the dis­pen­sa­tion of the active sub­stance in 100-micro­gram incre­ments and imme­di­ately trans­mit­ting all rel­e­vant data to the attending physi­cian via a smart­phone app. First series of the devices are manu­factured at Syqe using a 3D printer. They con­tain a replace­able mag­a­zine with 75 single doses, each with 10 to 15 mil­ligrams of cannabis in rig­or­ously con­trolled quality. During the inhala­tion pro­ce­dure, the dried herb is heated, but does not burn; the ­volatile sub­stances evap­o­rate. In con­trast to when it is taken orally, the pain-relieving, relaxing effect sets in just a few ­min­utes after inhalation. 

For the micro­dosing of cannabis in the car­tridges for the inhaler, Perry Davidson decided that the tech­nology from Harro Höfliger was the best option. “The admin­is­tra­tion of untreated plant mate­rial via a metered-dose inhaler is a very spe­cial chal­lenge, and there is very little empir­ical evi­dence to work with,“ he says. “During our research we quickly dis­cov­ered Harro ­Höfliger. Their diverse range of dosing sys­tems and rel­e­vant expe­ri­ence with unusual inhala­tion projects con­vinced us that they were the right choice. We’ve been col­lab­o­rating suc­cess­fully since early 2016.” 

Davidson was also impressed by the imag­i­na­tive ideas incor­po­rated in the ini­tial series of dosing tests by the spe­cial­ists at Harro Höfliger. Because the test cannabis was still on its way from the sup­plier, they simply used pow­dered indus­trial hemp, which is easily and legally available. 

About Syqe

Syqe Med­ical in Tel Aviv is devel­oping med­ical administra­tion forms for cannabis and other botan­i­cals and employs a multi-dis­ci­pli­nary team of elec­tronic and mechan­ical engi­neers, indus­trial designers, chemists, biol­o­gists, physi­cians and phar­ma­col­o­gists. The enter­prise was founded by Perry Davidson in 2011.

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Photos: Eyal Izhar, Syqe Medical