Mil­lions of peo­ple use cannabis as a medicine. That’s not based on clin­i­cal ev­i­dence, nor do we know which of the hun­dreds of com­pounds in the plant is re­spon­si­ble for its sup­posed ef­fects. EL­IZ­A­BETH FINKEL re­ports.

Cosmos - - Front Page -

THE BE­FORE SHOWED the boy hel­meted, hands tied be­hind his back, butting his head against a wall. The af­ter showed him calmly sit­ting at a ta­ble, sketch­ing. The dif­fer­ence: two drops of cannabis oil ad­min­is­tered be­low the tongue. The video had been sent to Meiri by Abi­gail Dar, an Is­raeli cham­pion for the use of cannabis in chil­dren with autism.

Early this year it was a dif­fer­ent story. Over the course of a day, Meiri’s lab re­ceived a stream of phone calls from Dar: a few autis­tic chil­dren had gone berserk af­ter re­ceiv­ing their two drops of oil.

Meiri, who is pri­mar­ily a cancer re­searcher, re­ceived the video and the calls be­cause he has, re­luc­tantly, be­come one of Is­rael’s cannabis ex­perts. “Even now I am re­luc­tant to tell peo­ple I work on med­i­cal cannabis,” he says. “I am not pro-cannabis; I think 90% is placebo.”

But Is­rael is in the grip of a vast med­i­cal ex­per­i­ment. Cannabis has taken hold here to treat a star­tling range of med­i­cal con­di­tions. Not just fa­mil­iar things like anorexia and pain in cancer pa­tients but autism, Crohn’s dis­ease, Tourette’s syn­drome, epilep­tic seizures, mul­ti­ple scle­ro­sis, arthri­tis, di­a­betes and more. With close to 30,000 users in a pop­u­la­tion of eight mil­lion, Meiri says “ev­ery­one knows some­one who is be­ing treated with cannabis”. While there is a sem­blance of or­derly medicine, with doc­tors pre­scrib­ing cannabis oil from eight reg­is­tered grow­ers, no one can say just what, ex­actly, is re­spon­si­ble for the ap­par­ent re­sponses.

A cannabis plant is a pot-pourri of more than 500 chem­i­cals whose abun­dance varies greatly across dif­fer­ent ge­netic strains and ac­cord­ing to growth con­di­tions – they’re not cul­ti­vars so much as chemovars. The medic­i­nal ef­fect may de­pend on tetrahy­dro­cannabi­nol (THC), the chem­i­cal that gives you the high, or cannabid­iol (CBD), which is thought to re­duce in­flam­ma­tion and pain, or a hun­dred other “cannabi­noids” unique to the plant with their own medic­i­nal pro­file (see chart, op­po­site page). Bot­tom line: with dozens of va­ri­eties grown un­der dif­fer­ent con­di­tions, Is­raeli pa­tients are re­ceiv­ing quite dif­fer­ent medic­i­nal con­coc­tions.

Is­rael’s predica­ment is tame by com­par­i­son to the United States. Here it is the Wild West. Fed­eral sher­iffs out­law med­i­cal re­search on the plant while cannabis cow­boys ped­dle chemovars (vary­ing in their con­tent of THC and CBD) for cures and profit. In the 29 US states that have le­galised med­i­cal cannabis, dis­pen­saries that look like some­thing out of a Harry Pot­ter tale sell can­dies, cook­ies, oils, oint­ments and joints to an es­ti­mated 2.3 mil­lion Amer­i­cans. As to their ex­act med­i­cal ben­e­fits and risks, no one knows. This is me­dieval medicine – akin to boil­ing willow bark to treat headache. It is also great busi­ness – the North Amer­i­can mar­ket for le­gal cannabis prod­ucts grew 30% in 2016, with sales top­ping $US6.7 bil­lion .

Is­rael’s med­i­cal cannabis mess is a lot eas­ier to deal with. To help ad­dress it, Meiri’s lab­o­ra­tory of Cancer Bi­ol­ogy and Cannabi­noid Re­search is con­duct­ing a re­verse clin­i­cal trial. While pa­tients us­ing med­i­cal cannabis fill in a monthly ques­tion­naire, the ranks of an­a­lyt­i­cal ma­chines burst­ing out of Meiri’s lab cre­ate chem­i­cal fin­ger­prints of the cannabis ex­tracts pa­tients are us­ing. The idea is to try and link in­di­vid­ual cannabis com­pounds to the pa­tient re­sponse.

It is an ap­proach that’s “two or three rungs down” from the ideal of ran­domised placebo-con­trolled clin­i­cal tri­als (RCTS), says Don­ald Abram­son, an on­col­o­gist at the Univer­sity of Cal­i­for­nia, San Fran­cisco, who pre­scribes cannabis as a pal­lia­tive for pa­tients with cancer. “But, if well done and there’s a strong ef­fect, ob­ser­va­tional stud­ies like these are in­valu­able.”

Is­rael is also one of the few places in the world push­ing for­ward with gold-stan­dard RCTS. But given

LAST YEAR DEDI MEIRI, a cannabis re­searcher at the Tech­nion, Is­rael’s old­est univer­sity, re­ceived a “be­fore and af­ter” video of an autis­tic boy.

that dozens of cannabis strains are al­ready be­ing used for a bal­loon­ing num­ber of con­di­tions, RCTS seem like a fin­ger in the dyke.

Coun­tries like Australia, where the fed­eral gov­ern­ment le­galised med­i­cal cannabis just last De­cem­ber, are en­ter­ing this brave new world with trep­i­da­tion. “Be­cause there has been no proper re­search, we’re now at a dif­fi­cult cross­roads,” says Univer­sity of Mel­bourne phar­ma­col­o­gist James An­gus, who chairs the fed­eral gov­ern­ment’s ad­vi­sory coun­cil on the med­i­cal use of cannabis. “Our health work­force has no guide­lines or ex­pe­ri­ence in pre­scrib­ing, and pa­tients are de­mand­ing it. We’ve run out of time.”

The Promised Land may well be the world’s best bet for de­liv­er­ance from the med­i­cal cannabis mess.

ANECDOTES ON THE med­i­cal use of cannabis go back to myth­i­cal Chi­nese em­peror Shen Neng in 2700 BCE. More pi­quant ref­er­ences can be found in an­cient Ro­man, Greek and In­dian texts. Or just google.

Thou­sands of years on from Shen Neng, it seems we still don’t have a great deal more than anecdotes to go on. As re­port from the US Na­tional Acad­e­mies of Sci­ence in Jan­uary 2017 states: “De­spite in­creased cannabis use and a chang­ing state-level pol­icy land­scape, con­clu­sive ev­i­dence re­gard­ing the short­and long-term health ef­fects – both harms and ben­e­fits – of cannabis use re­mains elu­sive.”

While the med­i­cal uses of the opium poppy, a vastly more dan­ger­ous plant, are well un­der­stood, cannabis has re­mained stuck in a no man’s land. It had been part of the US phar­ma­copeia till the 1930s, as an al­co­hol­based tinc­ture, un­til the fed­eral gov­ern­ment ef­fec­tively out­lawed its pos­ses­sion and sale through the Mar­i­juana Tax Act. More dra­co­nian penal­ties fol­lowed. It is still de­monised by fed­eral law as a ‘Sched­ule 1’ drug with no med­i­cal use, lumped in the same cat­e­gory as heroin, LSD and ec­stasy. Yet as a quick on­line search will show, the plant is lauded for a seem­ingly in­ex­haustible list of cu­ra­tive prop­er­ties.

In the past two decades the dis­par­ity be­tween ev­i­dence and anecdotes has grown ex­treme. De­spite a ma­jor­ity of states (be­gin­ning with Cal­i­for­nia in 1996) hav­ing le­galised cannabis to treat med­i­cal con­di­tions, fed­eral re­stric­tions on re­search re­mained iron­clad. So re­searchers can­not study whether such med­i­cal uses have any ba­sis in sci­ence. “What we have is a per­fect storm,” says Daniele Piomelli, a neu­ro­bi­ol­o­gist at the Univer­sity of Cal­i­for­nia, Irvine.

Piomelli has been re­search­ing cannabis as best as he can. To com­ply with the man­dates of the fed­eral Drug En­force­ment Agency (DEA), his pre­cious store of 50 mil­ligrams of THC must be kept in a locked safe, in a locked cool room, in a locked lab. “Any per­son on the street can go to a dis­pen­sary and for $10 ob­tain cannabis,” he says. “But if we bring it into the univer­sity

Cannabis con­tains more than 500 chem­i­cals. There are 104 cannabi­noids unique to the plant as well as flavonoids, ter­penes and fatty acids. Re­search is fo­cused on the non-psy­choac­tive cannabi­noids shown.

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