Pubdate: Sat, 17 May 2014
Source: Jerusalem Post (Israel)
Copyright: 2014 The Jerusalem Post
Contact: http://info.jpost.com/C002/Services/Feedback/editors.html
Website: http://www.jpost.com/
Details: http://www.mapinc.org/media/516
Author: Judy Siegel-Itzkovich

THE WORLD IS GOING TO POT

Research into cannabis and its wide variety of components by Prof.
Raphael Mechoulam was ignored for decades.

Half a century ago, the Weizmann Institute of Science in Rehovot and
the National Institutes of Health in the US said they "weren't
interested" in Prof. Raphael Mechoulam's research on the active
ingredients in cannabis. Unwilling to further pursue organic chemistry
research, they were rather shortsighted.

"There wasn't a single lab in the USA that worked on cannabis. When I
asked the NIH for a grant, they said: 'Sorry, we can't give it to you.
This isn't an American problem," he recalled. Later, the NIH
reconsidered and provided him with research money for 45 years. There
is currently huge pressure throughout the US for medical cannabis to
be made available to relevant patients. Even recreational use of the
drug has been approved in the states of Colorado and Washington, and
campaigns to legalize marijuana for non-medical use are being proposed
in other states.

Today, medical marijuana - smoked, baked into cookies, infused into
oils and produced in other forms - is sought worldwide to ease the
suffering of patients with cancer, AIDS, multiple sclerosis,
Parkinson's disease, Tourette's syndrome, Crohn's disease and others.
There are currently over 14,000 authorized Israeli users, and in four
years, the figure is expected to triple. But only now are clinical
trials on the positive and negative effects of cannabis constituents
and derivatives being launched.

The 83-year-old Mechoulam sits in his Jerusalem office at the Hebrew
University Institute for Drug Research on the Hadassah Medical
Organization campus in Ein Kerem.

Although he has long passed retirement age, he is welcome to continue
his research on campus financed by grants from Israel and abroad.

IN A Jerusalem Post interview in his office and lab, Mechoulam
recalled that his father, Dr. Moreno Mechoulam, was a pediatrician,
director of the Jewish Hospital in Sofia, Bulgaria, where Raphael was
born in 1930, and president of the local Zionist organization,
Maccabi. His mother was a housewife and woman of leisure.

But the idyll ended when anti-Semitic laws were enforced by the Nazis,
and his father was sent to a concentration camp, which he survived.
After the Communist takeover of pro-German Bulgaria in 1944, Mechoulam
studied chemical engineering, which he disliked. When his family
wanted to leave the country, he was not sure if medical students would
receive permission to leave, so he studied chemistry instead. The
family immigrated to Israel the year after the establishment of the
independent Jewish state.

He went into the academic program of the Israel Defense Forces and did
research on insecticides. He finished his doctoral degree in chemistry
in the 1950s and traveled to New York for a postdoctoral fellowship at
the (then) Rockefeller Institute. Returning to Israel, he lived in Tel
Aviv with his wife Dalia, a teacher, and traveled to Rehovot every
day. Raphael and Dalia, to whom he has been married for some 55 years,
have three children - son Roy, a mathematics professor; daughter
Hadas, a pediatric ophthalmologist; and daughter Dafna, a pediatric
neurologist - and seven grandchildren.

"MORPHINE WAS isolated from opium and then cocaine from coca leaves in
the 19th century, but the active cannabis ingredient wasn't known
until our work and hence it was also not known how cannabis worked,"
Mechoulam said. A year after he encountered apathy to his research
into cannabis both in Israel and in the US, "the chief pharmacologist
of the US National Institute for Mental Health came to see me. He said
that one US senator wanted to know how marijuana affects the brain,
because his son was using it."

Among his important foreign contacts is Dr. Nora Volkow, a
Mexican-born Jewish researcher in the field of addictions who happens
to be the granddaughter of Leon Trotsky, the Russian Marxist
revolutionary, Soviet politician and founder of the Red Army. She is
now director of the US National Institute on Drug Abuse.

The global pharmaceutical firms have not been enthusiastic about
financing basic and applied research into medical cannabis because it
has existed for millennia and thus can't be patented, he explained,
adding that nevertheless the potential medical benefits are
significant - but must be proven in clinical trials.

"I looked for interesting subjects at Weizmann. I was surprised that
so little was known in my field," he said.

So innocent that he didn't realize he could have applied to the Health
Ministry to get cannabis samples for research, Mechoulam contacted the
director of the investigative branch of the Israel Police, who was a
friend of a Weizmann colleague and was himself unaware of bureaucratic
restrictions. The police officer gave him five kilos of hashish that
had been smuggled in from Lebanon.

"I remember taking the hashish home on the bus. It had a very strong
smell, and my fellow passengers wondered what it was that I was carrying."

In decades of working with marijuana, the HU scientist declares that -
unlike some American presidents - he never smoked it or otherwise used
it.

"But our team did experiment with it after we isolated the THC
[tetrahydrocannabinol, the primary psychoactive component of
cannabis]. Five people, including my wife, got 10 milligrams of THC in
the form of oil dripped on a cake, and five others got a placebo.
Everybody was affected differently. She dreamed a bit, and she hasn't
touched marijuana since. Another person didn't feel high, but he
couldn't stop talking... another had an anxiety attack."

His excellent relationship with law enforcement continued, and
Mechoulam has been getting hashish - which also comes from cannabis,
but is processed differently than marijuana - for decades.

He coined a new term, "cannabinoids" (referring to the active
constituents of cannabis) - which became a whole new field of research
with implications not only in the treatment of pain, lack of appetite
and nausea but in virtually every other field of medicine.

In 1963, working with Dr. Yechiel Gaoni and Dr. Habib Edery, Mechoulam
was the first to isolate THC as the most important active ingredient
in hashish.

"We tested the compound on rhesus monkeys, and it made all of them
fall asleep; nothing else affected them that way. The team also
elucidated THC's structure and synthesized it. We published our
findings in the Journal of the American Chemical Society the following
year."

But when he felt he wasn't getting anywhere at Weizmann, he turned
down other offers, including one from the Technion-Israel Institute of
Technology in Haifa, and moved to the School of Pharmacy in Jerusalem.

There his group discovered in the 1990s the endocannabinoids
anandamide, produced by the brain, and 2-arachidonoyl glycerol (2-AG),
produced by peripheral organs.

Endocannabinoids are a group of neuromodulatory lipids (fats), and
their receptors in the brain are involved in a variety of
physiological processes including pain-sensation, appetite, mood and
memory; they mediate the psychoactive effects of marijuana.

Regulating endocannabinoids may have therapeutic potential in almost
all human disorders including cardiovascular, metabolic, inflammatory,
liver, skin, gastrointestinal, psychiatric, oncological, pain and
neurodegenerative diseases.

He also identified cannabidiol (CBD), one of about five dozen active
cannabinoids in cannabis. This natural chemical, which often
constitutes about two-fifths of extracts of the marijuana plant, does
not cause "highs" but is useful in oil form for treating numerous
diseases, particularly those involving inflammations. CBD also reduced
sugar levels in diabetes-prone mice and reduced the effects of cardiac
ischemia (inadequate blood supply to the heart).

"We did some clinical trials years ago. For example, together with
pediatric oncologist Dr. Aya Abramov at Shaare Zedek Medical Center,
we gave THC under the tongue to children undergoing very difficult
treatment that made them nauseous and caused vomiting. All of the kids
had positive results. In a total of 450 treatments, there wasn't a
single case with nausea and vomiting. But nobody followed up on it."

Today, there are synthetic drugs for it, said former HU rector
Mechoulam, who has received numerous prestigious awards including the
Israel Prize in exact sciences (2000), Rothschild Prize in chemical
sciences and physical sciences (2012), EMET Prize in chemistry (2012),
Hebrew University Medical Faculty Prize for excellence in research
(2010) and numerous foreign awards, and who in 1994 was elected to the
Israel Academy of Sciences and Humanities.

"Thirty-five years ago, we did a clinical study on epilepsy with CBD
in Brazil. The results there too were excellent, and there were no
side effects, but no other researchers followed it up. Studies by our
and other groups showed that CBD helped schizophrenia patients, but
again, nobody was interested. Hospital Helsinki committees [charged
with giving approval for suitable medical experimentation on humans]
don't always approve use of medical cannabis," said the HU researcher.

"Together with clinicians at the Geha Psychiatric Hospital we are
trying to get a permit to evaluate CBD on patients with anxiety and
suicidal tendencies, but we haven't received one yet. There are
hundreds of published articles on cannabinoids and cancer, but not one
well-established clinical trial. It's a vicious cycle; researchers
don't give the compounds to patients because there are no serious
clinical trials, and clinical trials are not conducted in the US
because there is no approval for giving the drugs."

Mechoulam said he "wouldn't give medical cannabis for everything.
Israel is going in the right direction by giving approval gradually
for different diseases. It's impossible to know if people who say
they're in terrible pain [actually are] because it's subjective and
can't be measured. I presume there is some abuse. Driving is a
problem, because it can cause confusion and slow reactions, but legal
users generally avoid driving."

He stresses that approval of recreational cannabis is a social issue
and not a medical one. Personally he does not support the approval of
recreational cannabis in Israel.

And he also regards alcoholism, gambling and smoking tobacco as "very
dangerous."

He predicted that in another decade, the approved use of medical
cannabis for all kinds of conditions will be central, as medications
will be prepared that work like THC but without the active ingredient
that causes a "high" effect on patients.

Mechoulam has not confined his interest only to cannabis. He has done
research on levona, the Hebrew word for frankincense or Boswellia
sacra, which was used as incense in the Holy Temple in Jerusalem. The
Hebrew University chemist, together with his then PhD student Arieh
Moussaieff, showed that a major ingredient of Middle Eastern incense
lowers anxiety and has an antidepressant-like effect on mice.

"The Talmud mentions Boswellia resin as a potion put in wine to
'benumb the senses' so that [those] condemned to death would not
worry... It [their findings] provides a biological basis for deeply
rooted cultural and religious traditions."

Thus, Mechoulam's research gives new meaning to the term "High
Priest."  
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MAP posted-by: Jo-D