THE DEMISE OF JCANT

The Journal of Cannabis Therapeutics is folding after a three-year run,
but editor Ethan Russo, MD, hopes no one will conclude that the field isn't
thriving. "Tough times for the journal," he says, "should not imply that
there's any dearth of information to support clinical cannabis. Exactly the
opposite is true." So why didn't JCANT make it?

Russo, a neurologist at the University of Montana, credits Lester
Grinspoon, MD, with advancing the journal idea in 1998. A 24-member
editorial board was recruited -authorities with diverse expertise- that
included Raphael Mechoulam, who had determined the structure of the THC
molecule, and Geoffrey Guy, whose company is developing cannabis-plant
extracts under license from the British government, and Tod Mikuriya, who
has been monitoring cannabis use by thousands of Californians.

The launch of JCANT in 2001, with the backing of Haworth Press, a
major publisher of scientific journals, seemed like perfect timing.
Discoveries in the 1990s had begun to elucidate the mechanism of the body's
own cannabinoid receptor system and to reveal its role in modulating
numerous vital functions. Studies were establishing the clinical potential
of phytocannabinoids (found in the plant) and synthetics (being developed
by drug companies). Russo "envisioned a publication that would highlight
the developing science, and hopefully serve as an educational resource for
physicians and scientists, as well as interested members of the lay public."

He gave JCANT three years to achieve certain key goals: at least 1,000
subscribers; orders from major university libraries; and -most important-
listing in Index Medicus, the citation database of biomedical journals
controlled by the National Library of Medicine. (Journals are evaluated by
NLM "experts" in a process analogous to an NIH review of a researcher's
grant application.)

"Advanced subscriptions were respectable," Russo wrote in a recent note
to friends and subscribers, "but the subscriber numbers did not follow
suit, nor approach our goal. North American physicians have been
particularly slow to familiarize themselves with the new literature, and to
attempt to understand what has motivated their patients to employ clinical
cannabis, frequently without their knowledge or endorsement.

"In 2002, we employed a generous grant from the Marijuana Policy
Project to attempt to enter the realm of medical libraries. Free sample
issues were offered to every such facility in the USA and Canada. Few
actual subscriptions resulted. A reality of modern publishing is that such
institutions have little shelf-space, and much sparser budgets for the new.
Even the University of Montana asked me, 'What current journal should be
abandoned to make room for this offering?' Mass mailings were met with
similar ennui."

In January of this year Index Medicus turned down JCANT's application.
By then Russo had come to realize that those few cannabinoid researchers
who conducted double-blind controlled studies -"the gold-standard of
current medical proof"- preferred to publish in bigger, more prestigious
journals. For example, William Notcutt who successfully tested GW's plant
extracts on chronic pain patients at the James Paget Hospital in Great
Yarmouth, submitted his paper to Anaesthesia (where it will soon appear).

"Although the threshold of prescription clinical cannabinoids as a
reality was nearing," wrote Russo in his requiem, "the available pool of
articles that would advance the knowledge and might lead to greater
recognition has diminished. Prospects for additional database listing seem
less than promising, and subscriber numbers have not risen despite
additional grants-in-aid."

Among JCANT's accomplishments Russo lists citations in the 2001 Report
of the National Commission on Ganja in Jamaica and Cannabis: Our Position
for a Canadian Public Policy, the report of the Canadian Senate in 2002.
Both commissions concluded that cannabis should be made available to patients.

Russo was lead author of a widely publicized paper that ran in Volume 2
describing the health status of
four patients who had been using government-issued marijuana for many years
(11 to 27) under the "Compassionate Investigational New Drug program" of
the U. S. Food and Drug Administration. The data were encouraging.
"Results demonstrate clinical effectiveness in these patients in treating
glaucoma, chronic musculoskeletal pain, spasm and nausea, and spasticity of
multiple sclerosis. All four patients are stable with respect to their
chronic conditions, and are taking many fewer standard pharmaceuticals than
previously. Mild changes in pulmonary function were observed in two
patients" [i.e., NIDA-wanna irritates the lungs]... These results support
the provision of clinical cannabis to a greater number of patients in need."

Russo has accepted a job as an advisor to G.W. Pharmaceuticals. The
company is hoping for approval by year's end to market three cannabis-plant
extracts (one high in THC, one high in CBD, and a 50-50 mix) in England. "I
expect that soon after we have prescription cannabis in England," says
Russo, "we'll have it in Western Europe, and Canada, Australia, and New
Zealand. All of a sudden, patients in the U.S. are going to be asking about
it and it will be harder for the doctors to say "There's been nothing
written about this...' They'll try, of course, but it'll be harder for them
to get away with it."

Russo says he can offer "an explanation, not an excuse for the ignorance of
my colleagues. The modern American physician has no training in this area.
They could get the training but they don't, and that's largely because of
the intimidation factor. It's a combination of ignorance and paranoia."

As if to illustrate Russo's point about the thriving state of the
cannabis-therapeutics field, several significant papers have been published
recently. "The Endogenous Cannabinoid System Regulates Seizure Frequency
and Duration in a Model of Temporal Lobe Epilepsy," by Melisa Wallace and
colleagues at Virginia Commonwealth University, appears in the current
Journal of Pharmacology and Experimental Therapeutics. Wallace et al
induced a form of epilepsy in rats that closely resembles the
partial-complex epilepsy characterized by recurrent grand mal seizures in
humans -"a refractory epilepsy condition that is not readily treated by
conventional anticonvulsants." They concluded that "activation of the CB1
receptor by cannabinoid drugs ... significantly alters seizure activity and
is more effective than conventional anticonvulsants."

Unfortunately, the authors saw fit to add, "Although the psychoactive
side effects of cannabinoids make their use in the treatment of epilepsy
impractical, understanding the mechanisms of endogenous
cannabinoid-mediated anticonvulsant action may lead to the development of
novel compounds that do not manifest behavioral toxicity." It will be a
shame -a tragedy for those with intractable epilepsy and their loved ones-
if this promising research gets sidetracked into a search for compounds
with no psychoactivity. The infamous "psychoactive side effects" of
cannabis are mild, and they become almost unnoticeable when one is taking
regular doses. Grand mal seizures can result in all kinds of damage to the
body.

Another paper of note appeared in the Oct. 3 issue of Science: "CB1
Cannabinoid Receptors and On-Demand Defense Against Excitotoxicity" by
Marsciano et al. Their hypothesis was that the brain releases an
endocannabinoid (anandamide) to protect neurons from damage caused by
abnormal electrical discharges ("spiking"). They exposed both wild-type
mice and mutant mice lacking CB1 receptors in parts of the brain to an
excitotoxin to bring on spiking. "Administration rapidly raised hippocampal
levels of anandamide and induced protective mechanisms in wild-type
principal hippocampal neurons. These protective mechanisms could not be
triggered in mutant mice. The endogenous cannabinoid system thus provides
on-demand protection against acute excitotoxicity in central nervous system
neurons."